M. F. Nørremark, R. Petersen, P. M. M. Ruppert, E. S. Jul, T. K. Doktor, R. Nielsen, J. F. Kappel, S. Larsen, J. W. Kornfeld, S. Mandrup, B. S. Andresen, J. Havelund, D. Neess, N. J. Færgeman
Aim
Acyl-CoA binding protein plays a vital role in lipid metabolism by mediating the intracellular flux and utilization of long-chain acyl-CoAs. We generated an adipocyte-wide ACBP knockout mouse and a brown adipose tissue-specific ACBP knockout mouse to investigate ACBP function in adipose tissue.
Methods
Male mice with conditional targeting of the Acbp gene in adipose tissue (Adipoq-Acbp−/−) or brown adipose tissue (Ucp1-Acbp−/−) were generated by crossing Acbpflox/flox mice with transgenic mice expressing Cre recombinase under the control of the adiponectin (Adipoq-Cre) or uncoupling protein 1 (Ucp1-Cre) promoter, respectively. Systemic energy expenditure was assessed by indirect calorimetry. Body composition was examined using nuclear magnetic resonance. Primary brown and white preadipocytes were isolated to examine their ability to differentiate to mature adipocytes. Lipid composition of adipose tissues was examined by lipidomics. Global changes in gene expression in adipose tissues were examined by RNA sequencing. Tissue respiration was determined using high-resolution respirometry.
Results
We demonstrate that loss of ACBP in adipose tissue does not affect body weight, fat and lean mass, food intake and systemic energy expenditure, even under cold stress. Global gene expression analysis shows only minor changes in gene expression, whereas lipidomic profiling reveals a subtle increase in acyl-carnitine levels in brown adipose tissue. Lipolytic activity in white adipose tissue as well as plasma glycerol, nonesterified fatty acid and triacylglycerol levels remained unaffected. In addition, no changes in mitochondrial respiration in BAT were observed.
Conclusion
Our findings suggest that ACBP is dispensable for adipose tissue function and systemic energy metabolism.
{"title":"Acyl-CoA Binding Protein in White and Brown Adipose Tissue Is Dispensable for Systemic Energy Metabolism in Mice","authors":"M. F. Nørremark, R. Petersen, P. M. M. Ruppert, E. S. Jul, T. K. Doktor, R. Nielsen, J. F. Kappel, S. Larsen, J. W. Kornfeld, S. Mandrup, B. S. Andresen, J. Havelund, D. Neess, N. J. Færgeman","doi":"10.1111/apha.70159","DOIUrl":"10.1111/apha.70159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Acyl-CoA binding protein plays a vital role in lipid metabolism by mediating the intracellular flux and utilization of long-chain acyl-CoAs. We generated an adipocyte-wide ACBP knockout mouse and a brown adipose tissue-specific ACBP knockout mouse to investigate ACBP function in adipose tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male mice with conditional targeting of the <i>Acbp</i> gene in adipose tissue (Adipoq-<i>Acbp</i><sup><i>−/−</i></sup>) or brown adipose tissue (Ucp1-<i>Acbp</i><sup><i>−/−</i></sup>) were generated by crossing <i>Acbp</i><sup><i>flox/flox</i></sup> mice with transgenic mice expressing Cre recombinase under the control of the adiponectin (<i>Adipoq-Cre</i>) or uncoupling protein 1 (<i>Ucp1-Cre</i>) promoter, respectively. Systemic energy expenditure was assessed by indirect calorimetry. Body composition was examined using nuclear magnetic resonance. Primary brown and white preadipocytes were isolated to examine their ability to differentiate to mature adipocytes. Lipid composition of adipose tissues was examined by lipidomics. Global changes in gene expression in adipose tissues were examined by RNA sequencing. Tissue respiration was determined using high-resolution respirometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that loss of ACBP in adipose tissue does not affect body weight, fat and lean mass, food intake and systemic energy expenditure, even under cold stress. Global gene expression analysis shows only minor changes in gene expression, whereas lipidomic profiling reveals a subtle increase in acyl-carnitine levels in brown adipose tissue. Lipolytic activity in white adipose tissue as well as plasma glycerol, nonesterified fatty acid and triacylglycerol levels remained unaffected. In addition, no changes in mitochondrial respiration in BAT were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that ACBP is dispensable for adipose tissue function and systemic energy metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12791089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Biological processes are structured over 24 h by endogenous time-keeping systems, called circadian clocks that are reset daily by external (e.g., ambient light) and internal synchronizers (e.g., glucocorticoids (GC)). The suprachiasmatic nuclei of the hypothalamus (SCN) are a key structure of the circadian timing system because they contain a master circadian clock that controls the daily timing of most behavioral and physiological functions, including the sleep–wake cycle and hormonal rhythms. In this issue of <i>Acta Physiologica</i>, Sládek et al. [<span>1</span>] provide convincing experimental evidence for the presence of functional GC receptors (GR) in the SCN of adult rats and mice.</p><p>GC synthesized in the adrenal glands are mostly known for their roles in stress responses, metabolism, and immunity. However, their daily rhythmic secretion with peaks around wake-up time provides for an important internal synchronizer of the circadian system, especially for peripheral tissues such as adipose tissue and liver, and brain areas like the raphe nuclei and central amygdala [<span>2</span>]. During development, the SCN of fetuses that express high levels of GR can be synchronized by maternal GC [<span>3, 4</span>]. Until now, it was thought that GR is no longer expressed in adult SCN cells [<span>5, 6</span>], leading to the prevailing view that GC and associated stress responses do not feedback directly to the master clock in adulthood. Accordingly, modulatory effects of glucocorticoids on the master clock functions, notably its synchronization to ambient light, were considered to be indirectly mediated via sensitive cerebral targets projecting to the SCN, like the raphe nuclei [<span>2, 7</span>].</p><p>By demonstrating high expression of GR and of <i>Nr3c1</i> encoding GR in the adult SCN cells, Sládek and collaborators challenge a current dogma in the field of circadian research. Depending on the detection method used (i.e., RT-qPCR, in situ hybridization, immunohistochemistry, western blot), the relative level of expression may vary considerably from one study to another. Nevertheless, the links between levels of expression of GR, their functionality and the physiological effects of GC on the studied structure should always be questioned. Here the authors demonstrate that in vivo administration of dexamethasone (DEX), a synthetic glucocorticoid, activates the transcription of GC target genes, such as <i>Gilz</i> and <i>Sgk1</i>, within the adult SCN [<span>1</span>]. From a physiological perspective, these observations reveal that SCN cells are directly sensitive to GC and receive direct feedback information from circulating GC. These new findings are consistent with the modulation of GR expression levels in the SCN by circulating GC concentrations [<span>8</span>].</p><p>Sládek et al. [<span>1</span>] also confirm that in vitro DEX treatment can induce phase-shifts in the fetal SCN clock, but not in the mature master clock. Interesting
{"title":"Glucocorticoid Feedback on the Adult Suprachiasmatic Clock","authors":"Dominique Sage-Ciocca, Etienne Challet","doi":"10.1111/apha.70156","DOIUrl":"10.1111/apha.70156","url":null,"abstract":"<p>Biological processes are structured over 24 h by endogenous time-keeping systems, called circadian clocks that are reset daily by external (e.g., ambient light) and internal synchronizers (e.g., glucocorticoids (GC)). The suprachiasmatic nuclei of the hypothalamus (SCN) are a key structure of the circadian timing system because they contain a master circadian clock that controls the daily timing of most behavioral and physiological functions, including the sleep–wake cycle and hormonal rhythms. In this issue of <i>Acta Physiologica</i>, Sládek et al. [<span>1</span>] provide convincing experimental evidence for the presence of functional GC receptors (GR) in the SCN of adult rats and mice.</p><p>GC synthesized in the adrenal glands are mostly known for their roles in stress responses, metabolism, and immunity. However, their daily rhythmic secretion with peaks around wake-up time provides for an important internal synchronizer of the circadian system, especially for peripheral tissues such as adipose tissue and liver, and brain areas like the raphe nuclei and central amygdala [<span>2</span>]. During development, the SCN of fetuses that express high levels of GR can be synchronized by maternal GC [<span>3, 4</span>]. Until now, it was thought that GR is no longer expressed in adult SCN cells [<span>5, 6</span>], leading to the prevailing view that GC and associated stress responses do not feedback directly to the master clock in adulthood. Accordingly, modulatory effects of glucocorticoids on the master clock functions, notably its synchronization to ambient light, were considered to be indirectly mediated via sensitive cerebral targets projecting to the SCN, like the raphe nuclei [<span>2, 7</span>].</p><p>By demonstrating high expression of GR and of <i>Nr3c1</i> encoding GR in the adult SCN cells, Sládek and collaborators challenge a current dogma in the field of circadian research. Depending on the detection method used (i.e., RT-qPCR, in situ hybridization, immunohistochemistry, western blot), the relative level of expression may vary considerably from one study to another. Nevertheless, the links between levels of expression of GR, their functionality and the physiological effects of GC on the studied structure should always be questioned. Here the authors demonstrate that in vivo administration of dexamethasone (DEX), a synthetic glucocorticoid, activates the transcription of GC target genes, such as <i>Gilz</i> and <i>Sgk1</i>, within the adult SCN [<span>1</span>]. From a physiological perspective, these observations reveal that SCN cells are directly sensitive to GC and receive direct feedback information from circulating GC. These new findings are consistent with the modulation of GR expression levels in the SCN by circulating GC concentrations [<span>8</span>].</p><p>Sládek et al. [<span>1</span>] also confirm that in vitro DEX treatment can induce phase-shifts in the fetal SCN clock, but not in the mature master clock. Interesting","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Birgitta W. van der Kolk, Sini Heinonen, James W. White, Anita Wagner, Jari E. Karppinen, Sina Saari, Maheswary Muniandy, Simo Metsikkö, Eugène T. Dillon, Per-Henrik Groop, Tuure Saarinen, Carel W. Le Roux, Kirsi A. Virtanen, Neil G. Docherty, Eija Pirinen, Anne Juuti, Kirsi H. Pietiläinen
Aim
We investigated how weight loss induced by bariatric surgery or lifestyle intervention affects skeletal muscle mitochondrial metabolism.
Methods
We studied two weight-loss cohorts: RYSA (BMI ≥ 35 kg/m2; n = 39, including 18 with diabetes) undergoing bariatric surgery, and CRYO (BMI ≥ 30 kg/m2; n = 19) undergoing a lifestyle intervention with a low-calorie diet. Assessments were performed at 5–6 and 12 months and included muscle proteome (LC–MS/MS), mitochondrial biogenesis by mtDNA amount (qPCR), number and morphology (transmission electron microscopy) in both cohorts, and mitochondrial oxidative capacity (high-resolution respirometry) in the surgery cohort.
Results
Both cohorts achieved clinically meaningful weight loss, greater following surgery (24.4% vs 9.0% at 12 months). Per 1% weight loss, bariatric surgery was associated with significant downregulation of glycolysis pathways at 12 months. OXPHOS complex subunit proteins were associated with upregulation in individuals without diabetes but downregulation in those with diabetes. Lifestyle intervention was associated with downregulated OXPHOS complex subunits at 5 months. Mitochondrial morphology remained unchanged, while mtDNA amount correlated negatively with weight loss percentage in both cohorts. In the surgery cohort, complex I and complex I + II-mediated respiration increased 3.2- and 2.9-fold at 12 months, reflecting improved oxidative capacity.
Conclusion
Bariatric surgery was associated with increased skeletal muscle mitochondrial respiration despite unchanged morphology and reduced mtDNA amount, whereas lifestyle-induced weight loss showed a transient downregulation of OXPHOS-related proteins with other mitochondrial markers remaining stable. Surgery-induced weight loss may reflect improved mitochondrial efficiency in skeletal muscle, potentially influenced by diabetes status. Long-term functional mitochondrial adaptations after weight loss require future studies.
Trial Registration
RYSA: ClinicalTrials.gov ID NCT02882685; CRYO: ClinicalTrials.gov ID NCT01312090
目的：我们研究减肥手术或生活方式干预对骨骼肌线粒体代谢的影响。方法：我们研究了两个减肥队列：接受减肥手术的RYSA （BMI≥35 kg/m2; n = 39，包括18名糖尿病患者）和接受低热量饮食生活方式干预的CRYO （BMI≥30 kg/m2; n = 19）。在5-6个月和12个月时进行评估，包括肌肉蛋白质组（LC-MS/MS），两个队列的线粒体生物发生（mtDNA数量（qPCR），数量和形态（透射电镜）），以及手术队列的线粒体氧化能力（高分辨率呼吸测量）。结果：两组患者均实现了临床意义上的体重减轻，手术后体重减轻幅度更大（12个月时分别为24.4%和9.0%）。每减重1%，减肥手术与12个月时糖酵解通路的显著下调相关。OXPHOS复合物亚基蛋白在非糖尿病个体中与上调相关，而在糖尿病个体中与下调相关。生活方式干预与5个月时下调OXPHOS复合物亚基相关。在两个队列中，线粒体形态保持不变，而mtDNA数量与体重减轻率呈负相关。在手术队列中，复合体I和复合体I + ii介导的呼吸在12个月时增加了3.2倍和2.9倍，反映出氧化能力的改善。结论：减肥手术与骨骼肌线粒体呼吸增加有关，尽管形态学不变，mtDNA数量减少，而生活方式引起的体重减轻显示出oxphos相关蛋白的短暂下调，但其他线粒体标志物保持稳定。手术引起的体重减轻可能反映了骨骼肌线粒体效率的提高，这可能受到糖尿病状态的影响。减肥后线粒体的长期功能适应需要进一步的研究。试验注册：RYSA: ClinicalTrials.gov ID NCT02882685；CRYO: ClinicalTrials.gov编号NCT01312090。
{"title":"Human Skeletal Muscle Mitochondria Responses to Weight Loss Induced by Bariatric Surgery or Lifestyle Intervention","authors":"Birgitta W. van der Kolk, Sini Heinonen, James W. White, Anita Wagner, Jari E. Karppinen, Sina Saari, Maheswary Muniandy, Simo Metsikkö, Eugène T. Dillon, Per-Henrik Groop, Tuure Saarinen, Carel W. Le Roux, Kirsi A. Virtanen, Neil G. Docherty, Eija Pirinen, Anne Juuti, Kirsi H. Pietiläinen","doi":"10.1111/apha.70150","DOIUrl":"10.1111/apha.70150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We investigated how weight loss induced by bariatric surgery or lifestyle intervention affects skeletal muscle mitochondrial metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied two weight-loss cohorts: RYSA (BMI ≥ 35 kg/m<sup>2</sup>; <i>n</i> = 39, including 18 with diabetes) undergoing bariatric surgery, and CRYO (BMI ≥ 30 kg/m<sup>2</sup>; <i>n</i> = 19) undergoing a lifestyle intervention with a low-calorie diet. Assessments were performed at 5–6 and 12 months and included muscle proteome (LC–MS/MS), mitochondrial biogenesis by mtDNA amount (qPCR), number and morphology (transmission electron microscopy) in both cohorts, and mitochondrial oxidative capacity (high-resolution respirometry) in the surgery cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both cohorts achieved clinically meaningful weight loss, greater following surgery (24.4% vs 9.0% at 12 months). Per 1% weight loss, bariatric surgery was associated with significant downregulation of glycolysis pathways at 12 months. OXPHOS complex subunit proteins were associated with upregulation in individuals without diabetes but downregulation in those with diabetes. Lifestyle intervention was associated with downregulated OXPHOS complex subunits at 5 months. Mitochondrial morphology remained unchanged, while mtDNA amount correlated negatively with weight loss percentage in both cohorts. In the surgery cohort, complex I and complex I + II-mediated respiration increased 3.2- and 2.9-fold at 12 months, reflecting improved oxidative capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Bariatric surgery was associated with increased skeletal muscle mitochondrial respiration despite unchanged morphology and reduced mtDNA amount, whereas lifestyle-induced weight loss showed a transient downregulation of OXPHOS-related proteins with other mitochondrial markers remaining stable. Surgery-induced weight loss may reflect improved mitochondrial efficiency in skeletal muscle, potentially influenced by diabetes status. Long-term functional mitochondrial adaptations after weight loss require future studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>RYSA: ClinicalTrials.gov ID NCT02882685; CRYO: ClinicalTrials.gov ID NCT01312090</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colonic bicarbonate secretion is mediated by the chloride/bicarbonate exchanger SLC26A3 and the cystic fibrosis transmembrane conductance regulator (CFTR). Dysfunction of either causes luminal acidosis, altered mucus properties, and inflammation. While physical and functional interactions have been demonstrated in heterologous systems, their relationship in native epithelium is not fully established. We investigated the distinct roles of SLC26A3 and CFTR using human intestinal organoids with inducible SLC26A3 overexpression.
Methods
Human colonic and rectal organoids from healthy controls and cystic fibrosis patients with F508del mutations were studied in the proliferative state with high endogenous CFTR expression and inducible SLC26A3 overexpression. Real-time surface pH measurements, electrophysiological analysis, forskolin-induced swelling assays, and confocal microscopy were employed.
Results
Steady-state surface pH was lower in CF versus healthy organoids (7.23 ± 0.03 vs. 7.34 ± 0.03). SLC26A3 overexpression normalized surface pH in CF organoids and CFTR-inhibited organoids, equalizing responses between genotypes. SLC26A3 overexpression corrected abnormal morphology and significantly improved intracellular MUC2 distribution in CF organoids. However, SLC26A3 did not restore fluid secretion in CF organoids or enhance CFTR-mediated electrogenic anion secretion in Ussing chambers.
Conclusions
SLC26A3 and CFTR perform distinct yet complementary functions. SLC26A3 dominates surface pH regulation and maintains bicarbonate efflux independently of CFTR, while CFTR drives agonist-stimulated fluid secretion. SLC26A3's ability to restore pH homeostasis and normalize mucin intracellular distribution in CF organoids demonstrates its critical importance for maintaining colonic mucosal health.
{"title":"Distinct Roles of SLC26A3 and CFTR in Surface pH Regulation and Bicarbonate Secretion in Human Intestinal Epithelium","authors":"Mahdi Amiri, Azam Salari, Ursula Seidler","doi":"10.1111/apha.70157","DOIUrl":"10.1111/apha.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Colonic bicarbonate secretion is mediated by the chloride/bicarbonate exchanger SLC26A3 and the cystic fibrosis transmembrane conductance regulator (CFTR). Dysfunction of either causes luminal acidosis, altered mucus properties, and inflammation. While physical and functional interactions have been demonstrated in heterologous systems, their relationship in native epithelium is not fully established. We investigated the distinct roles of SLC26A3 and CFTR using human intestinal organoids with inducible SLC26A3 overexpression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human colonic and rectal organoids from healthy controls and cystic fibrosis patients with F508del mutations were studied in the proliferative state with high endogenous CFTR expression and inducible SLC26A3 overexpression. Real-time surface pH measurements, electrophysiological analysis, forskolin-induced swelling assays, and confocal microscopy were employed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Steady-state surface pH was lower in CF versus healthy organoids (7.23 ± 0.03 vs. 7.34 ± 0.03). SLC26A3 overexpression normalized surface pH in CF organoids and CFTR-inhibited organoids, equalizing responses between genotypes. SLC26A3 overexpression corrected abnormal morphology and significantly improved intracellular MUC2 distribution in CF organoids. However, SLC26A3 did not restore fluid secretion in CF organoids or enhance CFTR-mediated electrogenic anion secretion in Ussing chambers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SLC26A3 and CFTR perform distinct yet complementary functions. SLC26A3 dominates surface pH regulation and maintains bicarbonate efflux independently of CFTR, while CFTR drives agonist-stimulated fluid secretion. SLC26A3's ability to restore pH homeostasis and normalize mucin intracellular distribution in CF organoids demonstrates its critical importance for maintaining colonic mucosal health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aimi D. K. Hamilton, Johanna Hornhaver, Laura V. Sparsoe, Mads Vaarby Sorensen, Helle Praetorius
Aim
Urinary tract infections (UTIs) are common and frequently caused by uropathogenic Escherichia coli (UPEC). Whether urinary pH has any influence on the development and progression of UTIs is still widely debated. In this study, we systematically address whether urinary pH affected progression and dissemination of UTIs.
Methods
To assess the effect of urine pH on the development of UTI in vivo, 8–10-week-old female Balb/cJRj mice were randomized to 100 mM NH4Cl (acid-load), 100 mM NaHCO3 (base-load), or demineralised water as drinking water intervention 24 h before UTI was induced via installation of either UPEC or vehicle in the urinary bladder.
Results
Acid load lowered urinary pH by 0.8–1.0 pH points (p < 0.0001), decreased [HCO3−] (p = 0.0002), and increased [titratable acid] (TA, p = 0.0007), [NH4+] (p < 0.0001) and net acid concentration (NAC, p < 0.0001), while base load raised urinary pH by 0.3–0.7 pH points (p = 0.0154), increased [HCO3−] (p = 0.0358), and decreased [TA] (p = 0.0154), [NH4+] (p = 0.0121) and NAC (p = 0.0064). The UPEC infection did not affect urine acid/base parameters. Compared to control, acid load led to elevated urinary levels of tumor necrosis factor α (TNF-α), keratinocyte chemoattractant (KC), interleukin 1β (IL-1β) and IL-6, and reduced bacterial burden in urine (737.6 ± 1315.0 CFU mL−1 vs. 29.5 ± 53.3 CFU mL−1, p = 0.0030) and kidney (2.39 ± 5.94 CFU mg−1 vs. 0.06 ± 0.14 CFU mg−1, p = 0.0054). The opposite tendency was observed with base load (2204.0 ± 3135.0 CFU mL−1 urine, 2.23 ± 2.95 CFU mg−1 kidney).
Conclusion
Thus, increased urine acid excretion reduced UPEC burden in urine and decreased risk of pyelonephritis while enhancing the urinary excretion of proinflammatory cytokines.
目的：尿路感染是泌尿系致病性大肠杆菌（UPEC）引起的常见疾病。尿pH值是否对尿路感染的发生和发展有影响仍存在广泛争议。在这项研究中，我们系统地探讨了尿pH值是否影响尿路感染的进展和传播。方法：为了评估尿pH值对体内尿路感染发展的影响，8-10周龄雌性Balb/cJRj小鼠在UPEC或载具植入膀胱24小时前，随机分为100 mM NH4Cl（酸负荷）、100 mM NaHCO3（基础负荷）或去矿水作为饮用水干预。结果：酸负荷使尿pH降低0.8 ~ 1.0个pH点（p = 0.0002），使[可滴定酸]（TA, p = 0.0007）、[NH4 +] (p3 -) （p = 0.0358）升高，使[TA] （p = 0.0154）、[NH4 +] （p = 0.0121）、NAC （p = 0.0064）降低。UPEC感染对尿酸碱参数无影响。与对照组相比，酸负荷导致尿中肿瘤坏死因子α (TNF-α)、角化细胞趋化剂（KC）、白细胞介素1β (IL-1β)和IL-6水平升高，尿液（737.6±1315.0 CFU mL-1比29.5±53.3 CFU mL-1, p = 0.0030）和肾脏（2.39±5.94 CFU mg-1比0.06±0.14 CFU mg-1, p = 0.0054）细菌负荷降低。基础负荷（尿2204.0±3135.0 CFU mL-1，肾2.23±2.95 CFU mg-1）则相反。结论：尿酸排泄量增加可减轻尿中upc负担，降低肾盂肾炎风险，同时促进尿中促炎细胞因子的分泌。
{"title":"Oral Acid Load Lowers Bacterial Burden and Elevates Urinary Proinflammatory Response in a Mouse Model of Urinary Tract Infection","authors":"Aimi D. K. Hamilton, Johanna Hornhaver, Laura V. Sparsoe, Mads Vaarby Sorensen, Helle Praetorius","doi":"10.1111/apha.70149","DOIUrl":"10.1111/apha.70149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Urinary tract infections (UTIs) are common and frequently caused by uropathogenic <i>Escherichia coli</i> (UPEC). Whether urinary pH has any influence on the development and progression of UTIs is still widely debated. In this study, we systematically address whether urinary pH affected progression and dissemination of UTIs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To assess the effect of urine pH on the development of UTI in vivo, 8–10-week-old female Balb/cJRj mice were randomized to 100 mM NH<sub>4</sub>Cl (acid-load), 100 mM NaHCO<sub>3</sub> (base-load), or demineralised water as drinking water intervention 24 h before UTI was induced via installation of either UPEC or vehicle in the urinary bladder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Acid load lowered urinary pH by 0.8–1.0 pH points (<i>p</i> < 0.0001), decreased [HCO<sub>3</sub><sup>−</sup>] (<i>p</i> = 0.0002), and increased [titratable acid] (TA, <i>p</i> = 0.0007), [NH<sub>4</sub><sup>+</sup>] (<i>p</i> < 0.0001) and net acid concentration (NAC, <i>p</i> < 0.0001), while base load raised urinary pH by 0.3–0.7 pH points (<i>p</i> = 0.0154), increased [HCO<sub>3</sub><sup>−</sup>] (<i>p</i> = 0.0358), and decreased [TA] (<i>p</i> = 0.0154), [NH<sub>4</sub><sup>+</sup>] (<i>p</i> = 0.0121) and NAC (<i>p</i> = 0.0064). The UPEC infection did not affect urine acid/base parameters. Compared to control, acid load led to elevated urinary levels of tumor necrosis factor α (TNF-α), keratinocyte chemoattractant (KC), interleukin 1β (IL-1β) and IL-6, and reduced bacterial burden in urine (737.6 ± 1315.0 CFU mL<sup>−1</sup> vs. 29.5 ± 53.3 CFU mL<sup>−1</sup>, <i>p</i> = 0.0030) and kidney (2.39 ± 5.94 CFU mg<sup>−1</sup> vs. 0.06 ± 0.14 CFU mg<sup>−1</sup>, <i>p</i> = 0.0054). The opposite tendency was observed with base load (2204.0 ± 3135.0 CFU mL<sup>−1</sup> urine, 2.23 ± 2.95 CFU mg<sup>−1</sup> kidney).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thus, increased urine acid excretion reduced UPEC burden in urine and decreased risk of pyelonephritis while enhancing the urinary excretion of proinflammatory cytokines.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sensory gating is a neurological mechanism that filters out irrelevant sensory input, protecting cognitive processing from sensory overload. Patients with schizophrenia usually lack sensory gating, which severely affects normal cognitive functions due to an overload of irrelevant information. Sensory gating and cognitive tasks have been found to need moderate activity in the medial prefrontal cortex (mPFC). However, the specific control mechanisms of the mPFC remain unknown. We assume that the “Excitation-Inhibition” imbalance in the mPFC can induce schizophrenia-like sensory gating and cognitive defects.
Methods
The current study utilized chemogenetics and FloxP-Cre techniques to examine the distinct roles of glutamatergic and GABAergic neurons in the mPFC in regulating sensory gating and cognitive functions, both in healthy and schizophrenia-like mouse models.
Results
Manipulation of neural activity in the mPFC, specifically inhibiting GABAergic neurons or stimulating glutamatergic neurons in the mPFC, caused schizophrenia-like sensory gating deficits, disturbances in temporal order and long-term recognition memory, and hyperlocomotion. Conversely, activating GABAergic neurons or inhibiting glutamatergic neurons mitigated these schizophrenia-like symptoms, including sensory gating deficits, temporal order memory impairments, and hyperlocomotion.
Conclusions
We discovered that a disturbance in the “Excitation-Inhibition” balance in the mPFC significantly contributes to schizophrenia-like sensory gating deficits, cognitive impairments, and hyperlocomotion. Remarkably, correcting this imbalance in schizophrenia-like mice alleviated these deficits, providing profound insights into the regulatory functions of glutamatergic and GABAergic neurons in the mPFC.
{"title":"Chemogenetic Restoration of the “Excitation-Inhibition” Imbalance in the Medial Prefrontal Cortex Ameliorates Schizophrenia-Like Sensory Gating Deficits","authors":"Xiaoyu Chen, Lichun He, Qiuxia Zhang, Yanci Luo, Yushan Cao, Huifeng Zhu, Weihai Chen","doi":"10.1111/apha.70151","DOIUrl":"10.1111/apha.70151","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Sensory gating is a neurological mechanism that filters out irrelevant sensory input, protecting cognitive processing from sensory overload. Patients with schizophrenia usually lack sensory gating, which severely affects normal cognitive functions due to an overload of irrelevant information. Sensory gating and cognitive tasks have been found to need moderate activity in the medial prefrontal cortex (mPFC). However, the specific control mechanisms of the mPFC remain unknown. We assume that the “Excitation-Inhibition” imbalance in the mPFC can induce schizophrenia-like sensory gating and cognitive defects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The current study utilized chemogenetics and FloxP-Cre techniques to examine the distinct roles of glutamatergic and GABAergic neurons in the mPFC in regulating sensory gating and cognitive functions, both in healthy and schizophrenia-like mouse models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Manipulation of neural activity in the mPFC, specifically inhibiting GABAergic neurons or stimulating glutamatergic neurons in the mPFC, caused schizophrenia-like sensory gating deficits, disturbances in temporal order and long-term recognition memory, and hyperlocomotion. Conversely, activating GABAergic neurons or inhibiting glutamatergic neurons mitigated these schizophrenia-like symptoms, including sensory gating deficits, temporal order memory impairments, and hyperlocomotion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We discovered that a disturbance in the “Excitation-Inhibition” balance in the mPFC significantly contributes to schizophrenia-like sensory gating deficits, cognitive impairments, and hyperlocomotion. Remarkably, correcting this imbalance in schizophrenia-like mice alleviated these deficits, providing profound insights into the regulatory functions of glutamatergic and GABAergic neurons in the mPFC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Collagen-VI has long waited in the wings of cardiac biology. Better known to neuromuscular researchers who study Ullrich congenital muscular dystrophy and Bethlem myopathy [<span>1</span>], this beaded filament collagen is often relegated to the diffuse background of the ventricular wall, grouped with generic “fibrotic” matrix rather than treated as a molecule with specific, testable roles in mechanics and signaling. The study by Krstic and colleagues in this issue invites a re-evaluation of that view [<span>2</span>]. By deleting the Col6a1 gene in rat and interrogating the heart from organ to myofilament scale, they reveal collagen-VI as a determinant of systolic performance and Ca<sup>2+</sup> handling and a potential player in arrhythmogenesis.</p><p>The central finding is paradoxical in the best physiological sense. In vivo, Col6a1-deficient rats show reduced cardiac ejection fraction, fractional shortening, stroke volume and output, consistent with impaired systolic function. Yet isolated Col6a1-null ventricular myocytes exhibit larger Ca<sup>2+</sup> transients and increased sarcoplasmic reticulum Ca<sup>2+</sup> load—changes that usually support stronger, not weaker, twitch force. Resolution comes at the tissue level: trabeculae from null rats generate less peak stress and display slower twitch kinetics, indicating that the major defect lies in force transmission rather than in activating Ca<sup>2+</sup>. Collagen-VI therefore appears not just as a passive constituent of the extracellular-space but as part of the mechanical line coupling intracellular contraction to chamber-level pumping.</p><p>This picture dovetails with earlier work on collagen-VI in myocardial infarction, where global deletion improved post-MI remodeling with less fibrosis and better-preserved ventricular function [<span>3, 4</span>]. These findings cast collagen-VI not as a neutral scaffold but as a driver of adverse fibrotic remodeling, aligning with broader views that highlight fibroblast–matrix signaling as a therapeutic target [<span>5</span>]. Krstic et al. now add that in the uninjured rat heart, the same gene deletion exacts a cost—baseline systolic depression and heightened susceptibility to triggered activity under β-adrenergic stress—so that collagen-VI emerges as a double-edged molecule, harmful in excess yet required in proper amounts for efficient force transmission and stable excitation–contraction coupling.</p><p>The calcium findings are particularly informative. Despite unchanged T-tubule regularity and RyR2 cluster architecture by confocal and STED imaging, Col6a1-deficient cardiomyocytes exhibit increased Ca<sup>2+</sup> transient amplitude and greater SR Ca<sup>2+</sup> content, as revealed by caffeine-evoked release. Under β-adrenergic stimulation, the difference is amplified: isoproterenol elicits larger transients, faster upstrokes, and, in about half of Col6a1-null myocytes, spontaneous diastolic Ca<sup>2+</sup> release events absent in wild-
{"title":"Untethered and Triggered: Collagen VI Loss at the Nexus of Force, Fibrosis, and Arrhythmia","authors":"Robert G. Gourdie","doi":"10.1111/apha.70155","DOIUrl":"10.1111/apha.70155","url":null,"abstract":"<p>Collagen-VI has long waited in the wings of cardiac biology. Better known to neuromuscular researchers who study Ullrich congenital muscular dystrophy and Bethlem myopathy [<span>1</span>], this beaded filament collagen is often relegated to the diffuse background of the ventricular wall, grouped with generic “fibrotic” matrix rather than treated as a molecule with specific, testable roles in mechanics and signaling. The study by Krstic and colleagues in this issue invites a re-evaluation of that view [<span>2</span>]. By deleting the Col6a1 gene in rat and interrogating the heart from organ to myofilament scale, they reveal collagen-VI as a determinant of systolic performance and Ca<sup>2+</sup> handling and a potential player in arrhythmogenesis.</p><p>The central finding is paradoxical in the best physiological sense. In vivo, Col6a1-deficient rats show reduced cardiac ejection fraction, fractional shortening, stroke volume and output, consistent with impaired systolic function. Yet isolated Col6a1-null ventricular myocytes exhibit larger Ca<sup>2+</sup> transients and increased sarcoplasmic reticulum Ca<sup>2+</sup> load—changes that usually support stronger, not weaker, twitch force. Resolution comes at the tissue level: trabeculae from null rats generate less peak stress and display slower twitch kinetics, indicating that the major defect lies in force transmission rather than in activating Ca<sup>2+</sup>. Collagen-VI therefore appears not just as a passive constituent of the extracellular-space but as part of the mechanical line coupling intracellular contraction to chamber-level pumping.</p><p>This picture dovetails with earlier work on collagen-VI in myocardial infarction, where global deletion improved post-MI remodeling with less fibrosis and better-preserved ventricular function [<span>3, 4</span>]. These findings cast collagen-VI not as a neutral scaffold but as a driver of adverse fibrotic remodeling, aligning with broader views that highlight fibroblast–matrix signaling as a therapeutic target [<span>5</span>]. Krstic et al. now add that in the uninjured rat heart, the same gene deletion exacts a cost—baseline systolic depression and heightened susceptibility to triggered activity under β-adrenergic stress—so that collagen-VI emerges as a double-edged molecule, harmful in excess yet required in proper amounts for efficient force transmission and stable excitation–contraction coupling.</p><p>The calcium findings are particularly informative. Despite unchanged T-tubule regularity and RyR2 cluster architecture by confocal and STED imaging, Col6a1-deficient cardiomyocytes exhibit increased Ca<sup>2+</sup> transient amplitude and greater SR Ca<sup>2+</sup> content, as revealed by caffeine-evoked release. Under β-adrenergic stimulation, the difference is amplified: isoproterenol elicits larger transients, faster upstrokes, and, in about half of Col6a1-null myocytes, spontaneous diastolic Ca<sup>2+</sup> release events absent in wild-","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ependymal cell-derived perilesional glial borders may play a beneficial role in neural regeneration after spinal cord injury (SCI). Yes-associated protein (YAP), a key transcriptional cofactor, is involved in the control of body organ size by regulating cell differentiation, proliferation, growth, and apoptosis; however, it remains unclear whether the roles and underlying mechanisms of YAP signaling regulate the ependymal cell-derived perilesional glial borders after SCI.
Methods
We established a dorsal cord incision injury mouse model. The YAPf/f; FoxJ1-CreERT2 (YAPFoxJ1-ERT2-CKO) mice and YAPf/f; FoxJ1-CreERT2; Rosa26tdTomato mice were generated to examine the roles of ependymal YAP signaling in SCI. The RNA-seq, western blot, immunostaining, and cell-fate tracing tools were used to investigate the underlying mechanisms of YAP signaling in the regulation of ependymal cell-derived perilesional glial borders after SCI.
Results
YAP was activated in ependymal cells after SCI. Interestingly, YAP deletion in ependymal cells (YAPFoxJ1-ERT2-CKO mice) aggravated the neuronal loss and impaired the formation of perilesional glial borders and then inhibited the functional recovery after SCI. Furthermore, YAP deletion inhibited the proliferation and differentiation of ependymal cells to astrocytes and oligodendrocytes and reduced the secretion of neurotrophic factors after SCI. Mechanically, RNA-seq revealed that the expression of Colorectal Neoplasia Differentially Expressed (CRNDE) was downregulated in YAPFoxJ1-ERT2-CKO mice. Furthermore, we found downregulation of P300 and β-catenin and upregulation of GSK-3β in YAP−/− ependymal cells after SCI.
Conclusion
Ependymal YAP signaling promotes the formation of ependymal cell-derived perilesional glial borders in mice through the P300-CRNDE-Wnt/β-catenin pathway after SCI, which provides a novel target for SCI.
{"title":"Ependymal Yes-Associated Protein Promotes the Neural Regeneration Through Enhancing the Ependymal Cell-Derived Perilesional Glial Borders in Mice After Spinal Cord Injury","authors":"Jiashu Lian, Xiaowu Lin, Jiali Shi, Mengxian Jia, Wenbin Zhang, Xin Yan, Sheng Lu, Dewei Xie, Jian Zhou, Zhoule Zhu, Ziwei Fan, Yaozhi He, Yumin Wu, Jianhong Dong, Wei Zhang, Kelun Huang, Minyu Zhu, Ying Wang, Zhihui Huang, Honglin Teng","doi":"10.1111/apha.70147","DOIUrl":"10.1111/apha.70147","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Ependymal cell-derived perilesional glial borders may play a beneficial role in neural regeneration after spinal cord injury (SCI). Yes-associated protein (YAP), a key transcriptional cofactor, is involved in the control of body organ size by regulating cell differentiation, proliferation, growth, and apoptosis; however, it remains unclear whether the roles and underlying mechanisms of YAP signaling regulate the ependymal cell-derived perilesional glial borders after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We established a dorsal cord incision injury mouse model. The YAP<sup>f/f</sup>; FoxJ1-CreERT2 (YAP<sup>FoxJ1-ERT2</sup>-CKO) mice and YAP<sup>f/f</sup>; FoxJ1-CreERT2; Rosa26<sup>tdTomato</sup> mice were generated to examine the roles of ependymal YAP signaling in SCI. The RNA-seq, western blot, immunostaining, and cell-fate tracing tools were used to investigate the underlying mechanisms of YAP signaling in the regulation of ependymal cell-derived perilesional glial borders after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>YAP was activated in ependymal cells after SCI. Interestingly, YAP deletion in ependymal cells (YAP<sup>FoxJ1-ERT2</sup>-CKO mice) aggravated the neuronal loss and impaired the formation of perilesional glial borders and then inhibited the functional recovery after SCI. Furthermore, YAP deletion inhibited the proliferation and differentiation of ependymal cells to astrocytes and oligodendrocytes and reduced the secretion of neurotrophic factors after SCI. Mechanically, RNA-seq revealed that the expression of Colorectal Neoplasia Differentially Expressed (CRNDE) was downregulated in YAP<sup>FoxJ1-ERT2</sup>-CKO mice. Furthermore, we found downregulation of P300 and β-catenin and upregulation of GSK-3β in YAP<sup>−/−</sup> ependymal cells after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ependymal YAP signaling promotes the formation of ependymal cell-derived perilesional glial borders in mice through the P300-CRNDE-Wnt/β-catenin pathway after SCI, which provides a novel target for SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Hundred Years of the Chemosensory Synapse: A Tribute to Fernando de Castro","authors":"Fernando de Castro, José López-Barneo","doi":"10.1111/apha.70145","DOIUrl":"10.1111/apha.70145","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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