Journal of Zhejiang University SCIENCE B最新文献

Asthma is a complex and chronic inflammatory airway disease associated with the abnormal activation of immune cells. T-cell senescence is linked to immune dysfunction and persistent inflammation, but the relationship between asthma and T-cell senescence remains unexplored. This study reveals significantly higher percentages of cluster of differentiation 4-positive (CD4⁺) senescent T cells (Tsens) in asthma patients than in healthy controls, while CD8⁺ Tsen percentages do not appear to increase. CD4⁺ Tsen percentages in both the blood and sputum are positively correlated with fractional exhaled nitric oxide (FeNO) values, eosinophil abundance, and T helper type 2 (Th2) cell abundance in the blood. The clinical manifestations of asthma were recreated in a house dust mite (HDM)-induced mouse model. In HDM-exposed mice, CD4⁺ Tsen percentages were also elevated in the lungs. To counteract T-cell senescence, therapeutic interventions, including interleukin-4 (IL-4) antibodies and dexamethasone, were administered to the mice. IL-4 neutralization reduced CD4⁺ Tsen percentages and inhibited p38 mitogen-activated protein kinase (MAPK) activation. Adoptive transfer of CD4⁺ Tsens did not induce spontaneous asthma in phosphate-buffered saline (PBS)-treated mice but exacerbated type 2 inflammation in HDM-treated mice. Our study revealed a significant increase in CD4⁺ Tsen (CD57⁺CD28^-) abundance in asthma patients and suggested that type 2 inflammation drives CD4⁺ T-cell senescence in asthma. Furthermore, adoptive transfer of CD4⁺ Tsens appears to exacerbate type 2 inflammation.

In the realm of precision psychiatry of mood disorders, the evolution of interpersonal psychotherapy (IPT) is gaining momentum, necessitating a personalized approach that also takes into account cultural aspects. This study underscores the importance of incorporating cultural factors into the dissemination and application of IPT in Asia. Through a comprehensive analysis of a case illuminating how cultural influences impact the onset and treatment outcomes of depression, we emphasize the critical need for culturally informed IPT practices in China. This personalized approach not only enhances treatment outcomes but also paves the way for further research on adapting IPT to diverse cultural contexts in Asia.

Pulmonary sclerosing pneumocytoma (PSP) was first reported by Liebow and Hubbell (1956). It was initially called pulmonary sclerosing hemangioma (PSH) because it was thought to be derived from endothelial cells with rich vascularity. However, the 2015 World Health Organization Classification of Lung Tumors removed the term "sclerosing hemangioma," since these tumors lack vascular origin (Travis et al., 2015), and the renamed tumor was considered a rare and benign lung tumor. However, several reports have described PSP with lymph node metastasis (Soo et al., 2017). Thus, PSP is not always benign and has the potential to metastasize. PSP shows varying levels of ¹⁸F-fluorodeoxy-glucose (¹⁸FDG) accumulation, with the maximum standardized uptake value (SUV_max) ranging from the background value to 6.4 (Chen et al., 2012; Jiang et al., 2018). Therefore, it is easily misdiagnosed as other malignant tumors and is often removed surgically or treated improperly. Here, we present a rare case of PSP in a young woman with lymph node metastasis, a high ¹⁸FDG uptake on positron emission tomography/computed tomography (PET/CT) scan, and an SUV_max of 6.1.

Transient receptor potential vanilloid subtype 1 (TRPV1), a polymodally activated, calcium-permeable non-selective cation channel, is broadly present in all parts of the body, with notable expression in the nociceptive neurons. Both physiological and pathological functions rely heavily on this ion channel, mediating responses to a variety of stimuli and contributing to the maintenance of bodily homeostasis. Its unique ability to respond to temperature changes, chemical ligands, and voltage fluctuations positions TRPV1 as a key target in understanding and modulating normal bodily functions, in addition to diagnosing and treating diseases. This review synthesizes current knowledge on the structure, gating mechanisms, and physiological and pathological roles of TRPV1, highlighting its potential as a therapeutic target across multiple disease states. By providing a comprehensive overview of the multifaceted functions of TRPV1, this review aims to inform and inspire future research, finally contributing to the advancement of new therapeutic techniques focusing on TRPV1 to enhance human health.

The pathological microenvironment of osteoporosis poses a substantial clinical challenge for bone defect regeneration. Through single-cell RNA-sequencing (scRNA-seq) analysis, we identified a reactive oxygen species (ROS)-overloading osteoblast subpopulation as a critical pathological feature of osteoporotic niches. Guided by scRNA-seq analysis, we engineered a microenvironment-adaptive hydrogel system through precise integration of antioxidant curcumin-encapsulated zeolitic imidazolate framework-8 nanoparticles (CCM@ZIF-8 NPs) within photo-crosslinkable alginate methacrylate (AlgMA) hydrogel (AlgMA/CCM@ZIF-8). This engineered design exhibited dual functions: effectively scavenging ROS in bone marrow-derived mesenchymal stem cells (BMSCs) while simultaneously suppressing osteoclast differentiation. The osteo-regenerative superiority of the AlgMA/CCM@ZIF-8 nanocomposite hydrogel was conclusively demonstrated in bone defect models of osteoporotic mice. This scRNA-seq-informed engineering strategy offers a promising approach for developing pathophysiology-adapted biomaterials to promote regenerative repair in osteoporotic bone defects.

Exogenous lipoid pneumonia (ELP) following hydrocarbon aspiration is an unusual but severe condition. This study aimed to summarize the cases of pneumonitis following fuel aspiration from a single center to serve as a useful reference for clinicians in the future. The clinical courses and outcomes of 11 patients with pneumonitis following fuel aspiration were collected and presented. Among them, four representative cases were described in detail to summarize the management experience of this disease, and these cases were analyzed to better understand the clinical features and management strategies of hydrocarbon pneumonitis following fuel aspiration. Almost all patients were found to present with cough and dyspnea, and the most common symptoms were dyspnea and chest pain. A high proportion (90.9%) of patients presented with bilateral lower pulmonary field involvement, and half of the patients showed pneumonic consolidation. One patient with irreversible lung injury received extracorporeal membrane oxygenation (ECMO) and a lung transplant. The other patients received oxygen support, antibiotics, steroids, and other supportive care. Antibiotics and steroids were the most commonly used treatments. While bronchoalveolar lavage (BAL) was beneficial for removing irritants, its utility could also be reduced due to significant risks. Finally, all patients had favorable outcomes. In conclusion, ELP was definitely harmful to patients' health, and hypoxemia was common among these patients. Supportive care, including antibiotics, steroids, and respiratory support, was the main treatment modality. It is recommended that the decision to employ BAL is made selectively. ECMO serves as a critical bridge to recovery or transplantation, and patients with timely and efficient treatment usually have a positive outcome.

Objective: To identify pyroptosis, apoptosis, and necroptosis (PANoptosis)-related genes (PRGs) in clear cell renal cell carcinoma (ccRCC) for patient stratification and prognosis prediction.

Methods: We used differential expression analysis and weighted gene co-expression network analysis (WGCNA) to identify ccRCC-specific PRGs. A prognostic model, the PANoptosis-index (PANI), was constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression. The PANI model, comprising PRGs, was validated through single-cell RNA-sequencing (scRNA-seq), immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Patient cohorts were categorized into high- and low-PANI groups, and the model's performance was appraised using various metrics. External validation was performed with the E-MTAB-1980 dataset. Functional and gene set enrichment analyses distinguished biological differences between groups. Mutational landscapes and tumor immune microenvironments were compared. Sensitivity to immunotherapy and antineoplastic drugs was also predicted using PANI. The effects of Z-DNA-binding protein 1 (ZBP1) on cell proliferation and migration were assessed by cell counting kit-8 (CCK-8) and Transwell assays.

Results: We identified five PRGs (ZBP1, tumor necrosis factor superfamily protein 14 (TNFSF14), cyclin-dependent kinase inhibitor 3 (CDKN3), parathyroid hormone-like hormone (PTHLH),and heme-oxygenase 1 (HMOX1)) constituting PANI, independently associated with ccRCC patient prognosis. The PANI-based nomogram, integrated with clinical factors, demonstrated high predictive accuracy for prognosis. High-PANI patients exhibited distinct co-mutation patterns in ccRCC driver genes and lower survival probabilities, with an enriched immune-related functional profile, indicating an activated immune environment. These patients also showed increased sensitivity to immunotherapy and antineoplastic drugs. The knockdown of ZBP1, a key PRG in the PANI, significantly reduced ccRCC cell proliferation and migration.

Conclusions: PANI provides precise prognosis and immunotherapy response predictions for ccRCC patients, facilitating individualized treatment strategies.

Vegetables are important dietary sources of folate for human nutrition. The influence of different nitrogen doses and forms on changes in primary nitrogen metabolism, such as amino acid and protein synthesis, in plants is well established. However, the impacts of the nitrate-N (N O 3-)-to-ammonium-N (N H 4+) ratio on folate synthesis and accumulation in vegetables are unclear. This study used a hydroponic experiment with six different N O 3-/ N H 4+ ratio treatments to investigate the effects of the integrated application of N O 3- and N H 4+ on the folate constituents and contents of pakchoi (Brassica rapa subsp. chinensis). The results indicated that an appropriate N O 3-/ N H 4+ ratio in nutrient solution could promote pakchoi growth and increase folate contents by increasing polyglutamylated 5-formyl-tetrahydrofolate (5-CHO-THF) and polyglutamylated 5-methyl-THF (5-CH₃-THF). The activities of enzymes related to folate biosynthesis (except folylpolyglutamate synthase (FPGS)) were lower with an N H 4+-N supply at the same nitrogen concentration. The statistical results revealed a significant negative correlation between folate contents and 14 detected metabolites (including fructose, sucrose, glutamine (Gln), shikimate, citrate, succinate, malate, α-oxoglutarate, p-aminobenzoate (pABA), and 6-hydroxymethyldihydropterin pyrophosphate (HMDH-P₂) in the folate biosynthesis pathway), implying that the enhancement of folates biosynthesis with N H 4+-N supply increased the consumption of the folate precursors and intermediate metabolites. Additionally, N H 4+-N supply could improve folate stability by increasing polyglutamylated folates and reducing γ-glutamyl hydrolase (GGH) activity; the latter could weaken folate deglutamylation. As the best growth and highest total folate content were obtained at the appropriate N O 3-/ N H 4+ ratio, strategic selection of the N O 3-/ N H 4+ ratio should be considered for the hydroponic cultivation of foliar vegetable crops.

Neurokinin-1 receptor (NK1R), a member of the G protein-coupled receptor (GPCR) family, contributes to multiple pathological processes, including pain, chronic inflammation, and cancer (Gutierrez et al., 2019; Robinson et al., 2023). Current reports and our previous work have proven that NK1R is highly expressed in many cancer cells, such as colorectal cancer and leukemia, and that targeted blocking of NK1R can effectively inhibit tumor cell proliferation (Li XQ et al., 2013; Li JY et al., 2016; Ge et al., 2019; Shi et al., 2021). In addition, GPCRs have been found not only in the plasma membrane but also in the membranes of endosomes and lysosomes with endocytosis (Irannejad et al., 2017; Yarwood et al., 2017), which is more pronounced in cancer cells with highly developed lysosomes (Ramírez-García et al., 2019).

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide. This necessitates the development of innovative drugs with high efficiency, low toxicity, and good tolerance. Bitter melon extract has been reported to have potent anticancer activity against OSCC. We evaluated the effects of nine triterpenoids from bitter melon extract on OSCC using cell counting kit-8 (CCK-8) proliferation and Transwell migration assays. Among the nine triterpenoids, momordicine I (MI) exhibited the strongest anticancer activity against OSCC. Animal experiments also showed that MI inhibited OSCC cell growth in vivo. Additionally, MI decreased the mitochondrial membrane potential and promoted apoptosis in OSCC. RNA-sequencing (RNA-seq) analysis revealed that MI induced an unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, which was confirmed by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cellular thermal shift assay (CETSA) and mass spectrometry (MS) analysis, combined with molecular docking, identified ribosomal proteins (ribosomal protein L7 (RPL7), RPL11, RPL12, RPL18, RPL30, RPL38, RPS13, and RPS25) as MI targets. By targeting ribosomal proteins, MI likely disrupts ribosome-mediated protein folding, leading to the UPR and ER stress. In summary, MI targets ribosomal proteins to induce ER stress and inhibit OSCC, highlighting its therapeutic potential.