Journal of Biomedical Research最新文献

This study aimed to characterize frequency- and latency-dependent network dysregulation in migraine using magnetoencephalography (MEG)-based static and dynamic functional connectivity analyses during auditory stimulation. Thirty interictal migraine patients and 30 matched healthy controls underwent whole-head MEG recordings during a lateralized auditory task. Static and dynamic functional connectivities were calculated using the corrected amplitude envelope correlation in seven canonical frequency bands (delta 2-120 Hz). Group differences were examined using nonparametric permutation tests, with false discovery rate and Bonferroni correction applied to account for multiple comparisons. Static functional connectivity abnormalities were confined to high-frequency bands (low-gamma, 30-59 Hz; high-gamma, 60-90 Hz; and ripple, 90-120 Hz), showing enhanced frontal-limbic and cross-hemispheric connectivity in migraine patients (Cohen's d = 1.05-1.37). Low-frequency bands showed no significant differences. Dynamic functional connectivity revealed rapid, frequency-specific abnormalities: early (25-50 ms) gamma/ripple hyperconnectivity and late delta/beta alterations, with hemispheric asymmetry. Thus, migraine is characterized by high-frequency oscillatory imbalance during auditory processing, with both persistent (static) and transient (dynamic) network disruptions concentrated in gamma/ripple bands, consistent with impaired predictive coding and sensory hypersensitivity.

A major threat to the global human population is zoonosis, which refers to viral infections transmitted from animals. Pigs are crucial to the transmission of the influenza A virus (IAV) because they express both human-type (α-2,6-linked) and avian-type (α-2,3-linked) sialic acid (SA) receptors, making them a direct source of zoonosis and providing essential "mixing vessels" for avian and swine viruses. We aimed to mitigate the IAV threat by disrupting pig influenza infection through gene targeting of the viral receptors in pigs. We utilized CRISPR/Cas9 to knock out the ST6GAL1 and ST3GAL4 genes, which encode enzymes responsible for synthesizing both the human and avian SA receptors in pigs. We observed a significant reduction in these SA receptors in the respiratory tract of the genetically modified pigs. The deletion of these genes conferred partial resistance to IAV infection in vitro, substantially decreasing viral susceptibility. Post-infection transcriptomic analysis revealed distinct expression profiles in ST6GAL1 ^-/- /ST3GAL4 ^-/- pigs compared with those of wild-type pig cells. Creating ST6GAL1 ^-/- /ST3GAL4 ^-/- pigs provides a large-animal model for studying cross-species transmission of IAV, offering a novel strategy to reduce pandemic risks by disrupting influenza transmission between pigs and humans. This approach suggests a new method for controlling pandemics by targeting animals rather than humans, making it potentially safer than many current alternatives.

The study aimed to assess the taxonomic diversity and composition of gut microbiota in Arkhangelsk residents, Northwestern Russia, with varying metabolic statuses. A population-based cross-sectional "Know Your Heart" study (2015-2017, participants aged 35-69 years) included a health examination and gut microbiota analysis ( n = 685). Participants were divided into four metabolic phenotypes: metabolically healthy non-obese (MHN), metabolically unhealthy non-obese (MUN), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Analyses were performed using RStudio software (v.4.2.0) with the vegan and phyloseq packages (v.1.42.0) for microbiota analysis. The sample was distributed across phenotypes as follows: MHN (47.6%), MUN (22.1%), MHO (10.4%), and MUO (19.9%). Beta-diversity analysis revealed significant differences in overall microbiome composition between MUO and MHN participants, while alpha-diversity did not differ significantly across phenotypes. The MHN group was characterized by a higher abundance of beneficial commensals such as Christensenellaceae R-7 group, Ruminococcaceae UCG-005, and Eubacterium xylanophilum group, which are taxa previously associated with metabolic health and longevity. In contrast, the MUO group showed an increased abundance of Streptococcus salivarius and Negativibacillus, taxa linked to gut dysbiosis and metabolic disorders. Blautia spp. emerged as a major hub in the microbiota of obese participants, consistent with its reported association with visceral fat. In conclusion, microbial composition was similar in obese participants despite metabolic dysfunction, whereas unidirectional taxonomic shifts were observed in those with metabolic dysfunction alone. The differences in the predominance of microbial taxa across metabolic phenotypes suggest that these taxa have a role in the development of metabolic disorders and obesity.

The genetic landscape of male infertility is highly complex. It is estimated that at least 1000-2000 genes are involved in human and mouse infertility. Although functional analyses have been performed on hundreds of genes, many others still have unknown functions. Generating gene-editing mice is a powerful tool for exploring whether a given gene is essential for male reproduction in vivo. In this study, we investigated the function of six genes, Efcab7, Tekt3, Mlf1, Rp1l1, Agbl2, and Tmsb15a, using the CRISPR/Cas9 system. Mating tests with mutant mice revealed that all six genes are dispensable for male fecundity when individually ablated. Meanwhile, phenotypic analyses of testicular appearance and weight, testis and epididymis morphology, and sperm motility parameters in these six mutant mice also showed no significant differences compared with wild-type mice. In summary, our results suggested that these six genes could be deprioritized for other researchers when they are interested in their roles in male infertility, thereby preventing duplicative research efforts.

Pulmonary fibrosis (PF) is a progressive lung disorder characterized by excessive deposition of extracellular matrix (ECM) in the alveoli, with irreversible fibrotic remodeling and destruction of alveolar structures. Clinically, PF is manifested by progressive dyspnea and a decline in lung function. These manifestations contribute to a poor prognosis and significantly diminish the quality of life of affected individuals. Current therapeutic options for PF remain limited, highlighting the urgent need to elucidate its molecular mechanisms in order to develop novel treatment strategies. Recent studies have revealed that autophagy and ferroptosis, two critical cell death pathways, engage in intricate crosstalk mechanisms that regulate the pathogenesis of PF. Autophagy maintains cellular homeostasis by mediating lysosome-dependent degradation, whereas ferroptosis is characterized by iron-dependent lipid peroxidation. The interplay between autophagy and ferroptosis plays a pivotal role in modulating fibrosis progression. However, the mechanistic interactions between autophagy and ferroptosis in PF remain poorly understood, particularly regarding their bidirectional crosstalk and their unique role in PF progression. This review aims to systematically synthesize the current understanding of autophagy-ferroptosis interactions in PF, thereby identifying potential therapeutic strategies and drug targets for PF treatment.

Non-obstructive azoospermia (NOA), characterized by impaired spermatogenesis and the complete absence of sperm in the ejaculate, represents one of the most severe forms of male infertility. Current diagnostic strategies rely on invasive procedures such as testicular sperm extraction, underscoring the urgent need for reliable, non-invasive alternatives. In the present study, we performed untargeted metabolomic profiling of human seminal plasma to identify biomarker panels capable of stratifying azoospermia subtypes through a stepwise approach. We identified distinct metabolite biomarker panels comparing NOA vs. obstructive azoospermia (OA), Sertoli cell-only syndrome vs. other NOA subtypes, and hypospermatogenesis vs. maturation arrest. Additionally, cross-species comparative analysis with high-resolution metabolomic data from purified mouse testicular cell populations implicated these biomarkers in specific germ cell stages and metabolic transitions during spermatogenesis. These findings establish a molecular framework for the non-invasive classification of azoospermia subtypes and provide novel insights into the metabolic disruptions underlying male infertility.

While a healthy lifestyle is known to reduce the risk of stroke, the extent to which blood pressure (BP) mediates this association remains unclear. The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence. Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline, we employed structural equation modeling to assess the mediating effects of systolic (SBP) and diastolic (DBP) blood pressure. During the follow-up, 2811 incident stroke cases were identified. A healthy lifestyle was significantly associated with a reduced risk of stroke, with SBP mediating 44.70% ( β = -0.0014, 95% confidence interval [CI]: -0.0016 to -0.0012) and DBP mediating 37.81% ( β = -0.0012, 95% CI: -0.0015 to -0.0009) of this association. The mediating effects were attenuated but remained significant for ischemic stroke (SBP: 33.21%; DBP: 27.24%). In conclusion, approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP. These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.