生物学最新文献

Vibriosis is the most important public health threat from seafood consumption and marine recreation. Pathogenic Vibrio spp. employ virulence factors, including hemolysins and secretion systems, frequently detected in human cases, but virulence data in northern and southern sea otters (Enhydra lutris kenyoni and E. l. nereis, respectively) are limited despite their potential as marine bioindicators. Genomic epidemiology was used to characterize virulence factors of Vibrio spp. genomes (n = 570), including V. alginolyticus (n = 55), V. diabolicus (n = 52), non-O1/O139 V. cholerae (n = 163), and V. parahaemolyticus (n = 287) collected in North America (2000-2019). Virulence factors of V. parahaemolyticus were compared between isolation sources: bivalves, environment, humans, and southern and northern sea otters. Hemolysins (tdh, trh) and type III secretion system 2 (T3SS2) gene prevalences were lowest in environmental isolates, while tdh and T3SS2 gene prevalences were higher in human and northern sea otter isolates than those from southern sea otters. A hemolysin allele (trh1) was detected almost exclusively in human and sea otter isolates. Despite V. parahaemolyticus genomic diversity, detected genomic clusters were comprised of highly related and tdh⁺/trh⁺ genomes from nonenvironmental sources including humans and sea otters. Observed pathology in Vibrio spp. positive sea otters frequently included septicemia, enteritis, and moderate-to-severe melena. Co-occurrence of T3SS2 and T6SS1 in V. parahaemolyticus was associated with pathological findings and ampicillin-susceptible genotypes, suggesting a trade-off between virulence and antimicrobial resistance. Based on these findings, V. parahaemolyticus undergoes selection pressures resulting in apparent expansion, i.e. genomic clustering, of tdh⁺/trh⁺ virulent strains infecting humans and sea otters.

Traditional antifungal drugs used against Candida albicans have several drawbacks, including the emergence of drug-resistant strains. In addition, developing novel antifungal agents requires long-term research and design. Drug repurposing, identifying and utilizing previously unknown functions of known drugs, such as antifungal activity, may be a quick method for mining efficient alternatives. Otilonium bromide (OB), an FDA-approved drug, is a quaternary ammonium compound used as a therapeutic drug for irritable bowel syndrome. We previously reported the inhibitory effect of OB against the spore germination of Cryptococcus neoformans. In this study, we found that the antifungal activity of OB against C. albicans was 2 μg/mL for both minimum inhibitory and fungicidal concentrations. OB could destroy the cell membrane and prevent C. albicans from undergoing yeast-to-hyphae transition, thus interfering with biofilm formation. Additionally, the efficacy of OB was abolished when iron ions were provided, suggesting that iron homeostasis was associated with the inhibition mechanism of OB. Interestingly, a therapeutic assay showed that OB demonstrated limited efficacy in reducing C. albicans burden in a murine systemic infection model. In summary, repurposing OB against C. albicans may facilitate the design of new antifungal drugs, and chemical modification could enhance the efficacy of OB to be more specific to fungal pathogens.

Foot-and-mouth disease virus (FMDV) can cause a severe infectious disease that primarily affects even-toed ungulates. FMDV is classified into the genus of Aphthovirus in the family Picornaviridae. FMDV's 3C protein is a nonstructural protein and, moreover, is a protease (3C^pro) that adopts a chymotrypsin-like fold and harbors a Cys-His-Asp catalytic triad. The 3C^pro plays crucial roles not only in cleaving the FMDV polyprotein but also in degrading various host proteins. Cleavage of the polyprotein contributes to generating different viral polypeptides. Degradation of host proteins possibly affects cellular signaling pathways, making FMDV impair innate immune responses. Here, we systematically reviewed FMDV 3C^pro concerning its multiple characteristics, including nucleotide and protein sequences, crystal structures, enzymatic activities, anti-3C^pro inhibitors, and more importantly, its functions in cleaving the viral polyprotein and host proteins. This review aims to provide a comprehensive insight into FMDV 3C^pro as a protease functioning in the course of viral propagation.

Since its initial discovery in Swedish pigs in 2009, porcine bocavirus (PBoV) has been detected across Asia, Europe, Africa, and North America. However, the pathogenic potential of PBoV has remained uncertain due to the lack of suitable cell culture systems for viral propagation. In this study, we report the first successful isolation of a Chinese PBoV strain (BK19) from diarrheic piglets in Hunan Province using trypsin-supplemented LLC-PK1 cells. The isolate was characterized through immunofluorescence assay, electron microscopy, plaque formation, and growth kinetics. Whole genome sequencing revealed 43.4-95.7% nucleotide identity with known PBoV strains, with phylogenetic analysis classifying BK19 within the G3 genogroup. Experimental infection of 5-8, 17-19, and 31-33 days old piglets demonstrated age-dependent pathogenicity, with all groups developing characteristic clinical signs including fever, respiratory distress, and diarrhea lasting 3-4 days. Viral shedding peaked in rectal swabs at 4 days post-infection (dpi), with persistent detection through 14 dpi in 5-8 and 17-19 days old groups. Postmortem examination revealed broad tissue tropism in 5-8 and 17-19 days old piglets and age-dependent pathological lesions in intestinal, pulmonary, lymphoid and renal tissues. Immunohistochemical analyses confirmed viral antigen presence in these tissues in 5-8 days old piglets, which correlated with enhanced proliferation of infected cells. These findings provide definitive evidence that PBoV is a primary pathogen in swine, with particular clinical significance for young piglets. This study establishes crucial tools for further research into PBoV biology and control strategies.

Background: Interleukin-6 (IL-6) is a pleiotropic cytokine that participates in multiple metabolic disorders. IL-6 is well recognized to induce hepcidin expression and decreased serum iron through the JAK2/STAT3 pathway under inflammatory conditions. Targeted inhibition of IL-6 represents a potential therapeutic regimen for multiple diseases. The current study aimed to explore the physiological concentration of IL-6 in sustaining systemic iron homeostasis.

Methods: IL-6-knockout mice (IL-6-/-) were established in the current study. Western blot measured the expression of key iron-related proteins in liver, kidney, spleen and duodenum, as well as hepatic hepcidin mRNA expression. Serum iron and hematologic parameters were detected. ELISA and Masson's trichrome staining were performed to detect renal TGF-β1 expression and collagen deposition. Furthermore, bone marrow-derived and peritoneal macrophages were prepared to identify the iron recycling.

Results: Serum iron and tissue iron content were markedly elevated in IL-6-/- mice. Mechanistically, decreased renal erythropoietin (EPO) synthesis contributed to iron utilization, macrophage-mediated recycling of iron was markedly reduced, thereby resulting in systemic iron accumulation. However, IL-6-/- mice displayed increased Hepcidin expression via p-ERK activation and a significant reduction in duodenal iron uptake.

Conclusion: This study highlighted the critical role of IL-6 in iron homeostasis both in physiological and pathological situations.

Microsporidia are opportunistic, obligate intracellular fungi capable of causing keratoconjunctivitis. Because the clinical manifestations of microsporidia keratoconjunctivitis are indistinguishable from those of other etiologies, and the organism is difficult to culture, its diagnosis is challenging. The transmission routes of microsporidia keratoconjunctivitis remain poorly defined, and zoonotic sources have long been suspected but rarely confirmed. Between September 2024 and October 2025, a total of 15 confirmed cases of microsporidia keratoconjunctivitis were identified at Peking University Third Hospital. The diagnosis was established based on Giemsa-stained corneal scrapings and/or metagenomic next-generation sequencing (mNGS) of conjunctival lavage samples. Among these 15 patients, microsporidia spores were observed in corneal scrapings from nine individuals, while 13 tested positive for Encephalitozoon hellem (E. hellem) by mNGS. Notably, all affected patients reported a history of parrot exposure. Self-reported parrot exposures included direct ocular contact (n = 3) and indirect contact (n = 12). Six patients reported that their parrots had exhibited ocular abnormalities and diarrhea before the onset of the patients' symptoms, and two patients stated that their parrots had died prior to their clinical presentation. Ocular and fecal samples from three parrots associated with four patients were collected, and all the parrots tested positive for E. hellem by mNGS. These findings provide both clinical and molecular evidence supporting pet parrots as a zoonotic source of microsporidia keratoconjunctivitis. This emerging zoonotic threat calls for greater clinical awareness and attention to animal exposure history during diagnosis.

As opportunistic intracellular pathogens, viruses rely on numerous sequential interactions between host and viral factors for their replication. Given the significance of molecular chaperones (heat shock protein 70 and heat shock protein 90) in mediating protein homeostasis, research has suggested that they are involved in viral infections in many ways. This study explored the roles of HSP70 and HSP90 in the Senecavirus A (SVA) life cycle. We demonstrate that HSP70 and HSP90 regulate virus internal ribosome entry site (IRES)-dependent translation activity by acting on SVA IRES. Additionally, we show that HSP70 promotes SVA IRES-dependent translation through association with SVA IRES domain II, and HSP90 may function through interaction with SVA IRES domain IV. Furthermore, we found that the structural proteins and four non-structural proteins (Lpro, 2B, 2C, 3A) were shown to interact with HSP70 and HSP90. Furthermore, we determined that HSP70 and Hsp90 activity is important for virus replication by stabilizing SVA proteins and preventing their degradation via the ubiquitin-proteasome, apoptosis, and autophagy-lysosome pathway. Our findings indicate that HSP70 and HSP90 activity is essential for SVA replication, offering new insights into the development of potential specific control strategies against SVA infection.

Stem cell-based therapies are emerging as a promising treatment for diabetes by differentiating these cells into insulin-producing cells (IPCs). However, using growth factors for differentiation has always been challenging. Physical differentiation of stem cells presents a promising approach to reduce reliance on chemical growth factors. One method of physical cell differentiation is cell imprinting. This study aimed to physically induce the differentiation of rat adipose-derived mesenchymal stem cells (rADSCs) into β-like cells using the cell-imprinting technique. For this purpose, RIN-5F cells were used to transfer their geometry and cell-specific topographies to a polydimethylsiloxane (PDMS) substrate. After cell imprinting, the rADSCs were seeded on the substrate, and their differentiation into β-like cells was evaluated after 14 and 21 days by assessing insulin production using dithizone staining and ELISA, as well as real-time PCR and immunocytochemistry (ICC) for expression analysis of the genes effective in cell differentiation into β-like cells, including PDX1, NKX6.1, NGN3, and insulin. The results of dithizone staining and ELISA confirmed insulin secretion by differentiated cells compared to stem cells (p ≤ 0.05). Real-time PCR and ICC results showed that after 21 days, the differentiated cells expressed key β-cell genes significantly more than stem cells (p ≤ 0.05).

Background: Fatty acid oxidation (FAO) is implicated in lung diseases, but its role in bronchial asthma is not fully understood. We investigated its effect on airway epithelial barrier integrity.

Methods: Using a house dust mite (HDM)-induced murine asthma model and HDM, IL-4, IL-13, or TNF-α stimulated human primary bronchial epithelial cells (BECs) and bronchial epithelial (Beas-2b) cells, we modulated FAO with L-carnitine (agonist) and Etomoxir (inhibitor). BECs and Beas-2b cells were infected with lentivirus-mediated CPT1A shRNA prior to stimulation. Barrier function, mitochondrial oxidative stress, inflammation, and metabolism were assessed.

Results: FAO level in lungs negatively correlated with increased inflammation and tissue injury in HDM-induced asthmatic mice (all p < 0.05), while positively regulating tight junction protein expression. In BECs and Beas-2b cells, Etomoxir treatment and CPT1A knockdown exacerbated the impairment of FAO caused by various stimulants (all p < 0.05). Furthermore, FAO negatively regulated HDM/cytokine-induced epithelial barrier damage, hyperactive inflammatory response, and mitochondrial dysfunction in Beas-2b cells (all p < 0.05). In contrast, treatment with L-carnitine significantly alleviated these pathophysiological features in both in vivo and in vitro models.

Conclusion: FAO plays a protective role in the occurrence and development of asthma by maintaining airway epithelial cell homeostasis and barrier function.