生物学最新文献

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.

Preeclampsia (PE) is a severe pregnancy complication with unclear molecular mechanisms. Our research investigated the effect of UNC5C-AS1 on human umbilical vein endothelial cell (HUVEC) function in PE. UNC5C-AS1 was downregulated in PE placentas. Upregulating UNC5C-AS1 promoted HUVEC migration, invasion, tube formation, and the expression of vascular permeability factors, while UNC5C-AS1 silencing exhibited an opposite effect. UNC5C-AS1 directly targeted the miR148a3p/EMP1 axis. MiR-148a-3p was up-regulated and EMP1 was downregulated in PE. The regulatory effects of UNC5C-AS1 overexpression on HUVEC functions were reversed by miR-148a-3p mimics, and this reversal was subsequently rescued by EMP1 upregulation. UNC5C-AS1 overexpression ameliorated tissue damage in the PE mouse model. UNC5C-AS1 alleviated the PE-associated injury and modulated HUVEC function by targeting miR-148a-3p/EMP1 axis.

Objectives: Reperfusion, an essential therapeutic strategy for salvaging ischemic myocardium in ischemic heart disease, paradoxically exacerbates myocardial injury. Ferroptosis is a pivotal mechanism underlying myocardial ischemia-reperfusion injury (MIRI). Nrf2 can regulate ferroptosis, which could undergo SUMOylation at lysine 110 (K110) and was subsequently de-SUMOylated by Senp1. This study aimed to determine whether Nrf2 de-SUMOylation could mitigate MIRI by inhibiting myocardial ferroptosis.

Methods: Nrf2 K110R mice, mimicking Nrf2 de-SUMOylation, were generated. Mice cardiac morphology and function were observed by hematoxylin-eosin staining (HE) and echocardiography under normal and MIRI conditions. Ferroptosis inhibitor liproxstatin-1 (Lip-1) was used to demonstrate ferroptosis participation in Nrf2 de-SUMOylation regulated MIRI. In vitro, SUMO1/sentrin-specific protease 1 Senp1 KO H9C2 cells were subjected to RSL₃-induced ferroptosis to explore underlying mechanism.

Results: Nrf2 K110R mice showed normal cardiac morphology and function at baseline. However, de-SUMOylation of Nrf2 alleviated myocardial ferroptosis, resulting in a reduction of MIRI severity in MIRI mice. The administration of Lip-1 attenuated the differences in MIRI between Nrf2 wild-type and K110R mice. Mechanistically, Nrf2 de-SUMOylation was associated with a reduction in Transferrin receptor (Tfr) expression level, thereby mitigating ferroptosis in cardiomyocytes.

Conclusion: This study highlighted the role of Nrf2 SUMOylation in promoting ferroptosis during MIRI and identified Nrf2 de-SUMOylation as a potential therapeutic target for MIRI.

Infectious prions (PrP^Sc) are largely resistant to proteolytic digestion, including proteinase K (PK) digestion. While nucleic acid extracts are generally considered non-infectious from a classical microbiology context (i.e. free of intact bacteria and viruses), we investigated whether standard DNA purification methods co-purify PrP^Sc, posing an unrecognized biosafety risk. Commercial DNA extraction kits can eliminate conventional pathogens but are likely ineffective against PrP^Sc due to resistance to kit reagents and enzymatic degradation. Two laboratories, the University of Minnesota Center for Prion Research and Outreach (MNPRO) and the Canadian Food Inspection Agency (CFIA), independently tested filter-based and magnetic bead-based DNA extraction kits using tissues from chronic wasting disease (CWD)-positive and -negative white-tailed deer (WTD; Odocoileus virginianus), as well as prion-infected and control Syrian hamster (Mesocricetus auratus) brains. CFIA used two filter-based kits (one automated, one manual), while MNPRO tested two manual kits (filter- and magnetic bead-based). PrP^Sc seeding activity was measured in extracted DNA and source tissues using real-time quaking-induced conversion (RT-QuIC). MNPRO found substantial to almost perfect agreement between RT-QuIC seeding activity of DNA eluates from both extraction methods and that of the source WTD tissue homogenate. CFIA optimized RT-QuIC to a 30-hour runtime, achieving 74% sensitivity and 94% specificity in 88 archived WTD DNA samples. Both laboratories concluded that commercial DNA extraction kits do not eliminate PrP^Sc, enabling carry-over into DNA eluates. Until infectivity is resolved by animal bioassay, DNA from PrP^Sc-positive tissues should be handled under biosafety protocols appropriate for the originating prion disease, with decontamination and containment procedures.

Viruses hijack host metabolic resources for replication. Previous studies have shown that classical swine fever virus (CSFV) infection induces host lipid metabolic reprogramming.However, research into the exact regulatory mechanisms between CSFV and lipid metabolism remains limited. Lipophagy refers to the degradation of lipid droplet contents to release free fatty acids(FFAs), CSFV induces autophagy to promote its replication, the regulatory mechanism between CSFV and lipophagy is unclear. In this study, we found that lipid droplets(LDs) initially accumulate and then decrease following CSFV infection. Autophagy activity was negatively correlated with lipid drople levels. Subsequent experiments revealed that CSFV induces lipophagy in Hepatic stellate cells(HSCs)and upregulates perilipin3(PLIN3) expression, a LD-associated protein that facilitates viral replication. Further studies demonstrated that PLIN3 activates the AMPK signaling pathway to promote lipophagy-mediated FFAs release. This FFA increase could be blocked by autophagy inhibitors. Notably, exogenous FFA addition reversed the shPLIN3-induced impairment of CSFV replication. Overall, this finding provides new insights into the mechanisms of virus-host lipid metabolism interactions.

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.

Ovarian cancer, one of the most lethal gynecologic malignancies, exhibits marked tumor heterogeneity. Potassium channel modulatory factor 1 (KCMF1), a RING zinc-finger protein with E3 ubiquitin ligase activity, has been implicated in tumorigenesis. However, the role of KCMF1 in ovarian cancer remains unclear. In this study, we found that KCMF1 was up-regulated in ovarian cancer tissues and that high KCMF1 expression correlated with poor survival of patients. Functional assays revealed that KCMF1 knockdown suppressed cell viability, hampered cell cycle progression, and inhibited proliferation in ovarian cancer cells. Moreover, silencing KCMF1 inhibited epithelial-mesenchymal transition (EMT), migration, and invasion in vitro. In vivo experiments confirmed that KCMF1 knockdown inhibited tumor growth and metastasis in nude mice. Conversely, KCMF1 overexpression had opposite effects in vitro and in vivo. IP-LC/MS and Label-free proteomic analysis identified nucleoredoxin (NXN), a multifunctional redox-active protein, as a potential substrate of KCMF1. Silencing NXN facilitated cell proliferation, migration, and invasion through activating the β-catenin signaling pathway. Mechanistically, we discovered that KCMF1 interacted with NXN and facilitates its degradation through K63-linked ubiquitination, thereby reducing NXN expression. Taken together, our study showed that KCMF1 promotes ovarian cancer progression through NXN, and KCMF1 might be a novel target for ovarian cancer therapy.