Swine NONO promotes IRF3-mediated antiviral immune response by Detecting PRRSV N protein.

Non-POU domain-containing octamer-binding protein (NONO) is a multi-functional nuclear protein which belongs to the Drosophila behavior/human splicing (DBHS) protein family. NONO is known to regulate multiple important biological processes including host antiviral immune response. However, whether NONO can inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication is less well understood. In this study, we demonstrated that swine NONO (sNONO) inhibited PRRSV replication, via increasing expression of IFN-ß, whereas NONO knockdown or knockout in PAM-KNU cells was more susceptible to PRRSV infection. As an IRF3 positive regulation factor, NONO promoted IFN-ß expression by enhancing activation of IRF3. During PRRSV infection, NONO further up-regulated IRF3-mediated IFN-ß expression by interacting with PRRSV N protein. Mechanistically, NONO functioned as a scaffold protein to detect PRRSV N protein and formed N-NONO-IRF3 complex in the nucleus. Interestingly, it was found that the NONO protein reversed the inhibitory effect of PRRSV N protein on type I IFN signaling pathway. Taken together, our study provides a novel mechanism for NONO to increase the IRF3-mediated IFN-ß activation by interacting with the viral N protein to inhibit PRRSV infection.

The prevalence and shedding of porcine epidemic diarrhea virus in intensive swine farms of China from 2022 to 2023.

Porcine epidemic diarrhea has emerged as a significant threat to the global swine industry. The shedding and exposure status of porcine epidemic diarrhea virus (PEDV) in intensive farms is not completely understood. In this study, a total of 56,598 clinical samples collected from 256 intensive pig farms in 20 provinces in China from 2022 to 2023, were evaluated for PEDV using quantitative real-time PCR. The overall PEDV prevalence was 11.78 % and 28.45 % at the sample and farm levels, respectively, which are relatively high in Northern China and the fourth and first quarter of the year. The PEDV-positive rates and viral loads in suckling piglet herds were higher than those in growing-finishing pigs and multiparous sows. Meanwhile, 15.61 % of pig pens, 9.51 % of corridors, 9.4 % of office areas, 9.23 % of production personnel, and 8.33 % of pig cart driver samples were positive for PEDV, indicating potential biosafety gaps in intensive pig farms. In addition, 93.41 % of inguinal lymph node tissue samples contained viral nucleic acids, revealing a possible persistent infection of PEDV in pig herds. Our study presents the first report of the large-scale detection of PEDV in intensive pig farms, which constitutes indirect evidence of virus circulation in pig herds. This study provides valuable data for preventing and controlling PEDV infection in the future.

Distinct effects of physical and functional ablation of brown adipose tissue on T3-dependent pathological cardiac remodeling.

Heart failure tends to deteriorate in colder climates, heightening the risk of major adverse cardiovascular events. Brown adipose tissue (BAT) serves as both a thermogenic organ and an atypical site for triiodothyronine (T3) synthesis in response to cold. This study investigates the potential role of BAT in contributing to abdominal aortic constriction (AAC)-induced pathological cardiac remodeling during cold exposure. In this study, we developed a mouse model of pathological cardiac remodeling using AAC. Physical excision of interscapular BAT (iBATx) was performed during cold exposure, and T3 synthesis levels were measured. Additionally, the impact of uncoupling protein 1 (UCP1) knockout on thermogenic function and pathological cardiac remodeling was investigated. In vitro studies were conducted to assess the effect of T3 on cardiomyocyte hypertrophy induced by phenylephrine (PE). Physical removal of interscapular BAT during cold exposure decreased T3 synthesis and mitigated pathological cardiac remodeling. Conversely, UCP1 knockout eliminated thermogenic function during cold exposure, while preserving BAT integrity increased T3 synthesis and exacerbated pathological cardiac remodeling. In vitro, T3 further aggravated cardiomyocyte hypertrophy caused by PE. These findings underscore the distinct effects of physical and functional BAT ablation on pathological cardiac remodeling, primarily through altering T3 levels rather than thermogenesis in cold environments. This research provides new insights into the differential roles of BAT in cardiac health, particularly under cold exposure conditions.

Delivery room resuscitation and short-term outcomes in very preterm infants: a multicenter cross-sectional study in China.

Objective: To explore the risk factors of delivery room (DR) resuscitation and assess the association of DR resuscitation with neonatal outcomes in very preterm infants (VPIs). Methods: A multicenter retrospective cross-sectional study included VPIs with gestational age (GA) <32 weeks born between January, 2022 and June, 2023 and admitted to neonatal intensive care units of six tertiary hospitals in Shenzhen within 24 h after birth. They were divided into routine care group, positive-pressure ventilation (PPV) group, and endotracheal intubation (ETT) group based on the highest intensity of resuscitation received at birth. The association of antepartum and intrapartum risk factors and short-term outcomes with the intensity of DR resuscitation was evaluated. Results: Of 683 infants included in this study, 170 (24.9%) received routine care, 260 (38.1%) received bag and mask ventilation or T-piece ventilation and 253 (37%) received ETT. Among the antepartum and intrapartum factors, exposure to antenatal steroids (ANS) decreased the likelihood of ETT. Increasing GA decreased the likelihood of receiving a higher level of DR resuscitation. Among the neonatal outcomes, increasing intensity of DR resuscitation was associated with a raise in the risk of Bronchopulmonary dysplasia. Higher levels of DR resuscitation were associated with the risk of early-onset sepsis. ETT was significantly associated with an increased risk of death. Conclusion: Among VPIs, low GA and no ANS use increased the risk of high-intensity DR resuscitation interventions; and those who receiving ETT were associated with an increased risk of adverse clinical outcomes.

AMBRA1 controls the translation of immune-specific genes in T lymphocytes.

T cell receptor (TCR) engagement causes a global cellular response that entrains signaling pathways, cell cycle regulation, and cell death. The molecular regulation of mRNA translation in these processes is poorly understood. Using a whole-genome CRISPR screen for regulators of CD95 (FAS/APO-1)-mediated T cell death, we identified AMBRA1, a protein previously studied for its roles in autophagy, E3 ubiquitin ligase activity, and cyclin regulation. T cells lacking AMBRA1 resisted FAS-mediated cell death by down-regulating FAS expression at the translational level. We show that AMBRA1 is a vital regulator of ribosome protein biosynthesis and ribosome loading on select mRNAs, whereby it plays a key role in balancing TCR signaling with cell cycle regulation pathways. We also found that AMBRA1 itself is translationally controlled by TCR stimulation via the CD28-PI3K-mTORC1-EIF4F pathway. Together, these findings shed light on the molecular control of translation after T cell activation and implicate AMBRA1 as a translational regulator governing TCR signaling, cell cycle progression, and T cell death.

Suppression of ZBP1-mediated NLRP3 inflammasome by the tegument protein VP22 facilitates pseudorabies virus infection.

The interaction between Z-DNA binding protein 1 (ZBP1) and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been uncovered in several viral infections. However, the role of this molecular pathway during infection with the alpha-herpesvirus pseudorabies virus (PRV) remains largely elusive. Here, we report that during PRV infection, ZBP1-mediated NLRP3 inflammasome activation is inhibited by the viral tegument protein VP22, thereby facilitating viral infection. Through a combination of RNA sequencing and genetic studies, we demonstrate that PRV VP22 functions as a virus-encoded virulence factor by evading the inhibitory effects of ZBP1 on virus infection. Importantly, the replication and pathogenicity of a recombinant PRV lacking VP22 are significantly increased in ZBP1-deficient cells and mice. Mechanistically, PRV VP22 interacts with ZBP1, impeding the recruitment of receptor-interacting protein kinase 3 and Caspase-8, thereby inhibiting NLRP3 activation. Furthermore, we show that the N-terminal 1-50 amino acid domain of VP22 dominantly destabilizes ZBP1-mediated function. Taken together, these findings identify a functional link between PRV infection and ZBP1-mediated NLRP3 inflammatory response, providing novel insights into the pathogenesis of PRV and other herpesviruses. IMPORTANCE: Z-DNA binding protein 1 (ZBP1) functions as a pivotal innate immune sensor that regulates inflammatory cell death during viral infections. However, its role in pseudorabies virus (PRV) infection remains unknown. Here, we demonstrate that ZBP1 serves as a restrictive factor by triggering the activation of the NLR family pyrin domain-containing 3 inflammasome, a process counteracted by PRV-encoded protein VP22. Furthermore, VP22 interferes with the interaction between ZBP1 and receptor-interacting protein kinase 3/Caspase-8, particularly through its N-terminal 1-50 amino acids. Importantly, deficiency in ZBP1 enhances the replication and virulence of recombinant viruses lacking VP22 or its N-terminal 1-50 amino acids. These findings reveal how PRV escapes ZBP1-mediated inflammatory responses during infection, potentially informing the rational design of therapeutic interventions.

Association of neuroimaging measures with facial emotional processing in healthy adults: a task fMRI study.

Investigating the neural processing of emotion-related neural circuits underlying emotional facial processing may help in understanding mental disorders. We used two subscales of the Toronto Alexithymia Scale to assess the emotional cognitive of 25 healthy participants. A higher score indicates greater difficulty in emotional perception. In addition, participants completed a n-back task during functional magnetic resonance imaging. Psychophysiological interaction analysis was used to explore the functional connectivity (FC) of neural circuits. Next, we used elastic-net regression analysis for feature selection and conducted correlation analysis between the neuroimaging measures and questionnaire scores. Following a 3-fold cross-validation, 5 neuroimaging measures emerged as significant features. Results of correlation analysis demonstrated that participants with higher TAS scores exhibited increased FC between the amygdala and occipital face area (OFA) during facial stimulus processing, but decreased connectivity during emotional processing. These findings suggested that individuals with poor emotional recognition exhibited increased connectivity among face-related brain regions during facial processing. However, during emotional processing, decreasing neural synchronization among neural circuits involved in emotional processing affects facial expression processing. These findings suggest potential neural marker related to subjective emotional perception, which may contribute to the diagnosis and treatment of emotional dysregulation in individuals with psychiatric conditions.

Does environmental regulation truly enhance corporate green environmental investment? Evidence from the supervision of independent directors in listed companies.

With the increasingly prominent environmental issues in China, the government and citizens alike have intensified their focus on corporate investments in green environmental protection. Nevertheless, as government regulations become more stringent, there is substantial debate over whether environmental regulatory policies can consistently encourage listed companies to increase green environmental investments. Simultaneously, independent board supervision plays a crucial role in promoting the compliance and sustainability of listed companies regarding environmental protection. This paper selected a sample of 246 Chinese listed companies from 2010 to 2019, and used a fixed effects model to examine the impact of environmental regulation on the environmental investment of listed companies in China. Moreover, we used a mediation effect model to analyze the role of independent director supervision in influencing the relationship between environmental regulation and companies' green environmental investment. Additionally, we discuss the heterogeneous impact of environmental regulations on corporate environmental investments. Our findings are as follows: first, during the sample period, the tightening of environmental regulations significantly reduces the growth of environmental investment among the studied firms. As government environmental regulatory policies gradually intensify, the negative impact on environmental investments by listed companies becomes increasingly evident. Second, independent directors help alleviate the adverse impacts of environmental regulations on the environmental investment levels of listed companies. This suggests that the inclusion of independent directors in board governance plays a role in assessing government environmental regulatory policies and overseeing corporate decisions related to environmental investment. Lastly, the heterogeneity analysis indicates that environmental regulation significantly negatively impacts the environmental investment of listed companies in pollution-intensive industries and those located in the western regions. Furthermore, environmental regulatory policies impose greater constraints on the environmental investments of small-sized listed companies compared to their large-sized counterparts.

LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/ß-catenin signaling pathway.

OBJECTIVE: This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms. METHODS: RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent in situ hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/ß-catenin signaling pathway. RESULTS: Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (p < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (p < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of ß-catenin (p < 0.05), p-GSK-3ß (p < 0.05), Cyclin D1 (p < 0.05), PCNA (p < 0.05), and thus reduced the cell proliferation. CONCLUSION: NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/ß-catenin signaling.

Discovery and analysis of the relationship between organic components in exhaled breath and bronchiectasis.

The prevalence of patients with bronchiectasis (BE) has been rising in recent years, which increases the substantial burden on the family and society. Exploring a convenient, effective, and low-cost screening tool for the diagnosis of BE is urgent. We expect to identify the accuracy (ACC) of breath biomarkers (BBs) for the diagnosis of BE through breathomics testing and explore the association between BBs and clinical features of BE. Exhaled breath samples were collected and detected by high-pressure photon ionization time-of-flight mass spectrometry in a cross-sectional study. Exhaled breath samples were from 215 patients with BE and 295 control individuals. The potential BBs were selected via the machine learning (ML) method. The overall performance was assessed for the BBs-based BE detection model. The significant BBs between different subgroups such as the severity of BE, acute or stable stage, combined with hemoptysis or not, with or without nontuberculous mycobacterium (NTM),P. aeruginosa(P.a) isolation or not, and the BBs related to the number of involved lung lobes and lung function were discovered and analyzed. The top ten BBs based ML model achieved an area under the curve of 0.940, sensitivity of 90.7%, specificity of 85%, and ACC of 87.4% in BE diagnosis. Except for the top ten BBs, other BBs were found also related to the severity, acute/stable status, hemoptysis or not, NTM infection,P.aisolation, the number of involved lobes, and three lung functional parameters in BE patients. BBs-based BE detection model showed good ACC for diagnosis. BBs have a close relationship with the clinical features of BE. The breath test method may provide a new strategy for BE screening and personalized management.

A Lysosome-Targeting hNEU1 Inhibitor Treats Myocardial Infarction: A Potential Therapeutic Breakthrough.

The overexpression of NEU1 has recently been certified as being associated with myocardial infarction. However, the pursuit of an efficacious human NEU1 (hNEU1) inhibitor remains challenging, and viral NEU1 (viNEU1) inhibitor drugs are significantly weaker in terms of hNEU1 inhibition. Recognizing that hNEU1 is located within the lysosome, we designed a series of lysosome-targeting compounds, derived from oseltamivir, aimed at hNEU1 inhibition. Among these compounds, OsMo exhibits the most potent activity. Our findings reveal that OsMo accumulates within lysosomes and releases its pharmacophore via enzymatic catalysis. OsMo enhances hNEU1 inhibition by accumulating pharmacophores at the target site. OsMo exhibits improved regulation of abnormal autophagy during myocardial injury, demonstrating superior efficacy in treating myocardial infarction in vivo. Furthermore, OsMo exhibits acceptable pharmacokinetic parameters. Importantly, the development of molecules with lysosome-targeting abilities represents a promising avenue for addressing myocardial injuries linked to hNEU1 overexpression.

Syndecan-3 inhibits LPS-induced Inflammation of Bovine Mammary Epithelial Cells through the NF-κB Signal Transduction Pathway.

In mastitis, excessive inflammation caused by lipopolysaccharide (LPS) is an important factor leading to mammary tissue damage. Therefore, exploring the regulatory factors that can inhibit the widespread inflammation caused by LPS is crucial. Syndecan-3 (SDC3) has been found to play an active role in anti-inflammatory infection by inhibiting leukocyte adhesion, reducing the accumulation of inflammatory products, such as reactive oxygen species, and competing with chemokines; however, the role and regulatory mechanism of SDC3 in mastitis remains unknown. Therefore, this study aimed to reveal the effect of SDC3 on LPS-induced inflammation in bovine mammary epithelial cells (BMECs) and explore its possible molecular mechanisms. First, we constructed a BMEC inflammatory model. It was found that cells stimulated with 10 µg/mL LPS for 24 h strongly induced the expression of inflammatory cytokines and had no toxic effect on cells, which was the best condition to simulate the BMECs inflammatory response in vitro. Subsequently, we used overexpression and RNAi interference, Real Time Quantitative PCR (RT-qPCR), and Western blot assays to explore the effects of SDC3 on LPS-induced inflammatory factors and their mechanisms. The results showed that overexpression of SDC3 could inhibit the transcriptional levels of inflammatory cytokines IL-6, IL-1ß, and TNFα induced by LPS and inhibit the activation of the NF-κB inflammatory pathway by inhibiting the expression of NF-κB p50 and p-IκBα and promoting the expression of IκBα. Our results suggest that SDC3 inhibits the LPS-induced inflammatory response of BMECs through the NF-κB pathway, in which NF-κB p50 may be an important target of SDC3. These findings lay the foundation for elucidating the molecular regulatory mechanisms of dairy cow mastitis.

Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts.

The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth's magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth's rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.

Highly efficient CuNi-ZrO2 nanocomposites for selective hydrogenation of levulinic acid to γ-valerolactone.

CuNi-ZrO2 nanocomposites were prepared by a simple coprecipitation technique of copper, nickel and zirconium ions with potassium carbonate. The structures of the nanocomposites were characterized by N2 physical adsorption, XRD, H2-TPR and STEM-EDS. The Cu0.05Ni0.45-ZrO2 nanocomposite showed outstanding catalytic performance in hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL), especially NaOH solution (0.5 mol L-1) as a solvent. 100% LA conversion and > 99.9% GVL selectivity are achieved over Cu0.05Ni0.45-ZrO2 catalyst at 200 °C, 3 MPa for 1.5 h. Characterization results suggest that the excellent reactivity of the Cu0.05Ni0.45-ZrO2 may be due to a better reducibility of nickel oxide in the CuONiO-ZrO2, dispersion of Ni in the Cu0.05Ni0.45-ZrO2 compared to nickel oxide in the NiO-ZrO2 and Ni in the Ni0.5-ZrO2 and promotion of OH-. The results demonstrate that the Cu0.05Ni0.45-ZrO2 nanocomposite has potential to realize high efficiency and low-cost synthesis of liquid fuels from biomass.

Setup errors analysis in iterative kV CBCT: A clinical study of cervical cancer treated with Volumetric Modulated Arc Therapy.

OBJECTIVE: This study aims to analyze setup errors in pelvic Volumetric Modulated Arc Therapy (VMAT) for patients with non-surgical primary cervical cancer, utilizing the onboard iterative kV cone beam CT (iCBCT) imaging system on the Varian Halcyon 2.0 ring gantry structure accelerator to enhance radiotherapy precision. METHOD: We selected 132 cervical cancer patients who underwent VMAT with daily iCBCT imaging guidance. Before each treatment session, a registration method based on the bony structure was employed to acquire iCBCT images with the corresponding planning CT images. Following verification and adjustment of image registration results along the three axes (but not rotational), setup errors in the lateral (X-axis), longitudinal (Y-axis), and vertical (Z-axis) directions were recorded for each patient. Subsequently, we analyzed 3642 iCBCT image setup errors. RESULTS: The mean setup errors for the X, Y, and Z axes were 4.50 ± 3.79 mm, 6.08 ± 6.30 mm, and 1.48 ± 2.23 mm, respectively. Before correction with iCBCT, setup margins based on the Van Herk formula for the X, Y, and Z axes were 6.28, 12.52, and 3.26 mm, respectively. In individuals aged 60 years and older, setup errors in the X and Y axes were significantly larger than those in the younger group (p < 0.05). Additionally, there is no significant linear correlation between setup errors and treatment fraction numbers. CONCLUSION: Data analysis underscores the importance of precise Y-axis setup for cervical cancer patients undergoing VMAT. Radiotherapy centers without daily iCBCT should appropriately extend the planning target volume (PTV) along the Y-axis for cervical cancer patients receiving pelvic VMAT. Elderly patients exhibit significantly larger setup errors compared to younger counterparts. In conclusion, iCBCT-guided radiotherapy is recommended for cervical cancer patients undergoing VMAT to improve setup precision.

Neutrophil extracellular traps: Potential targets for the treatment of rheumatoid arthritis with traditional Chinese medicine and natural products.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Abnormal formation of neutrophil extracellular traps (NETs) at the synovial membrane leads to the release of many inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Elastase, histone H3, and myeloperoxidase, which are carried by NETs, damage the soft tissues of the joints and aggravate the progression of RA. The balance of NET formation coordinates the pro-inflammatory and anti-inflammatory effects and plays a key role in the development of RA. Therefore, when NETs are used as effector targets, highly targeted drugs with fewer side effects can be developed to treat RA without damaging the host immune system. Currently, an increasing number of studies have shown that traditional Chinese medicines and natural products can regulate the formation of NETs through multiple pathways to counteract RA, which shows great potential for the treatment of RA and has a promising future for clinical application. In this article, we review the latest biological progress in understanding NET formation, the mechanism of NETs in RA, and the potential targets or pathways related to the modulation of NET formation by Chinese medicines and natural products. This review provides a relevant basis for the use of Chinese medicines and natural products as natural adjuvants in the treatment of RA.

Therapeutic inhibition of the JAK-STAT pathway in the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses a group of non-specific chronic intestinal inflammatory conditions of unclear etiology. The current treatment and long-term management primarily involve biologics. Nevertheless, some patients experience treatment failure or intolerance to biologics [1], making these patients a primary focus of IBD research. The Janus kinase (JAK)-Signal Transducers and Activator of Transcription (STAT) signal transduction pathway is crucial to the regulation of immune and inflammatory responses [2], and plays an important role in the pathogenesis of IBD. JAK inhibitors alleviate IBD by suppressing the transmission of JAK-STAT signaling pathway. As the first small-molecule oral inhibitor for IBD, JAK inhibitors greatly improved the treatment of IBD and have demonstrated significant efficacy, with tofacitinib and upadacitinib being approved for the treatment of ulcerative colitis (UC) [3]. JAK inhibitors can effectively alleviate intestinal inflammation in IBD patients who have failed to receive biologics, which may bring new treatment opportunities for refractory IBD patients. This review aims to elucidate the crucial roles of JAK-STAT signal transduction pathway in IBD pathogenesis, examine its role in various cell types within IBD, and explore the research progress of JAK inhibitors as therapeutic agents, paving the road for new IBD treatment strategies.

Visualization of Solvent Effect and Oxygen Content via a Red Room-Temperature Phosphorescent Material.

The development of pure organic room-temperature phosphorescent (RTP) materials greatly facilitates the integrated application of luminescent materials. Herein, a type of photoactivated red RTP material was constructed by simply doping 4-(benzo[c][1,2,5]thiadiazol-5-ylthio)benzonitrile (p-NNS) into a poly(methyl methacrylate) (PMMA) matrix. The obtained film realized a controllable photoactivation process by regulation of diverse solvent levels, demonstrating potential advantages in optical anti-counterfeiting applications. Furthermore, luminescent properties of the doped film were utilized to detect oxygen content from 2.00% to 4.90%, which revealed the exact consumption of ambient oxygen under UV light. Every CIE point of the luminescence corresponds to a certain oxygen content, illustrating the visualization of oxygen content. The remarkable regulation of solvent effect and oxygen content in this work will provide competitive material for further optical applications.

CFTR Inhibitors Display Antiviral Activity against Herpes Simplex Virus.

The cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl- channel, is closely associated with multiple pathogen infections, such as SARS-CoV-2. However, whether the function of the CFTR is involved in herpes simplex virus (HSV) infection has not been reported. To evaluate the association of CFTR activity with HSV infection, the antiviral effect of CFTR inhibitors in epithelial cells and HSV-infected mice was tested in this study. The data showed that treatment with CFTR inhibitors in different concentrations, Glyh-101 (5-20 µM), CFTRi-172 (5-20 µM) and IOWH-032 (5-20 µM), or the gene silence of the CFTR could suppress herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) replication in human HaCaT keratinocytes cells, and that a CFTR inhibitor, Glyh-101 (10-20 µM), protected mice from HSV-1 and HSV-2 infection. Intracellular Cl- concentration ([Cl-]i) was decreased after HSV infection via the activation of adenylyl cyclase (AC)-cAMP signaling pathways. CFTR inhibitors (20 µM) increased the reduced [Cl-]i caused by HSV infection in host epithelial cells. Additionally, CFTR inhibitors reduced the activity and phosphorylation of SGK1 in infected cells and tissues (from the eye and vagina). Our study found that CFTR inhibitors can effectively suppress HSV-1 and HSV-2 infection, revealing a previously unknown role of CFTR inhibitors in HSV infection and suggesting new perspectives on the mechanisms governing HSV infection in host epithelial cells, as well as leading to potential novel treatments.

Interfacial Cooperative Assembly of Surfactants and Opposite Wettability Nanoparticles Stabilizes Water-in-Oil Emulsions at High Temperature.

Pickering emulsions have promising applications in the development of unconventional oil and gas resources. However, the high-temperature environment of the reservoir is not conducive to the stabilization of Pickering emulsions. In addition, the preparation of Pickering emulsions under low-energy emulsification and low-concentration emulsifier conditions is a difficult challenge. Here, we report a high-temperature resistant water-in-paraffin oil Pickering emulsion, which is synergistically stabilized by polyglycerol ester (PGE) and nanoparticles with opposite wettability (lipophilic silica and hydrophilic alumina). This emulsion can be prepared under mild stirring (500 rpm) conditions and can be stable at 140 °C for at least 30 days. The synergistic effects of surfactant, silicon nanoparticles (MSNPs) with different wettability, and alumina nanoparticles (AONPs) on the stability of both emulsions and water-oil interfacial membranes were investigated through bottle experiments, cryogenic scanning electron microscopy (cryo-SEM), optical microscopy, fluorescence microscopy, etc. The results showed that both hydrophobic MSNPs and hydrophilic AONPs are adsorbed together at the water-oil interface to stabilize the W/O emulsion, which can be prepared by 500 rpm stirring. The stability of emulsions strongly depends on the wettability of MSNPs, and the MSNP with moderate hydrophobicity (for example, aqueous phase contact angle of 136°) makes the emulsion exhibit the highest stability against aggregation and settling at elevated temperatures. The emulsion stabilization mechanism was revealed in terms of the adsorption capacity of the surfactant by MSNPs, the adsorption morphology and desorption energy of nanoparticles at the water-oil interface adsorption layer, and emulsion rheology. These findings demonstrate a novel and simple strategy to prepare Pickering W/O emulsions with high-temperature stability at low shear strength.