Exploring antiviral effect and mechanism of Jinye Baidu granules（JYBD）against influenza A virus through network pharmacology and in vitro and invivo experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinye Baidu granules (JYBD) have been used to treat acute respiratory tract infections and demonstrated clinical efficacy for the treatment of emerging or epidemic respiratory viruses such as SARS-CoV-2 and influenza virus. AIM OF THE STUDY: This study is to investigate the antiviral effect of JYBD against influenza A viruses (IAV) in vitro and in vivo and elucidate its underlying mechanism. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography connected with Orbitrap mass spectrometer (UHPLC-Orbitrap MS) was employed to describe the chemical profile of JYBD. The potential pathways and targets involved in JYBD against IAV infection were predicted by network pharmacology. The efficacy and mechanism of JYBD were validated through both in vivo and in vitro experiments. Moreover, combination therapy with JYBD and the classic anti-influenza drugs was also investigated. RESULTS: A total of 126 compounds were identified by UHPLC-Orbitrap MS, of which 9 compounds were unambiguously confirmed with reference standards. JYBD could significantly inhibit the replication of multiple strains of IAV, especially oseltamivir-resistant strains. The results of qRT-PCR and WB demonstrated that JYBD could inhibit the excessive induction of pro-inflammatory cytokines induced by IAV infection and regulate inflammatory response through inhibiting JAK/STAT, NF-κB and MAPK pathways. Moreover, both JYBD monotherapy or in combination with oseltamivir could alleviate IAV-induced severe lung injury in mice. CONCLUSIONS: JYBD could inhibit IAV replication and mitigate virus-induced excessive inflammatory response. Combinations of JYBD and neuraminidase inhibitors conferred synergistic suppression of IAV both in vitro and in vivo. It might provide a scientific basis for clinical applications of JYBD against influenza virus infected diseases.

Modulating d-Orbital electronic configuration via metal-metal oxide interactions for boosting electrocatalytic methanol oxidation.

Coordinating the interfacial interaction between Pt-based nanoparticles (NPs) and supports is a significant strategy for the modulation of d-orbital electronic configuration and the adsorption behaviors of intermediates, which is of critical importance for boosting electrocatalytic performance. Herein, we demonstrated a specific synergy effect between the ordered PtFe intermetallic and neighboring oxygen vacancies (Ov), which provides an "ensemble reaction pool" to balance the barriers of both the activity, stability, and CO poisoning issues for the methanol oxidation reaction (MOR). In our proposed "ensemble reaction pool", the deprotonation of methanol occurs on the Pt site to form the intermediate *CO, where the strain derived from the PtFe intermetallic could alter the d-orbital electronic configuration of Pt, intrinsically weakening the *CO adsorption energy, and Ov in CeO2 promote hydroxyl species (*OH) adsorption, which will react with *CO, facilitating the dissociative adsorption of *CO, thus cooperatively enhancing the performance of MOR. The X-ray absorption fine structure (XAFS) analyses reveal the electron transfer in CeO2 and then convert Ce4+ to Ce3+. The density functional theory (DFT) calculations revealed that introducing Fe induces strain could modify the d-band center of Pt, and thus lower the energy barrier of the potential-determining step. Meanwhile, the introduction of CeO2 can favor the *OH adsorption, speeding up the oxidation and removal of *CO blocked at the Pt site. Furthermore, the determined atomic arrangement and surface composition of PtFe intermetallic further guarantee the stability of MOR by suppressing less-noble metal into the electrolyte.

Activation of peroxymonosulfate by sustainable biomass-based carbon nanotubes for controlling the spread of plant viruses in water environments.

With the increasing demand for water in hydroponic systems and agricultural irrigation, viral diseases have seriously affected the yield and quality of crops. By removing plant viruses in water environments, virus transmission can be prevented and agricultural production and ecosystems can be protected. But so far, there have been few reports on the removal of plant viruses in water environments. Herein, in this study, easily recyclable biomass-based carbon nanotubes catalysts were synthesized with varying metal activities to activate peroxymonosulfate (PMS). Among them, the magnetic 0.125Fe@NCNTs-1/PMS system showed the best overall removal performance against pepper mild mottle virus, with a 5.9 log10 removal within 1 min. Notably, the key reactive species in the 0.125Fe@NCNTs-1/PMS system is 1O2, which can maintain good removal effect in real water matrices (river water and tap water). Through RNA fragment analyses and label free analysis, it was found that this system could effectively cleave virus particles, destroy viral proteins and expose their genome. The capsid protein of pepper mild mottle virus was effectively decomposed where serine may be the main attacking sites by 1O2. Long viral RNA fragments (3349 and 1642 nt) were cut into smaller fragments (∼160 nt) and caused their degradation. In summary, this study contributes to controlling the spread of plant viruses in real water environment, which will potentially help protect agricultural production and food safety, and improve the health and sustainability of ecosystems.

Selective Methylation of Cyclic Ether Towards Highly Elastic Solid Electrolyte Interphase for Silicon-based Anodes.

Silicon (Si)-based anodes offer high theoretical capacity for lithium-ion batteries but suffer from severe volume changes and continuous solid electrolyte interphase (SEI) degradation. Here, we address these challenges by selective methylation of 1,3-dioxolane (DOL), thus shifting the unstable bulk polymerization to controlled interfacial reactions and resulting in a highly elastic SEI. Comparative studies of 2-methyl-1,3-dioxolane (2MDOL) and 4-methyl-1,3-dioxolane (4MDOL) reveal that 4MDOL, with its larger ring strain and more stable radical intermediates due to hyperconjugation effect, promotes the formation of high-molecular-weight polymeric species at the electrode-electrolyte interface. This elastic, polymer-rich SEI effectively accommodates volume changes of Si and inhibits continuous side reactions. Our designed electrolyte enables Si-based anode to achieve 85.4% capacity retention after 400 cycles at 0.5 C without additives, significantly outperforming conventional carbonate-based electrolytes. Full cells also demonstrate stable long-term cycling. This work provides new insights into molecular-level electrolyte design for high-performance Si anodes, offering a promising pathway toward next-generation lithium-ion batteries with enhanced energy density and longevity.

Ecological Effects of the Huge Invasive Species Removal Project in Coastal China.

Saltmarsh wetlands are recognized as some of the most ecologically valuable yet vulnerable ecosystems globally. However, since the 1970s, saltmarsh wetlands in coastal China have been seriously threatened by the invasive Spartina alterniflora. Although the Chinese government has initiated a nationwide S. alterniflora removal project, the potential benefits and risks of this project remain unknown. Here, we focus on the Yangtze River Estuary Saltmarsh Wetland (YRESW) and simulate its future ecosystem structure, function, and quality under three scenarios based on remote sensing and field investigation data. The simulation scenarios include the absence of a removal project, natural regeneration postproject (NRP), and planted restoration postproject. The results show that the removal project will reverse the escalating invasion trend of S. alterniflora in the YRESW. Compared to the baseline year of 2022, there is a remarkable increase in ecosystem structure (composition: +107%, configuration: +27%) and ecosystem quality (+10.5%) under the NRP scenario. Although blue carbon storage sharply decreases under both scenarios involving project implementation, planted restoration can restore YRESW's carbon sequestration capacity to 0.19 Tg C per year, achieving 87% of the carbon storage present before the project. This study underscores the necessity of comprehensive and detailed risk assessments in ecological projects, particularly when dominant species are involved. Our findings hold significant implications for stabilizing coastal wetland ecosystems and promoting sustainable development in coastal areas.

High-sensitivity miniaturized spectrometers using photonic crystal slab filters.

Miniaturized spectrometers have emerged as pivotal tools in numerous scientific and industrial applications, offering advantages such as portability, cost-effectiveness, and the capability for onsite analysis. Despite these significant benefits, miniaturized spectrometers face critical challenges, particularly in sensitivity. Reduced dimensions often lead to compromises in optical path length and component quality, which can diminish detection limits and limit their applications in areas such as low-light-level measurements. Here we developed a compact spectrometer that integrates an array of photonic crystal slab filters with band-stop spectral transmission characteristics into an image sensor. Compared to traditional gratings or bandpass filter strategies, where each detector can only read light of a single wavelength component, our band-stop strategy allows each detector to read the light of all wavelengths except the band-stop wavelength. This maximizes energy extraction from incident signals, significantly improving the sensitivity of the spectrometer. Spectral reconstruction is achieved mathematically using pre-calibrated band-stop responses combined with a single coded image. Our spectrometer delivers a spectral resolution of 1.9 nm and demonstrates sensitivity more than ten times greater than that of conventional grating spectrometers during fluorescence spectroscopy of Ascaris lumbricoides. The design is fully compatible with complementary metal-oxide-semiconductor (CMOS) technology, allowing for mass production at low costs and thus promising broad deployment in sensitive applications.

Generation controllable optical chain using an optical pen.

An aperiodic snake-like optical chain has been proposed and generated by using an optical pen technique, whose numbers and positions of focal points are controllable. Moreover, by introducing a fan phase together with a twisted phase into the optical pen technique, a self-rotation optical chain can be obtained; meanwhile, it transforms the bright optical chain into a twisted optical chain with a rotating hollow region in a three-dimensional (3D) space. The properties of the rotatable focal points and the variable diameters of cross-sectional intensities during the propagation of the optical chain are demonstrated in the experimental results. Consequently, this research framework can be applied in the techniques such as deep multiplexing and rotation angle multiplexing while also enabling the realization of multiple capture sites and more intricate manipulations.

Impact of an Epstein-Barr Virus Serology-Based Screening Program on Nasopharyngeal Carcinoma Mortality: A Cluster-Randomized Controlled Trial.

PURPOSE: Screening for nasopharyngeal carcinoma (NPC) has shown an improvement in early detection and survival rates of NPC in endemic regions. It is critical to evaluate whether NPC screening can reduce NPC-specific mortality in the population. METHODS: Sixteen towns in Sihui and Zhongshan cities, China, were selected; eight were randomly allocated to the screening group and eight to the control group. Residents age 30-69 years with no history of NPC were included from January 1, 2008, to December 31, 2015. Residents in the screening towns were invited to undergo serum Epstein-Barr virus (EBV) viral capsid antigen/nuclear antigen 1-immunoglobulin A antibody tests; others received no intervention. The population was followed until December 31, 2019. Nonparametric tests and Poisson regression models were used to estimate the screening effect on NPC mortality, accounting for the cluster-randomized design. The trial is registered with ClinicalTrials.gov (identifier: NCT00941538). RESULTS: A total of 174,943 residents in the screening group and 186,263 residents in the control group were included. NPC incidence and overall mortality were similar between the two groups. A total of 52,498 (30.0% of 174,943) residents participated in the serum EBV antibody test. The overall compliance rate for endoscopic examination and/or biopsies among baseline and ever-classified high-risk participants was 65.9% (1,110 of 1,685) and 67.6% (1,703 of 2,518), respectively. A significant 30% reduction in NPC mortality was observed in the screening group compared with the control group (standardized NPC-specific mortality rate of 8.2 NPC deaths per 1,000 person-years versus 12.5; adjusted rate ratio [RR], 0.70 [95% CI, 0.49 to 0.997]; P = .048). This benefit was most evident among individuals age 50 years and older (RR, 0.56 [95% CI, 0.37 to 0.85]; P = .007) compared with those younger than 50 years (RR, 0.96 [95% CI, 0.64 to 1.46]; P = .856). CONCLUSION: In this 12-year trial, EBV antibody testing resulted in a significant reduction in NPC mortality.

Effect of Different Injury Morphology of the Endplate on Intervertebral Disc Degeneration: Retrospective Cohort Study.

OBJECTIVES: To describe a simplified classification scheme for endplate injury morphology based on 3D CT and to examine possible associations between endplate injury morphology and vertebral space and other variables such as type of fracture and disc degeneration in a group of patients with thoracolumbar fractures. METHODS: This study was a retrospective cohort study. We collected patients with thoracolumbar fractures admitted from January 2015 to August 2020 and divided them into three groups based on the morphology of endplate injury (45 cases of mild endplate injury, 54 cases of moderate endplate injury, and 42 cases of severe endplate injury, SEI). Data of vertebral body and intervertebral space height and angle, the Pfirrmann grade, endplate healing morphology were collected during preoperative, postoperative, and long-term follow-up of patients in each group. One-way analysis of variance (ANOVA), chi-squared test, and repeated measurement ANOVA were used to compare and analyze the influence of endplate injury morphology on patient prognosis. RESULTS: Most moderate injuries to the endplate (fissure-type injury) and severe injuries (irregular depression-type injury, Schmorl's node-type injury) resulted in significant disc degeneration in the long-term transition. This study also showed significant differences in the height of the anterior margin of the injured spine and the intervertebral space height index during this process. CONCLUSIONS: The current study suggests that although the region of injury in endplate fissure-type injury is small preoperatively, it may be a major factor in leading to severe disc degeneration, loss of intervertebral height, and Cobb angle in the long term. The results of our study therefore may allow surgeons to predict the prognosis of patients with thoracolumbar fractures and guide their treatment.

Improving prognostic accuracy in lung transplantation using unique features of isolated human lung radiographs.

Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases. Latent features were transformed into principal components (PC) and correlated with known radiographic findings. PCs were combined with physiological data to classify clinical outcomes: (1) recipient time to extubation of <72 h, (2) ≥ 72 h, and (3) lungs unsuitable for transplantation. The top PC was significantly correlated with infiltration (Spearman R: 0·72, p < 0·0001), and adding radiographic PCs significantly improved the discrimination for clinical outcomes (Accuracy: 73 vs 78%, p = 0·014). CNN-derived radiographic lung features therefore add substantial value to the current assessments. This approach can be adopted by EVLP centers worldwide to harness radiographic information without requiring real-time radiological expertise.

Combining full-length transcriptome sequencing and next generation sequencing to provide insight into the growth superiority of the hybrid grouper (Cromileptes altivelas (♀) × Epinephelus lanceolatus (♂)).

The hybrid grouper (Cromileptes altivelas, ♀ × Epinephelus lanceolatus, ♂) is an economically important aquaculture species that exhibits certain growth advantages compared to its female parent, Cromileptes altivelas. However, the current understanding of the molecular mechanisms underlying the growth of hybrid groupers is lacking. Herein, we performed full-length transcriptome sequencing and next-generation sequencing on the hybrid grouper and its parents to identify growth-related genes and comprehensively analyze the regulatory mechanism of growth heterosis in the hybrid grouper. Approximately 44.70, 40.44, and 45.32 Gb of single-molecule real-time sequencing data were generated in C. altivelas (Cal), E. lanceolatus (Ela), and the hybrid (Hyb), which were combined into 204,322 non-redundant isoforms using the PacBio sequencing platform. Differentially expressed genes (DEGs) were identified between Hyb and Cal (3,494, 2,125, and 1,487 in brain, liver, and muscle tissues, respectively) and Hyb and Ela (3,415, 2,351, and 1,675 in brain, liver, and muscle tissues, respectively). Then, 27 DEGs (13 in the brain and 14 in the muscle) related to growth traits were identified using cluster and correlation network analysis. Quantitative RT-PCR validated 15 DEGs consistent with transcriptome sequencing (RNA-seq) trends. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these 15 genes were mainly involved in regulating the actin cytoskeleton, suggesting that this pathway plays an essential role in fish growth. In addition, we found that the phosphatase and tensin homologue (PTEN) is a key regulator of growth heterosis in Hyb. These results shed light on the regulatory mechanism of growth in the Hyb, which is important for marker-assisted selection programs to improve the growth quality of groupers.

Identifying subtypes of Type 2 diabetes mellitus based on real-world electronic medical record data in China.

AIMS: To replicate the European subtypes of type 2 diabetes mellitus (T2DM) in Chinese diabetes population, and investigate the risk of complications in different subtypes. METHODS: A diabetes cohort using real-world patient data was constructed and clustering was employed to subgroup the T2DM patients. Kaplan-Meier analysis and the Cox model were used to analyze the association between diabetes subtypes and the risk of complications. RESULTS: A total of 2,652 T2DM patients with complete clustering data were extracted. Among them, 466 (17.57 %) were classified as severe insulin-deficient diabetes (SIDD), 502 (18.93 %) as severe insulin-resistant diabetes (SIRD), 672 (25.34 %) as mild obesity-related diabetes (MOD), and 1,012 (38.16 %) as mild age-related diabetes (MARD). The risk of chronic kidney disease (CKD) and diabetic retinopathy (DR) were different in the four subtypes. Compared with MARD, SIRD had a higher risk of CKD (HR 2.01 [1.03, 3.91]), and SIDD had a higher risk of DR (HR 2.17 [1.12, 4.20]). The risk of stroke and coronary events had no difference. CONCLUSIONS: The European T2DM subtypes can be replicated in Chinese diabetes population. The risk of CKD and DR varied among different subtypes, indicating that proper interventions can be taken to prevent specific complications in different subtypes.

Modular alkene synthesis from carboxylic acids, alcohols and alkanes via integrated photocatalysis.

Alkenes serve as versatile building blocks in diverse organic transformations. Despite notable advancements in olefination methods, a general strategy for the direct conversion of carboxylic acids, alcohols and alkanes into alkenes remains a formidable challenge owing to their inherent reactivity disparities. Here we demonstrate an integrated photochemical strategy that facilitates a one-pot conversion of these fundamental building blocks into alkenes through a sequential C(sp3)-C(sp3) bond formation-fragmentation process, utilizing an easily accessible and recyclable phenyl vinyl ketone as the 'olefination reagent'. This practical method not only offers an unparalleled paradigm for accessing value-added alkenes from abundant and inexpensive starting materials but also showcases its versatility through various complex scenarios, including late-stage on-demand olefination of multifunctional molecules, chain homologation of acids and concise syntheses of bioactive molecules. Moreover, initiating from carboxylic acids, alcohols and alkanes, this protocol presents a complementary approach to traditional olefination methods, making it a highly valuable addition to the research toolkit for alkene synthesis.

One-Pot Telescoping S-Transfer and Trifluoromethylation for the Synthesis of 2-CF3S-Imidazoles with N-Oxides as Convenient Precursors.

Readily available 2-unsubstituted imidazole N-oxides were examined as starting materials for the preparation of fully substituted 1,4,5-aryl/alkyl 2-trifluoromethylsulfanyl-imidazoles. Whereas activation of the N-oxide function followed by attempted nucleophilic addition of the -SCF3 was in vain, the alternative approach involving "sulfur transfer reaction" and subsequent electrophilic trifluoromethylation with Togni reagent provided target products in high yield via a one-pot procedure. The structure of representative enantiomerically pure imidazol-2-yl trifluoromethyl sulfide was confirmed by X-ray analysis.

Electrochemiluminescence immunoassay system based on PCN-224-Mn and gold-platinum bimetallic nanoflowers for sensitive detection of ochratoxin A.

In this work, a novel Electrochemiluminescence Immunosensor was constructed using PCN-224-Mn and gold-platinum nanoflowers (AuPt NFs) for the ultrasensitive detection of ochratoxin A (OTA). PCN-224 modified with Mn (II) was synthesized as a probe material. The interaction efficiency of PCN-224 with S2O82- was also greatly improved. AuPt NFs were used as the substrate material for the electrodes. It has favorable biocompatibility, large specific surface area and can bind more antigen. Also greatly increased the electroactive surface area and conductivity of the electrode. OTA was detected using a competitive immunoassay strategy, in which OTA in the sample competes with the encapsulated antigen for a finite number of antibodies. ECLIA for the detection of OTA was designed to be highly sensitive, with a linear range from 0.0002 ng mL-1 to 1000 ng mL-1 and a LOD as low as 0.067 pg mL-1. In addition, it was evident from the electrochemical analyses that PCN-224-Mn had a stronger and more stable ECL signal compared to the plain PCN-224. The successful preparation of specific, sensitive and reproducible ECL immunosensors confirms the great promise for the detection of OTA or other small molecule mycotoxins.

Low-dose deoxynivalenol exposure triggers hepatic excessive ferritinophagy and mitophagy mitigated by hesperidin modulated O-GlcNAcylation.

The level and breadth of deoxynivalenol (DON) contamination in foods made with cereals have increased due to global warming. Consumption of DON-contaminated food and feed poses significant risks to human health and animal production. However, the mechanism by which prolonged exposure to low-dose DON leads to liver damage in animals and effective treatments remain unclear. Our investigation focused on the impact of varying DON exposure times on AML12 cells as well as the long-term liver damage caused by low-dose DON exposure in mice. In addition, this article investigated the unique role of hesperidin in mitigating hepatic ferroptosis induced by low-dose DON exposure. Our results imply that DON's suppression of O-GlcNAcylation exacerbated mitophagy by encouraging ferritinophagy and causing labile iron to aggregate within mitochondria. Furthermore, DON could increase NCOA4-mediated ferritinophagy by De-O-GlcNAcylation FTH to trigger ferroptosis-associated liver injury in mice. Notably, hesperidin alleviated the susceptibility to ferroptosis by increasing O-GlcNAcylation levels and effectively attenuated the liver injury induced by low-dose DON exposure. This finding provides a new strategy for dealing with liver injury caused by low-dose DON exposure.

Leydig cells pyroptosis in testis mediates deoxynivalenol-induced male reproductive toxicity in mice.

Deoxynivalenol (DON) is a toxic secondary metabolite produced by Fusarium spp. It is widely distributed among various cereals and has attracted much attention as a potential health threat to humans and domestic animals. However, the effects of DON on the reproductive systems of mammals are still ambiguous. In this study, the toxic effects of DON in the male reproduction of mice were investigated. The results showed that DON caused the shedding of sperm cells at all testis levels and the presence of inflammatory cells in the testicular interstitium. The rate of living sperm was significantly reduced, and the rate of sperm deformity was increased after DON exposure. The DON exposure resulted in decreased levels of testosterone (T) and increased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum. Measurements of oxidative stress markers showed that DON induced oxidative stress in mice testis. Meanwhile, DON triggered the assembly of NLRP3-ASC-Caspase-1 inflammatory complex and pyroptosis in both mice testis and TM3 cells, further causing the activation of GSDMD, promoting the leakage of inflammatory cytokines, including IL-1ß and IL-18. Notably, the inhibition of oxidative stress was found to protect pyroptosis in TM3 cells exposed to DON. We identified a novel mechanism of reproductive damage induced by DON, demonstrating the activation of the canonical Caspase-1-dependent pyroptosis pathway and clarifying the protection of antioxidation against pyroptosis damage. Our discovery provided support for the risk assessment of DON and target exploration for clinical treatment related to pyroptosis.

Effects of hydrogen-rich water on blood uric acid in patients with hyperuricemia: A randomized placebo-controlled trial.

Background: Consumption of hydrogen-rich water (HRW) has been shown to have anti-inflammatory and metabolic-modulatory benefits. Objective: A randomized, placebo-controlled trial was conducted to assess the potential blood uric acid-lowering effects of HRW consumption with different doses (low and high doses) and duration (4 and 8 weeks) in patients with hyperuricemia. Methods: The Placebo group consumed three bottles of ordinary drinking water (330 mL per bottle), the Low-HRW group consumed two bottles of HRW (330 mL per bottle, H2 ≥ 4.66 mg/L) and a bottle of ordinary water, and the High-HRW group consumed three bottles of HRW daily for 8 weeks. The primary outcome was the blood uric acid levels following different time points (4 and 8 weeks) compared to baseline. Results: A total of 100 participants completed the entire trial (32 in Placebo, 35 in Low-HRW, and 33 in High-HRW groups). The high-dose of HRW was more effective than low-dose HRW in controlling blood uric acid. Following an 8-week period, the High-HRW group exhibited a significant reduction in blood uric acid levels compared to the baseline (488.2 ± 54.1 µmol/L to 446.8 ± 57.1 µmol/L, P < 0.05). Conclusion: As a rather safe agent, the prolonged consumption of HRW may be feasible in the management of hyperuricemia. Clinical trial registration: chictr.org.cn, identifier ChiCTR2200066369.