Safety and efficacy of subthreshold micropulse yellow laser for persistent subretinal fluid after scleral bucking a randomized clinical trial.

Persistent subretinal fluid (PSF) after scleral bucking of rhegmatogenous retinal detachment may delay recovery and affect the final visual quality, but with no effective treatment. This study firstly investigated the safety and efficacy of 577 nm yellow subthreshold micropulse laser (SML) on PSF after scleral bucking surgery. This double-masked randomized clinical trial was conducted from December 2020 to October 2022 at Chongqing Aier Eye Hospital. Participants with PSF last for 1 month after scleral bucking surgery with break closed and retina reattachment were recruitment. These participants were treated by 577 nm yellow SML or sham treatment. Funduscopy, optical coherence tomography (OCT) volume change, best corrected vision acuity (BCVA) and visual field test were evaluated for six mouths follow-up. A total of 24 participants were randomized into SML group or Sham group equally. Compared with Sham group, the OCT volume within 6 mm of macular fovea was significantly less in SML group 6 months after therapy (P = 0.048). There were no statistically significant differences of OCT volume at 1, 2 and 3 months from baseline between groups. BCVA of ETDRS letters had no statistically significant difference. Pattern Standard Deviation amelioration (P = 0.039) had statistically significance in SML group compared with Sham group. There were no complications in the 2 groups. These preliminary findings suggest that 577 nm yellow SML therapy could accelerate PSF absorption after scleral bucking surgery.Trial registration: Chinese Clinical Trial Registry No. ChiCTR2000037838, 02/09/2020, https://www.chictr.org.cn/showproj.html?proj=51885 .

Highly enantioselective synthesis of both enantiomers of tetrahydroquinoxaline derivatives via Ir-catalyzed asymmetric hydrogenation.

A novel Ir-catalyzed asymmetric hydrogenation protocol for the synthesis of chiral tetrahydroquinoxaline (THQ) derivatives has been developed. By simply adjusting the reaction solvent, both enantiomers of mono-substituted chiral THQs could be selectively obtained in high yields with excellent enantioselectivities (toluene/dioxane: up to 93% yield and 98% ee (R); EtOH: up to 83% yield and 93% ee (S)). For 2,3-disubstituted chiral THQs, the cis-hydrogenation products were obtained with up to 95% yield, 20 : 1 dr, and 94% ee. Remarkably, this methodology was also applicable under continuous flow conditions, yielding gram-scale products with comparable yields and enantioselectivities (dioxane: 91% yield and 93% ee (R); EtOH: 90% yield and 87% ee (S)). Unlike previously reported Ir-catalyzed asymmetric hydrogenation protocols, this system exhibited a significant improvement as it required no additional additives. Furthermore, comprehensive mechanistic studies including deuterium-labeling experiments, control experiments, kinetic studies, and density functional theory (DFT) calculations were conducted to reveal the underlying mechanism of enantioselectivities for both enantiomers.

Estimation of CO2-Brine Interfacial Tension Based on an Advanced Intelligent Algorithm Model: Application for Carbon Saline Aquifer Sequestration.

The emission reduction of the main greenhouse gas, CO2, can be achieved via carbon capture, utilization, and storage (CCUS) technology. Geological carbon storage (GCS) projects, especially CO2 storage in deep saline aquifers, are the most promising methods for meeting the net zero emission goal. The safety and efficiency of CO2 saline aquifer storage are primarily controlled by structural and capillary trapping, which are significantly influenced by the interactions between fluid and solid phases in terms of the interfacial tension (IFT) between the injected CO2 and brine at the reservoir site. In this study, a model based on the random forest (RF) model and the Bayesian optimization (BO) algorithm was developed to estimate the IFT between the pure and impure gas-brine binary systems for application to CO2 saline aquifer sequestration. Then three heuristic algorithms were applied to validate the accuracy and efficiency of the established model. The results of this study indicate that among the four mixed models, the Bayesian optimized random forest model fits the experimental data with the smallest root-mean-square error (RMSE = 1.7705) and mean absolute percentage error (MAPE = 2.0687%) and a high coefficient of determination (R2 = 0.9729). Then the IFT values predicted via this model were used as an input parameter to estimate the CO2 sequestration capacity of saline aquifers at different depths in the Tarim Basin of Xinjiang, China. The burial depth had a limited influence on the CO2 storage capacity.

Application of 'CDC- Public Security Bureau-NGO' Joint Prevention and Control Mechanism Allied AIDS prevention and control in Guigang, Guangxi.

BACKGROUND: HIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the 'CDC-Public Security Bureau-NGO'. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions. METHODS: The research design of this study incorporates both a serial cross-sectional study and time-series analysis from 2014 to 2021, including a 4-year traditional intervention (2014-2017) and the 4-year 'CDC-Public Security Bureau-NGO' innovative intervention (2018-2021), was conducted to evaluate the effects of the new intervention. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018-2021; P and C values were used to evaluate the performance of the model. Mann-Kendall test and descriptive methods were used to analyzed the trend of traditional and innovative interventions models on HIV positive detection rate in FSWs and elderly clients. RESULTS: The condom usage rates during the last commercial sexual encounter for FSWs and elderly clients improved from 74.9% and 9.1%, respectively, to 96.9% and 28.1%. (P < 0.05), newly reported cases of HIV have decreased by 15.56% yearly and the HIV positive detection rate among middle-aged and elderly people has dropped by 14.47%. The innovative intervention model has significantly reduced the HIV infection rates. CONCLUSIONS: The 'CDC-Public Security Bureau-NGO' innovative intervention has achieved beneficial effects on HIV/AIDS prevention and control and provides a good reference for Guangxi, China.

Facile fabrication of a thermal/pH responsive IPN hydrogel drug carrier based on cellulose and chitosan through simultaneous dual-click strategy.

Herein, an interpenetrating network hydrogel (IPN-Gel) based on cellulose and chitosan was synthesized via simultaneous amino-anhydride and azide-alkyne click reaction in water in one pot. The samples were characterized by various analytical methods including FTIR, SEM, XRD, XPS, 1H NMR and so forth. The fabrication conditions were optimized by single factor experiments with water uptake (WU) and gel mass fraction (GMF) as two indexes. The WU and GMF of the IPN-Gel prepared under optimized conditions were 1192.37 % and 74.00 %, respectively. Its WU descended with the ascension in temperature, and first descended and then gradually ascended with the ascension in pH, confirming that the IPN-Gel had thermal/pH dual responsiveness. Using 5-Fu as a model drug, the release behavior of 5-Fu in IPN-Gel was explored. Its release behavior could be regulated by changing temperature and pH values, and it followed the Korsmeyer Peppas model. The viability of 4 T1 cells and HUVEC cells exceeded 80 % after 48 h of incubation at a high concentration of 200 µg/mL IPN-Gel, and hemolytic percentage was below the allowed limit of 5 %. The study provides a new strategy for the preparation of the IPN-Gel with biocompatibility, swelling reversibility and controllable drug release.

Therapeutic vaccine targeting dual immune checkpoints induces potent multifunctional CD8+ T cell anti-tumor immunity.

BACKGROUND: Vaccines targeting immune checkpoints represent a promising immunotherapeutic approach for solid tumors. However, the therapeutic efficacy of dual targeting immune checkpoints is still unclear in renal carcinoma. METHODS: An adenovirus (Ad) vaccine targeting B7H1 and B7H3 was developed and evaluated for its therapeutic efficacy in subcutaneous, lung metastasis or orthotopic renal carcinoma mouse and humanized models using flow cytometry, Enzyme-linked immunosorbent spot (ELISPOT), cytotoxic T lymphocyte (CTL) killing, cell deletion, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) assays. RESULTS: The Ad-B7H1/B7H3 immunization effectively inhibited tumor growth and increased the induction and percentages of CD8+ T cells in subcutaneous tumor models. The vaccine enhanced the induction and maturation of CD11c+ or CD8+CD11c+ cells, promoting tumor-specific CD8+ T cell immune responses. This was evidenced by increased proliferation of CD8+ T cells and enhanced CTL killing activity. Deletion of CD8+ T cells in vivo abolished the anti-tumor effect of the Ad-B7H1/B7H3 vaccine, highlighting the pivotal role of functional CD8+ T cell immune responses. Moreover, significant therapeutic efficacy of the Ad-B7H1/B7H3 vaccine was observed in lung metastasis, orthotopic, and humanized tumor models through multifunctional CD8+ T cell immune responses. CONCLUSIONS: The Ad vaccine targeting dual immune checkpoints B7H1 and B7H3 exerts a potent therapeutic effect for renal carcinoma and holds promise for solid tumor treatment.

In Situ Inorganic/Organic Protective Layer on Carbon Paper as Advanced Current Collector for Robust Li Metal Anode.

Lithium (Li) metal is regarded as the most promising anode for next-generation batteries with high energy density. However, the uncontrolled dendrite growth and infinite volume expansion during cycling seriously hinder the application of Li metal batteries (LMBs). Herein, an inorganic/organic protective layer (labeled as BPH), composed of in situ formed inorganic constituents and PVDF-HFP, is designed on the 3D carbon paper (CP) surface by hot-dipping method. The BPH layer can effectively improve the mechanical strength and ionic conductivity of the SEI layer, which is beneficial to expedite the Li-ion transfer of the entire framework and achieve stable Li plating/stripping behavior. As a result, the modified 3D CP (BPH-CP) exhibits an ultrahigh average Coulombic efficiency (CE) of ≈99.7% over 400 cycles. Further, the Li||LiFePO4 (LFP) cell exhibits an extremely long-term cycle life of over 3000 cycles at 5 C. Importantly, the full cell with high mass loading LiFePO4 (20 mg cm-2) or LiNi0.8Co0.1Mn0.1O2 (NCM, 16 mg cm-2) cathode exhibits stable cycling for 100 or 150 cycles at 0.5 C with high-capacity retention of 86.5% or 82.0% even at extremely low N/P ratio of 0.88 or 0.94. believe that this work enlightens a simple and effective strategy for the application of high-energy-density and high-rate-C LMBs.

Utility of next-generation sequencing for the etiological diagnosis of Orientia tsutsugamushi infection.

Background: Scrub typhus, an acute febrile disease caused by Orientia tsutsugamushi, is transmitted to humans through infected chigger mites. We present a case of scrub typhus in a previously healthy man from Shandong Province diagnosed using next-generation sequencing (NGS) and PCR and review recent literature on NGS for scrub typhus diagnosis. Methods: NGS was utilized for testing whole blood collected on admission. Confirmatory testing was done by detecting IgM and IgG antibodies to Orientia in acute and convalescent sera by ELISA. Orientia 47-kDa protein gene TaqMan and standard PCR of the 56-kDa protein gene and Sanger sequencing were performed on eschar scab DNA. Results: The NGS diagnosis was confirmed by 47-kDa protein gene TaqMan and sequencing of a fragment of the O. tsutsugamushi 56-kDa protein gene from the eschar scab. Analysis of this sequence and the NGS data indicated O. tsutsugamushi strain Cheeloo2020 is a novel genotype. Mapping of the NGS data against the O. tsutsugamushi Gilliam strain genome sequence identified 304 reads with high similarity. Conclusions: NGS is not only useful for multiplex diagnosis of scrub typhus, but also provides insight into the genetic diversity of O. tsutsugamushi. The common failure to submit sequences to databases makes it difficult to determine the minimal quantity and quality of NGS data being used for the positive identification of Orientia DNA in clinical specimens.

[Inhibition of type 3 deiodinase expression can improve mitochondrial function in skeletal muscle of sepsis by up-regulating peroxisome proliferator-activated receptor-γ coactivator-1α].

OBJECTIVE: To investigate the protective effects and mechanisms of targeted inhibition of type 3 deiodinase (Dio3) on skeletal muscle mitochondria in sepsis. METHODS: (1) In vivo experiments: adeno-associated virus (AAV) was employed to specifically target Dio3 expression in the anterior tibial muscle of rats, and a septic rat model was generated using cecal ligation and puncture (CLP). The male Sprague-Dawley (SD) rats were divided into shNC+Sham group, shD3+Sham group, shNC+CLP group, and shD3+CLP group by random number table method, with 8 rats in each group. After CLP modeling, tibial samples were collected and Western blotting analysis was conducted to assess the protein levels of Dio3, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), and silence-regulatory protein 1 (SIRT1). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was utilized to examine mRNA expression of genes including thyroid hormone receptors (THRα, THRß), monocarboxylate transporter 10 (MCT10), mitochondrial DNA (mtDNA), and PGC1α. Transmission electron microscopy was employed to investigate mitochondrial morphology. (2) In vitro experiments: involved culturing C2C12 myoblasts, interfering with Dio3 expression using lentivirus, and constructing an endotoxin cell model by treating cells with lipopolysaccharide (LPS). C2C12 cells were divided into shNC group, shD3 group, shNC+LPS group, and shD3+LPS group. Immunofluorescence colocalization analysis was performed to determine the intracellular distribution of PGC1α. Co-immunoprecipitation assay coupled with Western blotting was carried out to evaluate the acetylation level of PGC1α. RESULTS: (1) In vivo experiments: compared with the shNC+Sham group, the expression of Dio3 protein in skeletal muscle of the shNC+CLP group was significantly increased (Dio3/ß-Tubulin: 3.32±0.70 vs. 1.00±0.49, P < 0.05), however, there was no significant difference in the shD3+Sham group. Dio3 expression in the shD3+CLP group was markedly reduced relative to the shNC+CLP group (Dio3/ß-Tubulin: 1.42±0.54 vs. 3.32±0.70, P < 0.05). Compared with the shNC+CLP group, the expression of T3-regulated genes in the shD3+CLP group were restored [THRα mRNA (2-ΔΔCt): 0.67±0.05 vs. 0.33±0.01, THRß mRNA (2-ΔΔCt): 0.94±0.05 vs. 0.67±0.02, MCT10 mRNA (2-ΔΔCt): 0.65±0.03 vs. 0.57±0.02, all P < 0.05]. Morphology analysis by electron microscopy suggested prominent mitochondrial damage in the skeletal muscle of the shNC+CLP group, while the shD3+CLP group exhibited a marked improvement. Compared with the shNC+Sham group, the shNC+CLP group significantly reduced the number of mitochondria (cells/HP: 10.375±1.375 vs. 13.750±2.063, P < 0.05), while the shD3+CLP group significantly increased the number of mitochondria compared to the shNC+CLP group (cells/HP: 11.250±2.063 vs. 10.375±1.375, P < 0.05). The expression of mtDNA in shNC+CLP group was markedly reduced compared with shNC+Sham group (copies: 0.842±0.035 vs. 1.002±0.064, P < 0.05). Although no difference was detected in the mtDNA expression between shD3+CLP group and shNC+CLP group, but significant increase was found when compared with the shD3+Sham group (copies: 0.758±0.035 vs. 0.474±0.050, P < 0.05). In the shD3+CLP group, PGC1α expression was significantly improved at both transcriptional and protein levels relative to the shNC+CLP group [PGC1α mRNA (2-ΔΔCt): 1.49±0.13 vs. 0.68±0.06, PGC1α/ß-Tubulin: 0.76±0.02 vs. 0.62±0.04, both P < 0.05]. (2) In vitro experiments: post-24-hour LPS treatment of C2C12 cells, the cellular localization of PGC1α became diffuse; interference with Dio3 expression promoted PGC1α translocation to the perinuclear region and nucleus. Moreover, the acetylated PGC1α level in the shD3+LPS group was significantly lower than that in the shNC+LPS group (acetylated PGC1α/ß-Tubulin: 0.59±0.01 vs. 1.24±0.01, P < 0.05), while the expression of the deacetylating agent SIRT1 was substantially elevated following Dio3 inhibition (SIRT1/ß-Tubulin: 1.04±0.04 vs. 0.58±0.03, P < 0.05). When SIRT1 activity was inhibited by using EX527, PGC1α protein expression was notably decreased compared to the shD3+LPS group (PGC1α/ß-Tubulin: 0.92±0.03 vs. 1.58±0.03, P < 0.05). CONCLUSIONS: Inhibition of Dio3 in skeletal muscle reduced the acetylation of PGC1α through activating SIRT1, facilitating nuclear translocation of PGC1α, thereby offering protection against sepsis-induced skeletal muscle mitochondrial damage.

Unveiling the Interplay Between Depressive Symptoms' Alleviation and Quality of Life Improvement in Major Depressive Disorder: A Network Analysis Based on Longitudinal Data.

Background: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD. Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire - 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence. Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between "mood" (delta-QLES2) and "anhedonia" (delta-DEP1), between "physical health" (delta-QLES1) and "sleep problems" (delta-DEP3), and between "physical health" (delta-QLES1) and "sad mood" (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. "Anhedonia" (delta-DEP1), "sad mood" (delta-DEP2) and "loss of energy" (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants' satisfaction with function in daily life. Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.

The mediation effects of COVID-19-related traumatic stress symptoms and mentalization on the relationship between perceived stress and psychological well-being in healthcare workers transitioning to a post-pandemic world.

BACKGROUND: In context of COVID-19 as a collective trauma and the intense involvement of healthcare workers (HCWs) in the pandemic, perceived stress continues to have a tremendous impact on their psychological well-being. However, few studies have attempted to delineate the underlying mechanisms. This study examined whether COVID-19-related traumatic stress symptoms and mentalization act as mediators. METHODS: A sample of HCWs (N = 2610) from 22 hospitals in Beijing, China participated in this cross-sectional investigation. Data on their perceived stress, psychological well-being, the impact of event, and reflective function during the COVID-19 pandemic were collected using self-report questionnaires. Different mediating models were tested. RESULTS: COVID-19-related stress symptoms and mentalization independently mediate the association between perceived stress and psychological well-being. These two mediators also compose a serial mediation model. In particular, higher perceived stress inhibits the psychological well-being of HCWs through increased severity of traumatic stress symptoms, which in turn is associated with hypomentalizing. CONCLUSION: These findings shed light on the mechanisms underlying the relationship between perceived stress and psychological well-being in HCWs. We strongly recommend incorporating a mentalization framework with trauma-informed practice in prevention and intervention work with this population during this and future healthcare crisis.

Insights into the inhibitory effects of trichloroisocyanuric acid disinfectant on the phototransformation of polypropylene microplastics.

The chemical components in the natural aquatic environment have the potential to be involved in phototransformation of microplastics (MPs). Little information is available regarding the mediation effects of artificially introduced chemicals on MP phototransformation, especially those used in aquaculture water that are vulnerable to human interference. Herein, this study investigated the phototransformation process and mechanism of polypropylene microplastic (PP MPs) in presence of trichloroisocyanuric acid (TCCA) disinfectant with unique properties unlike the conventional inorganic chlorine disinfectants. The results showed that the presence of TCCA inhibited the surface photooxidation of PP MPs. Analysis of PP MP surface and reaction filtrate indicated that the inhibitory effects were likely derived from TCCA derivatives and the weakening in promoting effect of polypropylene microplastic-derived dissolved organic matter (PP-DOM) as photolytic byproducts, with the more important role of free chlorine in initial period and that of other chlorine species (i.e., the adsorbed chloride ions (Cl-), newly formed carbon-chlorine (CCl) bonds, chlorinated cyanurates, and chlorinated products) in middle and later period. The study highlights for the first time the important role of chlorine species derived from TCCA in phototransformation process of co-existed PP MPs and proposes a previously unrecognized phototransformation pathway, which will provide a new understanding and knowledge for the environmental behavior of MPs in aquaculture environment.

Copper dual-doping strategy of porous carbon nanofibers and nickel fluoride nanorods as bi-functional oxygen electrocatalysis for effective zinc-air batteries.

Designing and developing efficient, low-cost bi-functional oxygen electrocatalysts is essential for effective zinc-air batteries. In this study, we propose a copper dual-doping strategy, which involves doping both porous carbon nanofibers (PCNFs) and nickel fluoride nanoparticles with copper alone, successfully preparing copper-doped nickel fluoride (NiF2) nanorods and copper nanoparticles co-modified PCNFs (Cu@NiF2/Cu-PCNFs) as an efficient bi-functional oxygen electrocatalyst. When copper is doped into the PCNFs in the form of metallic nanoparticles, the doped elemental copper can improve the electronic conductivity of composite materials to accelerate electron conduction. Meanwhile, the copper doping for NiF2 can significantly promote the transformation of nickel fluoride nanoparticles into nanorod structures, thus increasing the electrochemical active surface area and enhancing mass diffusion. The Cu-doped NiF2 nanorods also possess an optimized electronic structure, including a more negative d-band center, smaller bandgap width and lower reaction energy barrier. Under the synergistic effect of these advantages, the obtained Cu@NiF2/Cu-PCNFs exhibit outstanding bi-functional catalytic performances, with a low overpotential of 0.68 V and a peak power density of 222 mW cm-2 in zinc-air batteries (ZABs) and stable cycling for 800 h. This work proposes a one-step way based on the dual-doping strategy, providing important guidance for designing and developing efficient catalysts with well-designed architectures for high-performance ZABs.

A New Orthonairovirus Associated with Human Febrile Illness.

BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).

Investigation of risk factors for invasive pulmonary aspergillosis among patients with COVID-19.

COVID-19 associated pulmonary aspergillosis (CAPA) had been reported, and raised concern about this secondary infection due to the high mortality. This study aimed to investigate the risk factors for CAPA. The enrolled 114 COVID-19 patients were further divided into CAPA group and non-CAPA group. Demographic characteristics, underlying diseases, laboratory parameters and therapeutic schedule between the two groups were compared to identify the independent risk factors for CAPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent risk factors were confirmed by receiver operating characteristic (ROC) curve analysis. Univariate analysis showed that renal transplant, IL-6 and CRP levels, decreased CD4 + T cell and CD8 + T cell, duration of antibiotics therapy, and prolonged mechanical ventilation were risk factors for development of CAPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that elevated IL-6 level, decreased CD4 + T cell and prolonged mechanical ventilation could be recognized as independent risk factors for CAPA in COVID-19 patients. Identification of these risk factors is essential to initiate antifungal therapy as soon as possible to improve outcome of patients with CAPA.

Design, synthesis and structure-activity relationship of novel pyrazole-4-carboxamide derivatives.

BACKGROUND: Plant diseases seriously decrease the yield and quality of agricultural crops. Fungicide treatments remain the main means of field fungi control. However, the residual activity of fungicides is rapidly reduced due to various factors in the natural environment, therefore the development of agents with novel modes of action is desirable. It is highly required to design and develop new fungicides to address the resistance issue. Designing low impact chemicals to safely and sustainably address needs of agriculture. RESULTS: In this work, we used the highly active fluxapyroxad and flutolanil as parent structures, to design and synthesize a series of pyrazole-4-carboxamide derivatives. Some of the pyrazole-4-carboxamide derivatives exhibit fungicidal activities that are comparable to or higher than those of the commercialized fungicides fluxapyroxad and bixafen. In particular, compounds TM-1, TM-2, TM-3, TM-4, TM-5, TM-7 and TM-8 showed excellent fungicidal activities against corn rust that were 2-4 times higher than those of fluxapyroxad and bixafen. Field trial results demonstrated that at the same dosage levels, compound TM-2 exhibited comparable field control efficacy against wheat rust as compared to triadimefon and pyrazophenamide. Molecular docking simulations reveal that compound TM-2 interacts with TRP 173 of succinate dehydrogenase (SDH) through hydrogen bonding, which could explain the probable mechanism of action between compound TM-2 and the target protein. CONCLUSION: These results indicate that compound TM-2 may be a promising fungicide candidate and provide valuable reference for further investigation. © 2024 Society of Chemical Industry.

Association of MTHFR gene polymorphisms with non-Hodgkin lymphoma risk: Evidence from 31 articles.

Background: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, particularly C677T and A1298C, have been implicated in various cancers, including non-Hodgkin lymphoma (NHL); however, their association with NHL risk remains inconclusive. Methods: We conducted an updated meta-analysis to assess the relationship between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk. Relevant studies were identified through systematic literature searches in multiple databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Results: The meta-analysis included 32 studies (8222 cases vs. 12956 controls) for MTHFR C677T and 26 studies (6930 cases vs. 11611 controls) for the A1298C polymorphism. Our meta-analysis revealed no significant associations between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk. However, subgroup analysis stratified by ethnicity and NHL subtype yielded interesting findings for the C677T polymorphism. Specifically, in the subgroup analysis of Caucasians, the C677T polymorphism was significantly associated with NHL risk (heterozygous: OR=1.16, 95% CI=1.02-1.32; allele comparison: OR=1.07, 95% CI=1.01-1.13). Furthermore, in the analysis stratified by NHL subtype, the C677T polymorphism was significantly associated with increased follicular lymphoma (FL) risk (homozygous: OR=1.25, 95% CI=1.02-1.53; recessive: OR=1.28, 95% CI=1.06-1.56). False-positive result possibility (FPRP) analysis verified that the association of the MTHFR C677T polymorphism with NHL risk for Caucasians and FL subtypes was a true positive and deserves attention. We also determined that the C677T polymorphism is an expression quantitative trait locus (eQTL) since it is associated with MTHFR gene expression. Conclusion: There was no overall association between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk, but stratified analyses revealed significant associations in specific subgroups. While meta-analyses inherently build upon existing studies, our work distinguishes itself by incorporating recent data, applying rigorous analytical techniques, and providing more evidence of the MTHFR C677T polymorphism as an eQTL.

Batch production prediction for the mechanical cutting industry based on process capability.

In the mechanical cutting industry, trial production is used for predicting and evaluating the quality of product processes before batch production, and it can be expressed through the qualification rate. However, it cannot objectively and comprehensively evaluate the quality of product processes. This study optimizes the analysis of outliers and stability in mathematical statistics to better apply it in the mechanical cutting industry; then, it combines them with process capability analysis. Simultaneously, considering the non-normal distribution of process parameters, a batch production-prediction model is proposed. The reliability of batch production-prediction model is verified by the diameter, roundness and roughness of structural common samples. Meanwhile, for other mechanical parts in the mechanical cutting industry, the model proposed in this paper can be used to quickly and accurately predict and evaluate batch production.

Redox-Responsive AIEgen Diselenide-Covalent Organic Framework Composites Targeting Hepatic Macrophages for Treatment of Drug-induced Liver Injury.

The escalating misuse of antipyretic and analgesic drugs, alongside the rising incidents of acute drug-induced liver injury, underscores the need for a precisely targeted drug delivery system. Herein, two isoreticular covalent organic frameworks (Se-COF and Se-BCOF) are developed by Schiff-base condensation of emissive tetraphenylethylene and diselenide-bridged monomers. Leveraging the specific affinity of macrophages for mannose, the first precise targeting of these COFs to liver macrophages is achieved. The correlation is also explored between the therapeutic effects of COFs and the NLRP3/ASC/Caspase-1 signaling pathway. Utilizing this innovative delivery vehicle, the synergistic delivery of matrine and berberine are accomplished, compounds extracted from traditional Chinese medicine. This approach not only demonstrated the synergistic effects of the drugs but also mitigated their toxicity. Notably, berberine, through phosphorylation of JNK and up-regulation of nuclear Nrf-2 and its downstream gene Mn-SOD expression, simultaneously countered excessive ROS and suppressed the activation of the NLRP3/ASC/Caspase-1 signaling pathway in injured liver tissues. This multifaceted approach proved highly effective in safeguarding against acute drug-induced liver injury, ultimately restoring liver health to normalcy. These findings present a novel and promising strategy for the treatment of acute drug-induced liver injury.