Liensinine alleviates sepsis-induced acute liver injury by inhibiting the NF-κB and MAPK pathways in an Nrf2-dependent manner.

Sepsis remains a serious public health issue that needs to be addressed globally. Severe liver injury caused by sepsis increases the risk of death in patients with sepsis. Liensinine (Lie) is one of the primary active components in Plumula nelumbinis and has anti-inflammatory and antioxidant effects. Nevertheless, the effects of Lie on septic liver injury are unclear. This research investigated the protective effect of Lie (10, 20 and 40 mg/kg) on liver damage via intraperitoneal administration of LPS (10 mg/kg) to C57BL/6 mice. Lie was given through intraperitoneal injection once a day for five days. Mice were treated with LPS intraperitoneally for 6 h at 1 h after Lie administration on the last day. The results suggested that Lie could decrease AST and ALT levels in serum, ameliorate histopathological changes and inhibit cell apoptosis in mice with LPS-induced septic liver injury. In addition, Lie inhibited increases in the mRNA levels of TNF-α, IL-1ß, iNOS and IL-6. Lie also increased the mRNA level of IL-10. Lie reduced the content of MDA, a marker of lipid peroxidation, and increased the activity of the antioxidant enzymes GSH-Px, CAT and SOD. Our results also showed that Lie could suppress the LPS-activated MAPK and NF-κB pathways and trigger the Nrf2 signaling pathway both in vitro and in vivo. Additionally, an Nrf2 inhibitor (ML385) weakened the suppressive effect of Lie on the MAPK and NF-κB pathways. Our results demonstrated that the suppressive effect of Lie on the MAPK and NF-κB pathways was partially reliant on activation of the Nrf2 pathway. In summary, these results indicate that Lie can improve inflammation and oxidative stress by activating Nrf2, which is a prospective therapeutic drug for alleviating septic liver injury.

Single-structure 3-axis Lorentz force magnetometer based on an AlN-on-Si MEMS resonator.

This work presents a single-structure 3-axis Lorentz force magnetometer (LFM) based on an AlN-on-Si MEMS resonator. The operation of the proposed LFM relies on the flexible manipulation of applied excitation currents in different directions and frequencies, enabling the effective actuation of two mechanical vibration modes in a single device for magnetic field measurements in three axes. Specifically, the excited out-of-plane drum-like mode at 277 kHz is used for measuring the x- and y-axis magnetic fields, while the in-plane square-extensional mode at 5.4 MHz is used for measuring the z-axis magnetic field. The different configurations of applied excitation currents ensure good cross-interference immunity among the three axes. Compared to conventional capacitive LFMs, the proposed piezoelectric LFM utilizes strong electromechanical coupling from the AlN layer, which allows it to operate at ambient pressure with a high sensitivity. To understand and analyze the measured results, a novel equivalent circuit model for the proposed LFM is also reported in this work, which serves to separate the effect of Lorentz force from the unwanted capacitive feedthrough. The demonstrated 3-axis LFM exhibits measured magnetic responsivities of 1.74 ppm/mT, 1.83 ppm/mT and 6.75 ppm/mT in the x-, y- and z-axes, respectively, which are comparable to their capacitive counterparts.

Correlation analysis between HLA-DQA1*0102/DQB1*0602 genotypes and narcolepsy patients in China.

Background and objective: At present, the etiology of narcolepsy is not fully understood, and it is generally believed to be an autoimmune reaction caused by interactions between environmental and genetic factors. Human leukocyte antigen (HLA) class II genes are strongly associated with this gene, especially HLA-DQB1*0602/DQA1*0102. In this study, we mainly analyzed the correlation between different genotypes of HLA-DQB1*0602/DQA1*0102 and clinical manifestations in Chinese patients with narcolepsy. Experimental method: Narcolepsy patients who were treated at the Department of Neurology, The First Affiliated Hospital of Shandong First Medical University from January 2021 to September 2023 were selected. General information, sleep monitoring data, cerebrospinal fluid (CSF) orexin levels, and human leukocyte antigen gene typing data were collected. The statistical analysis was performed using SPSS 26.0, and the graphs were drawn using GraphPad Prism 9.5. Main results: A total of 78 patients were included in this study. The DQA1 and DQB1 gene loci were detected in 54 patients, and only the DQB1 gene locus was detected in 24 narcoleptic patients. The most common allele at the HLA-DQB1 locus was *0602 (89.7%), and the most common genotype at this locus was *0602*0301 (19.2%), followed by *0602*0602 (17.9%). The most common phenotype of the HLA-DQA1 locus is *0102 (92.6%), and the most common genotype of this locus is *0102*0102 (27.8%), followed by *0102*0505 (14.8%). There were significant differences (p < 0.05) between HLA-DQB1*0602-positive and HLA-DQB1*0602-negative patients in terms of orexin-A levels, presence or absence of cataplexy, UNS, PSG sleep latency, REM sleep latency, N1 sleep percentage, oxygen depletion index, and average REM latency on the MSLT. The HLA-DQA1*0102-positive and HLA-DQA1*0102-negative patients showed significant differences (p < 0.05) in disease course, presence or absence of sudden onset, PSG REM sleep latency, N1 sleep percentage, and average REM latency on the MSLT. There were significant differences in the average REM latency of the MSLT between HLA-DQB1*0602/DQA1*0102 homozygous and heterozygous patients p < 0.05, and no differences were found in the baseline data, orexin-A levels, scale scores, or other sleep parameters. Conclusion: Different genotypes of HLA-DQA1*0102/DQB1*0602 are associated with symptoms of cataplexy in Chinese narcoleptic patients. Homozygous individuals have a shorter mean REM latency in the MSLT, greater genetic susceptibility, and relatively more severe sleepiness.

CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Discovery of a mitochondrial G-quadruplex targeted fluorescent ligand via a slight variation on the near-infrared heptamethine cyanine scaffold.

The heptamethine cyanine dyes are one kind of promising near-infrared (NIR) compounds, holding great potential in both diagnostic and therapeutic regions. Remolding such structures to realize detection of unclarified biotargets or interfering with them seems to be important in the field of chemical biology. In this study, we developed a fluorescent ligand (IR1) targeting mitochondrial G-quadruplexes (mitoG4s) by a slight variation on the typical NIR scaffold (IR780). This ligand could be applied for sensing mitoG4s by fluorescence, making it different from the unmodified dye whose fluorescence was quenched by mitoG4s. Then, IR1 was demonstrated to accumulate in the mitochondria through a mitochondrial membrane potential (MMP) dependent manner. Some of IR1 then bound to mitoG4s, causing mtDNA loss and mitochondrial dysfunction, which thereby triggered PANoptosis, including apoptosis, autophagy and pyroptosis. To the best of our knowledge, IR1 was the first NIR fluorescent ligand with emission centered at above 800 nm for mitoG4s, and the first example causing PANoptosis among the reported mitoG4-targeted ligands.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

Impact of pilot diesel injection timing on performance and emission characteristics of marine natural gas/diesel dual-fuel engine.

In diesel-ignited natural gas marine dual-fuel engines, the pilot diesel injection timing (PDIT) determines the premixing time and ignition moment of the combustible mixture in the cylinder. The PDIT plays a crucial role in the subsequent development of natural gas flame combustion. In this paper, four PDITs (- 8 °CA, - 6 °CA, - 4 °CA, and - 2 °CA) were studied. The results show that the advancement of PDIT increased the engine's power, thermal efficiency, and natural gas flame spread velocity, and increased NO emissions and CH4 emissions of the marine engine. The PDIT affected the ignition delay period and the rapid combustion period to a greater extent than the slow combustion period and the post combustion period. With each 2 °CA advancement of PDIT, the engine's power increased by 69.87 kW, thermal efficiency increased by 0.42%, radial flame spread velocity increased by 2 m/s, axial flame spread velocity increased by 1.7 m/s, NO emissions increased by 6.1%, and CH4 emissions increased by 3.75%.

Unraveling a Small Secreted Peptide SUBPEP3 That Positively Regulates Salt-Stress Tolerance in Pyrus betulifolia.

Small secreted peptides (SSPs) play important roles in regulating plants' growth and development in response to external stimulus, but the genes and functions of SSPs in many species are still unknown. Therefore, it is particularly significant to characterize and annotate SSP genes in plant genomes. As a widely used stock of pears, Pyrus betulifolia has strong resistance to biotic and abiotic stresses. In this study, we analyzed the SSPs genes in the genome of P. betulifolia according to their characteristics and homology. A total of 1195 SSP genes were identified, and most of them are signaling molecules. Among these, we identified a new SSP, subtilase peptide 3 (SUBPEP3), which derived from the PA region of preSUBPEP3, increasing the expression level under salt stress. Both adding synthetic peptide SUBPEP3 to the culture medium of pears and the overexpression of SUBPEP3 in tobacco can improve the salt tolerance of plants. In summary, we annotated the SSP genes in the P. betulifolia genome and identified a small secreted peptide SUBPEP3 that regulates the salt tolerance of P. betulifolia, which provides an important theoretical basis for further revealing the function of SSPs.

The combination of berberine and isoliquiritigenin synergistically improved adipose inflammation and obesity-induced insulin resistance.

White adipose tissue accumulation and inflammation contribute to obesity by inducing insulin resistance. Herein, we aimed to screen the synergistic components of the herbal pair Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma for the treatment of insulin resistance and explore the potential synergistic mechanisms. Enzyme-linked immunosorbent assay and quantitative PCR were used to detect expression levels of inflammatory genes in vitro and in vivo. Western blotting and immunohistochemistry were performed to detect protein levels of the insulin signaling pathway and macrophage markers. The effects on obesity-induced insulin resistance were verified using a diet-induced obesity (DIO) mouse model. Interactions between macrophage and adipocyte were assessed using a cellular supernatant transfer assay. Berberine (BBR) and isoliquiritigenin (ISL) alleviated mRNA levels and secretion of inflammatory genes in vitro and in vivo. Furthermore, BBR acted synergistically with ISL to ameliorate obesity and dyslipidemia in DIO mice. Meanwhile, the combination treatment significantly improved glucose intolerance and insulin resistance and decreased M1-macrophage accumulation and infiltration in the adipose tissue. Mechanistically, co-treatment with BBR and ISL upregulated the protein expression of the IRS1-PI3K-Akt insulin signaling pathway, enhanced glucose uptake in adipocyte, and suppressed the interaction between macrophage and adipocyte. BBR and ISL were identified as the synergistic components of the herbal pair Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma for treating insulin resistance. The synergistic combination of BBR with ISL can be a promising and effective strategy for improving obesity-induced adipose inflammation and insulin resistance.

Development and validation of a nomogram to predict medication risk based on a knowledge, attitude and practice (KAP) survey of residents in Shanxi Province, China.

Objective: Unsafe medication practices and medication errors are a major cause of harm in healthcare systems around the world. This study aimed to explore the factors that influence the risk of medication and provide medication risk evaluation model for adults in Shanxi province, China. Methods: The data was obtained from the provincial questionnaire from May to December 2022, relying on the random distribution of questionnaires and online questionnaires by four hospitals in Shanxi Province. Multiple linear regression analysis was used to explore the factors affecting the KAP score of residents. Univariate and multivariate logistic regression was used to determine the independent risk factors, and the nomogram was verified by receiver operating characteristic curve, calibration and decision curve analysis. Results: A total of 3,388 questionnaires were collected, including 3,272 valid questionnaires. The average scores of drugs KAP were 63.2 ± 23.04, 33.05 ± 9.60, 23.67 ± 6.75 and 33.16 ± 10.87, respectively. On the evaluation criteria of the questionnaire, knowledge was scored "fair", attitude and practice were scored "good". Sex, monthly income, place of residence, insurance status, education level, and employment were regarded as independent risk factors for medication and a nomogram was established by them. Conclusion: Males, low-income, and low-educated people are important factors affecting the risk of medication. The application of the model can help residents understand the risk of their own medication behavior and reduce the harm of medication.

Mitochondrial GPX4 acetylation is involved in cadmium-induced renal cell ferroptosis.

Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3-/- mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.

Helicid Alleviates Neuronal Apoptosis of Rats with Depression-Like Behaviors by Downregulating lncRNA-NONRATT030918.2.

Helicid (HEL) has been found to possess antidepressant pharmacological activity. The paper was to testify to the precise molecular mechanism through which HEL regulates lncRNA-NONRATT030918.2 to exert an antidepressant impression in depression models. A depression model stimulated using chronic unpredictable mild stress (CUMS) was created in rats, and the depressive state of the rats was assessed through behavioral experiments. Additionally, an in vitro model of PC12 cells induced by corticosterone (CORT) was established, and cytoactive was tested using the CCK8. The subcellular localization of the NONRATT030918.2 molecule was confirmed through a fluorescence in situ hybridization experiment. The relationship between NONRATT030918.2, miRNA-128-3p, and Prim1 was analyzed using dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation assay, and RNA pull-down assay. The levels of NONRATT030918.2, miRNA-128-3p, and Prim1 were tested using Q-PCR. Furthermore, the levels of Prim1, Bax, Bcl-2, and caspase3 were checked through Western blot. The HEL can alleviate the depression-like behavior of CUMS rats (P < 0.05), and reduce the mortality of hippocampal via downregulating the level of NONRATT030918.2 (P < 0.05). In CORT-induced PC12 cells, intervention with HEL led to decreased expression of NONRATT030918.2 and Prim1 (P < 0.05), as well as increased expression of miRNA-128-3p (P < 0.05). This suggests that HEL regulates the expression of NONRATT030918.2 to upregulate miRNA-128-3p (P < 0.05), which in turn inhibits CORT-induced apoptosis in PC12 cells by targeting Prim1 (P < 0.05). The NONRATT030918.2/miRNA-128-3p/Prim1 axis could potentially serve as a crucial regulatory network for HEL to exert its neuroprotective effects.

Urban-rural differences in the association between occupational physical activity and mortality in Chinese working population: evidence from a nationwide cohort study.

Background: Despite emerging studies suggesting that occupational physical activity (OPA) might be harmful to health, the available evidence is not definitive. Most of these research studies were conducted in high-income Western countries or in urbanized setting. In China, where over one-third of the population resides in rural area, the impact of OPA on health is not well understood. The goal of this study is to investigate how the association between OPA and mortality vary by urban-rural settings. Methods: Baseline data on OPA was gathered using the Global Physical Activity Questionnaire from 30,650 urban and 49,674 rural working adults as part of the 2013-2014 China Chronic Disease and Risk Factor Surveillance. Participants were followed for a median of 6.2 years, and death records were retrieved from the National Mortality Surveillance System until December 31, 2019. The multivariable Cox proportional hazard model was used to examine urban-rural differences in the association between OPA and all-cause and cardiovascular disease (CVD) mortality. Subgroup analyses were performed by sex, socioeconomic status, leisure time, transportation, and non-occupational physical activity. Findings: During the study period, 1342 deaths were recorded, of which 426 were caused by CVD. In rural area, working adults engaging in occupational moderate-to-vigorous physical activity (MVPA) for ≥40 h per week, compared to those without any, had an adjusted hazard ratio of 0.60 (95% CI: 0.49-0.73) for all-cause mortality and 0.55 (95% CI: 0.37-0.83) for CVD mortality. However, no significant association was found in urban area (0.84 [0.61-1.15] for all-cause mortality, Pinteraction = 0.036; and 0.94 [0.53-1.66] for CVD mortality, Pinteraction = 0.098). The negative associations of occupational MVPA with mortality were more pronounced in women, non-smokers, and those with less non-occupational physical activities. Hypertension, heart rate, and diabetes were important contributors to the relationship between occupational MVPA and mortality. Interpretation: The findings from the current study did not support the notion that high levels of OPA would induce harm. On the contrary, in rural setting, higher levels of OPA were associated with lower mortality risks. Furthermore, the observed urban-rural differences in the association between OPA and mortality underscored the need for context-specific public health guidelines on physical activities. Funding: R&D Program of Beijing Municipal Education Commission (KM202210025026),National Key Research and Development Program of China (2021YFC2500201), and Young Elite Scientist Sponsorship Program by BAST (BYESS2023385).

One-Stone-for-Two-Birds Method to Improve the SnO2 Layers for High Power-per-Weight Flexible Perovskite Solar Cell Mini-modules.

Maintaining the power conversion efficiency (PCE) of flexible perovskite solar cells (fPSCs) while decreasing their weight is essential to utilize their lightweight and flexibility as much as possible for commercialization. Strengthening the interfaces between functional layers, such as flexible substrates, charge transport layers, and perovskite active layers, is critical to addressing the issue. Herein, we propose a feasible and one-stone-for-two-birds method to improve the electron transport layer (ETL), SnO2, and the interface between the ETL and perovskite layer simultaneously. In detail, poly(acrylate ammonium) (PAAm), a low-cost polymer with a long chain structure, is added into the SnO2 aqueous solution to reduce the aggregation of SnO2 nanoparticles, resulting in the deposition of a conformal and high-quality ETL film on the tin-doped indium oxide film surface. Simultaneously, PAAm addition can effectively regulate the crystallization of the perovskite films, strengthening the interface between the SnO2 film and the buried surface of the perovskite layer. The outstanding PCEs of 22.41% on small-scale fPSCs and 18.54% on fPSC mini-modules are among the state-of-the-art n-i-p type fPSCs. Moreover, the fPSC mini-module on the 20 µm-thick flexible substrate shows a comparable PCE with that of the fPSC mini-module on the 125 µm-thick flexible substrate, exhibiting a high power-to-weight of 5.097 W/g. This work provides an easy but essential direction for further applications of fPSCs in diverse scenarios.

Clinical Characteristics and Diagnosis of Ph-Positive Mixed Phenotype Acute Leukemia.

BACKGROUND: The goal was to improve the clinical cognition of Ph-positive mixed phenotype acute leukemia and avoid misdiagnosis or delayed diagnosis. METHODS: The clinical manifestations and laboratory results (bone marrow cell morphology, multiparameter flow cytometry, and cytogenetics) of a case of Ph-positive mixed phenotype acute leukemia were analyzed, and related literature was reviewed. RESULTS: Blood routine: WBC 386.35 x 109/L, HGB 117.00 g/L, PLT 31 x 109/L; 80% of the original cells can be seen by artificial classification. Morphological examination of bone marrow cells showed that the proliferation of nucleated cells was obviously active, and the original cells accounted for 76%. The size of the original cells was somewhat uniform, most of the cells had less mass, were stained light grayish blue, the cytoplasm particles were not obvious, the nuclei were mostly round or quasi-round, some of them showed distortion and nuclear notch, and the chromatin was coarse. Some of the cells were rich in mass, small azurin granules were seen, the nuclei were regular, most of them were round, the chromatin was fine, the myeloperoxidase and esterase staining were negative, the eosinophils accounted for 2.5%, and the basophils accounted for 0.5%. Flow cytometry immunotyping: Two groups of abnormal cells were seen in the bone marrow. 1. A group included 12.32% of nuclear cells and showed abnormal myeloid primitive cell phenotype. Main expression: CD117, CD34, CD38, HLA-DR, CD33, CD64, CD123, weak expression: CD13, CD19. 2. The other group included 45.61% of the nuclear cells and had a B-lymphoblastic phenotype. Main expression: CD34, CD38, HLA-DR, CD123, CD19, CD10, CD9, cCD79a, TDT, weak expression of CD13, CD22. Mixed phenotype acute leukemia (M/B) immunophenotype was considered. Chromosome: 46,XY,t(9; 22)(q34;q11.2) [20]. BCR-ABL (P210) fusion gene was positive. CONCLUSIONS: Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.

Effect of Tocilizumab plus Corticosteroid on Clinical Outcome in Patients Hospitalized with Severe Fever with Thrombocytopenia Syndrome: A Randomized Clinical Trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P=0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P =0.002) compared to those receiving corticosteroid alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.

Experimental study on mechanical and hydraulic properties of xanthan gum improved low liquid limit silty soil.

The low liquid limit silty soil in the North China plain area is generally unsuitable for direct use as roadbed and slope soil. In order to improve the performance of low liquid limit silty soil, xanthan gum was used as an improver. Through a series of tests, the improvement effect of xanthan gum on low liquid limit silty soil was studied. The test results showed that Xanthan gum as an improver could significantly improve the unconfined compressive strength of silty soil. With the increase in dosage and curing age, the unconfined compressive strength of improved silty soil continued to improve and eventually tended to stabilize. The optimal dosage and curing period were 2% and 7 days, respectively. In addition, Xanthan gum could greatly improve the permeability and disintegration of low liquid limit silty soil. The permeability coefficient of improved silty soil with a content of 0.75% Xanthan gum and a 7-day curing period was 4.73 × 10-4 m·s-1, which was only 1.10% of that of plain silty soil at the same curing period. After immersion in water for 12 h, the soil only experienced slight disintegration. The scanning electron microscope image showed that the gel generated by the hydration reaction of Xanthan gum could improve the compactness and integrity of the soil by filling the voids, thus significantly improving the mechanical and hydraulic properties of the low liquid limit silty soil.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.