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State of charge (SOC) estimation is the core algorithm of the battery management system. However, the commonly used model-based, data-driven, or experiment-based methods struggle to independently achieve accurate SOC estimation under different working conditions and temperatures, which affects battery performance and safety. To this end, this paper proposes an online SOC estimation method that combines the model-driven and double-data-driven approaches. The unscented Kalman filter (UKF) based on the first-order RC model is used to achieve robust SOC estimation, while the data-driven long short-term memory (LSTM) neural network is used to achieve fast SOC estimation. The former model has an excellent dynamic performance and the latter has high steady-state accuracy. The SOC estimation results are input into the SOC estimation model of series LSTM so that the stable but inaccurate SOC values estimated by UKF in the first part and the accurate but fluctuating SOC values estimated by LSTM can be correlated and corrected, achieving a fast and accurate SOC estimation under various working conditions. The estimation results show that the above method has strong robustness and high accuracy, and effectively reduces model complexity and data redundancy. In addition, the root mean square error of SOC estimation under different working conditions is controlled within 1–2.3% at 0 °C, 25 °C, and 45 °C, which is better than the traditional single-SOC estimation method.

Background: Infertility can affect a couple’s mental health and marital and social relationships. The study aimed to investigate the prevalence of depression among infertile couples and their relationships with other factors. Methods: This study employed a cross-sectional survey. Validated tools were used to assess anxiety and depression, marital satisfaction, personality traits and sufficiency economy. The actor–partner interdependence model (APIM) was used for dyadic analysis. Results: The prevalence of depression in infertile couples was 6.7%. Aggression, extraversion and neuroticism were significantly correlated with depression, whereas the expectation of having children, marital satisfaction and sufficiency economy were negatively correlated with depression. The APIM model suggested that neuroticism and marital satisfaction were significant predictors of depression. Partner effect between the expectation of having children and depression was observed (p = 0.039). Conclusions: Like other populations, depression in infertile couples seems to be associated with aggression, extraversion and neuroticism. However, there are specific variables related to infertility that impact the depression levels of these couples. For instance, the expectation of having children can affect the partners of infertile couples, while the role of the sufficiency economy is a new factor that has been examined for depression in this sample and requires further exploration.

Neointimal hyperplasia and stent thrombosis remain issues with vascular stents. Here, the authors report on the development of a nitric oxide releasing hydrogel which allows for endothelialisation of the stent surface and prevents smooth muscle cell growth reducing hyperplasia and thrombosis in in vivo models.

Abstract Background Gasdermin D (GSDMD) is cleaved by several proteases including by caspase-1, a component of intracellular protein complexes called inflammasomes. Caspase-1 also converts pro-interleukin-1β (pro-IL-1β) and pro-IL-18 into bioactive IL-1β and IL-18, respectively. GSDMD amino-terminal fragments form plasma membrane pores, which mediate the secretion of IL-1β and IL-18 and cause the inflammatory form of cell death pyroptosis. Here, we tested the hypothesis that GSDMD contributes to joint degeneration in the K/BxN serum transfer-induced arthritis (STIA) model in which autoantibodies against glucose-6-phosphate isomerase promote the formation of pathogenic immune complexes on the surface of myeloid cells, which highly express the inflammasomes. The unexpected outcomes with the STIA model prompted us to determine the role of GSDMD in the post-traumatic osteoarthritis (PTOA) model caused by meniscus ligamentous injury (MLI) based on the hypothesis that this pore-forming protein is activated by signals released from damaged joint tissues. Methods Gsdmd +/+ and Gsdmd −/− mice were injected with K/BxN mouse serum or subjected to MLI to cause STIA or PTOA, respectively. Paw and ankle swelling and DXA scanning were used to assess the outcomes in the STIA model whereas histopathology and micro-computed tomography (μCT) were utilized to monitor joints in the PTOA model. Murine and human joint tissues were also examined for GSDMD, IL-1β, and IL-18 expression by qPCR, immunohistochemistry, or immunoblotting. Results GSDMD levels were higher in serum-inoculated paws compared to PBS-injected paws. Unexpectedly, ablation of GSDMD failed to reduce joint swelling and osteolysis, suggesting that GSDMD was dispensable for the pathogenesis of STIA. GSDMD levels were also higher in MLI compared to sham-operated joints. Importantly, ablation of GSDMD attenuated MLI-associated cartilage degradation (p = 0.0097), synovitis (p = 0.014), subchondral bone sclerosis (p = 0.0006), and subchondral bone plate thickness (p = 0.0174) based on histopathological and μCT analyses. Conclusion GSDMD plays a key role in the pathogenesis of PTOA, but not STIA, suggesting that its actions in experimental arthropathy are tissue context-specific.

Abstract Colorectal tumorigenesis is a heterogeneous disease driven by multiple genetic and epigenetic alterations. F-box and WD repeat domain containing 11 (FBXW11) is a member of the F-box protein family that regulates the ubiquitination of key factors associated with tumor growth and aggressiveness. Our study aimed to explore the role of FBXW11 in the development and metastasis of colorectal cancer (CRC). FBXW11 was overexpressed in colorectal tumor tissues and its overexpression was associated with a poor prognosis of CRC patients. The upregulation of FBXW11 not only promoted cell proliferation, invasion, and migration, but also contributed to maintaining stem-cell features in colorectal tumor cells. Further analysis revealed that FBXW11 targeted hypermethylated in cancer 1 (HIC1) and reduced its stability in CRC cells through ubiquitination. Moreover, the expression of sirtuin 1 (SIRT1), a deacetylase in tumor cells was upregulated by FBXW11 via regulating HIC1 expression. The mouse xenograft models of CRC confirmed that FBXW11 knockdown impeded colorectal tumor growth and liver metastasis in vivo. In summary, our study identified FBXW11 as an oncogenic factor that contributed to stem-cell-like properties and liver metastasis in CRC via regulating HIC1-mediated SIRT1 expression. These results provide a rationale for the development of FBXW11-targeting drugs for CRC patients.

As people pay more and more attention to quality of life, stomatology, as one of the main branches of modern medicine, has experienced rapid development. The research results of many fields, such as molecular biology, analytical chemistry, material chemistry and other disciplines, are gradually applied in the field of stomatology. Due to the advantages of fast response, flexible design, high specificity, high sensitivity and easy operation, fluorescent probe technology is widely used not only in environmental monitoring, food analysis, bioanalysis and life sciences, but also in stomatology as an increasingly powerful analytical and research tool. In this review, we will introduce the uses of fluorescent probes in stomatology for detection, diagnosis, imaging, treatment and screening from five aspects: oral and maxillofacial tumors, dental hard tissue diseases, oral soft tissue diseases, oral related ion diseases, and forensic dentistry. It is hoped that our review may contribute to the further development of fluorescent probes in terms of selectivity, sensitivity, non-toxicity, and stability, thus enhancing the pathogenesis, diagnosis and therapy of stomatological diseases, and laying the foundation for further study of oral disease mechanisms.

Radon is an excellent natural tracer for studying various geophysical processes. In the past centuries, radon isotopes measurement approaches for marine research have been fully developed but still suffer limitations. Here we present the setup and validation of an improved continuous online measurement system (PIC-ORn) to measure dissolved radon in the surface ocean and other water bodies. We demonstrated that the PIC measurement efficiency is ~2 times higher than a RAD7 and is less affected by relative humidity and produces reliable results. Laboratorial measurements indicated that the new PIC-ORn system responded timely to the change of radon activities in water. The new system was successfully deployed during a cruise to the northwest Pacific Ocean in June 2021. Despite low radon-in-water activities, the results obtained by the new PIC-ORn system matched the traditional measurement systems within the estimated uncertainties. The PIC-ORn detector takes advantage of higher efficiency, lower cost, and power consumption, and is less affected by air moisture. The new system does not rely on drying units, further reducing on-site supervision, which would benefit the researches in submarine groundwater advection and diffusion and ocean-atmosphere gas exchange.

BackgroundThe relationship between retirement and health is important to the formulation of retirement related policies but is a controversial topic, perhaps because selection bias has not been well-addressed in previous studies through traditional analysis methods. Using data from the China Health and Retirement Longitudinal Study (CHARLS), this study explored the potential impact of retirement on the health of elderly Chinese individuals, adjusting for selection bias.MethodsWe balanced the baseline differences between retirement groups and working groups based on nearest neighbor matching and genetic matching with a generalized boosted model (GBM), and regression analysis was used to evaluate the impact of retirement on the health of elderly individuals.ResultsNo significant difference was found in any of the covariates between the two groups after matching. Genetic matching performed better than nearest neighbor matching in balancing the covariates. Compared to the working group, the retirement group had a 0.78 (95% CI: 0.65–0.94, P = 0.026) times higher probability of self-reported physical pain, a 0.76 (95% CI: 0.62–0.93, P = 0.023) times higher probability of depression, and a 0.57-point (95% CI: 0.37–0.78, P < 0.001) improvement in cognitive status score. Among male, the retirement group had a 0.89-point (95% CI: 0.45–1.33, P < 0.001) improvement in cognitive status score for low education, a 0.65 (95% CI: 0.46–0.92, P = 0.042) times higher probability of self-reported physical pain for middle education. For female with low education, the cognitive status of the retirement group was significantly higher by 0.99 points (95% CI: 0.42–1.55, P = 0.004), the probability of depression was 0.56 (95% CI: 0.36–0.87, P = 0.031) times higher in the retirement group than in the working group. There was no difference for the middle and high education.ConclusionRetirement can exert a beneficial effect on the health of elderly individuals. Therefore, the government and relevant departments should consider this potential effect when instituting policies that delay retirement.

ObjectivesThis study aimed to describe the HIV/AIDS knowledge, sexual attitudes, and sexual behaviors of young students (14–25 years) in Chongqing, China, and to examine their use of preventive services and related factors.MethodA cross-sectional study was conducted with students from 67 schools from December 2019 to June 2021. The chi-square test, non-parametric test to assess the differences between respondents with different characteristics in the above aspects. Additionally, univariate and multivariate logistic regression analyses were conducted to examine factors associated with the awareness of HIV/AIDS knowledge. Confidence intervals without crossover or P < 0.05 was considered significant.ResultsA total of 31,782 participants were included in the study. A total of 62.62% of the respondents were considered to be aware of basic HIV/AIDS knowledge, including 78.44%, 62.15%, and 52.08% in undergraduate colleges, junior colleges and secondary vocational schools, respectively. In total, 60.96% of males and 29.42% of females accepted premarital sex, 15.49% of males and 6.18% of females reported being sexually experienced, and only 57.18% of the students used condoms every time they had sex. The percentage of condom use among students who were aware of HIV/AIDS knowledge was higher than that among students who were not aware. A total of 85.60% of the students thought they needed HIV/AIDS prevention and control knowledge, and 94.60% thought more health education activities on HIV/AIDS prevention needed to be conducted in schools. Entrance education, lectures or consultation hotlines, WeChat official accounts and other media platforms were rated as the most acceptable HIV/AIDS prevention education methods.ConclusionThese respondents lacked knowledge about HIV/AIDS, and an increasing number of students show an open attitude toward premarital sex and engage in risky sexual behaviors. It is urgent to enhance and widely disseminate comprehensive HIV/AIDS and sexual health education in multiple formats.

The alarming increase of ambient ozone (O3) levels across China raises an urgent need in understanding underlying mechanisms of regional O3 events for highly urbanized city clusters. Sichuan Basin (SCB) situated in southwestern China has experienced severe O3 pollution at times in summer from 2013 to 2020. Here, we use the WRF-CMAQ model with the Integrated Source Apportionment Method (ISAM) to investigate the evolution mechanism and conduct source attribution of an extreme O3 episode in the SCB from June 1 to 8, 2019. This typical summer O3 episode is associated with the synoptic-driven meteorological phenomenon and transboundary flow of O3 and precursors across the SCB. Weak ventilation in combination with stagnant conditions triggered the basin-wide high O3 concentrations and enhanced BVOC emissions substantially contribute up to 57.9 μg/m3 MDA8 O3. CMAQ-ISAM indicates that precursor emissions from industrial and transportation have the largest impacts on elevating ambient O3 concentrations, while power plant emissions exhibit insignificant contributions to basin-wide O3 episodes. These results improve the understanding of the summertime O3 episode in the SCB and contribute insights into designing O3 mitigation policy.

Abstract Combining isolated atomic active sites with those in nanoparticles for synergizing complex multistep catalysis is being actively pursued in the design of new electrocatalyst systems. However, these novel systems have been rarely studied due to the challenges with synthesis and analysis. Herein, a synergistically catalytic performance is demonstrated with a 0.89 V (vs reversible hydrogen electrode) onset potential in the four‐step oxygen reduction reaction (ORR) by localizing tungsten single atoms around tungsten nitride nanoparticles confined into nitrogen‐doped carbon (W SAs/WNNC). Through density functional theory calculations, it is shown that each of the active centers in the synergistic entity feature a specific potential‐determining step in their respective reaction pathway that can be merged to optimize the intermediate steps involving scaling relations on individual active centers. Impressively, the W SAs/WNNC as the air cathode in all‐solid‐state Zn‐air and Al‐air batteries demonstrate competitive durability and reversibility, despite the acknowledged low activity of W‐based catalyst toward the ORR.

Abstract Background The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). Methods This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). Results Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. Conclusion The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

BackgroundPembrolizumab and cemiplimab have been approved as treatment for advanced non-small-cell lung cancer (NSCLC) with high programmed death ligand-1 (PD-L1) expression. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared with that of cemiplimab in the treatment of advanced NSCLC with high PD-L1 expression from a societal perspective in the United States.Materials and methodsCost-effectiveness analysis integration of the network meta-analysis framework was performed using data from the EMPOWER-Lung 1, KEYNOTE 024, and KEYNOTE 042 phase 3 randomized clinical trials. A network meta-analysis including 2289 patients was constructed, and the Markov and partitioned survival (PS) models were used to assess the cost-effectiveness of pembrolizumab compared with that of cemiplimab for the treatment of high PD-L1 expression (≥50% of tumor cells). The time horizon was 10 years. The main outcomes were overall costs, incremental cost-effectiveness ratios (ICERs), quality-adjusted life-years (QALYs), life-years, incremental net health benefits (INHB), and incremental net monetary benefits (INMB). The robustness of the model was verified using one-way and probabilistic sensitivity analyses, and subgroup analyses were conducted.ResultsTreatment of advanced NSCLC with high PD-L1 expression with pembrolizumab achieved 0.093 QALYs and was associated with an incremental cost of $10,657 compared with cemiplimab, yielding an ICER of $114,246/QALY. The ICER in the PS model was similar to that in the Markov model, with a difference of $3,093/QALY. At a willingness-to-pay (WTP) threshold of $100,000/QALY, INHB, and INMB of pembrolizumab were -0.013 QALYs and -$1,329, respectively, and the probability of cemiplimab was 51% when compared with pembrolizumab. When the WTP threshold increased to $150,000/QALY, the INHB and INMB of pembrolizumab were 0.022 QALYs and $3,335, respectively, and the probability of pembrolizumab was 51.85%. One-way sensitivity analysis indicated that the models were sensitive to pembrolizumab and cemiplimab costs. Subgroup analysis revealed that treatment with pembrolizumab was related to a higher INHB in several subgroups, including patients with brain metastases at baseline.ConclusionOur findings suggest that the WTP threshold should be considered when choosing between cemiplimab and pembrolizumab to treat advanced NSCLC with high PD-L1 expression. Reducing the cost of pembrolizumab may lead to valuable outcomes.

ContextPrevious studies on the association between thyroid function and carotid plaque have shown contradictory results, which may be attributable to the sensitivity to thyroid hormone indices. This study aimed to analyze the association between thyroid hormone sensitivity and risk of carotid plaque in patients with coronary heart disease (CHD) and further explore this association according to sex, age, smoking, and drinking status.MethodsThis large-scale, multi-center, retrospective, cross-sectional study included 6679 patients with CHD (age 35–75). Central sensitivity to thyroid hormone was evaluated by the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyroid-stimulating hormone index (TSHI), and thyrotroph thyroxine resistance index (TT4RI). Peripheral sensitivity to thyroid hormone was assessed by free triiodothyronine/free thyroxine (FT3/FT4) ratio. Taking no carotid plaque as a reference, this study used logistic regression to analyze the association between central and peripheral thyroid hormone sensitivity and carotid plaque in patients with CHD.ResultsOf the 6679 patients with CHD, 4843 (72.50%) had carotid plaque. In the multi-adjusted models, the TFQI (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.26–1.78; P < 0.001), PTFQI (OR: 1.76; 95% CI: 1.46–2.12; P < 0.001), TSHI (OR: 1.21; 95% CI: 1.10–1.33; P < 0.001), and TT4RI (OR: 1.00; 95% CI: 1.00–1.01; P = 0.003) were positively associated with the risk of carotid plaque. Compared with that in females and people > 60 years, the OR value for carotid plaque was higher in males and people ≤ 60 years. Similarly, smokers and drinkers had higher OR values for carotid plaque than non-smokers and non-drinkers. Conversely, FT3/FT4 ratio (OR: 0.75; 95% CI: 0.70–0.81; P < 0.001) was negatively associated with carotid plaque, and the OR value for carotid plaque was lower in males, patients ≤ 60 years, smokers, and drinkers.ConclusionThis study showed that thyroid hormone sensitivity is significantly associated with carotid plaque in patients with CHD. This association is more significant in males, patients ≤ 60 years, smokers, and drinkers.

Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related deaths in women worldwide. Currently, patients’ survival remains a challenge in BC due to the lack of effective targeted therapies and the difficult condition of patients with higher aggressiveness, metastasis and drug resistance. Small extracellular vesicles (sEVs), which are nanoscale vesicles with lipid bilayer envelopes released by various cell types in physiological and pathological conditions, play an important role in biological information transfer between cells. There is growing evidence that BC cell-derived sEVs may contribute to the establishment of a favorable microenvironment that supports cancer cells proliferation, invasion and metastasis. Moreover, sEVs provide a versatile platform not only for the diagnosis but also as a delivery vehicle for drugs. This review provides an overview of current new developments regarding the involvement of sEVs in BC pathogenesis, including tumor proliferation, invasion, metastasis, immune evasion, and drug resistance. In addition, sEVs act as messenger carriers carrying a variety of biomolecules such as proteins, nucleic acids, lipids and metabolites, making them as potential liquid biopsy biomarkers for BC diagnosis and prognosis. We also described the clinical applications of BC derived sEVs associated MiRs in the diagnosis and treatment of BC along with ongoing clinical trials which will assist future scientific endeavors in a more organized direction.

Submarine groundwater discharge (SGD), including both land-based fresh groundwater that enters the ocean from coastal aquifers as well as recirculated seawater that is continuously recharged and discharged on the seabed, has been considered as an important component of the global water and biogenic element (e.g., nitrogen, phosphorus, silicon and carbon) sources and a significant pathway for material exchange at the land-sea interface of coastal ecosystems. Some researchers reported that SGD associated nutrient additions to coastal waters have caused unwanted ecological issues, including red tides, coastal acidification and hypoxia. Natural radon isotope (222Rn, t1/2 = 3.8 d) is an excellent tracer for studying SGD and other oceanographic processes including air-sea gas exchange, sediment-water diffusion, and earthquake prediction. However, the conventional radon measurement methods suffer many technical disadvantages. We consequently developed a convenient submersible radon determination approach (“OUC-Rn”) using a commercial pulsed ionization chamber (PIC) radon sensor and gas extraction membrane module to produce high precision and high resolution observations. We demonstrate the radon degassing efficiency of the membrane contactor is comparable to the shower-head type air-water exchanger but is independent of operating position. The radon measurement efficiency of the PIC is 2-fold higher than the RAD7 detector and is far less influenced by moisture. We successfully deployed the system in 2.5 meters water depth over a 100 hours period in an anthropogenic influenced bay. Based on our high temporal resolution observations, the SGD flux was estimated to be 0-43.0 cm/d (mean: 25.4 ± 14.5 cm/d). The SGD fluxes pattern plotted together with the tidal variations revealed that tidal pumping may be the main force driving seawater recirculation into aquifers and thus affecting nutrient, carbon and other dissolved matters dynamics in coastal regions.

Exosomes are a heterogeneous subset of extracellular vesicles (EVs) that biogenesis from endosomes. Besides, exosomes contain a variety of molecular cargoes including proteins, lipids and nucleic acids, which play a key role in the mechanism of exosome formation. Meanwhile, exosomes are involved with physiological and pathological conditions. The molecular profile of exosomes reflects the type and pathophysiological status of the originating cells so could potentially be exploited for diagnostic of cancer. This review aims to describe important molecular cargoes involved in exosome biogenesis. In addition, we highlight exogenous factors, especially autophagy, hypoxia and pharmacology, that regulate the release of exosomes and their corresponding cargoes. Particularly, we also emphasize exosome molecular cargoes as potential biomarkers in liquid biopsy for diagnosis of cancer.

Objective: Nivolumab improves overall survival (OS) and is associated with fewer adverse events than sorafenib for the treatment of advanced hepatocellular carcinoma (aHCC). However, the cost-effectiveness of nivolumab compared with sorafenib treatment for aHCC remains unclear. This study evaluated the cost-effectiveness of nivolumab and sorafenib in the treatment of aHCC.Materials and methods: A partitioned survival model that included three mutually exclusive health states was used to evaluate the cost-effectiveness of nivolumab and sorafenib for treating aHCC. The clinical characteristics and outcomes of the patients in the model were obtained from the CheckMate 459. We performed deterministic one-way sensitivity and probabilistic sensitivity analyses to evaluate the robustness of the model. Subgroup analyses were also performed. Costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were measured.Results: The base case analysis showed that compared with sorafenib, treatment with nivolumab was associated with an increment of 0.50 (2.45 vs. 1.95) life-years and an increment of 0.32 (1.59 vs. 1.27) QALYs, as well as a $69,762 increase in cost per patient. The ICER was $220,864/QALY. The INHB and INMB were −0.15 QALYs and −$22,362 at a willingness-to-pay (WTP) threshold of $150,000/QALY, respectively. The probabilistic sensitivity analysis demonstrated that the probability of nivolumab being cost-effective was only 10.38% at a WTP threshold of $150,000/QALY. The model was most sensitive to the costs of sorafenib and nivolumab according to the one-way sensitivity analysis. When the price of sorafenib exceeded $0.93/mg or nivolumab was less than $24.23/mg, nivolumab was more cost-effective. The subgroup analysis illustrated that the probability of cost-effectiveness was >50% in the Barcelona Clinic Liver Cancer Stage B subgroups for nivolumab at a WTP threshold of $150,000/QALY. This study also showed that the probability of cost-effectiveness was

Pine wilt disease (PWD) is regarded as one of the most serious conifer diseases affecting pines worldwide. To date, an in-depth study of the driving mechanisms behind short-distance PWD spread is lacking. In this study, we collected PWD forest subcompartment data in Fushun, China, and analysed the effects of factors on the short-distance transmission of PWD; the analysed factors included the number of neighbouring PWD-infected forest subcompartments, the canopy density, the slope direction, and different traffic corridor types. The results suggested that the spatial spill-over effect of nearby PWD-infected subcompartments contributed the most to short-distance PWD transmission, with an impact of up to 78% on its propagation. The impact of the traffic corridor was 20%. With the help of a beetle vector, PWD can spread to nearby forest subcompartments, and this spatial PWD spill-over effect showed a linearly decaying trend as the distance to neighbouring subcompartments increased. Different traffic corridor types exhibited significant PWD transmission impact differences. County roadways and highways had great impacts, while others had relatively small impacts. For each additional 100 m of distance from a county roadway, highway, national, or provincial roadway, the PWD infection risks in forest subcompartments were reduced by 18%, 11%, 5%, and 3%, respectively. In this study, we quantified the influence of driving factors on the short-distance spread of PWD and provided a theoretical basis for the control of PWD transmission; the results obtained herein are critical for maintaining the ecological security of forests, promoting ecological forest management and stabilising forest carbon sinks.

Polysaccharides are important active ingredients of living organisms. In this study, two new polysaccharides, Tricholoma sinoportentosum polysaccharide (TS-P) and Termitomyces albuminosus (TA-P), were extracted and purified using anion exchange column chromatography. The structure of each polysaccharide was identified by HPGPC, FT-IR, HPLC, GC-MS and NMR, and the biological activities were also investigated. The results of the structure identification showed that TS-P was composed of arabinose, mannose, glucose and galactose at a ratio of 1:1:3:2 and its main chain was composed of (1→4)-Arap residues, (1→4,6)-D-Manp residues and two (1→6)-Galp residues. The TA-P was composed of arabinose, glucose and galactose at a ratio of 2:4:8. Its main chain was composed of two (1→4)-β-L-Arap residues, one (1→4)-Glcp residues, three (1→2,6)-Galp residues and five (1→6)-Galp residues. The immunoassay showed that TS-P and TA-P could significantly promote the proliferation of T cells, B cells and RAW264.7 cells. The cell cycle results showed that for B cells and macrophages, TS-P and TA-P mainly affected the G0/G1 phases of the cell cycle; for T cells, TS-P affected G2/M phase, while TA-P mainly affected the G0/G1 phases. TS-P could significantly promote B cells to secrete IgA, IgG and IgD (p < 0.01), while TA-P could significantly promote the secretion of IgA and IgG (p < 0.01). The chemical structure and biological activity of TS-P and TA-P were first studied and compared to lay a theoretical foundation for the application of fungal polysaccharide.

Abstract Background The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC. Methods We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS). Results We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67–0.86, p0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea. Conclusion These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors. Graphical abstract

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), an emerging tickborne infectious disease caused by a novel banyangvirus (SFTS virus, SFTSV), was endemic in several Asian countries with a high mortality up to 30%. Until recently, SFTSV-associated re-infection have not been reported and investigated. Case presentation A 42-year-old female patient was identified as a case of SFTS with re-infection, with two episodes of SFTSV infection on June 2018 and May 2020. The diagnosis of SFTS was confirmed by detection of SFTSV RNA in the blood samples using real-time reverse-transcription polymerase chain reaction and antibodies specific for SFTSV using enzyme linked immunosorbent assay. The changes of viremia and antibody response differed between the two episodes. Phylogenetic analysis showed the two viral genome sequences were in the same clade, but showing 0.6% dissimilarity of the nearly whole nucleotide sequence. Analysis of clinical data revealed that the second episode showed milder illness than that of the first episode. Conclusions Epidemiological and clinical findings, viral whole genomic sequences, and serological evidence, provided evidence for the re-infection of SFTSV rather than prolonged viral shedding or relapse of the original infection. The patients with re-infection of SFTSV may be at high odds of clinically inapparent or mildly symptomatic. More attention should be directed towards the long-term follow up of the recovered patients in the future, to explicitly acquire the decay profile of their immunity response. Graphic abstract

Mesenchymal stem cells (MSCs) are characterized by self-renewal, rapid proliferation, multipotent differentiation, and low immunogenicity. In addition, the tropism of MSCs towards injured tissues and tumor lesions makes them attractive candidates as cell carriers for therapeutic agent delivery and genetic material transfer. The interaction between tumor cells and MSCs in the tumor microenvironment plays an important role in tumor progression. Oral cancer is one of the most common malignant diseases in the head and neck. Although considerable improvements in the treatment of oral cancer were achieved, more effective and safer novel agents and treatments are still needed, and deeper studies on the etiology, pathology, and treatment of the oral cancer are desirable. In the past decades, many studies have reported the beneficial effects of MSCs-based therapies in the treatment of various diseases, including oral cancers. Meanwhile, other studies demonstrated that MSCs may enhance the growth and metastasis of oral cancer. In this paper, we reviewed the research progress of the effects of MSCs on oral cancers, the underlying mechanisms, and their potential applications in the treatment of oral cancers.

ContextThyroid hormones influence glucose homeostasis through central and peripheral regulation. To date, the association between thyroid hormone sensitivity and elevated blood glucose (EBG) in patients with coronary heart disease (CHD) remains unknown. The purpose of this study was to investigate the association between thyroid hormone sensitivity and risk of EBG in patients with CHD, and to further explore their association in different sexes and ages.MethodsThis large multicenter retrospective study included 30,244 patients with CHD (aged 30–80 years) between 1 January 2014 and 30 September 2020. Parameters representing central and peripheral sensitivity to thyroid hormones were calculated. Central sensitivity to thyroid hormones was assessed by calculating the Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), and Thyrotropin Thyroxine Resistance Index (TT4RI), and Parametric Thyroid Feedback Quantile-based Index (PTFQI); peripheral sensitivity to thyroid hormones was evaluated using the ratio of free triiodothyronine (FT3) /free thyroxine (FT4). Taking normal glucose tolerance (NGT) as a reference, logistic regression was used to analyse the relationship between central and peripheral thyroid hormone sensitivity and EBG in patients with CHD.ResultsAmong the 30,244 participants, 15,493 (51.23%) had EBG. The risk of EBG was negatively correlated with TSHI (OR: 0.91; 95%CI: 0.91 to 0.92; P < 0.001), TT4RI (OR: 0.99; 95% CI: 0.99 to 0.99; P

Type 1 early infantile epileptic encephalopathy (EIEE1) is a rare X-link neurodevelopmental disorder caused by mutations in the ARX gene. The mechanism remains unclear due to the lack of cellular models for the disease. We previously have generated an iPSC line (OGHFUi001-A) from a male EIEE1 patient with a hemizygous R330L mutation in the ARX gene. Here we corrected the R330L mutation genetically using CRISPR/Cas9 technology to generate an isogenic control, which was an ideal control to investigate the pathogenesis of the mutation in this disease.

Measurement(s) area of different crop types • area of cropland Technology Type(s) machine learning Factor Type(s) type of crop • year of data collection Sample Characteristic - Environment cultivated environment • cropland ecosystem Sample Characteristic - Location Northeast China • China Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13567526

Traditional mobile robots with fixed structures lack the ability to cope with complex terrains and tasks. Reconfigurable modular mobile robots have received considerable attention as they can automatically reassemble according to the changing environment or task. In this paper, a new self-reconfiguration wave-like crawling (SWC) robot is presented to improve the mobile robots’ locomotion capacity. First, the mechanical design of the wave-like crawling mechanism is detailed. Then, the series and parallel connections are introduced to achieve self-reconfiguration. In addition, the kinematic model of the SWC robot is established. Finally, experiments were performed to verify the robotic system with wireless data transmission.

Terahertz metamaterials are some of the core components of the new generation of high-frequency optoelectronic devices, which have excellent properties that natural materials do not have. The unit structures are generally much smaller than the wavelength, so preparation is mainly based on semiconductor processes, such as coating, photolithography and etching. Although the processing resolution is high, it is also limited by complex processing, long cycles, and high cost. In this paper, a design method for dual-band terahertz metamaterials and a simple, rapid, low-cost metamaterial preparation scheme based on step-motor-driven electrohydrodynamic jet technology are proposed. By transforming an open-source 3D printer, the metamaterial structures can be directly printed without complex semiconductor processes. To verify effectiveness, the sample was directly printed using nano conductive silver paste as consumable material. Then, a fiber-based multi-mode terahertz time-domain spectroscopy system was built for testing. The experimental results were in good agreement with the theoretical simulation.

The interannual variability (IAV) of global vegetation greenness needs careful assessment as it relates to the stability of the climate, conservation of biodiversity, sustainable ecosystem services, and global food security. Here, we investigated the spatial feature and temporal evolvement of global vegetation greenness interannual variability from 1982 to 2015 using the Global Inventory Modeling and Mapping Studies (GIMMS) Normalized Difference Vegetation Index third generation (NDVI3g) data. Generally, regions with herbaceous and short woody plants had larger IAV of vegetation greenness than those with tall woody biome types (7.9% versus 2.9%). On average, all the biomes displayed increasing IAV of vegetation greenness from 1982 to 2015, with notable increases over northern high latitudes (0.135%/year), Eastern Europe (0.037%//year), and Central Australia (0.231%/year). Croplands in China and India experienced decreasing IAV of vegetation greenness (–0.037%/year for China and –0.004%/year for India). The changing IAV of vegetation greenness had implications for climatic, environmental, and anthropogenic changes that influence vegetation dynamics. Some note-worthy factors include climate warming, the CO _2 fertilization effect, agricultural practice improvement, cropland abandonment, and China’s Grain-for-Green Program.

With increasing livestock production due to high demand for consumption, the planted area of green fodder, an essential livestock supplement, has grown rapidly and will continue to grow in China. However, the climate feedback of this rapid land cover conversion is still unclear. Using multisource data (e.g. remote sensing observation and meteorological data), we compared the land surface temperature of green fodder plantation areas and native grassland in the northeastern Tibetan Plateau. The green fodder area was detected to be cooler than the native grassland by −0.54 ± 0.98 °C in the daytime throughout the growing season. The highest magnitude (−1.20 ± 1.68 °C) of cooling was observed in August. A nonradiative process, indicated by the energy redistribution factor, dominated the cooling effects compared to the radiative process altered by albedo variation. The results indicate the potential cooling effects of increasing green fodder area on native grassland, highlighting the necessity of investigating climate feedback from anthropogenic land use change, including green fodder expansion.

Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking either GSDM compared with wild-type (WT) mice, indicating that fracture healing was compromised in mutant mice. However, compound loss of GSDMD and GSDME did not exacerbate the outcomes, suggesting shared actions of both GSDMs in fracture healing. Mechanistically, bone injury induced IL-1β and IL-18 secretion in vivo, a response that was mimicked in vitro by bone debris and ATP, which function as inflammatory danger signals. Importantly, the secretion of these cytokines was attenuated in conditions of GSDMD deficiency. Finally, deletion of IL-1 receptor reproduced the phenotype of Gsdmd or Gsdme deficient mice, implying that inflammatory responses induced by the GSDM-IL-1 axis promote bone healing after fracture.

Abstract Impressive clinical benefit is seen in clinic with PD‐1 inhibitors on portion of cancer patients. Yet, there remains an urgent need to develop effective synergizers to expand their clinical application. Tumor‐associated macrophage (TAM), a type of M2‐polarized macrophage, eliminates or suppresses T‐cell‐mediated anti‐tumor responses. Transforming TAMs into M1 macrophages is an attractive strategy of anti‐tumor therapy. Here, we conducted a high‐throughput screening and found that Carfilzomib potently drove M2 macrophages to express M1 cytokines, phagocytose tumor cells, and present antigens to T cells. Mechanistically, Carfilzomib elicited unfolded protein response (UPR), activated IRE1α to recruit TRAF2, and activated NF‐κB to transcribe genes encoding M1 markers in M2 macrophages. In vivo, Carfilzomib effectively rewired tumor microenvironment through reprogramming TAMs into M1‐like macrophages and shrank autochthonous lung cancers in transgenic mouse model. More importantly, Carfilzomib synergized with PD‐1 antibody to almost completely regress autochthonous lung cancers. Given the safety profiles of Carfilzomib in clinic, our work suggested a potentially immediate application of combinational treatment with Carfilzomib and PD‐1 inhibitors for patients with solid tumors.

Taking China’s first application of domestic shield tunneling in a water-rich sand layer for crossing a high-speed railway as research background, the influence of changes in the shield tunneling parameters on ground settlement is analyzed based on field tests, and a construction control method suitable for shield tunneling under a risk source in a water-rich sand layer is proposed. The test results show that the use of 10% sodium bentonite as the soil modifier for soil pressure balance shield tunneling into the water-rich sand layer has advantages, while adding 50% loess into the bentonite slurry in the gravel sand layer can greatly improve the impermeability of the soil; the settlement of soil can be effectively reduced by using the special segment with grouting holes for deep grouting and applying the adaptive transformation of the shield cutter. Based on the statistical analysis results, a reasonable range for the cutter head torque, cutter head speed, chamber pressure, bentonite injection volume, and advanced speed in the water-rich sand layer can provide a construction control basis for similar projects and provide data support for the compilation of relevant specifications.

Abstract Background We aimed to identify which part of the patients with metastatic renal cell carcinoma (mRCC) is not suitable for cytoreductive nephrectomy (CN). Methods The data of mRCC patients was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate cox regression analysis and nomogram were performed for selecting factors independently associated with survival. Propensity score matching (PSM) was applied to reduce potential bias when comparing survival of mRCC patients treated by CN or non-surgery (NS). The survival analysis of subgroups was estimated by the Kaplan–Meier method and compared by log-rank testing. The summary of subgroup analysis was showed by forest plots. Results The records of 21,411 patients with mRCC were obtained from the SEER database. After screening, a total of 6532 patients were included for further analysis, of which 6043 underwent CN and 489 underwent NS. Age, T stage, N stage and tumor size were involved in subgroup analysis by PSM according to the result of multivariate cox regression analysis and clinical experience. Survival benefit was not found in T4 stage patients. Further analysis showed that T4&N1 and T4&age ≥ 76 yr subgroups could not obtain survival benefit from CN. Conclusion CN should not be performed in T4 stage mRCC patients who were in status of N1 stage or older than 76 years, because surgery cannot take significant survival benefit for them.

Abstract High gas mines and outburst mines contribute to more than 30% of the coal production capacity in China. In view of this, coordinating the development and use of coal and gas has become an urgent concern for China's coal industry. After years of efforts, the concept of a co‐mining mode for coal and gas in China has gone through many stages, including theoretical discussion, engineering application, and assumption of concepts. Three modes have been gradually developed: the Huainan mode, based on pressure relief co‐mining of a protective layer; the Jincheng mode, based on directional long borehole co‐mining; and the YangQuan/SongZao mode, based on cross‐layer borehole co‐mining. These modes provide strong direction and the impetus to solve current predicaments and challenges of coal mining in China. Under the concept of “green” extraction and the corresponding urgent needs for environmental protection, high efficiency, and energy‐saving extraction, experts and scholars in the coal industry are also exploring development trends for coal in the future. For example, researchers have suggested idealized mining methods for replacing traditional mining methods, including fluidized mining technology, intelligent unmanned mining technology, precision mining technology, green development of abandoned mines technology, and mining based on other technical means.

Abstract Agency problems arise in any environment involving a principal–agent relationship. This study examines the effect of horizontal fiscal externalities on the optimal matching grant rate in a model where agency costs are inevitable. Because this study takes agency costs into account, the main results should differ from the standard conclusions of the tax competition literature. This study finds that the degree of agency costs and benefit spillovers determine the relationship between tax competition and the optimal matching grant rate. If agency costs are relatively small, and benefit spillover is zero, the optimal matching grant rate should increase with the factors of production demand elasticities with respect to the factor tax rate and vice versa. Tax competition thus may ease the inefficiency arising from agency costs only if the disutility of effort is so large that the benefits from tax competition exceed the costs when benefit spillover is zero.

Abstract Background Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence and chemo-resistance. Previous studies suggested that miR-153 played essential roles in lung cancer. However, the molecular mechanism of miR-153 in regulating the stemness of non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we investigated the role of miR-153 in regulation of the stemness of NSCLC. Methods The stemness property of lung stem cancer cells was detected by sphere formation assay, immunofluorescence, and Western blot. Luciferase reporter assay was performed to investigate the direct binding of miR-153 to the 3′-UTR of JAG1 mRNA. Animal study was conducted to evaluate the effect of miR-153 on tumor growth in vivo. The clinical relevance of miR-153 in NSCLC was evaluated by Rt-PCR and Kaplan-Meier analysis. Results MiR-153 expression was decreased in lung cancer tissues. Reduced miR-153 expression was associated with lung metastasis and poor overall survival of lung cancer patients. Jagged1, one of the ligands of Notch1, is targeted by miR-153 and inversely correlates with miR-153 in human lung samples. More importantly, we found that miR-153 inhibited stem cell-like phenotype and tumor growth of lung adenocarcinoma through inactivating the Jagged1/Notch1 axis. Conclusion MiR-153 suppresses the stem cell-like phenotypes and tumor growth of lung adenocarcinoma by targeting Jagged1 and provides a potential therapeutic target in lung cancer therapy.

Integration of two or more biomolecules with synergetic and complementary effects on a material surface can help to obtain multi-functions for various biomedical applications. However, the amounts of biomolecules integrated and their physiological functions are compromised due to the limited surface anchoring sites. Herein, we propose a novel concept of film engineering strategy “from surface to bulk synergetic modification”. This new concept is realized by employing the surface amine groups of plasma polymerized allylamine (PPAm) film for grafting a molecule e.g., thrombin inhibitor, bivalirudin (BVLD), meanwhile its bulk amine groups is used as a universal depot for storing and releasing therapeutic nitric oxide (NO) gas as supplement to the functions of BVLD. It is demonstrated that such a “from surface to bulk synergetic modification” film engineering can impart the modified-substrates with anti-platelet and anti-coagulant dual functions, giving rise to a highly endothelium-mimetic thromboresistant property. We believe that our research provides a very promising strategy to deliver multifunctional surface versatilely that require NO release in combination with other properties, which will find broad biomedical applications in blood-contacting devices, and et al. Moreover, it also provides a brand-new film engineering strategy for tailoring surface multi-functionalities of a wide range of materials. Keywords: Surface chemistry, Amine-bearing coating, Synergic modification, Biomolecule grafting, Nitric oxide loading

Abstract Although transition metal sulfides have presented prospect in electrochemical sensing, their electrocatalytic performance still cannot meet the demands for practical applications due to the difficulties in mass transport and electron transfer. In this work, double-shelled CuS nanocages (2-CuS NCs) were prepared for enzyme-free ascorbic (AA) sensor through a Cu2O- templated method. The unique double-shelled hollow structure displayed large specific surface areas, ordered diffusion channels, increased volume occupying rate, and accelerated electron transfer rate, resulting in enhanced electrochemical dynamic. As a sensing electrode for AA, 2-CuS NCs modified glassy carbon electrode (2-CuS NCs/GCE) exhibited eminent electrocatalytic activity in terms of satisfying sensitivity (523.7 μA mM−1 cm−2), short response time (0.31 s), and low limit of detection (LOD, 0.15 μM). 2-CuS NCs look promising for analytical sensing of AA in electrochemical sensors thanks to its prominent electrocatalytic kinetics issued from double-shelled hollow porous structure.

In this paper, we propose an adaptive beamforming algorithm for large uniform linear arrays (ULAs), where only a nested subarray is utilized to calculate the beamforming coefficients for the original ULA. In this algorithm, the steering vectors and powers of the signal-of-interest (SOI) and interferences are firstly estimated using the Capon spatial spectrum and known array structure, and the interference-plus-noise covariance matrix (INCM) is then constructed. Subsequently, an augmented INCM is formed via vectorization and spatial smoothing operations. Finally, the beamformer weight vector is determined by the augmented INCM and the estimated SOI steering vector. Our proposed algorithm exploits the enhanced degrees of freedom of the nested array, and thus can be applied to a large ULA to reduce the implementation complexity. Moreover, it fundamentally eliminates the SOI component. Numerical results demonstrate that the proposed algorithm performs better than the existing approaches.

Abstract Background Both mandibular condylar hyperplasia and condylar osteochondroma can lead to maxillofacial skeletal asymmetry and malocclusion, although they exhibit different biological behavior. This study attempted to compare the histological features of mandibular condylar hyperplasia and condylar osteochondroma using hematoxylin-and-eosin (H&E) staining, and immunohistochemistry staining of PCNA and EXT1 with quantitative analysis method. Results The H&E staining showed that condylar hyperplasia and condylar osteochondroma could be divided into four histological types and exhibited features of different endochondral ossification stages. There was evidence of a thicker cartilage cap in condylar osteochondroma as compared condylar hyperplasia (P = 0.018). The percentage of bone formation in condylar osteochondroma was larger than was found in condylar hyperplasia (P = 0.04). Immunohistochemical staining showed that PCNA was mainly located in the undifferentiated mesenchymal layer and the hypertrophic cartilage layer, and there were more PCNA positive cells in the condylar osteochondroma (P = 0.007). EXT1 was mainly expressed in the cartilage layer, and there was also a higher positive rate of EXT1 in condylar osteochondroma (P = 0.0366). The thicker cartilage cap, higher bone formation rate and higher PCNA positive rate indicated a higher rate of proliferative activity in condylar osteochondroma. The more significant positive rate of EXT1 in condylar osteochondroma implied differential biological characteristic as compared to condylar hyperplasia. Conclusions These features might be useful in histopathologically distinguishing condylar hyperplasia and osteochondroma.

The livestock product consumption per capita in China has almost doubled in the past three decades. The planting of green fodder has increased in the agropastoral ecotone of China to meet the increasing demand for livestock feed, and the green fodder expansion can have subsequent consequences on the environment. However, information on the area and distribution of green fodder is very limited. Here, we developed a pixel- and phenology-based algorithm to map green fodder and track its dynamics in the northeastern Tibetan Plateau, a typical alpine pasture region in China, using all the available Landsat images and Google Earth Engine (GEE). We developed a simple approach for the rapid identification of green fodder fields by using a new green fodder index that considers the unique phenology of green fodder, which has higher greenness and water content in the late growing season than other vegetation. A total of 858 Landsat images were used to generate green fodder maps in northeastern Tibetan Plateau (including Zeku, Guinan, and Tongde Counties) in three periods (circa 2010, 2015, and 2019). The overall accuracies of our green fodder maps were 93–97% and the Matthews correlation coefficients were 0.76–0.83. We found a rapid expansion of green fodder from 16.3 km2 in 2010 to 136.1 km2 in 2019. Newly cultivated green fodder occurred in both existing croplands and natural grasslands. Our study demonstrated the potential of the phenology-based approach, all the available Landsat images, and GEE for tracing the historical dynamics of green fodder at 30-m resolution in alpine regions. Our findings advance our understanding of changes in forage area, production, the supply–demand gap, and the ecological and climatic consequences of green fodder expansion.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality, however with no effective therapy available. Methods: The effect of favipiravir (FPV) in treating SFTS was evaluated by an integrated analysis on data collected from a single-arm study (n=428), a surveillance study (n=2350) and published data from a randomized controlled trial study (n=145). A 1:1 propensity score matching was performed to include 780 patients: 390 received FPV and 390 received supportive therapy only. Case fatality rates (CFRs), clinical progress, and adverse effects were compared. Findings: FPV treatment had significantly reduced CFR from 20.0% to 9.0% (odds ratio 0.38, 95% confidence interval 0.23-0.65), however showing heterogeneity when patients were grouped by age, onset-to-admission interval, initial viral load and therapy duration. The effect of FPV was significant only among patients aged ≤70 years, with onset-to-admission interval ≤5 days, therapy duration ≥5 days or baseline viral load ≤1 × 106 copies/mL. Age-stratified analysis revealed no benefit in the aging group >70 years, regardless of their sex, onset-to-admission interval, therapy duration or baseline viral load. However, for both ≤60 and 60-70 years groups, therapy duration and baseline viral load differentially affected FPV therapy efficiency. Hyperuricemia and thrombocytopenia, as the major adverse response of FPV usage, were observed in >70 years patients. Interpretation: FPV was safe in treating SFTS patients but showed no benefit for those aged >70 years. Instant FPV therapy could highly benefit SFTS patients aged 60-70 years. Funding: China Natural Science Foundation (No. 81825019, 82073617 and 81722041) and China Mega-project for Infectious Diseases (2018ZX10713002 and 2015ZX09102022).

Offshore wind farms (OWFs) can influence marine stratifications, leading to fuel nutrition in the upper ocean and regulating ocean carbon fluxes. Evaluating this dynamic effect facilitates the planning of OWFs deployment for enlarging marine carbon sequestration, which is urgent in the pursuit of China’s carbon neutrality targets. However, it is impossible to observe the target influence in the planning stage of deployments, and it is impractical to build a high-resolution (100~101 m) model to cover the entire waters adjacent to China. The theoretical calculations, therefore, are the first step and top priority. The simplified theory presents two suggestions in the design of future OWF deployments in the study area. The first suggestion is made from the perspective of OWF positioning. To the east of the cities of Zhoushan, Putian, and Shantou, the oceans are dynamically sensitive to OWF deployments. The second suggestion is made from the perspective of the length scale of OWFs. A broader OWF results in a smaller vertical disturbance in the coastal waters, but the situation is opposite in the open seas. The OWF deployment strategy, proposed in the aim of ensuring idealized marine stratification responses, thus varies geographically. This study provides a panoramic view of the sensitivity of marine stratification to OWFs in the study regions. It can be seen as a steppingstone in detailed research of the target phenomenon.

Abstract Atomically dispersed Pt species are advocated as a promising electrocatalyst for the oxygen reduction reaction (ORR) to boost noble metal utilization efficiency. However, when assembled on various substrates, isolated Pt single atoms are often demonstrated to proceed through the two‐electron ORR pathway due to the unfavorable O─O bond cleavage thermodynamics in the absence of catalytic ensemble sites. In addition, although their distinct local coordination environments at the exact single active sites are intensively explored, the interactions and synergy between closely neighboring single atom sites remain elusive. Herein, atomically dispersed Pt monomers strongly interacting on a Mo2C support is demonstrated as a model catalyst in the four‐electron ORR, and the beneficial interactions between two closely neighboring and yet non‐contiguous Pt single atom sites (named as quasi‐paired Pt single atoms) are shown. Compared to isolated Pt single atom sites, the quasi‐paired Pt single atoms deliver a superior mass activity of 0.224 A mg−1Pt and near‐100% selectivity toward four‐electron ORR due to the synergistic interaction from the two quasi‐paired Pt atom sites in modulating the binding mode of reaction intermediates. Our first‐principles calculations reveal a unique mechanism of such quasi‐paired configuration for promoting four‐electron ORR.

Enhanced-efficiency nitrogen fertilizer (EENF) is a recommend nitrogen fertilizer for rice production because of its advantage on improving nitrogen use efficiency. However, its efficacy on CH4, the dominant greenhouse gas, emission from rice fields showed great variation under field conditions. And the factors influencing its efficacy are still unclear. We synthesized the results of 46 field studies and analyzed the impact of product type, rice variety, and primary agronomic measures (rice cropping system, nitrogen (N) application rate, and water management options) on the effectiveness of EENF on the CH4 emission and rice yield. Overall, EENF, including inhibitors (IS) and slow/control-released fertilizer (S/CRF), significantly reduced CH4 emission by 16.2% and increased rice yield by 7.3%, resulting in a significant reduction in yield-scaled CH4 by 21.7%, compared with conventional N fertilizer. Nitrapyrin, DMPP (3,4-dimethylpyrazole phosphate), and HQ (Hydroquinone) + Nitrapyrin showed relative higher efficacy on the mitigation of CH4 emission than other EENF products; and HQ showed relative lower efficacy on rice yield than other EENF products. The reduction in CH4 emission response of hybrid rice varieties to IS and S/CRF was greater than that of inbred rice varieties. IS significantly reduced the CH4 emission and increased the rice yield under all three rice cropping systems, and showed the highest efficacy in the late rice season of double rice cropping system. Whereas, S/CRF did not significantly reduce the CH4 emission from rice seasons of single rice cropping system and rice-upland crops rotation system. IS did not reduce the CH4 emission when N application rate less than 100 kg ha−1, and S/CRF did not affect the CH4 emission when N application rate less than 100 kg ha−1 or above 200 kg ha−1. Continuous flooding was unfavorable for IS and S/CRF to mitigate CH4 emission and enhance rice yield. These results emphasized the necessary to link EENF products with rice varieties and agronomic practices to assess their efficacy on CH4 emissions and rice yield.

Rutaceae plants are known for being a rich source of coumarins. Preliminary molecular docking showed that there was no significant difference for coumarins in Clausena and Murraya, both of which had high scoring values and showed good potential inhibitory activity to the MAO-B enzyme. Overall, 32 coumarins were isolated from Murraya exotica L., including a new coumarin 5-demethoxy-10′-ethoxyexotimarin F (1). Their structures were elucidated on the basis of a comprehensive analysis of 1D and 2D NMR and HRMS spectroscopic data, and the absolute configurations were assigned via a comparison of the specific rotations and the ECD exciton coupling method. The potential of new coumarin (1) as a selective inhibitor of MAO-B was initially evaluated through molecular docking and pharmacophore studies. Compound (1) showed selectivity for the MAO-B isoenzyme and inhibitory activity in the sub-micromolar range with an IC50 value of 153.25 ± 1.58 nM (MAO-B selectivity index > 172).