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Arable soil and crop productivity are severely affected by salinization. Therefore, soil amendments are an important measure for improving saline-alkali soil for agricultural development. Desulfurized gypsum is a common soil amendment that has been used repeatedly alongside organic materials to improve the biological, physical, and chemical properties of saline soil. This study takes the typical saline-alkali farmland soil in Yulin as the research object, and five treatments were established: a blank treatment (CK), a single application 2.5 t ha−1 of desulfurized gypsum (T), 2.5 t ha−1 of desulfurized gypsum and 1.5 t ha−1 of green manure (TL), application 2.5 t ha−1 of desulfurized gypsum and 1.5 t ha−1 of straw (TS), and 2.5 t ha−1 of desulfurized gypsum and 1.5 t ha−1 of organic fertilizer (TV). The results show that the TV treatment achieved a significant improvement in soil nutrients, organic carbon, enzyme activity, and maize yield. In 2022 (2023), the compared of organic matter, TN, TP, TK, AP, and AK increased significantly compared with the CK treatment when the TV treatment was applied. Soil phosphatase activity (SPA), soil urease activity (SUA) and soil sucrase activity (SSA) significantly higher in the TV treatment compared with the other treatments and increased significantly over the two-year period. Furthermore, soil organic carbon (SOC), easily oxidizable organic carbon (EOC), dissolved organic carbon (DOC) and microbial biomass carbon (MBC) also significantly increased with the 2022 and 2023 TV treatments. Correlation analysis revealed a positive relationship between maize yield and soil nutrients, organic carbon, and enzyme activity (P < 0.05). Thus, the TV treatment was determined to be the optimal treatment for soil improvement. This conclusion was supported by analyses performed using membership function analysis, gray correlation analysis, and entropy TOPSIS model evaluation. Therefore, this method increases soil quality, improves soil fertility, achieves high maize yields, and provides a scientific basis for enhancing and utilizing saline-alkali soil in the Loess Plateau.

ObjectiveSleep disorders is a worldwide public health problem. We sought to examine the association between sarcopenia, a decline in skeletal muscle mass and function, and sleep disorders within the adult demographic of the United States during the period spanning 2011 to 2018.MethodsDiagnosis of sarcopenia and sleep disorders was ascertained through appropriate calculations and a structured questionnaire. The primary correlation analysis was conducted using a weighted multivariate logistic regression model. Furthermore, to confirm the presence of a potential non-linear association between sarcopenia and sleep disorders, additional analyses were performed using multivariate logistic regression and restricted cubic spline (RCS) regression with dose-response curve analysis. Subgroup analyses were also conducted to explore the influence of relevant socio-demographic factors and other covariates.ResultsThe final analysis encompassed 5,616 participants. Model 4, inclusive of all pertinent covariates, revealed a positive correlation between sarcopenia and sleep disorders, yielding an odds ratio (OR) of 1.732 (95% CI: 1.182–2.547; P = 0.002). Further analysis, utilizing the restricted cubic spline model, indicated a decreasing trend in sleep disorders as sarcopenia indices rose. Stratified analyses across diverse variables underscored the significant impact of sarcopenia on sleep disorders prevalence in several subgroups. Specifically, males, individuals aged 40 and above, non-Hispanic whites, those with high school education or equivalent, unmarried individuals, obese individuals (BMI ≥ 30), alcohol drinkers, former smokers, diabetics, and those engaging in less rigorous recreational activities exhibited a more pronounced association between sarcopenia and sleep disorders. The incidence of sleep disorders exhibited an upward trend as the incidence of sarcopenia declined among study participants.ConclusionsIn summary, our study provides evidence of an association between sarcopenia and the prevalence of sleep disorders, with a negative correlation observed between the sarcopenia index and the odds ratio of sleep disorders. These findings suggest that maintaining optimal muscle mass may have a beneficial impact on sleep-related issues. In terms of exploring the mechanisms underlying the relationship between sarcopenia and sleep disorders, more in-depth research is warranted to ascertain the definitive causal relationship.

Deltacoronavirus, widely distributed among pigs and wild birds, pose a significant risk of cross-species transmission, including potential human epidemics. Metagenomic analysis of bird samples from Qinghai Lake, China in 2021 reported the presence of Deltacoronavirus. A specific gene fragment of Deltacoronavirus was detected in fecal samples from wild birds at a positive rate of 5.94% (6/101). Next-generation sequencing (NGS) identified a novel Deltacoronavirus strain, which was closely related to isolates from the United Arab Emirates (2018), China (2022), and Poland (2023). Subsequently the strain was named A/black-headed gull/Qinghai/2021(BHG-QH-2021) upon confirmation of the Cytochrome b gene of black-headed gull in the sample. All available genome sequences of avian Deltacoronavirus, including the newly identified BHG-QH-2021 and 5 representative strains of porcine Deltacoronavirus (PDCoV), were classified according to ICTV criteria. In contrast to Coronavirus HKU15, which infects both mammals and birds and shows the possibility of cross-species transmission from bird to mammal host, our analysis revealed that BHG-QH-2021 is classified as Putative species 4. Putative species 4 has been reported to infect 5 species of birds but not mammals, suggesting that cross-species transmission of Putative species 4 is more prevalent among birds. Recombination analysis traced BHG-QH-2021 origin to dut148cor1 and MW01_1o strains, with MW01_1o contributing the S gene. Surprisingly, SwissModle prediction showed that the optimal template for receptor-binding domain (RBD) of BHG-QH-2021 is derived from the human coronavirus 229E, a member of the Alphacoronavirus, rather than the anticipated RBD structure of PDCoV of Deltacoronavirus. Further molecular docking analysis revealed that substituting the loop 1–2 segments of HCoV-229E significantly enhanced the binding capability of BHG-QH-2021 with human Aminopeptidase N (hAPN), surpassing its native receptor-binding domain (RBD). Most importantly, this finding was further confirmed by co-immunoprecipitation experiment that loop 1–2 segments of HCoV-229E enable BHG-QH-2021 RBD binding to hAPN, indicating that the loop 1–2 segment of the RBD in Putative species 4 is a probable key determinant for the virus ability to spill over into humans. Our results summarize the phylogenetic relationships among known Deltacoronavirus, reveal an independent putative avian Deltacoronavirus species with inter-continental and inter-species transmission potential, and underscore the importance of continuous surveillance of wildlife Deltacoronavirus.

The potentially lethal zoonotic disease alveolar echinococcosis (AE) is caused by the metacestode larval stages of the tapeworm Echinococcus multilocularis. Metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular parasite–host interactions. The host has developed various ways to resist a parasitic infection, and the production of reactive oxygen species (ROS) is one of the most important strategies. Here, we found that scavenging of ROS reduced metacestode larval growth and germinative cell proliferation in in vivo models. Furthermore, using in vitro-cultured metacestode vesicles, we found that increased ROS levels enhanced metacestode growth and germinative cell proliferation, which was achieved by positively activating the ROS-EmERK-EmHIF1α axis. These results indicate that, beside its capacity to damage the parasite, ROS also play critical roles in metacestode growth and germinative cell proliferation. This study suggests that the effects of ROS on parasite may be bidirectional during AE infection, reflecting the parasite’s adaptation to the oxidative stress microenvironment.

This study introduces newly discovered chrysin derivatives that show potential as candidate molecules for treating inflammatory bowel disease (IBD). Compound 4b, among the synthesized compounds, displayed significant inhibitory effects on monocyte adhesion to colon epithelium induced by TNF-α, with an IC50 value of 4.71 μM. Further mechanistic studies demonstrated that 4b inhibits the production of reactive oxygen species (ROS) and downregulates the expression of ICAM-1 and MCP-1, key molecules involved in monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. In vivo experiments have shown that compound 4b exhibits a dose-dependent inhibition of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, thereby validating its effectiveness as a colitis inhibitor in animal models. These results indicate that 4b shows considerable promise as a therapeutic agent for managing IBD.

Arsenic (As) accumulation in plants is a global concern. Although the application of arbuscular mycorrhizal fungi (AMF) has been suggested as a potential solution to decrease As concentration in plants, there is currently a gap in a comprehensive, quantitative assessment of the abiotic and biotic factors influencing As accumulation. A meta-analysis was performed to quantitatively investigate the findings of 76 publications on the impacts of AMF, plant properties, and soil on As accumulation in plants. Results showed a significant dose-dependent As reduction with higher mycorrhizal infection rates, leading to a 19.3% decrease in As concentration. AMF reduced As(V) by 19.4% but increased dimethylarsenic acid (DMA) by 50.8%. AMF significantly decreased grain As concentration by 34.1%. AMF also improved plant P concentration and dry biomass by 33.0% and 62.0%, respectively. The most significant reducing effects of As on AMF properties were seen in single inoculation and experiments with intermediate durations. Additionally, the benefits of AMF were significantly enhanced when soil texture, soil organic carbon (SOC), pH level, Olsen-P, and DTPA-As were sandy soil, 0.8%–1.5%, ≥7.5, ≥9.1 mg/kg, and 30–60 mg/kg, respectively. AMF increased easily extractable glomalin-related soil protein (EE-GRSP) and total glomalin-related soil protein (T-GRSP) by 23.0% and 28.0%, respectively. Overall, the investigated factors had significant implications in developing AMF-based methods for alleviating the negative effects of As stress on plants.

BackgroundPrevious studies have explored the associations between circulating inflammatory cytokines and blinding eye diseases, including glaucoma, cataract and macular degeneration. However, the causality of these associations remains controversial. This study employs a bidirectional Mendelian randomization (MR) study to investigate the causal relationships between 41 circulating inflammatory cytokines and these blinding eye diseases.MethodsSummary data for glaucoma, cataract, macular degeneration and 41 circulating inflammatory cytokines were publicly available. The inverse variance weighted (IVW) method was employed as the main analysis method. Additionally, various sensitivity tests, including MR–Egger regression, weighted median, weight mode, Cochran’s Q test, MR pleiotropy Residual Sum and Outlier test, and leave-one-out test, were conducted to evaluate sensitivity and stability of results.ResultsThe IVW analysis identified six circulating inflammatory cytokines causally associated with the risk of blinding eye diseases: Monokine induced by interferon-gamma (MIG) for glaucoma, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-10, and platelet derived growth factor BB (PDGFbb) for cataract, and MIG and hepatocyte growth factor (HGF) for macular degeneration. However, it is noteworthy that none of these associations remained significant after Bonferroni correction (p

Aconitine (AC), which is the primary bioactive diterpene alkaloid derived from Aconitum L plants, have attracted considerable interest due to its unique structural feature. Additionally, AC demonstrates a range of biological activities, such as its ability to enhance cardiac function, inhibit tumor growth, reduce inflammation, and provide analgesic effects. However, the structure-activity relationships of AC are remain unclear. A clear understanding of these relationships is indeed critical in developing effective biomedical applications with AC. In line with these challenges, this paper summarized the structural characteristics of AC and relevant functional and bioactive properties and the structure-activity relationships presented in biomedical applications. The primary temporal scope of this review was established as the period spanning from 2010 to 2023. Subsequently, the objective of this review was to provide a comprehensive understanding of the specific action mechanism of AC, while also exploring potential novel applications of AC derivatives in the biomedical field, drawing upon their structural characteristics. In conclusion, this review has provided a comprehensive analysis of the challenges and prospects associated with AC in the elucidation of structure-bioactivity relationships. Furthermore, the importance of exploring modern biotechnology approaches to enhance the potential biomedical applications of AC has been emphasized.

IntroductionDementia and musculoskeletal disorders (MSDs) are major public health problems. We aimed to investigate the genetic causality of common MSDs and dementia.MethodsTwo-sample Mendelian randomization (MR) was used in this study. MR analysis based on gene-wide association study (GWAS) data on osteoarthritis (OA), dementia with Lewy bodies, and other MSDs and dementia types were obtained from the Genetics of Osteoarthritis consortium, IEU-open GWAS project, GWAS catalog, and FinnGen consortium. Rigorously selected single-nucleotide polymorphisms were regarded as instrumental variables for further MR analysis. Inverse-variance weighted, MR–Egger regression, weight median, simple mode, and weight mode methods were used to obtain the MR estimates. Cochran’s Q test, MR–Egger and MR-Pleiotropy Residual Sum and Outlier analysis, and the leave-one-out test were applied for sensitivity testing.ResultsThe inverse-variance weighted method showed that hip OA was genetically associated with a lower risk of dementia, unspecified dementia, dementia in Alzheimer’s disease, and vascular dementia. Kneehip OA was inversely associated with unspecified dementia and vascular dementia. Rheumatoid arthritis, juvenile idiopathic arthritis and seronegative rheumatoid arthritis were inversely associated with frontotemporal dementia, and rheumatoid arthritis was inversely associated with unspecified dementia. Simultaneously, ankylosing spondylitis was an independent risk factor for dementia, dementia with Lewy bodies, and dementia in Alzheimer’s disease. Sensitivity tests showed that heterogeneity and horizontal pleiotropy did not exist in these associations. The leave-one-out test showed that these associations were stable.ConclusionWe found that some MSDs were associated with the risk of dementia and provide evidence for the early detection of dementia in patients with MSDs and for the impact of inflammation on the central nervous system.

ObjectiveThis article aimed to evaluate the efficiency trends and influencing factors of essential public health services in Hainan Province after the healthcare reform launched in 2009 in China.MethodsThe efficiency of essential public health services (EPHS) at primary health institutions was assessed using data envelopment analysis (DEA), and the efficiency change was analyzed by employing the Malmquist productivity index (MPI). We used Tobit regression to identify the influence of environmental factors on the efficiency of public health services. The bootstrap method was adopted to reduce the impact of random errors on the result.ResultsThe bootstrapping bias-corrected efficiency revealed that the average values of technical efficiency, pure technical efficiency, and scale efficiency were 0.7582, 0.8439, and 0.8997, respectively, which meant that the EPHS in Hainan Province were not at the most effective state. The average bias-corrected MPI was 1.0407 between 2010 and 2011 and 1.7404 between 2011 and 2012. MPIs were less than 1.0000 during other periods investigated, ranging from 0.8948 to 0.9714, indicating that the efficiency of EPHS has been decreasing since 2013. The Tobit regression showed that the regression coefficients of per capita GDP, population density, the proportion of older people aged over 65, and the proportion of ethnic minority population were 0.0286, −0.0003, −0.0316, and − 0.0041 respectively, which were statistically significant (p

The optimal power flow problem in power systems is characterized by a number of complex objectives and constraints, which aim to optimize the total fuel cost, emissions, active power loss, voltage magnitude deviation, and other metrics simultaneously. These conflicting objectives and strict constraints challenge existing optimizers in balancing between active power and reactive power, along with good trade-offs among many metrics. To address these difficulties, this paper develops a co-evolutionary algorithm to solve the constrained many-objective optimization problem of optimal power flow, which evolves three populations with different selection strategies. These populations are evolved towards different parts of the huge objective space divided by large infeasible regions, and the cooperation between them renders assistance to the search for feasible and Pareto-optimal solutions. According to the experimental results on benchmark problems and the IEEE 30-bus, IEEE 57-bus, and IEEE 118-bus systems, the proposed algorithm is superior over peer algorithms in solving constrained many-objective optimization problems, especially the optimal power flow problems.

The increasing number of peri-implant diseases and the unsatisfactory results of conventional treatment are causing great concern to patients and medical staff. The effective removal of plaque which is one of the key causes of peri-implant disease from the surface of implants has become one of the main problems to be solved urgently in the field of peri-implant disease prevention and treatment. In recent years, with the advancement of materials science and pharmacology, a lot of research has been conducted to enhance the implant antimicrobial properties, including the addition of antimicrobial coatings on the implant surface, the adjustment of implant surface topography, and the development of new implant materials, and significant progress has been made in various aspects. Antimicrobial materials have shown promising applications in the prevention of peri-implant diseases, but meanwhile, there are some shortcomings, which leads to the lack of clinical widespread use of antimicrobial materials. This paper summarizes the research on antimicrobial materials applied to implants in recent years and presents an outlook on the future development.

Long non-coding RNAs (LncRNAs) play essential roles in multiple physiological processes including bone formation. Investigators have revealed that LncRNAs regulated bone formation through various signaling pathways and micro RNAs (miRNAs). However, several problems exist in current research studies on osteogenic LncRNAs, including sophisticated techniques, high cost for in vivo experiment, as well as low homology of LncRNAs between animal model and human, which hindered translational medicine research. Moreover, compared with gene editing, LncRNAs would only lead to inhibition of target genes rather than completely knocking them out. As the studies on osteogenic LncRNA gradually proceed, some of these problems have turned osteogenic LncRNA research studies into slump. This review described some new techniques and innovative ideas to address these problems. Although investigations on osteogenic LncRNAs still have obtacles to overcome, LncRNA will work as a promising therapeutic drug for osteoporosis in the near future.

PurposeIschemic stroke (IS), a serious cerebrovascular disease, greatly affects people's health and life. Genetic factors are indispensable for the occurrence of IS. As a biomarker for IS, the MMP-9 gene is widely involved in the pathophysiological process of IS. This study attempts to find out the relationship between MMP-9 polymorphisms and IS susceptibility.MethodsA total of 700 IS patients and 700 healthy controls were recruited. The single nucleotide polymorphism (SNP) markers of the MMP-9 gene were genotyped by the MassARRAY analyzer. Multifactor dimensionality reduction (MDR) was applied to generate SNP–SNP interaction. Furthermore, the relationship between genetic variations (allele and genotype) of the MMP-9 gene and IS susceptibility was analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs).ResultsOur results demonstrated that rs2250889 could significantly increase the susceptibility to IS in the codominant, dominant, overdominant, and log-additive models (p < 0.05). Further stratification analysis showed that compared with the control group, rs2250889 was associated with IS risk in different case groups (age, female, smoking, and non-drinking) (p < 0.05). Based on MDR analysis, rs2250889 was the best model for predicting IS risk (cross-validation consistency: 10/10, OR = 1.56 (1.26–1.94), p < 0.001).ConclusionOur study preliminarily confirmed that SNP rs2250889 was significantly associated with susceptibility to IS.

IntroductionThe presence of soluble human programmed cell death-ligand 1 (shPD-L1) in the blood of patients with cancer has been reported to be negatively correlated with disease prognosis. However, little information exists about the mechanisms underlying high levels of shPD-L1 for promoting disease progression.MethodsIn this study, we first analyzed the correlations between shPD-L1 and apoptosis of T cells in patients with cancer, then tested the effect of shPD-L1 on T-cell functions and the production of regulatory T cells.ResultsWe found that the apoptosis of human peripheral PD-1+CD4+ T cells was significantly elevated in patients with cancer compared with healthy donors and was positively correlated with circulating PD-L1 levels in patients with cancer. In vitro, monomeric shPD-L1 significantly inhibited the proliferation, cytokine secretion, and cancer cell-killing activity of peripheral blood mononuclear cells (PBMCs) activated by either agonist antibodies or HATac (high-affinity T cell activation core)-NYE (NY-ESO-1 antigen). It also promoted CD4+ T cells to express forkhead family transcription factor 3 (FoxP3) for the conversion of induced T regulatory cells, which was more significant than that mediated by soluble human PD-L1 fusion protein (shPD-L1-Fc).DiscussionThese results confirm that soluble PD-L1 could be a candidate for inhibiting the functions of activated T cells, promoting peripheral tolerance to tumor cells, and implicating in system tumor immune escape in addition to the tumor microenvironment. This is an important mechanism explaining the negative correlation between peripheral blood PD-L1 levels and cancer prognosis. Therefore, understanding the roles of hPD-L1 in peripheral blood will be helpful for the development of precision immunotherapy programs in treating various tumors.

Taxifolin is a flavonoid compound, originally isolated from the bark of Douglas fir trees, which is often found in foods such as onions and olive oil, and is also used in commercial preparations, and has attracted the interest of nutritionists and medicinal chemists due to its broad range of health-promoting effects. It is a powerful antioxidant with excellent antioxidant, anti-inflammatory, anti-microbial and other pharmacological activities. This review focuses on the breakthroughs in taxifolin for the treatment of diseases from 2019 to 2022 according to various systems of the human body, such as the nervous system, immune system, and digestive system, and on the basis of this review, we summarize the problems of current research and try to suggest solutions and future research directions.

Trees can invest up to one-third of the carbon (C) fixed by photosynthesis into belowground allocation, including fine root exudation into the rhizosphere. It is still unclear how climate and soil warming affect tree root C exudation, in particular quantifying longer-term warming effects remains a challenge. In this study, using a C-free cuvette incubation method, in situ C exudation rates from tree fine roots of a mature spruce dominated temperate forest were measured in regular intervals during the 14th and 15th year of experimental soil warming (+ 4°C). In addition, a short-term temperature sensitivity experiment (up to + 10°C warming within 4 days) was conducted to determine the inherent temperature sensitivity of root exudation. Root exudation rates in the long-term warmed soil (17.9 μg C g–1 root biomass h–1) did not differ from those in untreated soil (16.2 μg C g–1 root biomass h–1). However, a clear increase (Q10 ∼5.0) during the short-term temperature sensitivity experiment suggested that fine root exudation can be affected by short-term changes in soil temperature. The absence of response in long-term warmed soils suggests a downregulation of C exudation from the individual fine roots in the warmed soils. The lack of any relationship between exudation rates and the seasonal temperature course, further suggests that plant phenology and plant C allocation dynamics have more influence on seasonal changes in fine root C exudation. Although exudation rates per g dry mass of fine roots were only marginally higher in the warmed soil, total fine root C exudation per m2 soil surface area increased by ∼30% from 0.33 to 0.43 Mg C ha–1 yr–1 because long-term soil warming has led to an increase in total fine root biomass. Mineralization of additional fine root exudates could have added to the sustained increase in soil CO2 efflux from the warmed forest soil at the experimental site.

Barnacle exhibits high adhesion strength underwater for its glue with coupled adhesion mechanisms, including hydrogen bonding, electrostatic force, and hydrophobic interaction. Inspired by such adhesion mechanism, we designed and constructed a hydrophobic phase separation hydrogel induced by the electrostatic and hydrogen bond interaction assembly of PEI and PMAA. By coupling the effect of hydrogen bond, electrostatic force and hydrophobic interaction, our gel materials show an ultrahigh mechanical strength, which is up to 2.66 ± 0.18 MPa. Also, benefit from the coupled adhesion forces, as well as the ability to destroy the interface water layer, the adhesion strength on the polar materials can be up to 1.99 ± 0.11 MPa underwater, while that of the adhesion strength is about 2.70 ± 0.21 MPa under silicon oil. This work provides a deeper understanding of the underwater adhesion principle of barnacle glue. Furthermore, our bioinspired strategy would provide an inspiration for the fabrication of high mechanical gel materials, and the rapid strong adhesive used in both water and organic solvents.

PurposeDyslipidemia is a feature of polycystic ovary syndrome (PCOS) that may augment metabolic disturbances. Serum fatty acids are important biomedical indicators of dyslipidemia. The aim of this study was to determine the distinct serum fatty acids in various PCOS subtypes and their association with metabolic risk in women with PCOS.MethodsFatty acids in the serum of 202 women with PCOS were measured using gas chromatography-mass spectrometry. Fatty acids were compared between PCOS subtypes and correlated with glycemic parameters, adipokines, homocysteine, sex hormones, and sex hormone-binding globulin (SHBG).ResultsThe levels of total monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) in the reproductive subtype of PCOS were lower than those in the metabolic subtype. Docosahexaenoic acid, a PUFA, was associated with higher SHBG after correction for multiple comparisons. Eighteen species of fatty acids emerged as potential biomarkers associated with the metabolic risk factors measured, independent of body mass index (BMI). Among them, myristic acid (C14:0), palmitoleic acid (C16:1), oleic acid (C18:1n-9C), cis-vaccenic acid (C18:1n-7), and homo-gamma-linolenic acid (C20:3n-6) were the strongest lipid species that were consistently associated with metabolic risk factors, particularly insulin-related parameters in women with PCOS. As for adipokines, 16 fatty acids were positively associated with serum leptin. Among them, C16:1 and C20:3n-6were significantly associated with leptin levels.ConclusionOur data demonstrated that a distinct fatty acid profile comprising high C14:0, C16:1, C18:1n-9C, C18:1n-7, and C20:3n-6levels is associated with metabolic risk in women with PCOS, independent of BMI.

IntroductionThe lateral habenula (LHb) is a promising deep brain stimulation (DBS) target for treatment-resistant depression (TRD). However, the optimal surgical trajectory and its safety of LHb DBS are lacking.MethodsWe reported surgical trajectories for the LHb in six TRD patients treated with DBS at the General Hospital of the Chinese People's Liberation Army between April 2021 and May 2022. Pre-operative fusions of magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to design the implantation trajectory of DBS electrodes. Fusions of MRI and CT were conducted to assess the safety or precision of LHb DBS surgery or implantable electrodes locations.ResultsResults showed that the optimal entry point was the posterior middle frontal gyrus. The target coordinates (electrode tips) were 3.25 ± 0.82 mm and 3.25 ± 0.82 mm laterally, 12.75 ± 0.42 mm and 13.00 ± 0.71 mm posterior to the midpoint of the anterior commissure–posterior commissure (AC-PC) line, and 1.83 ± 0.68 mm and 1.17 ± 0.75 mm inferior to the AC-PC line in the left and right LHb, respectively. The “Ring” angles (relative to the AC-PC level on the sagittal section plane) of the trajectories to the left and right LHb were 51.87° ± 6.67° and 52.00° ± 7.18°, respectively. The “Arc” angles (relative to the midline of the sagittal plane) were 33.82° ± 3.39° and 33.55° ± 3.72°, respectively. Moreover, there was small deviation of actual from planned target coordinates. No patient had surgery-, disease- or device-related adverse events during the perioperative period.ConclusionOur results suggested that LHb-DBS surgery via frontal trajectory is safe, accurate, and feasible. This is an applicable work to report in detail the target coordinates and surgical path of human LHb-DBS. It has of great clinical reference value to treat more cases of LHb-DBS for TRD.

Rabbit Viral Hemorrhagic Disease (RHD) is a highly contagious and fatal infection, resulting in considerable economic losses to the rabbit industry. Consequently, it is essential to develop a fast and accurate diagnostic method for RHDV GI.1. In this study, a rapid simple reverse transcriptase recombinase polymerase amplification (RTRPA) for RHDV GI.1 was successfully developed using specific primers to RHDV GI.1 VP60 gene. Results indicated that the entire amplification process could be achieved in an isothermal condition at 40°C for 30 minutes, with good specificity and no reaction to other common rabbit disease pathogens, and a high sensitivity of upto 0.1LD50 of RHDV GI.1. Then, RT-RPA method was used to detect 1144 clinical samples, and the positive rates were 0.95%, 1.29% and 2.50% in Zaozhuang, Linyi, and Liaocheng in Shandong Province, respectively (the Fisher's exact test, P = 0.413), suggesting that there is no significant difference in RHDV GI.1 infection among the different regions. In conclusion, this study established a RT-RPA assay which is suitable for quick detection and monitoring of RHDV GI.1, thus making it a viable option for epidemiological surveillance.

Mulberry (Morus alba L.) has a special significance in the history of agriculture and economic plant cultivation. Mulberry has strong environmental adaptability, a wide planting range, and abundant output. It is not only an important resource for silkworm breeding but also a raw ingredient for various foods and has great potential for the development of biological resources. The bioactivities of mulberry in different planting areas are not the same, which is an obstacle to the development of mulberry. This study collected information on the planting conditions of mulberry branches in 12 planting areas, such as altitude, temperature difference, and precipitation. A comparison of the levels of 12 constituents of mulberry branches from mulberry grown in different planting areas was then made. An in vitro model was used to study the bioactivities of mulberry branches in the 12 planting areas, and mathematical analysis was used to explain the possible reasons for the differences in the composition and bioactivities of mulberry branches in different planting areas. After studying mulberry samples from 12 planting areas in China, it was found that a small temperature difference could affect the antiapoptotic effect of mulberry branch on microvascular endothelial cells by changing the levels and proportions of rutin, hyperoside, and morusin. Adequate irrigation can promote the antioxidation of the mulberry branch on microvascular endothelial cells by changing the levels and proportions of scopoletin and quercitrin. The results of the analysis of planting conditions and the levels of active constituents and their correlation with bioactivities support the improvement of mulberry planting conditions and have great significance in the rational development of mulberry resources. This is the first time that a mathematical analysis method was used to analyze the effects of planting conditions on mulberry biological activity.

IntroductionAutophagy can be triggered by oxidative stress and is a double-edged sword involved in the progression of multiple malignancies. However, the precise roles of autophagy on immune response in gastric cancer (GC) remain clarified.MethodsWe endeavor to explore the novel autophagy-related clusters and develop a multi-gene signature for predicting the prognosis and the response to immunotherapy in GC. A total of 1505 patients from eight GC cohorts were categorized into two subtypes using consensus clustering. We compare the differences between clusters by the multi-omics approach. Cox and LASSO regression models were used to construct the prognostic signature.ResultsTwo distinct clusters were identified. Compared with cluster 2, the patients in cluster 1 have favorable survival outcomes and lower scores for epithelial-mesenchymal transition (EMT). The two subtypes are further characterized by high heterogeneity concerning immune cell infiltration, somatic mutation pattern, and pathway activity by gene set enrichment analysis (GSEA). We obtained 21 autophagy-related differential expression genes (DEGs), in which PTK6 amplification and BCL2/CDKN2A deletion were highly prevalent. The four-gene (PEA15, HSPB8, BNIP3, and GABARAPL1) risk signature was further constructed with good predictive performance and validated in 3 independent datasets including our local Tianjin cohort. The risk score was proved to be independent prognostic factor. A prognostic nomogram showed robust validity of GC survival. The risk score was significantly associated with immune cell infiltration status, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint molecules. Furthermore, the model was efficient for predicting the response to tumor-targeted agent and immunotherapy and verified by the IMvigor210 cohort. This model is also capable of discriminating between low and high-risk patients receiving chemotherapy.ConclusionAltogether, our exploratory research on the landscape of autophagy-related patterns may shed light on individualized therapies and prognosis in GC.

ObjectivesOlfactory disorder is one of the sensory features that reflects a decline in cognitive function. However, olfactory changes and the discernibility of smell testing in the aging population have yet to be fully elucidated. Therefore, this study aimed to examine the effectiveness of the Chinese Smell Identification Test (CSIT) in distinguishing individuals with cognitive decline from those with normal aging and to determine whether the patients with MCI and AD show changes in their olfactory identification abilities.MethodsThis cross-sectional study included eligible participants aged over 50 years between October 2019 and December 2021. The participants were divided into three groups: individuals with mild cognitive impairment (MCI), individuals with Alzheimer's disease (AD), and cognitively normal controls (NCs). All participants were assessed using neuropsychiatric scales, the Activity of Daily Living scale, and the 16-odor cognitive state test (CSIT) test. The test scores and the severity of olfactory impairment were also recorded for each participant.ResultsIn total, 366 eligible participants were recruited, including 188 participants with MCI, 42 patients with AD, and 136 NCs. Patients with MCI achieved a mean CSIT score of 13.06 ± 2.05, while patients with AD achieved a mean score of 11.38 ± 3.25. These scores were significantly lower than those of the NC group (14.6 ± 1.57; P < 0.001). An analysis showed that 19.9% of NCs exhibited mild olfactory impairment, while 52.7% of patients with MCI and 69% of patients with AD exhibited mild to severe olfactory impairment. The CSIT score was positively correlated with the MoCA and MMSE scores. The CIST score and the severity of olfactory impairment were identified as robust indicators for MCI and AD, even after adjusting for age, gender, and level of education. Age and educational level were identified as two important confounding factors that influence cognitive function. However, no significant interactive effects were observed between these confounders and CIST scores in determining the risk of MCI. The area under the ROC curve (AUC) generated from the ROC analysis was 0.738 and 0.813 in distinguishing patients with MCI and patients with AD from NCs based on the CIST scores, respectively. The optimal cutoff for distinguishing MCI from NCs was 13, and for distinguishing AD from NCs was 11. The AUC for distinguishing AD from MCI was 0.62.ConclusionsThe olfactory identification function is frequently affected in patients with MCI and patients with AD. CSIT is a beneficial tool for the early screening of cognitive impairment among elderly patients with cognitive or memory issues.

In recent years, organic fluorescent probes with tumor microenvironment (TME)-responsive fluorescence turn-on properties have been increasingly used in imaging-guided tumor resection due to their higher signal-to-noise ratio for tumor imaging compared to non-responsive fluorescent probes. However, although researchers have developed many organic fluorescent nanoprobes responsive to pH, GSH, and other TME, few probes that respond to high levels of reactive oxygen species (ROS) in the TME have been reported in imaging-guided surgery applications. In this work, we prepared Amplex® Red (ADHP) with excellent ROS response performance as an ROS-responsive nanoprobe and studied its application in image-guided tumor resection for the first time. To confirm whether the nanoprobe can be used as an effective biological indicator to distinguish tumor sites, we first detected 4T1 cells with the ADHP nanoprobe, demonstrating that the probe can utilize ROS in tumor cells for responsive real-time imaging. Furthermore, we conducted fluorescence imaging in vivo in 4T1 tumor-bearing mice, and the ADHP probe can rapidly oxidize to form resorufin in response to ROS, which can effectively reduce the background fluorescence signal compared with the single resorufin probe. Finally, we successfully carried out image-guided surgery of 4T1 abdominal tumors under the guidance of fluorescence signals. This work provides a new idea for developing more TME-responsive fluorescent probes and exploring their application in image-guided surgery.

Redox imbalance can trigger cell dysfunction and damage and plays a vital role in the origin and progression of many diseases. Maintaining the balance between oxidants and antioxidants in vivo is a complicated and arduous task, leading to ongoing research into the construction of redox nanomaterials. Nanodrug platforms with redox characteristics can not only reduce the adverse effects of oxidative stress on tissues by removing excess oxidants from the body but also have multienzyme-like activity, which can play a cytotoxic role in tumor tissues through the catalytic oxidation of their substrates to produce harmful reactive oxygen species such as hydroxyl radicals. In this review, various redox nanomaterials currently used in disease therapy are discussed, emphasizing the treatment methods and their applications in tumors and other human tissues. Finally, the limitations of the current clinical application of redox nanomaterials are considered.

Sustainable business model innovation (SBMI) and green technology innovation (GTI) are keys to creating shared social and business value, and both are essential elements of responsible innovation. However, SBMI or GTI is unable to develop a sustainable business. The main purpose of this study is to analyze sustainable dual innovation as a conceptual framework based on the panel data of 1468 Chinese manufacturing A-share listed companies from 2010 to 2020, and it has obtained three essential findings. First, there is a significant matching effect between SBMI and GTI on sustainable corporate performance (SCP). Companies report higher levels of SCP when there is a higher congruence in SBMI with GTI. Secondly, organizations with high SBMI-low GTI realize superior SCP compared to organizations with low SBMI-high GTI. The high SBMI-low GTI becomes an ideal choice for most companies and avoids the “destructive factors” brought by low SBMI-high GTI. Finally, a highly aggressive corporate strategy has a “magnifying effect” on the impact of the combination of SBMI and GTI on SCP. The research provides a comprehensive understanding and collective impact of SBMI and GTI on SCP. Overall, findings provide a theoretical basis for enterprises to decide on the consistency/inconsistency trade-off between SBMI and GTI. Moreover, it encourages to enterprises must develop an aggressive strategy to balance.

Immuno-checkpoint inhibitors (ICIs) bring a promising prospect for patients with cancers, which restrains the growth of tumor cells by enhancing anti-tumor activity. Nevertheless, not all patients benefit from the administration of ICIs monotherapy. The partial response or resistance to ICIs is mainly due to the complex and heterogenous tumor microenvironment (TME). The combined therapy is necessary for improving the efficacy of tumor treatment. Chemotherapy is reported not only to kill tumor cells directly, but also to stimulate effective anti-tumor immune responses. Several combined therapies of ICIs and chemotherapeutic agents have been approved for the first-line treatment of cancers, including PD-1/PD-L1 inhibitors. This review summarizes the potential mechanisms of the combined therapy of ICIs and chemotherapeutic agents in inducing immunogenic cell death (ICD) and reprogramming TME, and elucidates the possible anti-tumor effects of combined therapy from the perspective of metabolic reprogramming and microbiome reprogramming.

Nitrous oxide (N2O) emissions are highly variable due to the complex interaction of climatic and ecological factors. Here, we obtained in-situ annual N2O emission flux data from almost 180 peer-papers to evaluate the dominant drivers of N2O emissions from forests and unfertilized grasslands at a global scale. The average value of N2O emission fluxes from forest (1.389 kg Nha-1yr-1) is almost twice as large as that from grassland (0.675 kg Nha-1yr-1). Soil texture and climate are the primary drivers of global forest and grassland annual N2O emissions. However, the best predictors varied according to land use and region. Soil clay content was the best predictor for N2O emissions from forest soils, especially in moist or wet regions, while soil sand content predicted N2O emissions from dry or moist grasslands in temperate and tropical regions best. Air temperature was important for N2O emission from forest, while precipitation was more efficient in grassland. This study provides an overall understanding of the relationship between natural N2O emissions and climatic and environmental variables. Moreover, the identification of principle factors for different regions will reduce the uncertainty range of N2O flux estimates, and help to identify region specific climate change mitigation and adaptation strategies.

BackgroundGrowing evidence suggests that tumor metastasis necessitates multi-step microenvironmental regulation. Lymph node metastasis (LNM) influences both pre- and post-operative bladder cancer (BLCA) treatment strategies. Given that current LNM diagnosis methods are still insufficient, we intend to investigate the microenvironmental changes in BLCA with and without LNM and develop a prediction model to confirm LNM status.Method"Estimation of Stromal and Immune cells in Malignant Tumors using Expression data" (ESTIMATE) algorithm was used to characterize the tumor microenvironment pattern of TCGA-BLCA cohort, and dimension reduction, feature selection, and StrLNM signature construction were accomplished using least absolute shrinkage and selection operator (LASSO) regression. StrLNM signature was combined with the genomic mutation to establish an LNM nomogram by using multivariable logistic regression. The performance of the nomogram was evaluated in terms of calibration, discrimination, and clinical utility. The testing set from the TCGA-BLCA cohort was used for internal validation. Moreover, three independent cohorts were used for external validation, and BLCA patients from our cohort were also used for further validation.ResultsThe StrLNM signature, consisting of 22 selected features, could accurately predict LNM status in the TCGA-BLCA cohort and several independent cohorts. The nomogram performed well in discriminating LNM status, with the area under curve (AUC) of 75.1% and 65.4% in training and testing datasets from the TCGA-BLCA cohort. Furthermore, the StrLNM nomogram demonstrated good calibration with p >0.05 in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis (DCA) revealed that the StrLNM nomogram had a high potential for clinical utility. Additionally, 14 of 22 stably expressed genes were identified by survival analysis and confirmed by qPCR in BLCA patient samples in our cohort.ConclusionIn summary, we developed a nomogram that included an StrLNM signature and facilitated the preoperative prediction of LNM status in BLCA patients.

IntroductionAnimal intestines are extremely rich in microbial ecosystems. Numerous studies in different fields, such as epidemiology and histology, have revealed that gut microorganisms considerably mediate the survival and reproduction of animals. However, gut microbiology studies of homogeneously distributed wild cranes are still rare. This study aimed to understand the structural composition of the gut microbial community of wild cranes and elucidate the potential roles of the microorganisms.MethodsWe used high-throughput sequencing to analyze the gut microbial community structure of wild cranes in the Zhalong Nature Reserve.ResultsA total of 1,965,683 valid tags and 5248 OTUs were obtained from 32 fecal samples. Twenty-six bacteria phyla and 523 genera were annotated from the intestinal tract of the red-crowned crane. Twenty-five bacteria phyla and 625 genera were annotated from the intestine of the white-naped crane. Firmicutes, Proteobacteria, and Bacteroidetes are the dominant bacterial phyla in the intestinal tract of red-crowned cranes, while Catellicoccus, Lactobacillus, Neisseria, and Streptococcus were the dominant genera. The dominant bacterial phyla in the intestinal tract of white-naped cranes were Firmicutes, Proteobacteria, Bacteroidetes, Epsilonbacteraeota, Actinobacteria, and Fusobacteria. However, the dominant genera were Catellicoccus, Lactobacillus, Neisseria, Campylobacter, Streptococcus, Anaerobiospirillum, Romboutsia, Turicibacter, Haemophilus, and Lautropia. Firmicutes had significantly higher relative abundance in the intestine of the red-crowned than white-naped cranes (P < 0.05). However, the relative abundance of Actinobacteria and Bacteroidetes was significantly higher (P < 0.05) in the intestines of white-naped than red-crowned cranes. The diversity of the intestinal flora between the two crane species was significantly different (P < 0.05). Besides, the alpha diversity of the intestinal flora was higher for white-naped than red-crowned cranes. Eight of the 41 functional pathways differed in the gut of both crane species (P < 0.05).DiscussionBoth species live in the same area and have similar feeding and behavioral characteristics. Therefore, host differences are possibly the main factors influencing the structural and functional differences in the composition of the gut microbial community. This study provides important reference data for constructing a crane gut microbial assessment system. The findings have implications for studying deeper relationships between crane gut microbes and genetics, nutrition, immunity, and disease.

IntroductionAn emerging public health issue is brought on by the worldwide increase of thyroid nodules (TNs). The goal of the current study is to determine the global prevalence of TNs among the general population.MethodsWe screened articles published from January 2000 to May 2022. TN prevalence was calculated with the DerSimonian–Laird random effects model with arcsine transformation.ResultsA total of 20,358 entries were found in our research, and 102 of them met our inclusion criteria. A total of 9,276,178 individuals have been diagnosed as TNs; the overall prevalence was 24.83% (95% CI 21.44–28.55), regardless of the diagnostic techniques. TNs have become more prevalent during 2012–2022 (29.29%) compared with 2000–2011 (21.53%, p = 0.02). In addition, we discovered that women (36.51%) were more likely to have TNs than men (23.47%, p < 0.01). Interestingly, we found that obesity was correlated with the prevalence of TNs. Additionally, age-specific-stratified TN prevalence was found in our results.DiscussionThis meta-analysis shows that, regardless of country development and economic status, TNs are spreading more widely over the world. Our findings showed a strong correlation between rising TN prevalence and older age, female sex, and elevated weight. To stop the TN epidemic from spreading over the world, increased awareness, the understanding of the disease, and quick action are required.

In this work, TiO2 was selected as an additive to the Sm0.2Ce0.8O2-δ (SDC) electrolyte and its influence on the electrolyte properties were investigated. The tetrabutyl titanate hydrolysis product was introduced into the SDC samples as a source of TiO2. The lattice contraction of SDC was observed by XRD when the smaller ionic radius Ti4+ (0.605Å) were substituted for Ce4+ (0.97 Å). XRD analysis shows that the doping content of the TiO2 in SDC should be limited to 1 wt% to maintain the single-phase cubic fluorite structure of the SDC and avoid impurity phases. SEM characterizations suggest that the addition of TiO2 significantly promoted the grain growth and the sintering activity, especially when doping with 0.5 wt% of TiO2. The electrochemical measurements reveal that the addition of TiO2 had little effect on the conductivity of SDC samples, which was 0.0306 S cm−1 at 700°C. This study shows that 0.5 wt% TiO2 doping can effectively improve the sintering activity without reducing the SDC performance.

High-quality sustainable development is the common goal pursued by all countries in the world. China’s high-quality development (HQD) includes five concepts of “innovation, coordination, green, opening-up, and sharing”. In this context, we established an evaluation system that included these five fundamental characteristics, used the comprehensive entropy method and BP neural network to evaluate and predict the high-quality development of Hubei Province in China, and conducted a spatiotemporal deductive analysis. The study found that: 1) Economic growth still has an important impact on HQD, for all the five main indicators, “opening-up” and “innovation” have the highest impact weights, which are 0.379 and 0.278, respectively, while the proportions of coordination and sharing are both less than 0.1. 2) There are huge differences in the level of high-quality development between regions in Hubei Province. From 2010 to 2020, the average comprehensive index of Wuhan City was greater than 0.5, which is 7 times that of the second Xiangyang City, and 46 times that of the last Shennongjia district. 3) In the past few years, the overall high-quality development of Hubei Province has shown a fluctuating upward trend. However, due to the impact of COVID-19, during the following years, its comprehensive development index will decline by an average of 5% annually, but starting from 2022, it will gradually increase. As a result, tailored and coordinated sustainable environmental policies of integrating institutional and open-market measures should be provided.

Background and purposeDistinguishing between intracranial atherosclerosis-related occlusion (ICAS-O) and non-ICAS-O can benefit strategies of identifying the need for surgical plans prior to thrombectomy. We investigated the association between vertebrobasilar artery calcification (VBAC) and ICAS-O in acute ischemic stroke patients undergoing thrombectomy.MethodsPatients were recruited from a prospective single-center registration study who had undergone thrombectomy between October 2017 and October 2021. The enrolled patients were divided into ICAS-O and non-ICAS-O, as determined by the intraarterial therapy process. The occurrences of VBAC were recorded on intracranial non-contrast computed tomography (NCCT) scans before thrombectomy. The association between VBAC and ICAS-O was assessed using binary logistic regression.ResultsA total of 2732 patients who had undergone digital subtraction angiography were reviewed, and 314 thrombectomy patients (mean age: 65.4 years, 36.6% female) with NCCT were enrolled in this study. VBAC was detected before thrombectomy in 113 (36%) out of 314 patients. Age, hypertension, and diabetes were associated with VBAC, and a higher frequency of VBAC was identified in patients presenting posterior circulation. ICAS-O accounts for 43% (135/314) in eligible patients. From multivariable analyses, VBAC was identified as an independent predictor of ICAS-O (adjusted odds ratio, 6.16 [95% CI, 2.673–14.217], P < 0.001). Meanwhile, the (VBAC[+] atrial fibrillation[-]) group displayed higher rates of ICAS-O than the (VBAC[-] atrial fibrillation [-]) group (P < 0.001).ConclusionsWe demonstrated that VBAC is an independent risk factor for ICAS-O in patients who underwent thrombectomy. Patients free of atrial fibrillation with VBAC have more trend to be ICAS-O.

A circadian rhythm is an internalized timing system that synchronizes the cellular, behavioral, and physiological processes of organisms to the Earth’s rotation. Because all physiological activities occur at a specific time, circadian rhythm disturbances can lead to various pathological disorders and diseases. Growing evidence has shown that the circadian clock is tightly connected to male fertility, and circadian perturbations contribute to infertility. The night shiftwork, insufficient sleep, and poor sleep quality are common causes of circadian disturbances, and many studies have reported that they impair sperm quality and increase the risk of male infertility. However, research on the impacts of light, body temperature, and circadian/circannual rhythms is relatively lacking, although some correlations have been demonstrated. Moreover, as the index of sperm quality was diverse and study designs were non-uniform, the conclusions were temporarily inconsistent and underlying mechanisms remain unclear. A better understanding of whether and how circadian disturbances regulate male fertility will be meaningful, as more scientific work schedules and rational lifestyles might help improve infertility.

BackgroundWe assessed the incidence and clinical characteristics of acute kidney injury (AKI) in acute respiratory distress syndrome (ARDS) patients and its effect on clinical outcomes.MethodsWe conducted a single-center prospective longitudinal study. Patients who met the Berlin definition of ARDS in the medical ICU in China-Japan Friendship Hospital from March 1, 2016, to September 30, 2020, were included. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 48 h after ARDS was diagnosed or after 48 h, respectively.ResultsOf the 311 ARDS patients, 161 (51.8%) developed AKI after ICU admission. Independent risk factors for AKI in ARDS patients were age (OR 1.027, 95% CI 1.009–1.045), a history of diabetes mellitus (OR 2.110, 95%CI 1.100–4.046) and chronic kidney disease (CKD) (OR 9.328, 95%CI 2.393–36.363), APACHE II score (OR 1.049, 95%CI 1.008–1.092), average lactate level in the first 3 days (OR 1.965, 95%CI 1.287–3.020) and using ECMO support (OR 2.359, 95%CI 1.154–4.824). Early AKI was found in 91 (56.5%) patients and late AKI was found in 70 (43.5%). Early AKI was related to the patient’s underlying disease and the severity of hospital admission, while late AKI was related to the application of nephrotoxic drugs. The mortality rate of ARDS combined with AKI was 57.1%, which was independently associated with shock (OR 54.943, 95%CI 9.751–309.573).ConclusionA significant number of patients with ARDS developed AKI, and the mortality rate for ARDS patients was significantly higher when combined with AKI. Therapeutic drug monitoring should be routinely used to avoid drug toxicity during treatment.

The observations of transient luminous events from space-borne platform extend our exploration on the mysteries of sprite phenomenology from continental thunderstorms to oceanic thunderstorms. By combining with ground-based measurements of causative strokes for hundreds of red sprites observed by the Imager of Sprites and Upper Atmospheric Lightnings (ISUAL) during 2004–2016, there is a consensus that negative cloud-to-ground (CG) strokes spawned by oceanic thunderstorms are more readily to produce sprites. The existing ground-based observations in both Caribbean Sea and near the coast of South China, mainly due to the contributions from numerous amateurs, are generally consistent with the implications of ISUAL observations. However, the physical mechanisms that might cause the enhancement of negative CG strength in the ocean remain not completely understood. There have been analyses on several cases of oceanic thunderstorms abundant in producing negative sprites. It seems that the production of negative sprites heavily depends on the size of parent thunderstorms, and they are often generated by thunderstorm conditions that are also favorable for gigantic jets.

Cancer occurrence and progression may be facilitated by aberrant expression of ATPase H+ transporting accessory protein 1 (ATP6AP1). However, the clinical relevance of ATP6AP1 in breast cancer remains unclear. In this study, we investigated the association between ATP6AP1 and breast cancer. Data collected from patients with breast cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used in this study. To determine the relationship between ATP6AP1 and breast cancer survival rates, Kaplan-Meier analysis was used. To determine the prognostic value of ATP6AP1, a receiver operating characteristic (ROC) curve was constructed. To identify the major pathways involving ATP6AP1, we performed functional enrichment analysis using gene set enrichment analysis (GSEA). We analyzed the association between ATP6AP1 expression and tumor immunity using the ESTIMATE algorithm and single-sample GSEA (ssGSEA). A nomogram based on a Cox regression analysis was constructed to predict the impact of ATP6AP1 on prognosis. ATP6AP1 expression was significantly upregulated in breast cancer tissues. Moreover, patients with elevated ATP6AP1 expression had shorter total survival rates than those with lower expression levels (p = 0.032). The area under the receiver operating characteristic curve for ATP6AP1 was 0.939. Gene set enrichment analysis revealed that reaction iron uptake and transport, proteasome degradation, glutathione metabolism, and pyruvate metabolism were enriched in the ATP6AP1 high expression phenotype. The relationship between immune infiltration cells and ATP6AP1 expression, including macrophages, B cells, dendritic cells, cytotoxic cells, NK cells, and T cells, was found to be negative, suggesting that ATP6AP1 overexpression results in immunosuppression. Based on the Cox regression analyses, the calibration plot of the nomogram demonstrated effective performance in predicting breast cancer patients. ATP6AP1 may facilitate breast cancer progression by inhibiting antitumor immunity and promoting iron metabolism and may be a biomarker for breast cancer prognosis.

BackgroundThe association between reproductive lifespan and risk of hypertension among postmenopausal women is unclear.MethodsA total of 94,141 postmenopausal women with a mean age of 64.8 years from the China Hypertension Survey were enrolled at baseline from 2012 to 2015. A standardized questionnaire was used to collect relevant information by well-trained interviewers. Blood pressure and physical examination of the participants were performed by trained medical staff. Logistic regression was used to estimate the odds ratios for hypertension by years of reproductive lifespan.ResultsThe average years of reproductive lifespan in Chinese women was 34.0 years. Women who were longer in reproductive lifespan were more likely to have older age at recruitment, higher body mass index, larger waist circumference, lower mean systolic blood pressure, and higher mean diastolic blood pressure (p < 0.05). After adjustments, odds ratios (95% confidence interval) for hypertension were 1.035 (0.988–1.085), 1.007 (0.966–1.048), 1.000 (reference), 0.932 (0.899–0.967), and 0.953 (0.909–0.997) for those with reproductive lifespan at ≤ 28, 29–31, 32–34 (reference), 35–37, and ≥ 38 years, respectively, with a significantly inverse association was seen in those with reproductive lifespan at 35–37 and ≥ 38 years. The overall risk of hypertension declined with the increase in reproductive lifespan, and the risk of hypertension was reduced by 1.1% for every 1-year increase in the reproductive lifespan (odds ratio, 0.989; 95% confidence interval, 0985–0.994) per year. The negative association between reproductive lifespan and hypertension was evident among age at recruitment groups, body mass index categories, and education levels, with the strongest association among women aged ≥ 70 years. Positive associations between reproductive lifespan and risk of hypertension were evident among women aged < 60 years, and this association was stronger among current alcohol drinkers.ConclusionBased on the large nationally representative sample, Chinese postmenopausal women with a shorter reproductive lifespan have a higher risk of hypertension.

The role of tRNAs is best known as adapter components of translational machinery. According to the central dogma of molecular biology, DNA is transcribed to RNA and in turn is translated into proteins, in which tRNA outstands by its role of the cellular courier. Recent studies have led to the revision of the canonical function of transfer RNAs (tRNAs), which indicates that tRNAs also serve as a source for short non-coding RNAs called tRNA-derived small RNAs (tsRNAs). tsRNAs play key roles in cellular processes by modulating complicated regulatory networks beyond translation and are widely involved in multiple diseases. Herein, the biogenesis and classification of tsRNAs were firstly clarified. tsRNAs are generated from pre-tRNAs or mature tRNAs and are classified into tRNA-derived fragments (tRFs) and tRNA halves (tiRNA). The tRFs include five types according to the incision loci: tRF-1, tRF-2, tRF-3, tRF-5 and i-tRF which contain 3′ tiRNA and 5′ tiRNA. The functions of tsRNAs and their regulation mechanisms involved in disease processes are systematically summarized as well. The mechanisms can elaborate on the specific regulation of tsRNAs. In conclusion, the current research suggests that tsRNAs are promising targets for modulating pathological processes, such as breast cancer, ischemic stroke, respiratory syncytial virus, osteoporosis and so on, and maintain vital clinical implications in diagnosis and therapeutics of various diseases.

The spatial distribution pattern of the economic development among counties is an important external representation of a balanced and sustainable regional development in China. With the rapid development of globalization and localization, spatial pattern of economic growth is increasingly obvious. The mechanisms of regional economic growth in China are also gradually gaining attention. However, there is still a lack of research at the province and county levels. As a result, based on the per capita GDP of each county in Hubei province from 2005 to 2020 as the research index, the spatial autocorrelation and the spatial variation function are used to analyze the spatial pattern evolution and the county economy mechanism in Hubei province. The results show that 1) there is a remarkable phenomenon of county-level economic spatial agglomeration in Hubei province. The urban area of Wuhan and its surrounding counties are high–high (HH-type) county agglomeration areas. The low–low (LL-type) counties are mainly distributed in the western parts of Hubei province and scattered in the northeastern and southern parts of Hubei province; 2) the county economy of Hubei province presents a spatial distribution pattern of “high in the east and low in the west.” The hot areas of the county economy are primarily located in the urban area of Wuhan and its surrounding areas. In the process of development, the hot spot areas tend to shift to Yichang, Jingmen, and Xiangyang. The cold spot areas are located on the edges of the western, northeastern, and southeastern areas of Hubei province; 3) the spatial continuity and self-organization of the county economic development are strengthened. The structural differentiation trend caused by spatial autocorrelation is also strengthened. The county economy is relatively balanced from the southeast to the northwest, and the spatial difference in economic development in other directions is increasing; and 4) the spatial evolution of county economic development in Hubei province is the result of the comprehensive effects of historical and cultural background, economic development, traffic location, and policy system, and the A-shaped point-axis structure is a reliable spatial structure for regional development in Hubei province.

PurposeHirayama disease (HD) has been largely believed to affect only distal muscles. However, the proximal upper extremities have been affected in some cases, which can be confused with motor neuron diseases.MethodsBaseline data, deep tendon reflex, Hoffmann sign, cervical curvature, sagittal Cobb angle, atrophied spinal cord, high signal intensity, loss of attachment, and affected muscles and segments on electromyography (EMG) were retrospectively obtained and compared between patients with HD with proximal involvement and patients with simple distal HD in one center from September 2007 to April 2022.ResultsIn this study, fifteen patients with proximal HD and 30 patients with simple distal HD were included. The proximal group had a larger proportion of patients with decreased biceps reflex, decreased triceps reflex, brisk or hyperactive knee reflex, positive Hoffmann sign, and cervical kyphosis. The curvatures of the upper part of the cervical spine (C2-4) were lost to a greater degree in the proximal group. More affected segments were observed on magnetic resonance imaging (MRI) and electromyography in the proximal group.ConclusionThe injured segments were longer and the upper curvature of the cervical spine was poorer in patients with HD with proximal involvement. These findings indicated that proximal involvement may indicate more serious HD.

The larval stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. The tumor-like growth and development of the metacestode larvae within host organs are driven by a population of somatic stem cells, the germinative cells, which represent the only proliferative cells in the parasite. Host-derived factors have been shown to promote germinative cell proliferation. Since cells sense the external signal mainly in G1 phase of the cell cycle, host factors are expected to exert impacts on the machinery regulating G1/S phase of the germinative cells, which still remains largely unknown in E. multilocularis. In this study, we described the characterization of two key members of the G1/S phase cell-cycle regulation, EmCyclinD and EmCDK4/6. Our data show that EmCyclinD and EmCDK4/6 display significant sequence similarity to their respective mammalian homologs, and that EmCyclinD interacts with EmCDK4/6, forming a kinase-active complex to activate its substrate Rb1. EmCyclinD was actively expressed in the germinative cells. Addition of human EGF caused an elevated expression of EmCyclinD while inhibition of the EGFR-ERK signaling pathway in the parasite reduced the expression of EmCyclinD and downstream transcriptional factors. Treatment with Palbociclib, a specific CDK4/6 inhibitor, downregulated the expression of cell cycle-related factors and impeded germinative cell proliferation and vesicle formation from protoscoleces. Our data demonstrated that the EmCyclinD-EmCDK4/6 complex participates in the cell cycle regulation of germinative cells which is mediated by host EGF via the EGFR-ERK-EmCyclinD pathway in E. multilocularis.

BackgroundIschemic stroke (IS) is a complex neurological disease affected by genetics and environment. Matrix metalloproteinase-2 (MMP2) is involved in extracellular matrix (ECM) degradation, inflammation and angiogenesis to regulate the development and recovery of IS.PurposesThe aim of this study was to explore the association of rs1053605, rs243849 and rs14070 in MMP2 with the risk of IS in Chinese Shaanxi population.MethodsIn this study, 677 IS patients and 681 normal controls were recruited. Rs1053605, rs243849 and rs14070 in MMP2 were genotyped. Logistic regression analysis was applied to evaluate the association of rs1053605, rs243849 and rs14070 in MMP2 with IS susceptibility and the association of environmental factors with MMP2 genetic susceptibility to IS.ResultsThe results of the overall analysis demonstrated that rs14070 in MMP2 significantly reduced the risk of IS in Chinese Shaanxi population (OR = 0.767, 95% CI = 0.619–0.952, P = 0.016). Subgroup analysis illustrated that rs243849 in MMP2 evidently increased the risk of IS among drinkers, while rs14070 in MMP2 apparently reduced IS susceptibility among females, participants with aged >55, smokers and drinkers.ConclusionsCollectively, rs243849 and rs14070 in MMP2 were significantly associated with the risk of IS in Chinese Shaanxi population, and the effect of MMP2 to IS may be associated with its genetic susceptibility.

BackgroundChronic subdural hematoma (CSDH) is common in elderly people with a clear or occult traumatic brain injury history. Surgery is a traditional method to remove the hematomas, but it carries a significant risk of recurrence and poor outcomes. Non-surgical treatment has been recently considered effective and safe for some patients with CSDH. However, it is a challenge to speculate which part of patients could obtain benefits from non-surgical treatment.ObjectiveTo establish and validate a new prediction model of self-absorption probability with chronic subdural hematoma.MethodThe prediction model was established based on the data from a randomized clinical trial, which enrolled 196 patients with CSDH from February 2014 to November 2015. The following subjects were extracted: demographic characteristics, medical history, hematoma characters in imaging at admission, and clinical assessments. The outcome was self-absorption at the 8th week after admission. A least absolute shrinkage and selection operator (LASSO) regression model was implemented for data dimensionality reduction and feature selection. Multivariable logistic regression was adopted to establish the model, while the experimental results were presented by nomogram. Discrimination, calibration, and clinical usefulness were used to evaluate the performance of the nomogram. A total of 60 consecutive patients were involved in the external validation, which enrolled in a proof-of-concept clinical trial from July 2014 to December 2018.ResultsDiabetes mellitus history, hematoma volume at admission, presence of basal ganglia suppression, presence of septate hematoma, and usage of atorvastatin were the strongest predictors of self-absorption. The model had good discrimination [area under the curve (AUC), 0.713 (95% CI, 0.637–0.788)] and good calibration (p = 0.986). The nomogram in the validation cohort still had good discrimination [AUC, 0.709 (95% CI, 0.574–0.844)] and good calibration (p = 0.441). A decision curve analysis proved that the nomogram was clinically effective.ConclusionsThis prediction model can be used to obtain self-absorption probability in patients with CSDH, assisting in guiding the choice of therapy, whether they undergo non-surgical treatment or surgery.

Small, totally endophytic renal masses present a technical challenge for surgical extirpation due to poor identifiability during surgery. The method for the precise localization of totally endophytic tumours before nephron-sparing surgery could be optimized. An asymptomatic 70-year-old male presented with a right-sided, 16-mm, totally endophytic renal mass on computed tomography (CT). CT-guided percutaneous microcoil localization was carried out prior to laparoscopy to provide a direction for partial nephrectomy. During the 25 minutes of the localization procedure, the patient underwent five local CT scans, and his cumulative effective radiation dosage was 5.1 mSv. The span between localization and the start of the operation was 15 hours. The laparoscopic operation time was 105 minutes, and the ischaemia time was 25 minutes. The postoperative recovery was smooth, and no perioperative complications occurred. Pathology showed the mass to be renal clear cell carcinoma, WHO/ISUP grade 2, with a 2-mm, clear surgical margin. The patient remained free of recurrence on follow-up for eleven months. To our knowledge, this application of microcoil implantation prior to laparoscopic partial nephrectomy towards an intrarenal mass could be an early reported attempt for the localized method applied in renal surgery. The percutaneous microcoil localization of endophytic renal tumours is potentially safe and effective prior to laparoscopic partial nephrectomy.