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Abstract Background Edaravone has been widely used in amyotrophic lateral sclerosis (ALS) treatment, and a sublingual (SL) tablet has been developed to offer a more convenient alternative for injection. We present a cost-utility analysis to comprehensively evaluate the costs and health outcomes of oral and intravenous edaravone for the treatment of ALS in Chinese medical context. Methods Cost-utility analysis of SL tablets of edaravone versus intravenous edaravone at home was performed by constructing a 20-year Markov model of ALS stage 1–4 and death. The data were extracted from the literature with model assumptions. Typical sensitivity analysis and scenario analysis for administering SL tablets at home versus intravenous tablets at the hospital were performed. Results In the base case analysis, with SL tablets and intravenous injections both at home, the model estimated an additional cost of ¥12,670.04 and an additional 0.034 QALYs over 20 years (life time) of modeling analysis, and the ICER was ¥372,648.24 per QALY. However, in the scenario of intravenous administration at the hospital, SL tablet was demonstrated dominance to intravenous injection. Conclusions Using 3 times the GDP per capita of China in 2023 as the threshold, the SL tablet edaravone was not cost-effective in the context of home treatment for both formulationst, but was dominance to intravenous injection in hospital treatment. The results highlighted the importance of treatment context for health economic analysis.

Abstract Signaling systems of microorganisms are responsible for regulating the physiological and metabolic processes and also play vital roles in the communications of cells. Identifying signaling molecules mediating the cross-talks is challenging yet highly desirable for comprehending the microbial interactions. Here, we demonstrate that a pathogenic Gram-negative Chromobacterium violaceum exerts significant influence on the morphological differentiation and secondary metabolism of Gram-positive Streptomyces. The physiological metabolisms are directly modulated by three novel cinnamoyl lipids (CVCL1, 2, and 3) from C. violaceum CV12472, whose biosynthesis is under the control of N-acylhomoserine lactone signaling system. Furthermore, a receptor of CVCLs in Streptomyces ansochromogenes 7100 is determined to be SabR1, the cognate receptor of γ-butenolide signaling molecules. This study reveals an unprecedented mode of microbial interactions, and the quorum sensing signaling systems in these two groups of bacteria can be bridged via CVCLs, suggesting that CVCLs can modulate the physiological metabolism of cross-phylum microorganisms.

Abstract Background Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.

Abstract Cobalt phthalocyanine immobilized on carbon nanotube has demonstrated appreciable selectivity and activity for methanol synthesis in electrocatalytic CO2/CO reduction. However, discrepancies in methanol production selectivity and activity between CO2 and CO reduction have been observed, leading to inconclusive mechanisms for methanol production in this system. Here, we discover that the interaction between cobalt phthalocyanine molecules and defects on carbon nanotube substrate plays a key role in methanol production during CO2/CO electroreduction. Through detailed operando X-ray absorption and infrared spectroscopies, we find that upon application of cathodic potential, this interaction induces the transformation of the planar CoN4 center in cobalt phthalocyanine to an out-of-plane distorted configuration. Consequently, this potential induced structural change promotes the transformation of linearly bonded *CO at the CoN4 center to bridge *CO, thereby facilitating methanol production. Overall, these comprehensive mechanistic investigations and the outstanding performance (methanol partial current density over 150 mA cm−2) provide valuable insights in guiding the activity and selectivity of immobilized cobalt phthalocyanine for methanol production in CO2/CO reduction.

Abstract Acellular dermal matrix (ADM) is one of the most promising scaffold materials due to its ability to retain natural extracellular matrix structure. Micronized acellular dermal matrix (mADM) was prepared with no intact cell nuclei and preserved growth factors by High Hydrostatic Pressure (HHP) approach. And mADM-collagen wound dressings were developed with different proportion of type I collagen and recombinant humanized type III collagen. The porous structure of the mADM-collagen wound dressings made them a good candidate for preventing excessive fluid accumulation, while the collagens with gel-like texture combined with mADM powder to form pasty texture wound dressing, which preserving the moisture at the wound site. Moreover, the paste texture of the mADM-collagen wound dressing was easy to reshape to conform any wound shapes and body contours. Furthermore, the resulted mADM-collagen wound dressings showed good biocompatibility by supporting fibroblasts adhesion and proliferation in vitro. Subsequently, a murine model of full-thickness skin wounds was employed to assess its effects on wound healing. Notably, mADM-75% Col-I exhibited superior effects throughout the wound healing process, specifically it promoted neovascularization, skin appendage growth and new skin regeneration. This formulation closely mimicked the collagen ratio found in healthy skin, facilitating the favorable wound repair. These results indicated the superior performance of this mADM-collagen wound dressing providing an optimal environment for wound healing. Graphical Abstract

Abstract Nasopharyngeal carcinoma (NPC), primarily found in the southern region of China, is a malignant tumor known for its highly metastatic characteristics. The high mortality rates caused by the distant metastasis and disease recurrence remain unsolved clinical problems. In clinic, the berberine (BBR) compound has widely been in NPC therapy to decrease metastasis and disease recurrence, and BBR was documented as a main component with multiple anti-NPC effects. However, the mechanism by which BBR inhibits the growth and metastasis of nasopharyngeal carcinoma remains elusive. Herein, we show that BBR effectively inhibits the growth, metastasis, and invasion of NPC via inducing a specific super enhancer (SE). From a mechanistic perspective, the RNA sequencing (RNA-seq) results suggest that the RAS–RAF1–MEK1/2–ERK1/2 signaling pathway, activated by the epidermal growth factor receptor (EGFR), plays a significant role in BBR-induced autophagy in NPC. Blockading of autophagy markedly attenuated the effect of BBR-mediated NPC cell growth and metastasis inhibition. Notably, BBR increased the expression of EGFR by transcription, and knockout of EGFR significantly inhibited BBR-induced microtubule associated protein 1 light chain 3 (LC3)-II increase and p62 inhibition, proposing that EGFR plays a pivotal role in BBR-induced autophagy in NPC. Chromatin immunoprecipitation sequencing (ChIP-seq) results found that a specific SE existed only in NPC cells treated with BBR. This SE knockdown markedly repressed the expression of EGFR and phosphorylated EGFR (EGFR-p) and reversed the inhibition of BBR on NPC proliferation, metastasis, and invasion. Furthermore, BBR-specific SE may trigger autophagy by enhancing EGFR gene transcription, thereby upregulating the RAS–RAF1–MEK1/2–ERK1/2 signaling pathway. In addition, in vivo BBR effectively inhibited NPC cells growth and metastasis, following an increase LC3 and EGFR and a decrease p62. Collectively, this study identifies a novel BBR-special SE and established a new epigenetic paradigm, by which BBR regulates autophagy, inhibits proliferation, metastasis, and invasion. It provides a rationale for BBR application as the treatment regime in NPC therapy in future.

Background: Non-optimum temperatures are associated with a considerable mortality burden. However, there is a lack of evaluation of labour productivity losses related to premature deaths due to non-optimum temperatures. This study aimed to quantify the labour productivity burden associated with premature deaths related to non-optimum temperatures and explore the potential socio-economic vulnerabilities. Methods: Daily all-cause mortality data were collected from 1,066 locations in 7 countries (Australia, Brazil, Canada, Chile, New Zealand, South Korea, and Thailand). Productivity-Adjusted Life-Year (PALY) loss due to each premature death was calculated to measure the labour productivity loss, by multiplying the years of working life lost by the proportion of the equivalent full-time (EFT) workers. A two-stage times series design and the generalized linear regression model with a quasi-Poisson family were applied to assess the association between non-optimum temperatures and the PALY loss due to premature deaths. Results: We observed a U-shaped relationship between temperature and PALY lost due to premature mortality. We estimated that 2.51% (95% eCI: 2.05%, 2.92%) of PALY losses could be attributed to non-optimal temperatures, with cold-related deaths contributing 1.26% (95% eCI: 0.94%, 1.54%) and heat-related deaths contributing 1.25% (95% eCI: 0.96%, 1.51%). Cold temperature contributed to the most PALYs lost in those aged 45–54 and 55–64, while heat-related losses predominated among the 15–44 age group. We also observed that the fractions of PALY lost attributed to extreme heat were positively associated with the relative deprivation index, while negatively associated with GDP per capita. Conclusion: This multi-country study highlights that non-optimum temperatures led to a considerable labour productivity loss and socioeconomically disadvantaged communities experience greater losses.

BackgroundBeta-2 microglobulin (β2M) is acknowledged as a prognostic biomarker for B-cell malignancies. However, insights into the impact of β2M on B-cell malignancy risk, and vice versa, are limited.MethodsWe conducted a genome-wide meta-analysis (GWMA), bidirectional two-sample Mendelian randomization (TSMR) analysis, and pathway enrichment analysis to explore the causal relationship between β2M and B-cell malignancies and the underlying biological processes.ResultsThe GWMA identified 55 lead SNPs across five genomic regions (three novel: WDR72, UMOD, and NLRC5) associated with β2M. In the UKB, genetically predicted β2M showed a positive association with diffuse large B-cell lymphoma (DLBCL; odds ratio [OR]: 1.742 per standard deviation increase in β2M; 95% confidence interval [CI]: 1.215–2.498; P = 3.00 × 10−3; FDR = 7.50× 10−3) and Hodgkin lymphoma (HL; OR: 2.270; 95% CI: 1.525–3.380; P = 5.15 × 10−5; FDR =2.58 × 10−4). However, no associations were found with follicular lymphoma (FL), chronic lymphoid leukemia (CLL), or multiple myeloma (MM). Reverse TSMR analysis revealed no association between genetically predicted B-cell malignancies and β2M. In FinnGen, β2M was found to be associated with an increased risk of DLBCL (OR: 2.098; 95% CI: 1.358-3.242; P = 8.28 × 10−4; FDR = 4.14 × 10−3), HL (OR: 1.581; 95% CI: 1.167-2.142; P = 3.13 × 10−3; FDR = 5.22 × 10−3), and FL (OR: 2.113; 95% CI: 1.292-3.455; P = 2.90 × 10−3; FDR = 5.22 × 10−3). However, no association was found with CLL or MM. Reverse TSMR analysis indicated that genetically predicted DLBCL, FL, and MM may perturb β2M levels. Pathway enrichment analysis suggested that the innate immune system represents a convergent biological process underlying β2M, DLBCL, and HL.ConclusionsOur findings suggested that elevated levels of β2M were associated with an increased risk of DLBCL and HL, which is potentially linked to dysfunction of the innate immune system.

IntroductionIn riverine ecosystems, dynamic interplay between hydrological conditions, such as flow rate, water level, and rainfall, significantly shape the structure and function of bacterial and microeukaryotic communities, with consequences for biogeochemical cycles and ecological stability. Lake Taihu, one of China’s largest freshwater lakes, frequently experiences cyanobacterial blooms primarily driven by nutrient over-enrichment and hydrological changes, posing severe threats to water quality, aquatic life, and surrounding human populations. This study explored how varying water flow disturbances influence microbial diversity and community assembly within the interconnected river–lake systems of the East and South of Lake Taihu (ET&ST). The Taipu River in the ET region accounts for nearly one-third of Lake Taihu’s outflow, while the ST region includes the Changdougang and Xiaomeigang rivers, which act as inflow rivers. These two rivers not only channel water into Lake Taihu but can also cause the backflow of lake water into the rivers, creating distinct river–lake systems subjected to different intensities of water flow disturbances.MethodsUtilizing high-throughput sequencing, we selected 22 sampling sites in the ET and ST interconnected river-lake systems and conducted seasonally assessments of bacterial and microeukaryotic community dynamics. We then compared differences in microbial diversity, community assembly, and co-occurrence networks between the two regions under varying hydrological regimes.Results and discussionThis study demonstrated that water flow intensity and temperature disturbances significantly influenced diversity, community structure, community assembly, ecological niches, and coexistence networks of bacterial and eukaryotic microbes. In the ET region, where water flow disturbances were stronger, microbial richness significantly increased, and phylogenetic relationships were closer, yet variations in community structure were greater than in the ST region, which experienced milder water flow disturbances. Additionally, migration and dispersal rates of microbes in the ET region, along with the impact of dispersal limitations, were significantly higher than in the ST region. High flow disturbances notably reduced microbial niche width and overlap, decreasing the complexity and stability of microbial coexistence networks. Moreover, path analysis indicated that microeukaryotic communities exhibited a stronger response to water flow disturbances than bacterial communities. Our findings underscore the critical need to consider the effects of hydrological disturbance on microbial diversity, community assembly, and coexistence networks when developing strategies to manage and protect river–lake ecosystems, particularly in efforts to control cyanobacterial blooms in Lake Taihu.

Abstract Introduction This study aimed to explore influencing factors and clinical significance of ultra-long-term microischemia following intracranial aneurysm (IA) embolization and establish a theoretical foundation for reducing both the incidence of ultra-long-term microischemia and cognitive dysfunction in patients post embolization. Methods A retrospective analysis was conducted on data from 147 patients who received endovascular treatment for IAs. Patients were categorized into microischemic and control (non-microischemic) groups on the based on the findings of high-resolution magnetic resonance vessel wall imaging (HR-VWI) examinations performed 3 days postoperatively and 6 months postoperatively. Risk factors for the occurrence of ultra-long-term microischemia were determined by univariate analysis and multivariate logistic regression analysis. Results Out of 147 patients included in the study, 51 (34.69%) developed microischemia while the remaining 96 (65.31%) did not experience this condition. Analysis revealed that factors such as sex, age, history of underlying diseases (hypertension, diabetes mellitus), aneurysmal site characteristics, the presence or absence of stenosis in the aneurysm-bearing artery, modified Fisher score at admission, Barthel’s index at discharge, immunoinflammatory index at 3 days postoperatively and at the 6-month follow-up, the presence or absence of aneurysmal wall enhancement, and the presence or absence of aneurysmal lumen showed no statistically significant differences between the two groups (all P > 0.05). By contrast, variables like in operative time, rupture status of the aneurysm before surgery according to World Federation of Neurologic Surgeons (WFNS) grade, aneurysm size, number of stents used, number of guidewires and catheters used, and Evans index between the two groups were found to have statistically significant disparities between those who developed microischemia and those who did not (P 0.3, and the quantity of stents were independent risk factors for the occurrence of ultra-long-term microischemia after aneurysm embolization and provided good predictive performance. Cognitive dysfunction was closely associated with microischemia, with its severity increasing with an increase in the number of ischemic foci.

Abstract Nonlinear optical activities, especially second harmonic generation (SHG), are key phenomena in inversion-symmetry-broken two-dimensional (2D) transition metal dichalcogenides (TMDCs). On the other hand, anisotropic nonlinear optical processes are important for unique applications in nano-nonlinear photonic devices with polarization functions, having become one of focused research topics in the field of nonlinear photonics. However, the strong nonlinearity and strong optical anisotropy do not exist simultaneously in common 2D materials. Here, we demonstrate strong second-order and third-order susceptibilities of 64 pm/V and 6.2×10−19 m2/V2, respectively, in the even-layer PdPSe, which has not been discovered in other common TMDCs (e.g., MoS2). Strikingly, it also simultaneously exhibited strong SHG anisotropy with an anisotropic ratio of ~45, which is the largest reported among all 2D materials to date, to the best of our knowledge. In addition, the SHG anisotropy ratio can be harnessed from 0.12 to 45 (375 times) by varying the excitation wavelength due to the dispersion of $${\chi }^{(2)}$$ χ ( 2 ) values. As an illustrative example, we further demonstrate polarized SHG imaging for potential applications in crystal orientation identification and polarization-dependent spatial encoding. These findings in 2D PdPSe are promising for nonlinear nanophotonic and optoelectronic applications.

Abstract Background Floods are the most frequent weather-related disaster, causing significant health impacts worldwide. Limited studies have examined the long-term consequences of flooding exposure. Methods Flood data were retrieved from the Dartmouth Flood Observatory and linked with health data from 499,487 UK Biobank participants. To calculate the annual cumulative flooding exposure, we multiplied the duration and severity of each flood event and then summed these values for each year. We conducted a nested case-control analysis to evaluate the long-term effect of flooding exposure on all-cause and cause-specific mortality. Each case was matched with eight controls. Flooding exposure was modelled using a distributed lag non-linear model to capture its nonlinear and lagged effects. Results The risk of all-cause mortality increased by 6.7% (odds ratio (OR): 1.067, 95% confidence interval (CI): 1.063–1.071) for every unit increase in flood index after confounders had been controlled for. The mortality risk from neurological and mental diseases was negligible in the current year, but strongest in the lag years 3 and 4. By contrast, the risk of mortality from suicide was the strongest in the current year (OR: 1.018, 95% CI: 1.008–1.028), and attenuated to lag year 5. Participants with higher levels of education and household income had a higher estimated risk of death from most causes whereas the risk of suicide-related mortality was higher among participants who were obese, had lower household income, engaged in less physical activity, were non-moderate alcohol consumers, and those living in more deprived areas. Conclusions Long-term exposure to floods is associated with an increased risk of mortality. The health consequences of flooding exposure would vary across different periods after the event, with different profiles of vulnerable populations identified for different causes of death. These findings contribute to a better understanding of the long-term impacts of flooding exposure.

Abstract Background Laser-assisted hatching (LAH) stands as the predominant technique for removing the zona pellucida (ZP) in embryos, primarily consisting of two methods: drilling laser-assisted hatching (D-LAH) and thinning laser-assisted hatching (T-LAH). Presently, both methods have limitations, and their comparative efficacy for embryo implantation and clinical pregnancy remains uncertain. Aim Evaluate the impact of D-LAH and T-LAH on clinical pregnancy rates within assisted reproductive technology (ART). Methods We systematically searched electronic databases including PubMed, Web of Science, and Cochrane Library until July 20, 2022. This study encompassed observational studies and randomized controlled trials (RCTs). A 95% confidence interval (CI) was utilized for assessing the risk ratio (RR) of pregnancy outcomes. The level of heterogeneity was measured using I2 statistics, considering a value exceeding 50% as indicative of substantial heterogeneity. Results The meta-analysis scrutinized 9 studies involving 2405 clinical pregnancies from D-LAH and 2239 from T-LAH. Findings suggested no considerable variation in the clinical pregnancy rates between the two techniques (RR = 0.93, 95% CI: 0.79–1.10, I2 = 71%, P = 0.41). Subgroup analyses also revealed no substantial differences. However, D-LAH exhibited a notably higher occurrence of singleton pregnancies compared to T-LAH (RR = 2.28, 95% CI: 1.08–4.82, I2 = 89%, P = 0.03). There were no noteworthy distinctions observed in other secondary outcomes encompassing implantation rate, multiple pregnancies, ongoing pregnancy, miscarriage, premature birth, and live birth. Conclusion Both the primary findings and subgroup analyses showed no marked variance in clinical pregnancy rates between D-LAH and T-LAH. Therefore, patients with varying conditions should select their preferred LAH technique after assessing their individual situation. However, due to the restricted number of studies involved, accurately gauging the influence of these laser techniques on clinical outcomes is challenging, necessitating further RCTs and high-quality studies to enhance the success rate of ART. Trial registration PROSPERO: CRD42022347066.

Abstract Purpose Previous studies suggest an association between chronic kidney disease (CKD) and cognitive impairment. The purpose of this study was to explore the association between the diverse stages of CKD and the cognitive performance of elderly American adults. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were used. Multivariate adjusted logistic regression, subgroup analysis, and the restricted cubic spline model were used to assess the associations of CKD stage and estimated glomerular filtration rate (eGFR) with cognitive performance. The measures used to evaluate cognitive function included the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, the Animal Fluency test, and the Digit Symbol Substitution test (DSST). Results This study included 2234 participants aged ≥ 60 years. According to the fully adjusted model, stages 3–5 CKD were significantly associated with the CERAD test score (OR = 0.70, 95% CI [0.51, 0.97], p = 0.033), the Animal Fluency test score (OR = 0.64, 95% CI [0.48, 0.85], p = 0.005), and the DSST score (OR = 0.60, 95% CI [0.41, 0.88], p = 0.013). In addition, the incidence of poor cognitive function increased with decreasing eGFR, especially for individuals with low and moderate eGFRs. Both the DSST score (p nonlinearity

This paper introduces the flexible control and trajectory planning medical two-arm surgical robots, and employs effective collision detection methods to ensure the safety and precision during tasks. Firstly, the DH method is employed to establish relative rotation matrices between coordinate systems, determining the relative relationships of each joint link. A neural network based on a multilayer perceptron is proposed to solve FKP problem in real time. Secondly, a universal interpolator based on Non-Uniform Rational B-Splines (NURBS) is developed, capable of handling any geometric shape to ensure smooth and flexible motion trajectories. Finally, we developed a generalized momentum observer to detect external collisions, eliminating the need for external sensors and thereby reducing mechanical complexity and cost. The experiments verify the effectiveness of the kinematics solution and trajectory planning, demonstrating that the improved momentum torque observer can significantly reduce system overshoot, enabling the two-arm surgical robot to perform precise and safe surgical tasks under algorithmic guidance.

Brucella BP26 proves to be a highly immunogenic antigen with excellent specificity in brucellosis detection. In China, the authorized use of the Bp26-deleted vaccine M5ΔBP26 for preventing small ruminant brucellosis highlights the importance of developing accurate detection methods targeting BP26, particularly for the diagnosis of differentiation between infected and vaccinated animals (DIVA). Using the traditional mouse hybridoma technique, we successfully obtained 12 monoclonal antibodies (mAbs) targeting BP26. The efficacy of these mAbs in detecting various animal brucellosis cases using the competitive ELISA method was evaluated. Among them, only the E10 mAb exhibited significant efficiency, being inhibited by 100, 97.62, and 100% of brucellosis-positive sera from cattle, small ruminants, and canines, respectively. The E10-based competitive enzyme-linked immunosorbent assay (cELISA) outperformed the BP26-based indirect enzyme-linked immunosorbent assay (iELISA) in accuracy, particularly for cattle and small ruminant brucellosis, with cELISA sensitivity reaching 97.62% compared to 64.29% for iELISA for small ruminants. Although cELISA showed slightly lower specificity than iELISA, it still maintained high accuracy in canine brucellosis detection. The epitope of mAb E10 was identified in the amino acid sequence QPIYVYPDDKNNLKEPTITGY, suggesting its potential as a diagnostic antigen for brucellosis. In conclusion, the E10-based cELISA presents an effective means of detecting animal brucellosis, particularly significant for DIVA diagnosis in China, where the BP26-mutant vaccine is widely used.

Primary cilia, serving as the central hub for cellular signal transduction, possess the remarkable ability to translate diverse extracellular signals, both chemical and mechanical, into intracellular responses. Their ubiquitous presence in the reproductive system underscores their pivotal roles in various cellular processes including development, differentiation, and migration. Emerging evidence suggests primary cilia as key players in reproductive physiology and associated pathologies. Notably, primary cilia have been identified in granulosa cells within mouse ovaries and uterine stromal cells, and perturbations in their structure and function have been implicated in a spectrum of reproductive dysfunctions and ciliary-related diseases. Furthermore, disruptions in primary cilia-mediated signal transduction pathways under pathological conditions exacerbate the onset and progression of reproductive disorders. This review provides a comprehensive overview of current research progress on primary cilia and their associated signaling pathways in reproductive physiology and diseases, with the aim of furnishing theoretical groundwork for the prevention and management of primary cilia-related structural and functional abnormalities contributing to reproductive system pathologies.

Study region: The study region of this paper is the Wusuli River basin, which is comprised of nine sub-basins. The basin is located on the border between China and Russia. Study focus: We investigated the hydrological connectivity of the Wusuli River basin, an international boundary river that has received little attention. The spatial and temporal evolution of hydrological connectivity over the last 38 years was characterized using a geostatistical connectivity function combined with the remote sensing technique. In particular, some key sub-basins were identified to help strengthen China-Russian cooperation on ecological protection of the basin. New hydrological insights for the region: The results show that the hydrological connectivity in the northwestern region of the Wusuli River basin was unstable with several surges from 1984 to 2021. Analyzed from a temporal perspective, the effective range of hydrological connectivity is expanding and connectivity is showing an overall upward trend due to increased fluctuations in rainfall. Analyzed from a spatial perspective, the connectivity of the right bank of the Wusuli River is better than that of the left bank due to the influence of topography. Stable connectivity pathways are a must for efficient hydrological connectivity within a watershed. Another finding is that the capacity of the Wusuli River basin to resist extreme rainfall is weakening.

The precipitation reaches its maximum and is most concentrated during the period of the first flood season in South China around the Dragon Boat Festival every year, which is usually referred to as"Dragon-boat Precipitation". The Dragon-boat Precipitation causes serious floods and exerts a serious impact on the production of early rice. It is urgent to study the frequency and intensity of rainstorms during the Dragon-boat Precipitation in South China for disaster prevention and reduction. Using daily precipitation data from 192 national meteorological observation stations in South China from 1961 to 2022, the spatiotemporal characteristics and variation of precipitation during the Dragon-boat Precipitation period in South China were analyzed with different methods, such as EOF analysis, linear trend analysis, and M-K mutation analysis. A comprehensive index representing the intensity of the Dragon-boat Precipitation rainstorm events in South China is constructed. Then, it is used to analyze the characteristics and variations of the number and intensity of the rainstorm events during the Dragon-boat Precipitation period in South China in the recent 62 years, as well as the annual index of the Dragon-boat Precipitation intensity. The results indicate that the consistent increase of the annual intensity index is the main characteristic of the Dragon-boat Precipitation in South China. During the Dragon-boat Precipitation period in the recent 62 years, there were 229 rainstorm events in South China, with an average of 3.7 times per year. In South China, the average precipitation and the number of rainstorm events did not change significantly, but the annual intensity index of Dragon-boat precipitation increased significantly at a rate of 1.2·(10 a)-1. The assessment showed that the strongest Dragon-boat precipitation rainstorm event in South China in the past 62 years would occur during June 4-21, 2022. The annual variation shows that there are four peaks of Dragon-boat Precipitation in South China, which occurred in 2022, 2020, 2008, and 2006.

During the summer of 2022, two periods of extreme high temperature events occurred in Chongqing. Using observations from 34 sites in the Chongqing and ERA5 reanalysis data, the main circulation anomalies during this period were analyzed. The results indicate that the strengthening and eastward extension of the South Asian High, along with the abnormal intensification and westward-northward extension of the Western Pacific Subtropical High (hereafter referred to as the Subtropical High), and the occurrence of an anomalously strong blocking high pressure north of the Sea of Japan extending to the Sea of Okhotsk (hereinafter referred to as the Okhotsk Blocking High), resulted in the stagnation of cold air above the 40°—50°N region, rendering it unable to influence the Yangtze River basin, including Chongqing. Chongqing was situated in a region of abnormally intense subsidence and moisture divergence under the western section of the Subtropical High, leading to persistent extreme high temperatures in the area. Analysis of the Subtropical High and South Asian High indices for different levels of regional high-temperature events since 2001 revealed that the Subtropical High extending westward to its most extreme position, while the center of the South Asian High was anomalously eastward in the summer of 2022. These factors directly contributed to Chongqing's extreme high temperatures. Additionally, the summer of 2022 witnessed anomalously warm sea surface temperatures in the western equatorial Pacific, with the average anomaly value in the 130°E—150°W, 30°—60°N region being the highest since 1961 for the same period, which strengthened the Okhotsk Blocking High. Under the influence of the La Niña event, Hadley circulation within the 110°—120°E range featured strong subsidence movements at 20°—30°N. This subsidence, combined with the central subsidence area of the Subtropical High, led to the abnormal intensification and westward extension of the Subtropical High, which in turn triggered the extreme high temperatures in Chongqing.

The optimization design problem of nuclear reactor radiation shield is a typical multi-objective optimization problem with almost 10 sub-objectives and the sub-objectives are always demanded to be under tolerable limits. In this paper, a design method combining multi-objective optimization algorithms with paralleling discrete ordinate transportation code is developed and applied to shield design of the Savannah nuclear reactor. Three approaches are studied for light-weighted and compact design of radiation shield. Comparing with directly optimization with 10 objectives and the single-objective optimization, the approach by setting sub-objectives representing weight and volume as optimization objectives while treating other sub-objectives as constraints has the best performance, which is more suitable to reactor shield design.

In the domain of bionic walking control for biped robots, optimizing the parameters of the central pattern generator (CPG) presents a formidable challenge due to its high-dimensional and nonlinear characteristics. The traditional particle swarm optimization (PSO) algorithm often converges to local optima, particularly when addressing CPG parameter optimization issues. To address these challenges, one improved particle swarm optimization algorithm aimed at enhancing the stability of the walking control of biped robots was proposed in this paper. The improved PSO algorithm incorporates a spiral function to generate better particles, alongside optimized inertia weight factors and learning factors. Evaluation results between the proposed algorithm and comparative PSO algorithms were provided, focusing on fitness, computational dimensions, convergence rates, and other metrics. The biped robot walking validation simulations, based on CPG control, were implemented through the integration of the V-REP (V4.1.0) and MATLAB (R2022b) platforms. Results demonstrate that compared with the traditional PSO algorithm and chaotic PSO algorithms, the performance of the proposed algorithm is improved by about 45% (two-dimensional model) and 54% (four-dimensional model), particularly excelling in high-dimensional computations. The novel algorithm exhibits a reduced complexity and improved optimization efficiency, thereby offering an effective strategy to enhance the walking stability of biped robots.

In order to improve the walking stability of a biped robot in multiple scenarios and reduce the complexity of the Central Pattern Generator (CPG) model, a new CPG walking controller based on multivariate linear mapping was proposed. At first, in order to establish a dynamics model, the lower limb mechanical structure of the biped robot was designed. According to the Lagrange and angular momentum conservation method, the hybrid dynamic model of the biped robot was established. The initial value of the robot’s passive walking was found by means of Poincaré mapping and cell mapping methods. Then, a multivariate linear mapping model was established to form a new lightweight CPG model based on a Hopf oscillator. According to the parameter distribution of the new CPG model, a preliminary parameter-tuning idea was proposed. At last, the joint simulation of MATLAB and V-REP shows that the biped robot based on the new CPG control has a stable periodic gait in flat and uphill scenes. The proposed method could improve the stability and versatility of bipedal walking in various environments and can provide general CPG generation and a tuning method reference for robotics scholars.

BackgroundThe regional disparity of heatwave-related mortality over a long period has not been sufficiently assessed across the globe, impeding the localisation of adaptation planning and risk management towards climate change. We quantified the global mortality burden associated with heatwaves at a spatial resolution of 0.5°×0.5° and the temporal change from 1990 to 2019.Methods and findingsWe collected data on daily deaths and temperature from 750 locations of 43 countries or regions, and 5 meta-predictors in 0.5°×0.5° resolution across the world. Heatwaves were defined as location-specific daily mean temperature ≥95th percentiles of year-round temperature range with duration ≥2 days. We first estimated the location-specific heatwave-mortality association. Secondly, a multivariate meta-regression was fitted between location-specific associations and 5 meta-predictors, which was in the third stage used with grid cell-specific meta-predictors to predict grid cell-specific association. Heatwave-related excess deaths were calculated for each grid and aggregated. During 1990 to 2019, 0.94% (95% CI: 0.68-1.19) of deaths [i.e., 153,078 cases (95% eCI: 109,950-194,227)] per warm season were estimated to be from heatwaves, accounting for 236 (95% eCI: 170-300) deaths per 10 million residents. The ratio between heatwave-related excess deaths and all premature deaths per warm season remained relatively unchanged over the 30 years, while the number of heatwave-related excess deaths per 10 million residents per warm season declined by 7.2% per decade in comparison to the 30-year average. Locations with the highest heatwave-related death ratio and rate were in Southern and Eastern Europe or areas had polar and alpine climates, and/or their residents had high incomes. The temporal change of heatwave-related mortality burden showed geographic disparities, such that locations with tropical climate or low incomes were observed with the greatest decline. The main limitation of this study was the lack of data from certain regions, e.g., Arabian Peninsula and South Asia.ConclusionsHeatwaves were associated with substantial mortality burden that varied spatiotemporally over the globe in the past 30 years. The findings indicate the potential benefit of governmental actions to enhance health sector adaptation and resilience, accounting for inequalities across communities.

Background: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. Objectives: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. Methods: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. Results: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0–7 (0.9 °C). An IQR increase in inter-day TV0–7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0–7 and inter-day TV0–7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. Conclusions: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Assessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979–2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17–13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56–14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27–15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics.

Abstract The effects of calcium phosphate (CaP) materials on macrophage polarization state vary with their physicochemical properties. The study aims to elucidate the impact of phosphate ion‐mediated energy metabolism on M2 macrophage polarization and the corresponding regulatory mechanism. The phosphate ions released from CaP ceramic as bioenergetic factor is identified; its concentration is closely associated with the polarized state. After being taken up by the sodium‐dependent phosphate transporter 1, extracellular phosphate ions produce energy via oxidative phosphorylation by facilitating tricarboxylic acid flux, thereby contributing to M2 macrophage polarization. Further mechanistic analysis reveals that the elevation of the bioenergetic basis can drive macrophage M2 polarization via the AMP‐activated protein kinase‐mammalian target of rapamycin (AMPK‐mTOR) axis. Another regulatory effect is that of the adenosine triphosphate (ATP), a signaling molecule. Intracellular ATP is released into the extracellular space and degraded to adenosine, which serves as a signaling molecule through the A2b adenosine receptor to activate the cyclic adenosine monophosphate (cAMP) pathway, thereby promoting M2 macrophage polarization. Overall, these findings may transform the existing knowledge on cell metabolism and energy homeostasis from bystanders to pivotal factors guiding M2 macrophage polarization and have implications for the future design of biomimetic CaP scaffolds.

High-purity copper is essential for fabricating advanced microelectronic devices, particularly integrated circuit interconnects. As the industry increasingly emphasizes scalable and efficient purification methods, this study investigates the multi-physics interactions during the semi-continuous directional solidification process, utilizing a Cu-1 wt.%Ag model alloy. Coupled simulation calculations examine the spatial distribution patterns of the impurity element silver (Ag) within semi-continuously solidified ingots under varying pulling rates and melt temperatures. The objective is to provide technical insights into the utilization of the semi-continuous directional solidification method for high-purity copper purification. The findings reveal that increasing the pulling rate and melt temperature leads to a downward shift in the solid–liquid interface relative to the mold top during processing. Alongside the primary clockwise vortex flow, a secondary weak vortex emerges near the solid–liquid interface, facilitating the migration of the impurity element Ag toward the central axis and amplifying radial impurity fluctuations. Furthermore, diverse pulling rates and melt temperature conditions unveil a consistent trend along the ingot’s height, which is characterized by an initial increase in average Ag content, followed by stabilization and then a rapid ascent during the late stage of solidification, with higher pulling rates and melt temperatures expediting this rapid ascent. Leveraging these insights, a validation experiment using 4N-grade recycled copper in a small-scale setup demonstrates the effectiveness of the semi-continuous directional solidification process for high-purity copper production, with copper samples extracted at 1/4 and 3/4 ingot heights achieving a 5N purity level of 99.9994 wt.% and 99.9993 wt.%, respectively.

In the design of offshore engineering foundations, a critical consideration involves determining the peak shear strength of marine soft clay sediment. To enhance the accuracy of estimating this value, a database containing 729 direct shear tests on marine soft clay sediment was established. Employing a machine learning approach, the Particle Swarm Optimization algorithm (PSO) was integrated with the Adaptive Boosting Algorithm (ADA) and Back Propagation Artificial Neural Network (BPANN). This novel methodology represents the initial effort to employ such a model for predicting the peak shear strength of the soil. To validate the proposed approach, four conventional machine learning algorithms were also developed as references, including PSO-optimized BPANN, Support Vector Machine (SVM), BPANN, and ADA-BPANN. The study results show that the PSO-BPANN model, which has undergone optimization via Particle Swarm Optimization (PSO), has prediction accuracy and efficiency in determining the peak shear performance of marine soft clay sediments that surpass that offered by traditional machine learning models. Additionally, a sensitivity analysis conducted with this innovative model highlights the notable impact of factors such as normal stress, initial soil density, the number of drying–wetting cycles, and average soil particle size on the peak shear strength of this type of sediment, while the impact of initial soil moisture content and temperature is comparatively minor. Finally, an analytical formula derived from the novel algorithm allows for precise estimation of the peak shear strength of marine soft clay sediment, catering to individuals lacking a background in machine learning.

Abstract Oncogenic super-enhancers (SEs) generate noncoding enhancer/SE RNAs (eRNAs/seRNAs) that exert a critical function in malignancy through powerful regulation of target gene expression. Herein, we show that a JUN-mediated seRNA can form R-loop to regulate target genes to promote metastasis of nasopharyngeal carcinoma (NPC). A combination of global run-on sequencing, chromatin-immunoprecipitation sequencing, and RNA sequencing was used to screen seRNAs. A specific seRNA associated with NPC metastasis (seRNA-NPCM) was identified as a transcriptional regulator for N-myc downstream-regulated gene 1 (NDRG1). JUN was found to regulate seRNA-NPCM through motif binding. seRNA-NPCM was elevated in NPC cancer tissues and highly metastatic cell lines, and promoted the metastasis of NPC cells in vitro and in vivo. Mechanistically, the 3’ end of seRNA-NPCM hybridizes with the SE region to form an R-loop, and the middle segment of seRNA-NPCM binds to heterogeneous nuclear ribonucleoprotein R (hnRNPR) at the promoter of distal gene NDRG1 and neighboring gene tribbles pseudokinase 1 (TRIB1). These structures promote chromatin looping and long-distance chromatin interactions between SEs and promoters, thus facilitating NDRG1 and TRIB1 transcription. Furthermore, the clinical analyses showed that seRNA-NPCM and NDRG1 were independent prognostic factors for NPC patients. seRNA-NPCM plays a critical role in orchestrating target gene transcription to promote NPC metastasis.

Abstract Background Sustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking. Methods We adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9 −/− mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage. Results ScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DR low S100A high monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression. Conclusions This study identifies HLA-DR low S100A high monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.

Abstract Background Ji Chuan Jian (JCJ), a classic Traditional Chinese Medicine (TCM) formula, has been widely applied in treating Parkinson’s disease (PD) in China, However, the interaction of bioactive compounds from JCJ with the targets involved in PD remains elusive. Methods Based on the transcriptome sequencing and network pharmacology approaches, the chemical compounds of JCJ and gene targets for treating PD were identified. Then, the Protein-protein interaction (PPI) and “Compound-Disease-Target” (C-D-T) network were constructed by using of Cytoscape. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to these target proteins. Finally, AutoDock Vina was used for applying molecular docking. Results In the present study, a total number of 2669 differentially expressed genes (DEGs) were identified between PD and healthy controls using whole transcriptome RNA sequencing. Then, 260 targets of 38 bioactive compounds in JCJ were identified. Of these targets, 47 were considered PD-related targets. Based on the PPI degree, the top 10 targets were identified. In C-D-T network analysis, the most important anti-PD bioactive compounds in JCJ were determined. Molecular docking revealed that potential PD-related targets, matrix metalloproteinases-9 (MMP9) were more stably bound with naringenin, quercetin, baicalein, kaempferol and wogonin. Conclusion Our study preliminarily investigated the bioactive compounds, key targets, and potential molecular mechanism of JCJ against PD. It also provided a promising approach for identifying the bioactive compounds in TCM as well as a scientific basis for further elucidating the mechanism of TCM formulae in treating diseases.

Due to the effects of global climate change, the permafrost temperature in the Qinghai-Tibet Plateau (QTP) has rapidly increased over the past decades. The development of thermokarst landforms is one distinctive indicator of permafrost degradation, while the change of the rate of permafrost degradation in recent 10 years has not been systematically investigated in QTP. In this paper, the annual average growth rate (AAGR) of ground deformation, the change of thaw slump areas, and the change of active layer thickness (ALT) of thermokarst landforms are monitored integrating SAR (synthetic aperture radar) and optical images for years 2007 to 2020 in Qilian Mountain, northern QTP. The ground deformation rate and seasonal amplitude were estimated by InSAR method, and the descending and ascending InSAR data are compared the validate the results. Based on the deformation results, AAGR was introduced to evaluate the permafrost degradation degree. Moreover, the ALT were estimated based on the seasonal deformation amplitude and Stefan model. The spatio-temporal characteristics of ground deformation and its relationship with thaw slump and temperature are explored. Experimental results show that the deformation rate increased about 150 % from 2007 to 10 to 2017–20. The maximum AAGR of deformation rate in the study area can reach 20.6 %. The thaw slump area has an obvious trend of expansion from 2009 to 2015, and its distribution agreed well with the deformation map. The ALT results ranged from 0.5 m to 2.8 m, indicating an obvious increase trend from 2007 to 2020. Based on the estimated increased ground deformation, thaw slump area, and ALT, it is inferred that frozen ground was undergoing serious degradation in the last 10 years. This study demonstrates the capability of multi-temporal InSAR in observing the accelerated permafrost thaw-freezing process and monitoring the permafrost parameters.

The optimal allocation of agricultural water and land resources is of great significance in ensuring sustainable food production and economic benefits of farmers. However, agriculture, as an important carbon cycle ecosystem, has paid limited attention to carbon sequestration in the optimal allocation of water and land resources. Therefore, this study developed a new water-carbon-economy coupling model (WCECM) for optimal allocation of agricultural water and land resources. In this model, the minimum water scarcity, maximum carbon sequestration and maximum economic benefits are taken as the optimization objectives. In addition, surface water volume and groundwater volume and planting area etc. were defined as constraints, respectively. Then, the model was solved using the Non-dominated Sorting Genetic Algorithm III (NSGA-III) and the Entropy-weighted-TOPSIS evaluation method. The developed model was demonstrated in the largest Farm, Youyi Farm, which is one of commercial grain production base in China to analyze the optimization of water and land resources from 2010 to 2019. We found that the new WCECM, based on the simulation of a complex coupled water-carbon-economy system, can realize the optimal allocation of agricultural water and land resources to protect regional water resources, increase carbon sequestration and adjust the agricultural planting structure. In detail, through the multi-objective optimization model, the planting structure and the allocation ratio of surface water and groundwater irrigation water consumption are more suitable for this study area. After the optimization, the area planted with Rice was significantly reduced, the area planted with Maize was increased, and the area planted with Soybean did not change significantly compared with the first two crops. The planting structure has changed from focusing on paddy cultivation to dryland cultivation, with the ratio of Rice area, Maize area and Soybean area being 3:6:1. The water consumption is constrained within manageable limits, with an average annual irrigation water consumption of 2.01 × 108 m3. The amount of carbon sequestered has increased significantly, with an average annual increase of 7.8 × 108 kg. Meanwhile, the optimized economic benefits increased slightly, with a value of ¥2.35 billion. In short, optimization of water and land resources is beneficial for improving farmers' incomes, increasing carbon sequestration in agriculture, and conserving water resources.

Land degradation is a major impediment to achieving sustainable development. However, there is currently no harmonized global map of land degradation status and hotspots. This paper aims to obtain the status and hotspots map of global land degradation by multiple methods and indicators to give essential references for land degradation neutrality. The results show that there are significant differences in the distribution and degree of land degradation between the different methods and indicators. Validation through observation points reveals that most of the methods and indicators can reflect land degradation in arid and semi-arid areas, while there are suitable methods or indicators in tropical and high-latitude areas. The degree of degradation has a large difference after overlay analysis, which shows that there are shortcomings of different methods and indicators for monitoring the degree of land degradation. However, the overlay of land degradation extent displays a high consistency, reflecting the current state of global land degradation to a certain extent. These areas with high overlay value can be recognized as hotspots of land degradation. It is also found there are consistent water-energy change characteristics in the hotspot area, such as increased land surface temperature and air temperature and decreased soil moisture and precipitation. These results conclude that studies on the degree of land degradation need to be considered in an integrated manner about the regional background. The combination of multiple methods and indicators is recommended for land degradation extent studies in large areas. Comparison of different methods and indicators is important guidance for global land degradation research. Accelerating ecological monitoring and restoration of land degradation hotspots is the first step towards land degradation neutrality.

The legs of insects play an important role in their daily behaviour, especially reproduction. Entomologists have performed much research on the role of the leg in different behaviours of beetles, an important group in the insect family, but relatively little has been done to study the ultrastructure and transcriptome of their legs. Hence, we systematically studied the ultrastructure and gene expression of the leg of G. cantor, a polygynous beetle, and compared its male and female diversity. In this study, we found the fore-leg, mid-leg and hind-leg of the female were significantly longer than those of the male. From the perspective of intuitive structural differences, we also compared the ultrastructures of the adhesion structure (tarsal) of males and females. The tarsal functional structure of the adult leg mainly includes sensilla and an adhesion structure. The sensilla on the tarsal joint mainly include sensilla chaetica (SCh II, SCh III) and sensilla trichodea (ST II). The adhesion structure includes disc-shaped bristles (di), lanceolate bristles (la), serrated bristles (se), spatula-shaped bristles (spl) and mushroom-shaped bristles (mus). Although there was no significant difference in sensillum distribution or type between males and females, there were significant differences in the distribution and species of adhesion structures between the fore-leg, mid-leg, and hind-leg of the same sex and between males and females. Therefore, different adhesion structures play different roles in various behaviours of beetles. On the other hand, the transcriptome results of male and female legs were screened for a subset of olfaction- and mechanics-related genes. We discovered that the male leg showed upregulation of 1 odorant binding protein (OBP), 2 Olfactory receptors (ORs) and 2 Chemosensory proteins (CSPs). Meanwhile, the female leg showed upregulation of 3 OBPs, 1 OR, 1 Gustatory receptor (GR) and 3 Mechanosensitive proteins (MSPs). An in-depth examination of the ultrastructure and molecular composition of the legs can elucidate its function in the reproductive behavior of G. cantor. Moremore, this investigation will serve as a cornerstone for subsequent research into the underlying behavioral mechanisms.

Abstract The interpretation of stalagmite δ18O in terms of reflecting Asian summer monsoon (ASM) precipitation is still elusive. Here, we present high‐resolution stalagmite trace element ratios (X/Ca, X = Mg, Sr, Ba) records from southwest China covering 116.09 to 4.07 ka BP. δ18O, δ13C, and X/Ca values exhibit clear precessional cycles, with δ18O values reflecting ASM circulation/intensity, while X/Ca ratios capture local precipitation or evapotranspiration variations. Our results show that Northern Hemisphere summer insolation (NHSI) is the main driver of ASM intensity and precipitation phase variation, but global ice volume modulates the response magnitude of summer precipitation to insolation. During the Last Glacial Maximum, high ice volumes caused significant monsoon precipitation to decrease. In contrast to modern observations of the tripolar distribution of precipitation in China, our record is consistent with paleo‐precipitation records in southern and northern China.

Porcine circovirus type 2 (PCV2) is one of the most serious pathogens in pig herds worldwide. The Capsid protein (Cap), a structural protein of PCV2, is involved in the host's immune response; it induces neutralizing-antibody production and has good immunogenicity. The main PCV2 subtype currently prevalent in the Chinese pig herd is PCV2d. In this study, We constructed a recombinant Bacillus subtilis (B. subtilis) capable of secreting Cap protein, named pHT43-Cap/B. subtilis; we concentrated the supernatant of the recombinant bacteria and observed virus-like particles (VLPs) of PCV2d formed by Cap protein under transmission electron microscopy, named PCV2d-VLPs. The immunocompetence of the pHT43-Cap/B. subtilis and PCV2d-VLPs were then assessed by oral administration and by intramuscular injection into mice, respectively. The results showed that the levels of PCV2d-Cap protein-specific IgG in the serum and of PCV2d-Cap protein-specific sIgA in the small intestinal fluid of pHT43-Cap/B. subtilis immunized mice were elevated compared to the control group, both of them highly significant (p

The bamboo structure has received more and more attention as a green, renewable construction with an increasing focus on environmental issues. Cracking at joints or openings and brittle fracture of bamboo are urgent problems in bamboo structures, leading to reduced rigidity, decreased load capacity, and even endangering structural safety. This research aims to explore the mechanism of self-tapping screw reinforcement in improving the brittle fracture characteristic of bamboo laminate. To achieve an optimal effect of reinforcement, fracture tests of bamboo laminated with different numbers of self-tapping screws and screw positions were conducted to study their impact on fracture behaviors. Through the analysis of the ultimate load, the deformation capacity, the initial energy release rate, and the energy release rate caused by the self-tapping screws reinforcement, a model for calculating the energy release rate of bamboo laminate with self-tapping screws is established. Based on the model, the load-bearing capacity of steel-bamboo connections with self-tapping screws can be reasonably estimated.

The inferior short-circuit current density (JSC) of the conjugated block copolymers (CBCs) based single component organic solar cells (SCOSCs), compared with that of binary all-polymer systems, is the main reason for their limited power conversion efficiency (PCE). To improve the JSC of SCOSCs by enhancing the light-harvesting ability, we designed and synthesized three narrower bandgap acceptor monomers with different chlorine-substituted terminals, and incorporated them into the CBCs. As the position of chlorine substitution altered, the blend morphology, the device performance, and the physical mechanism changed accordingly. It is worth noting that the PB-b-PYCl-2-based SCOSCs exhibited a significantly improved JSC, accompanied by the best PCE of 13.42 %, and good thermal stability. This study illustrated the terminal chlorination strategy is a promising way to modify the device performance of the SCOSCs.

Abstract Overwintering is a critical part of the annual cycle for species that live in temperate, polar, and alpine regions. Consequently, low-temperature biology is a key determinant of temperate species distribution. Termites are distributed predominantly in tropical regions, and a limited number of species are found in the temperate zone. Here, in the termite Reticulitermes speratus, we report the discovery of an underground chamber that protects kings and queens to survive the winter, which is separate from the one they used during the warmer breeding season. In the spring, the royals inhabited decayed logs on the ground, then moved to their underground chamber located in the roots of stumps in the fall. The winter minimum temperature measured in the royal chamber was higher than that in the logs on the ground. In overwintering termites, the kings and queens had higher cold tolerance than workers and soldiers. Air temperatures dropped below the critical temperature multiple times, as evidenced from the past 140 years of weather records in Kyoto. These results demonstrated the survival strategies of reproductives to overcome the environment at the latitudinal limits. This study helps further the understanding of the termite’s seasonal phenology, long-term survivorship, and life cycle.

Abstract Background Atopic dermatitis (AD) is an inflammatory skin condition distinguished by an activated Th2 immune response. The local skin microbial dysbiosis is a contributing factor to the development of AD. The pathogenic coagulase-positive Staphylococcus aureus is the primary species responsible for the progression of AD. Even though Staphylococcus pseudintermedius is an animal-origin pathogen, it is increasingly becoming a source of concern in human diseases. As another coagulase-positive Staphylococci, it is crucial to pay more attention to S. pseudintermedius isolated from the lesion site. Results In our investigation, we presented a case of cheilitis in a patient with atopic dermatitis (AD). We utilized culture and next-generation genomic sequencing (NGS) to identify the bacteria present on the skin swabs taken from the lip sites both prior to and following treatment. Our findings indicated that the predominant bacteria colonizing the lesion site of AD were S. pseudintermedius and S. aureus, both of which were eradicated after treatment. The Multi-locus sequence typing (MLST) of S. pseudintermedius and S. aureus demonstrated coordinated antibiotic susceptibility, with ST2384 and ST22 being the respective types. Although the skin abscess area resulting from S. pseudintermedius infection was significantly smaller than that caused by S. aureus in mice, the expression of cytokines interleukin-4 (IL-4) and interleukin-5 (IL-5) were significantly higher in the S. pseudintermedius-infected mice. Conclusions The S. pseudintermedius strain isolated from the lesion site of the AD patient exhibited a higher expression of IL-4 and IL-5 when colonized on mouse skin, as compared to S. aureus. This observation confirms that S. pseudintermedius can effectively induce the Th2 response in vivo. Our findings suggest that animal-origin S. pseudintermedius may play a role in the development of AD when colonized on the skin, emphasizing the importance of taking preventive measures when in contact with animals.

Abstract We propose a robust fuzzy design model for a sustainable closed-loop supply chain network. The model is based on a risk dynamic regulation mechanism. In this way, we can solve the problem of sudden disruptions and uncertain demand in the supply chain of Chinese herbal medicines. We also develop a hybrid algorithm solution to solve the model and design a resilient supply chain network. The specific steps are as follows: (1) The risk dynamic regulation mechanism is created with strong risk resistance by considering the information sharing platform, facility defense, drying station scheduling, safety stock, and shared inventory. (2) Based on the dynamic risk regulation mechanism, we establish a sustainable Chinese herbal medicine supply chain network design model. Then, we use the robust fuzzy method and the epsilon constraint to deal with the uncertainty and integrate the model. (3) We introduce opposition-based learning, cosine convergence factor, and levy flight to the original Whale and Grey wolf algorithms to obtain the Hybrid algorithm, which is used to solve the processed model. The results show the model and algorithm proposed in this paper have strong applicability and advantages in designing closed-loop supply chain networks for Chinese herbal medicine and provide references for relevant decision-makers.

Abstract Background Temperature variability (TV) is associated with increased mortality risks. However, the independent impacts of interday and intraday are still unknown. Methods We proposed a new method to decompose TV into interday TV and intraday TV through algebra derivation. Intraday TV was defined as the weighted average standard deviation (SD) of minimum temperature and maximum temperature on each day. Interday TV was defined as the weighted SD of daily mean temperatures during the exposure period. We then performed an illustrative analysis using data on daily mortality and temperature in France in 2019–2021. Results The novel interday and intraday TV indices were good proxies for existing indicators, inlcluding diurnal temperature range (DTR) and temperature change between neighbouring days (TCN). In the illustrative analyses, interday and intraday TVs showed differentiated mortality risks. Mortality burden related to TV was mainly explained by the intraday component, accounting for an attributable fraction (AF) of 1.81% (95% CI: 0.64%, 2.97%) of total mortality, more than twice the AF of interday TV (0.86%, 95% CI: 0.47%, 1.24%). Conclusions This study proposed a novel method for identifying and isolating the different components of temperature variability and offered a comprehensive way to investigate their health impacts.

Abstract Background Diabetes mellitus (DM) is a prevalent non-communicable metabolic disease, and S100A11 is a newly identified gene closely related to metabolism. The association of S100A11 with diabetes is unclear. This study aimed to assess the relationship between S100A11 and markers of glucose metabolism in patients with different glucose tolerance and gender. Methods This study included 97 participants. Baseline data were obtained, and the serum levels of S100A11 and metabolic markers (glycated hemoglobin [HbA1c], insulin release test, and oral glucose tolerance test) were measured. Linear and nonlinear correlations between serum S100A11 levels and HOMA-IR, HOMA of β, HbA1c, insulin sensitivity index (ISI), corrected insulin response (CIR), and oral disposition index (DIo) were analyzed. The expression of S100A11 was also detected in mice. Results Serum S100A11 levels increased in patients with impaired glucose tolerance (IGT) of both genders. S100A11 mRNA and protein expression increased in obese mice. There were nonlinear correlations between S10011 levels and CIR, FPI, HOMA-IR, whole-body ISI in the IGT group. S100A11 was nonlinearly correlated with HOMA-IR, hepatic ISI, FPG, FPI, and HbA1c in the DM group. In the male group, S100A11 was linearly correlated with HOMA-IR and nonlinearly correlated with DIo (derived from hepatic ISI) and HbA1c. In the female population, S100A11 was nonlinearly correlated with CIR. Conclusions Serum S100A11 levels were highly expressed in patients with IGT and in the liver of obese mice. In addition, there were linear and nonlinear correlations between S100A11 and markers of glucose metabolism, demonstrating that S100A11 has a role in diabetes. Trial registration ChiCTR1900026990