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Abstract Activin A and hepatic stellate cells (HSCs) are involved in tissue repair and fibrosis in liver injury. This study investigated the impact of activin A on HSC activation and migration. A microfluidic D4-chip was used for examining the cell migration of mouse hepatic stellate cell line MHSteC. The analysis of differentially expressed genes revealed that activin βA (Inhba), activin receptor type 1A (Acvr1a) and type 2A (Acvr2a) mRNAs were more significantly expressed in human HSCs than in the hepatocytes. Moreover, activin A promoted MHSteC proliferation and induced MHSteC migration. Furthermore, the MHSteCs treated with activin A exhibited increased levels of migration-related proteins, N-cadherin, Vimentin, α-SMA, MMP2 and MMP9, but a decreased level of E-cadherin. Additionally, activin A treatment significantly increased the p-Smad3 levels and p-Smad3/Smad3 ratio in the MHSteCs, and the Smad3 inhibitor SIS3 attenuated activin A-induced MHSteC proliferation and migration. Simultaneously, activin A increased the calcium levels in the MHSteCs, and the migratory effects of activin A on MHSteCs were weakened by the intracellular calcium ion-chelating agent BAPTA-AM. These data indicate that activin A can promote MHSteC activation and migration through the canonical Smad3 signaling and calcium signaling.

Abstract Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength (Zn-Prot M) can alleviate heat stress (HS)-induced intestinal barrier function damage of broilers. A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers. Under high temperature (HT), a 1 (Control, HT-CON) + 2 (Zn source) × 2 (added Zn level) factorial arrangement of treatments was used. The 2 added Zn sources were Zn-Prot M and Zn sulfate (ZnS), and the 2 added Zn levels were 30 and 60 mg/kg. Under normal temperature (NT), a CON group (NT-CON) and pair-fed group (NT-PF) were included. Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1, occludin, junctional adhesion molecule-A (JAMA), zonula occludens-1 (ZO-1) and zinc finger protein A20 (A20) in the jejunum, and HS also remarkably increased serum fluorescein isothiocyanate dextran (FITC-D), endotoxin and interleukin (IL)-1β contents, serum diamine oxidase (DAO) and matrix metalloproteinase (MMP)-2 activities, nuclear factor kappa-B (NF-κB) p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum. However, dietary supplementation with Zn, especially organic Zn as Zn-Prot M at 60 mg/kg, significantly decreased serum FITC-D, endotoxin and IL-1β contents, serum DAO and MMP-2 activities, NF-κB p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers, and notably promoted mRNA and protein expression levels of claudin-1, ZO-1 and A20. Conclusions Our results suggest that dietary Zn, especially 60 mg Zn/kg as Zn-Prot M, can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.

In the current study, the corrosion behavior of HSLA-65 steel was investigated in a simulated marine environment inoculated with P. aeruginosa. In the electrochemical measurements, the negative shift in OCP, lower values of corrosion potential, pitting potential, and increased corrosion current density of the HSLA-65 steel in the biotic medium signified its low corrosion resistance in the presence of P. aeruginosa. The observation of the surface morphology revealed biofilm formation on the steel surface in the P. aeruginosa-inoculated culture medium, which significantly accelerated the pitting corrosion of the steel. The pit observed on the steel surface in the biotic medium was about 3.9 times deeper than in the sterile medium. In addition, the weight loss of the steel in the biotic medium was about 2.4 times higher compared to that in the sterile medium. These findings suggest that the P. aeruginosa biofilm significantly accelerated the corrosion of HSLA-65 steel in the simulated marine environment.

Abstract We derive the exact solutions for electrically charged black holes both in the absence and presence of a cosmological constant in the gravitational theory with Lorentz violation induced by a background Kalb–Ramond (KR) field. The corresponding thermodynamic properties are investigated. It is found that the standard first law of thermodynamics and the Smarr formula remain valid for the charged KR black holes. Nevertheless, the Lorentz-violating effect influences their ranges of local thermodynamic stability and the first- and second-order phase transition points. Furthermore, to examine the impact of Lorentz violation on the motion of test particles in the spacetime, we analyze the shadow and the innermost stable circular orbit (ISCO) of these black holes. Our results reveal that both the shadow and ISCO radii exhibit a high sensitivity to the Lorentz-violating parameter $$\ell $$ ℓ , with a decrease observed as $$\ell $$ ℓ increases.

Abstract The low ionic conductivity of composite solid-state electrolytes due to the lack of free Li-ions and Li dendrite growth induced by the low transference number seriously hinder their application. Herein, we find that the giant dielectric ceramic of Li0.3Ti0.02Ni0.68O (LTNO) with ultra-high dielectric constant can greatly promote the dissociation of Li salt to generate abundant movable Li-ions and realize a high room-temperature ionic conductivity (4.09 × 10–4 S cm−1) as well as a low activation energy (0.16 eV). The oxygen vacancies on the surface of LTNO can effectively immobilize the anions to achieve a high Li transference number (0.61). Furthermore, the enhanced dielectric properties of the composite electrolyte induce homogenous Li plating/stripping to suppress the growth of Li dendrites. As a result, the Li||Li symmetric cells exhibit long lifespan of 2400 h and 1150 h at 0.1 mA cm−2 and 0.2 mA cm−2, respectively. The Li||LiNi0.8Co0.1Mn0.1O2 solid-state full cells show a high capacity retention of 83% after 430 cycles at 2C. This work highlights the critical role of high dielectric property and oxygen defects of fillers in composite solid-state electrolytes, and provides a demonstration for the application of giant dielectric materials in solid-state Li metal batteries.

Abstract Background This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. Methods By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. Results The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P

Laser powder bed fusion (LPBF) technology enables personalized customization of medical implants. However, the clinical titanium alloy is biologically inert and can't address bacterial infections. It has been proved that Copper (Cu) -bearing titanium alloys exhibit excellent antibacterial ability and potentials for clinical application. However, it still unclear that the effect of Cu content on the comprehensive properties of LPBF-produced titanium alloy which usually has high strength but poor ductility and corrosion resistance caused by its α′ martensite. This study systematically investigates the effects of Cu content (x = 2, 5, 8 wt%) on the microstructure, mechanical properties, corrosion resistance, antibacterial properties, and cytrocompatibility of the LPBF-produced Ti-xCu alloys. These results prove that the LPBF produced Ti–5Cu alloy possesses the optimal comprehensive performance and has promising clinical application prospects as implant materials.

In order to investigate the influence of gradual stress relieving treatment on the microstructure, texture evolution, grain structure, and misorientation distribution of the hot-rolled Ti6Al4V–5Cu (α+β) alloy deformed in various thickness reduction ratios (TRR's) of 15%, 58%, and 73% to maintain the burger orientation relationship (BOR), different stress reliving treatment was specially designed for relieving the residual stresses occurred due to the hot deformation process. Using IPF maps, the majority of the α grains, specifically the elongated ones were found nearly at 45 ° with respect to the rolling and transverse direction. The study also show that the heat treatment schedule on the 58% deformed alloy significantly promote the transformation of β to α phase and a special microstructure with an equiaxed grains is produced. The local misorientation angle distribution due to stress reliving treatment has also discussed. Using EBSD analysis, the alloy processed under highest TRR's (i.e., 73%) and subsequent stress relieving treatment could result a serious internal crystalline instability with various degree of element diffusion rate, which promote a severe and ease of alloy coarsening. Thus, coarsening encourage the formation of grains with the highest softening potential, comparatively. It is obvious that the stress-relived treatment does not result a change in microstructure. However the internal residual stresses on the hot deformation were relieved, the texture intensity had increased quietly. A significant textural behavior could be achieved on the 73% hot-rolled alloys by the stress-relieving process to align the α/β fiber texture interface in parallel coincidence to maintain the BOR.

Abstract This study investigates the stability of an artificial dam used in an underground reservoir in a coal mine under periodic weighting imposed by overlying rock strata. For this purpose, cyclic loading and unloading tests with different stress amplitudes were designed. Differences in the mechanical performance of the artificial dam with and without overlying strata were analyzed using a uniaxial compression test. The mechanical properties of the structure under constant-amplitude cyclic loading and unloading were characterized. Further, the law of influence of stress amplitude on stability was discussed. A formula for predicting the mechanical performance of the artificial dam with its overlying rocks (hereafter referred to as the complex) was finally derived and was suitable for clarifying the law of damage in the complex under cyclic loading and unloading. The results showed that the complex had changed the internal structure of rocks. The strength and deformation of the complex were intermediate to that of either single structure. All three underwent brittle failure. During the constant-amplitude loading and unloading tests, the hysteresis loop could be divided into three phases, namely, sparse, dense, and sparse again, with a shift in the turning point in rock deformation memory effect. As the stress amplitude increased during the test, the damping ratio of the specimens decreased, and the area of the hysteresis loop increased non-linearly. The dynamic elastic modulus decreased first and then increased. The confidence interval for the formula fitted based on the test results was above 97%. Damage to the complex caused by constant-amplitude loading and unloading could be divided into three stages. An increase in peak stress served as a catalyst for the evolution of small cracks within the specimens into median and large cracks, thereby accelerating the damage process.

Huainan mining area is a typical high-gas area, with broken soft coal seam, low permeability, high gas content, and difficulty in extraction. In order to probe into the technical feasibility and gas control effect of the horizontal well for segmental hydraulic fracture in roof of coal seam in mining area, a three-dimensional in-situ stress test of coal seam was carried out using the stress relief method based on the analysis of the characteristics of the 13-1 coal reservoir, which was the main coal seam in the mining area. The results shown that, the three-dimensional stress field was mainly σh,max > σv > σh,min, which had sufficient conditions for the implementation of horizontal well with segmental hydraulic fracture in roof of coal seam. MFrac Suite software was used to simulate the fracture parameters of horizontal section at 1, 3 and 5 m from the coal seam. The maximum half-length of the fracture was 107.33 m and the minimum was 89.47 m, which was ideal for fracturing, indicating that the horizontal well with segmental hydraulic fracture had better geological adaptability and feasibility in Huainan mining area. Taking the CBM01 well, a horizontal well with L-type roof segmental fracturing in the 13-1 coal seam of Panyi coal mine, as the research object, the effect of gas control and management was comprehensively analyzed by means of borehole detection and numerical simulation. The results shown that, CBM01 well significantly reduced the gas pressure and gas content of coal seam after 415 d of extraction. The gas pressure at 50 and 65 m from the horizontal well decreased from 6.4 MPa to 2.6 and 2.7 MPa, respectively, by more than 55%. The gas content decreased from 13.5 m3/t to a maximum of 9.11 m3/t, a minimum of 6.92 m3/t, an average of 7.92 m3/t in an area of about 15-20 m on each side of the horizontal section, and decreased to less than 8 m3/t within about 10 m. Finally, a numerical simulation method was used to predict the gas production effect of CBM 01 well extracting for 10 a and the effect with gas control. The cumulative gas production of gas well was about 272.08×104 m3 in 10 a, and the gas content in the range of about 150 m on one side of the horizontal section was reduced to less than 8 m3/t, and the pressure was reduced to less than 3 MPa. Comprehensive research results shown that the horizontal well technology of segmental hydraulic fracturing in roof of coal seam had greater advantage and application effect in gas control and management in Huainan mining area.

The construction of 14 large-scale coal bases and 89 demonstration bases for the comprehensive utilization of bulk solid waste in China marks that the utilization of bulk solid waste in mining areas has been incorporated into the national strategic development layout. The long-term high-intensity development and utilization of coal resources has caused the near depletion of shallow-buried coal seam resources in mining areas, and the large-scale solid waste accumulation and surface subsidence of coal power and chemical bases has become a problem restricting the green, low-carbon and high-quality development of mining areas. Co-operative utilization of bulk coal-based solid waste and green filling is an effective way to liberate the “three down and one up” pressed coal, extend the service life of mines, and realize the harmless, resourceful, and large-scale “three” utilization of solid waste. Based on the types and production of coal-based solid waste in Shanxi Province, the “East China Energy Granary” Anhui Lianghuai Base and Ningdong Energy and Chemical Base, it elaborates in detail the harmless disposal of coal-based solid waste through heavy metal adsorption and desorption and complexation passivation technology with coal gangue, fly ash, furnace slag, gasification slag and desulphurization gypsum as the main materials, listing the classification and application of coal-based solid waste, and the application of coal gangue, fly ash, furnace slag, gasification slag and desulphurization gypsum as the main materials. List the ways of resource utilization of coal-based solid waste classified and applied to low calorific value coal-based solid waste for power generation, preparation of building materials such as cement, bricks and tiles, etc. Comparatively analyze the ways of reclamation and backfilling of coal mining subsidence area and downhole filling and large-scale utilization of coal-based solid waste, highlighting the superiority of downhole filling of coal-based solid waste. Based on the deep coal resources of coal electrification bases, the theory and key technologies of green filling mining are proposed, including the synergistic technology of deep coal gangue source reduction and mining and filling, the technology of efficient preparation and deep underground transportation of filling materials, and the deep multi-field coupling mechanism of coal-based solid waste filling materials, and the technological principles and methods of the whole process of deep filling mining of multi-source coal-based solid waste from the source, process to the end are investigated to solve the technical problems of deep underground filling of mining areas. The technical problems of filling are solved. According to the geological conditions and filling purposes of Renjiazhuang Coal Mine in Ningdong Base, Huoerxinhe Coal Mine in Shanxi Province and Huaibei Mining Area, the key technologies of low-level filling by overdrilling, multi-separation layer stepped grouting under the conditions of atypical characteristics of key layers and synergistic utilization of coal-based solid wastes have been proposed, which comprehensively combine the advantages of disposal and utilization of solid wastes from mines, development and utilization of deep coal resources, control of subsidence of the ground surface, and ecological environment protection, and form a comprehensive plan for the disposal and utilization of bulk solid wastes from coal power and chemical bases. Coal power and chemical base bulk solid waste synergistic utilization and green mining mode, providing reference for high quality coal mining and low damage to the environment.

In order to study the consolidation bearing capacity of coal-based solid waste paste backfill in deep high ground temperature environment of coal mine, uniaxial compression and acoustic emission tests were used to test the strength and failure characteristics of paste backfill under different curing temperature conditions (20 ℃, 35 ℃ and 50 ℃) and ages (3 d, 7 d, 14 d and 28 d). The microstructure and mineral composition of the filling cement were measured by SEM, and the influence of curing temperature on the hydration reaction was revealed from the microscopic point of view. The results show that: with the increase of curing temperature, its influence on hydration reaction gradually changes from promotion to inhibition, and the 28 d compressive strength reaches the maximum at 35 ℃; acoustic emission events mainly occur in the compaction and failure stages. The increase of curing temperature promotes the activity of acoustic emission in advance, and the failure mode of filling body gradually changes from ductile failure to brittle failure; due to the thermal damage, high temperature curing accelerates the early hydration reaction rate of the filling body, and causes damage to the C-S-H and pore structure of the filling body in the later stage of curing, which has an adverse effect on the increase of its long-term strength.

Abstract Background Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. Methods Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran’s Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. Results Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003–1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096–2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. Conclusion This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.

Background: KIDINS220 encodes a transmembrane scaffold protein, kinase D-interacting substrate of 220 kDa, that regulates neurotrophin signaling. Variants in KIDINS220 have been linked to spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome or prenatal fatal cerebral ventriculomegaly and arthrogryposis (VENARG). This study aimed to investigate the genotype-phenotype correlation of pathogenic KIDINS220 variants. Methods: We performed whole-exome sequencing on a patient with SINO syndrome and epilepsy. Identified pathogenic variants were confirmed using Sanger sequencing and evaluated with in silico tools. A comprehensive literature review was conducted to analyze the genetic and phenotypic data of both the newly diagnosed patient and previously reported cases with KIDINS220 variants. Results: We identified novel compound heterozygous variants in KIDINS220, c.1556C > T (p.Thr519Met) and c.2374C > T (p.Arg792*), in the patient. Our analysis revealed that biallelic loss-of-function variants in KIDINS220 are associated with VENARG or autosomal recessive SINO (AR-SINO), whereas carboxy-terminal truncated variants that escape nonsense-mediated mRNA decay and lack amino acid residues 1507–1529 are linked to autosomal dominant SINO (AD-SINO). Patients with AR-SINO exhibit more severe clinical features compared to those with AD-SINO. Conclusions: Our study expands the spectrum of KIDINS220 variants associated with AR-SINO and provides a valuable genotype-phenotype correlation for pathogenic KIDINS220 variants.

Objective: The present study aimed to explore the potential causal relationship between childhood asthma and chronic obstructive pulmonary disease (COPD) in European and East Asian populations with Mendelian randomization (MR) analysis. Methods: Based on summary data from genome-wide association studies, single nucleotide polymorphisms (SNPs) associated with childhood asthma were used as instrumental variables. The MR analysis employed the inverse variance weighting, MR-Egger regression and weighted median method to estimate the causal effect between childhood asthma and COPD in European and East Asian populations. Cochran's Q test, MR-PRESSO method and MR-Egger intercept were used to detect heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis applied to assess the effect of removing individual SNP on the estimate of causal association. Results: The MR analysis showed no genetic causal relationship between childhood asthma and COPD. The results of Cochran's Q test, MR-PRESSO and MR-Egger regression indicated the absence of heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis showed no significant difference in the statistical results after exclusion of single SNPs. Conclusions: The MR analysis revealed that there is no causal relationship between childhood asthma and COPD at the genetic level in both European and East Asian populations. Additionally, due to the presence of shared confounding factors and pathogenic genes, further research is needed to comprehensively assess the relationship between childhood asthma and COPD.

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation techniques. Sonogenetics, a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells, is gaining prominence along with optogenetics, electrogenetics, and magnetogenetics. Upon stimulation with ultrasound, these proteins trigger a cascade of cellular activities and functions. Unlike traditional ultrasound modalities, sonogenetics offers enhanced spatial selectivity, improving precision and safety in disease treatment. This technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications, including neuromodulation, oncologic treatments, stem cell therapy, and beyond. Although current literature predominantly emphasizes ultrasonic neuromodulation, this review offers a comprehensive exploration of sonogenetics. We discuss ultrasound properties, the specific ultrasound-sensitive proteins employed in sonogenetics, and the technique's potential in managing conditions such as neurological disorders, cancer, and ophthalmic diseases, and in stem cell therapies. Our objective is to stimulate fresh perspectives for further research in this promising field.

BackgroundThe aim of the present study was to investigate the intrinsic relationship between cultural values and social network index among college students. In addition, the present study explored the mediating role of self-monitoring in the relationship between horizontal collectivism cultural values and social network index, as well as the moderating role of self-efficacy, to provide a theoretical approach based on the intrinsic mechanism for college students to establish a good social network.MethodsA simple random cluster sampling method was used to investigate 376 college students with cultural values scale, self-monitoring scale, self-efficacy scale, and social network index scale, structural equation model was constructed using M-plus and SPSS.ResultsThe result indicated that individual horizontal collectivist cultural values positively predict social network index (β = 0.477). Self-monitoring plays an intermediary role between cultural values and social network index, and self-efficacy plays a moderating role between self-monitoring and social network index.ConclusionThe level of an individual’s social network activity is affected by the cultural values of horizontal collectivism and self-monitoring. Improving individual self-monitoring ability and self-efficacy can effectively improve the interpersonal relationships of college students.

Osteoporosis is a common systemic metabolic disease characterized by a decrease in bone density and bone mass, destruction of bone tissue microstructure, and increased bone fragility leading to fracture susceptibility. Pharmacological treatment of osteoporosis is the focus of current research, and anti-osteoporosis drugs usually play a role in inhibiting bone resorption, promoting bone formation, and having a dual role. However, most of the drugs have the disadvantages of single target and high toxic and side effects. There are many types of traditional Chinese medicines (TCM), from a wide range of sources and mostly plants. Herbal plants have unique advantages in regulating the relationship between osteoporosis and the immune system, acupuncture therapy has significant therapeutic effects in combination with medicine for osteoporosis. The target cells and specific molecular mechanisms of TCM in preventing and treating osteoporosis have not been fully elucidated. At present, there is a lack of comprehensive understanding of the pathological mechanism of the disease. Therefore, a better understanding of the pathological signaling pathways and key molecules involved in the pathogenesis of osteoporosis is crucial for the design of therapeutic targets and drug development. In this paper, we review the development and current status of anti-osteoporosis drugs currently in clinical application and under development to provide relevant basis and reference for drug prevention and treatment of osteoporosis, with the aim of promoting pharmacological research and new drug development.

Defect detection is critical to industrial quality control in leather production engineering. The various sizes and locations of defects in leather, as well as significant differences within the same class and indistinctive variations between different classes of defects, contribute to the complexity of the problem. To address this challenge, we propose a Multi-Layer Residual Convolutional Attention (MLRCA) approach. MLRCA enhances its ability to capture both intra-class and inter-class differences by enhancing the semantic feature representation in the backbone network. To improve multiscale fusion effects, we also incorporate the MLRCA module into the feature pyramid network (FPN) and propose a new multi-layer residual convolution attention feature pyramid network (ML-FPN). This approach enables more accurate identification of leather defects at a more detailed level by selectively capturing contextual information from different domains. We then implement the Side-Aware Boundary Localization (SABL) detection head, which accurately locates defects and helps the network distinguish between similar defect categories for more precise positioning. To validate the effectiveness of our approach, we conducted ablation experiments on the created leather dataset. Comparative experiments demonstrate the excellent capability of our model to detect minor defects. The model achieved 83.4, 89.7, and 85.6 for the AP, AP50, and AP75 evaluation metrics. In addition, the model achieves 71.3, 89.9, and 88.9 for APS, APM, and APL. Our approach has been confirmed feasible through experimentation and provides new insights for automated leather defect detection methods.

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuli-responsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials.

The climate change and extension of human activities are shedding more stresses on ecosystems. Ecological zoning could help manage the ecosystem and deal with environmental problems more effectively. Geology and topography could affect the ecology primarily and are vital perspectives on ecological zoning. It is worth preliminarily understanding the spatial-temporal patterns of ecological-environmental attributes within various geological-topographical ecological zones (GTEZs). The objective of this study was to delineate GTEZs and present a spatial-temporal analysis on soil and land surface parameters within GTEZs. Firstly, Landsat imageries, high resolution satellite imagery products, digital elevation model, regional geological map, black soil thickness, soil bulk density, meteorological data, and ground survey were collected and conducted. Secondly, GTEZs in Hailun District were delineated according to geological and topographical background. Thirdly, soil composition, and monthly land surface temperature (LST), enhanced vegetation index (EVI), net primary productivity (NPP) were derived from ground survey and Landsat imageries. Finally, spatial-temporal patterns of various ecological-environmental attributes within different GTEZs were preliminarily revealed and analyzed. Results show that sand alluvial plain zone and silt-clay undulating plain zone mainly possess thick soil with fine-medium granule and higher bulk density, and are mainly covered by crops and grass, vegetation flourish the most in August with the highest monthly EVI and NPP. While the sand-conglomerate hill zone, sandstone hill zone, and granite hill zone possess relatively thin soil with medium-coarse granule and lower bulk density, and are mainly covered by forest, vegetation flourish the most in June and July, and has the highest yearly total NPP. With thinner soil thickness and higher NPP, hill zones tend to have more vulnerability to disturbance and more contribution to carbon neutrality target.

Globally, anthropogenic disturbance and climate change caused a rapid decline of submerged macrophytes in lake ecosystems. Potamogeton crispus (P. crispus), a species that germinates in winter, explosively expanded throughout many Chinese lakes, yet the underlying mechanism remained unclear. Here, this study examined the long-term changes in the distribution patterns of P. crispus in Lake Gaoyou by combining remote sensing images and hydrometeorological data from 1984 to 2022 and water quality data from 2009 to 2022. It aims to unravel the relationships between the distribution patterns of P. crispus and hydrometeorological and water quality factors. The results showed that the area of P. crispus in Lake Gaoyou showed a slight increase from 1984 to 2009, a marked increase from 2010 to 2019, followed by a decline after 2020. Spatially, P. crispus was primarily distributed in the western and northern parts of Lake Gaoyou, with less distribution in the central and southeastern parts of the lake. Wind speed (WS), temperature (Temp), water level (WL), ammonia nitrogen (NH3-N), and Secchi depth (SD) were identified as the key factors regulating the variation in the P. crispus area in Lake Gaoyou. We found that the P. crispus area showed an increasing trend with increasing Temp, WL, and SD and decreasing WS and NH3-N. The influence of environmental factors on the area of P. crispus in Lake Gaoyou varied among seasons. The results indicated that hydrometeorology (WS, Temp, and WL) may override water quality (NH3-N and SD) in driving the succession of P. crispus distribution. The findings of this study offer valuable insights into the recent widespread expansion of P. crispus in shallow lakes across Eastern China.

In order to improve the mechanical properties of backfill, steel slag and straw fiber were used as materials to prepare backfill. The law of sand-cement ratio, mass concentration, steel slag content and straw fiber on strength and rheological parameters of backfill was analyzed by orthogonal test method, and the influence mechanism of steel slag content and straw fiber on physical properties of backfill was revealed. The results show that mass concentration exerts the most substantial impact on rheological parameters, emerging as a significant determinant. Moreover, the yield stress diminishes with escalating tailings-cement ratio, while it escalates with higher mass concentration, steel slag content and straw fiber content. Augmenting the tailings-cement ratio and steel slag content serves to impede the amplification effect of mass concentration on yield stress. Notably, the tailings-cement ratio emerges as the most influential factor affecting the uniaxial compressive strength (UCS) of the backfill, albeit the UCS diminishes with rising tailings-cement ratio. Elevating the mass concentration and steel slag content can counteract the debilitation caused by an increase in the tailings-cement ratio on the UCS of the backfill. Furthermore, heightened mass concentration can bolster the reinforcing impact of steel slag content on early UCS. The increase of tailings-cement ratio increases the size and range of the void inside the backfill, subsequently leading to the degradation of its macroscopic compressive strength. The adhesion between straw fiber and mortar matrix constitutes a pivotal factor in improving the integration of backfill, whereas steel slag contributes to improving the mechanical properties by enhancing the distribution of void structures within the backfill. This research not only offer data support and scientific guidance for the design of backfill ratio parameters but also facilitate the broader application of straw fiber and steel slag in mine backfilling operations.

Abstract The Schizothoracinae fish are a natural group of cyprinids widely distributed in rivers and lakes in the Qinghai-Tibetan Plateau (QTP) and adjacent regions. These fish parallelly evolved with the QTP uplift and are thus important for uncovering geological history, the paleoclimatic environment, and the mechanisms of functional adaptation to environmental change. However, a dataset including species occurrences and functional traits, which are essential for resolving the above issues and guiding relevant conservation, remains unavailable. To fill this gap, we systematically compiled a comprehensive dataset on species occurrences and functional traits of Schizothoracinae fish from our long-term field samplings and various sources (e.g., publications and online databases). The dataset includes 7,333 occurrence records and 3,204 records of 32 functional traits covering all the genera and species of Schizothoracinae fish (i.e., 12 genera and 125 species or subspecies). Sampling records spanned over 180 years. This dataset will serve as a valuable resource for future research on the evolution, historical biogeography, responses to environmental change, and conservation of the Schizothoracinae fish.

Abstract The mix proportion of multi-source coal-based solid waste (CSW) for underground backfilling affects transportation and support performance of backfill materials, and even the backfilling cost. In this study, the optimal mix proportion of desulfurization gypsum (DG), furnace bottom slag (FBS) and gasification fine slag (GFS) is determined by the Response Surface Methodology–Box Behnken Design (RSM-BBD). Then the fluidity, bleeding rate, 3-day strength, 7-day strength and preparation cost are evaluation indicators, the optimal mix proportion of backfill materials is determined by the multi-objective decision-making method (MDM). Finally, the microstructure of the backfill material with optimal mix proportion was studied by TGA, MIP, SEM–EDS and XRD. The results show that the mix proportion of CSW with the optimal comprehensive index is coal gangue (CG): coal fly ash (CFA): DG: FBS: GFS = 1:1.5:0.2:0.1:0.1, the mass concentration is 78%, and ordinary Portland cement (OPC)/CSW = 7.5%. The weight loss phenomenon of the backfill material with the optimal mix proportion occurs continuously during the heating process, mainly due to the evaporation of crystal water, structural water and hydroxyl water. There are dense narrow-necked pores in the backfill material, and the pore connectivity is poor. There is no hydration reaction occurs between CSW particles, and the strength increase of the backfill material mainly depends on the hydration reaction of cement. In ettringite, part of Al2O3 is replaced by SiO2, and part of CaSO4 is replaced by CaCO3. This study provides a reference for the engineering application of underground backfilling with multi-source CSW.

A series of experiments was conducted to study the performance and mechanisms of Cemented Ultrafine Tailings Backfill (CUTB). Firstly, the optimum fiber type was selected by single factor multilevel test. Secondly, the effects of cement content, rice husk ash content, fiber content and fiber length on backfill properties were analyzed by orthogonal test and microstructure test, and the influence mechanism of fiber and rice husk ash content was revealed. Finally, fuzzy mathematics theory is used to optimize the ratio parameters. The results show, compared to glass and basalt fiber, polypropylene fiber yields the most substantial enhancement in backfill strength. The increase of cement content, polypropylene fiber content and length can reduce slump, but the change of rice husk ash content has no obvious effect. Increased cement or fiber content effectively restrained the formation of primary fractures in CUTB, thus enhancing its integrity. Adding an optimal dosage range of 0–4 % of rice husk ash boosted the early compressive strength, albeiting at the expense of later compressive strength. Fiber addition with the optimum content range between 0.1 and 0.4 % enhanced the strengthening effect of cement content on compressive strength. Fiber primarily enhances the macroscopic strength of backfill through the dispersion and co-loading of forces, whereas rice husk ash enhances strength by optimizing void structure distribution. The optimal ratio parameters of a cement content of 310 kg/m³, rice husk ash content of 8.0 %, fiber content of 0.4 %, and fiber length of 9 mm were proposed finally.

In this study, the interaction evolution between the α precipitates that are thermally actived and deformation-induced α′ martensite in a metastable β-Zr alloy during tensile deformation was investigated. Following a two-step heat treatment, it results in the simultaneous precipitation of the thermally activated α phase in both within the β grain (αIN) and at the grain boundaries (αGB). The microstructure after deformation demonstrates that the α′ martensite induced by deformation initially nucleates and subsequently develops into elongated plates that are parallel with each other in the spaces between the αIN. As deformation continues, the α′ martensite grows rapidly in the length direction, firstly facing initial obstruction from αIN, but finally penetrating it and persisting to develop further. However, the growing α′ martensite encounters αGB, it is prevented completely from growing in length direction and instead grows quickly in width direction. Furthermore, α′ martensite plates further thicken and merge with each other, ultimately enveloping the complete β grain, including αIN, to construct an α′ martensite domain featuring an unusual shell-core arrangement. The shell layer is αGB and the core layer is α′ martensite surrounding αIN. Meanwhile, the secondary deformation product, namely {101‾1} twins, will form within α′ martensite domain in subsequent deformation process.

Abstract Conventional circuit elements are constrained by limitations in area and power efficiency at processing physical signals. Recently, researchers have delved into high-order dynamics and coupled oscillation dynamics utilizing Mott devices, revealing potent nonlinear computing capabilities. However, the intricate yet manageable population dynamics of multiple artificial sensory neurons with spatiotemporal coupling remain unexplored. Here, we present an experimental hardware demonstration featuring a capacitance-coupled VO2 phase-change oscillatory network. This network serves as a continuous-time dynamic system for sensory pre-processing and encodes information in phase differences. Besides, a decision-making module for special post-processing through software simulation is designed to complete a bio-inspired dynamic sensory system. Our experiments provide compelling evidence that this transistor-free coupling network excels in sensory processing tasks such as touch recognition and gesture recognition, achieving significant advantages of fewer devices and lower energy-delay-product compared to conventional methods. This work paves the way towards an efficient and compact neuromorphic sensory system based on nano-scale nonlinear dynamics.

Abstract Pyroptosis is a form of programmed cell death characterized by cell swelling, pore formation in the plasma membrane, lysis, and releases of cytoplasmic contents. To date, the molecular mechanism of human and murine Gasdermin D-mediated pyroptosis have been fully investigated. However, studies focusing on molecular mechanism of bovine Gasdermin D (bGSDMD)-mediated pyroptosis and its function against pathogenic infection were unclear. In the present study, we demonstrate that bovine caspase-1 (bCaspase-1) cleaves bGSDMD at amino acid residue D277 to produce an N-terminal fragment (bGSDMD-p30) which leads to pyroptosis. The amino acid residues T238 and F239 are critical for bGSDMD-p30-mediated pyroptosis. The loop aa 278-299, L293 and A380 are the key sites for autoinhibitory structure of the full length of bGSDMD. In addition, bCaspase-3 also cleaves bGSDMD at residue Asp86 without inducing cell death. Therefore, our study provides the first detailed elucidation of the mechanism of bovine GSDMD-mediated pyroptosis. The results will establish a significant foundation for future research on the role of pyroptosis in bovine infectious diseases.

Abstract Repurposing a closed mine as lower reservoir is a cost-effective way for the construction of pumped storage hydropower (PSH) plant. This method can eliminate the expenses of mine reclamation, reservoir construction, and land acquisition, resulting in significant cost savings and benefits for the PSH project, known as the PSH benefit. The construction of PSH plants within a closed mine is divided into surface mode and semi-underground mode in this paper. Through a general comparison of two in-situ cases, the finding highlight that the surface mode can achieve a larger potential installed capacity and lower construction cost. Furthermore, the PSH benefit is quantified and internalized as an economic parameter in the ultimate pit limit (UPL) optimization by allocating it into unit ore. Taken an undisclosed open-pit iron mine as example, the UPL is optimized by considering the PSH benefit. The internalized PSH benefit is calculated to be 6.59 CN¥/t when the installed capacity is 2000 MW, and ore amount within the optimized UPL is increased by 1.4%. The results indicated that the PSH benefit does influence the shape and size of UPL, but not significantly. Besides, converting several bottoms in a single open-pit into lower and upper reservoirs presents more challenges for UPL optimization, which further explorations is needed.

Background: To study the changes in intestinal flora in patients with ulcerative colitis (UC), and to explore its correlations with micro ribonucleic acid (miR)-21 and serum tumor necrosis factor-a (TNF-α). Methods: A total of 150 patients with UC were selected and divided into remission group and seizure group according to the severity of disease. At the same time, 150 healthy people receiving physical examination in the hospital during the same period were selected as control group. The levels of fecal miR-21 and TNF-α in all subjects were determined via reverse transcription-polymerase chain reaction (RT-PCR). The correlation between miR-21 and TNF-α and their associations with the changes in intestinal bacteria in UC were analyzed using Pearson correlation analysis. The risk factors affecting the occurrence of UC were explored via multivariate logistic regression analysis. Results: The levels of fecal miR-21 and TNF-α in patients with UC were significantly higher than those in control group, and they were also significantly higher in seizure group than those in remission group. There was a positive correlation between the levels of miR-21 and TNF-α. The number of fecal intestinal flora (Bifidobacterium, Lactobacillus, Enterobacterium and Enterococcus) was different in patients with varying degrees of disease. MiR-21 and TNF-α were negatively correlated with the content of Bifidobacterium and Lactobacillus, but positively correlated with the content of Enterobacterium and Enterococcus. According to multivariate logistic regression analysis, miR-21 and TNF-α were risk factors for the seizure of UC. Conclusion: MiR-21 can promote the expression of TNF-α, and lead to the alteration of intestinal flora, thereby enhancing the occurrence and development of UC.

Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation, the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures. In the present work, degradable magnesium (Mg) alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4–0 absorbable suture as control. The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4, 8, and 12 weeks after operation. The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure. Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups. In the histological analysis, for Mg alloy suture groups, chondrocytes appear to proliferate at 4 weeks postoperatively, and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively. The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed, where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis. In vivo degradation of the magnesium alloy wire was completed within 12 weeks. The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.

Abstract Background Alzheimer’s disease (AD) is a degenerative neurological disorder. Recent studies have indicated that histone deacetylases (HDACs) are among the most prominent epigenetic therapy targets and that HDAC inhibitors have therapeutic effects on AD. Here, we identified sodium valproate (VPA), a pan-HDAC inhibitor, and WT161, a novel HDAC6 selective inhibitor, as potential therapeutic agents for AD. Underlying molecular mechanisms were investigated. Methods A cellular model, N2a-APPswe, was established via lentiviral infection, and the APPswe/PSEN1dE9 transgenic mouse model was employed in the study. LC–MS/MS was applied to quantify the concentration of WT161 in the mouse brain. Western blotting, immunohistochemical staining, thioflavin-S staining and ELISA were applied to detect protein expression in cells, tissues, or serum. RNA interference was utilized to knockdown the expression of specific genes in cells. The cognitive function of mice was assessed via the nest-building test, novel object recognition test and Morris water maze test. Results Previous studies have focused mainly on the impact of HDAC inhibitors on histone deacetylase activity. Our study discovered that VPA and WT161 can downregulate the expression of multiple HDACs, such as HDAC1 and HDAC6, in both AD cell and mouse models. Moreover, they also affect the expression of APP and APP secretases (BACE1, PSEN1, ADAM10). RNA interference and subsequent vitamin C induction further confirmed that the expression of APP and APP secretases is indeed regulated by HDAC1 and HDAC6, with the JNK pathway being the intermediate link in this regulatory process. Through the above pathways, VPA and WT161 effectively reduced Aβ deposition in both AD cell and mouse models and significantly improved cognitive function in AD mice. Conclusions In general, we have discovered that the HDAC6-JNK-APP secretases cascade is an important pathway for VPA and WT161 to exert their therapeutic effects on AD. Investigations into the safety and efficacy of VPA and WT161 were also conducted, providing essential preclinical evidence for assessing these two epigenetic drugs for the treatment of AD.

316L SS is widely used but is prone to algae adhesion, making biofouling a big challenge for the long-term functionality and reliability in freshwater. Most reported organic antifouling coatings are not suitable for use in freshwater environments, making copper-containing stainless steels a good candidate for freshwater antifouling. Anti-fouling resistance of 316L-Cu SS and 316L SS was compared using a self-built natural simulation ecosystem in this study. The results demonstrated that the algae adhesion percentage on 316L-Cu SS is much lower than that on 316L SS from both macro and micro perspectives using a single-lens reflex camera and high sensitivity structured illumination microscope. Results of this study clearly revealed that the mechanism of algae resistance for 316L-Cu SS is the release of Cu2+ can inhibit the adhesion of proteins and polysaccharides, weakening the adhesion of the extracellular polymeric substances to the metal substrate and even make the attached diatoms fracture or damage. This study provides a novel strategy to prevent algae adhesion on metal surface for an array of underwater equipment used in freshwater and contributes towards the advancement of materials used for underwater equipment, fostering enhanced performance and reduced maintenance in freshwater applications and the mitigation of algae fouling in aquatic environments.

Childhood asthma, a common chronic childhood disease, leads to high mortality and morbidity in the world. Airway smooth muscle cells (ASMCs) is a group of multifunctional cells that has been found to be correlated with the pathogenesis of asthma. Astragaloside IV (AS-IV) is a compound extracted from Astragalus membranaceus, which has the anti-asthmatic effect. However, the role of molecular mechanisms regulated by AS-IV in the biological processes of ASMCs in asthma remains unclear. Our current study aims to investigate the downstream molecular mechanism of AS-IV in modulating the aberrant proliferation and pyroptosis of ASMCs in asthma. At first, we determined that the viability of ASMCs could be efficiently suppressed by AS-IV treatment (200 μM). Moreover, AS-IV promoted the pyroptosis and suppressed PDGF-BB-induced aberrant proliferation. Through mechanism investigation, we confirmed that AS-IV could suppress high mobility group box 1 (HMGB1) expression and prevent it from entering the cytoplasm. Subsequently, AS-IV blocked the interaction between HMGB1 and advanced glycosylation end product-specific receptor (RAGE) to inactivate NF-κB pathway. Finally, in vivo experiments demonstrated that AS-IV treatment can alleviate the lung inflammation in asthma mice. Collectively, AS-IV alleviates asthma and suppresses the pyroptosis of AMSCs through blocking HMGB1/RAGE axis to inactivate NF-κB pathway.

AbstractExtra-thick key strata (ETKS) are a key factor causing coal bursts. In this study, field monitoring, physical and numerical modelling, and theoretical analysis were comprehensively adopted to investigate the effect of ETKS on the static and dynamic stress and its impact on coal bursts. Firstly, the coal bursts and the stability of ETKS were investigated. The roof strata structure and the mining-induced stress in a large scale panel under ETKS were analyzed. Then, the coal burst mechanism under ETKS is discussed. The results show that when the panel reaches the 4th and 5th longwall faces, the inferior ETKS and the main ETKS break, respectively, and large-scale cantilever-articulated structures involving the ETKS are formed. This moment, the overburden load is transferred downwards massively, and the coal seam becomes overstressed and accumulates massive elastic energy. Meanwhile, the collaborative collapse of multiple strata in the large cantilever-articulated structures causes the sudden release of elastic energy and high-energy seismicity, which exerts strong dynamic disturbances on the overstressed coal mass and leads to coal burst. Finally, strategies for coal burst control under ETKS including deep-hole pre-splitting blasting and panel size optimization are proposed and validated.

Intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) syndrome elicited neuron injury (especially in the hippocampus and cortex), contributing to cognitive dysfunction. This study investigated the effects and clarified the mechanisms of ETS domain-containing protein Elk-4 (ELK4) on the cognitive function and neuroinflammation of mice with IH. Mouse microglia BV2 cells were induced with IH by exposure to fluctuating O2 concentrations (alternating from 5 % to 21 % every 30 min), and mice with OSA were developed and subjected to lentivirus-mediated gene intervention. ELK4 expression was significantly reduced in IH-induced microglia and brain tissues of mice with OSA. Overexpression of ELK4 attenuated oxidative stress, decreased the pro-inflammatory factors IL-1β, IL-6, and TNF-α, and increased the level of the anti-inflammatory factors IL-10 and TGF-β1, as well as the neuroprotective factor BDNF. ELK4 promoted the transcription of fibronectin type III domain-containing protein 5 (FNDC5) by binding to the promoter of FNDC5. Knockdown of FNDC5 in IH-induced microglia and animals reversed the protective effects of ELK4 on OSA-associated neuroinflammation and cognitive dysfunction. Overall, the results demonstrated that ELK4 overexpression repressed microglial activation by inducing the transcription of FNDC5, thus attenuating neuroinflammation and cognitive dysfunction induced by OSA.

The western Pacific warm pool (WPWP) is a major thermal driver of atmospheric deep convection and global atmospheric circulation in the tropics, and changes in its ocean heat content (OHC) affect the local and global climates. Four state-of-the-art ocean reanalyses and one objective analysis were used to study the variations in the WPWP OHC, ocean heat content tendency (OHCT), and ocean heat transport (OHT). The variabilities of both the OHC and OHCT integrated from 0 to 300 m are consistent between the datasets and are closely related to the El-Niño southern oscillation cycle. The integrated OHC from 0 to 2000 m shows an overall increasing trend in the WPWP. The WPWP mainly gains heat from the eastern boundary and loses heat from the northern boundary. The heat transport through the eastern boundary of the WPWP is mainly facilitated by the westward flowing south and north equatorial currents as well as the equatorial countercurrent around the depth of the thermocline, whereas the OHT at the northern boundary is mainly driven by the western boundary current of the Pacific Ocean, which shows complex flow structures.

Despite their numerous excellent properties, metal sulfides are not particularly efficient at converting energy and purifying the environment, which limits their further applications. Fortunately, the energy conversion and environmental purification efficiencies of these materials have experienced notable advancements in recent years, accompanied by an improved understanding of their underlying mechanisms. Herein, progress in experimental researches in recent years on the engineering of single component metal sulfides by controlling morphology, construction of heterojunctions, and incorporating elements is reviewed. Methods to design and prepare metal sulfide‐based composites by building binary or ternary heterojunctions of metal sulfide/semiconductor/conductor are also discussed in detail. These materials are used in energy conversion and environmental purification systems, where they act as photocatalytic materials not only to split water, reduce carbon dioxide or nitrogen, but also to degrade pollutants (organic and inorganic) in water and gas. Finally, it is concluded by summarizing the research frontiers of metal sulfide nanomaterials in energy and environmental applications, as well as proposing potential challenges and future research directions. This work may contribute to a better understanding of metal sulfide nanocomposites and provide clues for the fabrication of more efficient metal sulfide‐based nanostructures for clean energy production and environmental remediation.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has increased rapidly in recent years. The BRAF inhibitor vemurafenib is effective against BRAFV600E-positive PTC; however, acquired resistance to single agent therapy frequently leads to tumor recurrence and metastasis, underscoring the need to develop tailored treatment strategies. We previously showed that the oncogenic kinase PIM1 was associated with the malignant phenotype and prognosis of PTC. In this study, we showed that sustained expression of the PIM1 protein in PTC was affected by the BRAFV600E mutation. Based on this regulatory mechanism, we tested the synergistic effects of inhibitors of BRAF (BRAFi) and PIM1 in BRAFV600E-positive PTC cell lines and xenograft tumors. LC-MS metabolomics analyses suggested that BRAFi/PIMi therapy acted by restricting the amounts of critical amino acids and nucleotides required by cancer cells as well as modulating DNA methylation. This study elucidates the role of BRAFV600E in the regulation of PIM1 in PTC and demonstrates the synergistic effect of a novel combination, BRAFi/PIMi, for the treatment of PTC. This discovery, along with the pathways that may be involved in the powerful efficacy of BRAFi/PIMi strategy from the perspective of cell metabolism, provides insight into the molecular basis of PTC progression and offers new perspectives for BRAF-resistant PTC treatment.

Oligosaccharides are low-molecular-weight carbohydrates between monosaccharides and polysaccharides. They can be extracted directly from natural products by physicochemical methods or obtained by chemical synthesis or enzymatic reaction. Oligosaccharides have important physicochemical and physiological properties. Their research and production involve many disciplines such as medicine, chemical industry, and biology. Functional oligosaccharides, as an excellent functional food base, can be used as dietary fibrer and prebiotics to enrich the diet; improve the microecology of the gut; exert antitumour, anti-inflammatory, antioxidant, and lipid-lowering properties. Therefore, the industrial applications of oligosaccharides have increased rapidly in the past few years. It has great prospects in the field of food and medicinal chemistry. This review summarized the preparation, structural features and biological activities of oligosaccharides, with particular emphasis on the application of functional oligosaccharides in the food industry and human nutritional health. It aims to inform further research and development of oligosaccharides and food chemistry.

Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. Helicoverpa armigera as a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla on larval maxillary galea were 100–1000 times more sensitive to sucrose than those on adult antennae, tarsi, and proboscis. Using the Xenopus expression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt toward the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.

Objective The escalating global aging population underscores the need to effectively manage geriatric diseases, constituting a significant public health concern. Community-based rehabilitation has emerged as a crucial and accessible paradigm for the rehabilitation of older adults. In China, however, the practical implementation of community-based rehabilitation faces formidable challenges, including a dearth of specialized rehabilitation therapists, substantial disparities between demand and supply, and suboptimal satisfaction rates. We aimed to develop a community-based rehabilitation management platform for older adults centered around digital health technology, with the plan to conduct a cluster randomized controlled trial to gather more evidence to explore the best practices and service models of community-based rehabilitation based on digital health technology. Methods This cluster randomized controlled trial will be conducted in Zunyi City, China. We will recruit 286 adults aged ≥60 years and randomly allocate 20 subdistricts in a 1:1 ratio into either the intervention group, which will use the Rehabilitation Journey application, or the control group, which will be given a Rehabilitation Information Booklet for Older Adults. Both groups will undergo a 12-month rehabilitation management program, encompassing six months of guidance and an additional six months of follow-up through online and offline methods. The evaluation indicators will be assessed at enrollment and at 3 rd , 6 th , and 12 th month. Discussion This study endeavors to furnish novel insights to develop a tailored community-based rehabilitation management program for older adults, delivering customized, intelligent, and precise rehabilitation services.

Abstract Background Here we described a new threading technique for the universal fixation of any posterior chamber intraocular lens (IOL). Methods Twenty-seven eyes of 27 patients whose surgery done by Surgeon A with the needle-guided method or the suture needle retrograde threading (SNRT) method for intrascleral IOL fixation were enrolled in the first group. Thirty-four eyes of 34 patients whose surgery done by Surgeon A, Surgeon B or Surgeon C with the SNRT method for intrascleral IOL fixation were grouped into three sub-groups by surgeon. Information regarding age, sex, best-available visual acuity (BCVA), intraocular pressure (IOP), past ophthalmological history, threading time (from puncturing to externalizing suture) and complications during and after the surgery were gathered. Results The analysis showed that the threading time was less in the SNRT group than needle-guided group by Surgeon A. There was one eye with suture needle slipping from the guide needle when guiding out of the eye. The threading procedure was completed one time without suture ruptures or loop slippage in the SNRT group operated by Surgeon A. And using the SNRT method, Surgeon A, Surgeon B, and Surgeon C did not show any significant difference in threading time. No complications (e.g., vitreous hemorrhage, hyphemia, retinal detachment, suprachoroidal hemorrhage, or hypotony) were observed during surgery or postoperatively in all cases. No leakage occurred at the site of the puncture after the operation. Conclusions The described technique appears to be a safe, simple, easy-to-learn, and universal surgical method, which is suitable for various types of IOLs.

Abstract Background The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. Methods A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. Results In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-β (IFN-β) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. Conclusions Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

Abstract Backgroud Multiple studies have identified pathogenic germline variants in cancer susceptibility genes (CSGs) in Chinese lung cancer patients; however, accurate assessment of these variants' contributions to cancer predisposition is always hampered by the absence of data on the prevalence of these variants in the general population. It is necessary to conduct a large‐scale case–control study to identify CSGs that significantly increase the risk of lung cancer. Materials and methods We performed targeted sequencing of a CSGs panel in 1117 lung cancer patients and 16,327 controls from the general Chinese population. Results In comparison to controls, lung cancer patients had a considerably higher prevalence of pathogenic and likely pathogenic (P/LP) variations. Among lung cancer patients, 72% of P/LP variants carriers did not have a family cancer history, who would be ignored if germline testing was only provided for patients meeting family history‐based criteria. Furthermore, compared to individuals with late‐onset lung cancer, patients with early‐onset lung cancer had a considerably higher prevalence of P/LP variations. With odds ratios (ORs) ranging from 4‐fold (BRCA1: OR, 4.193; 95%CI, 1.382–10.768) to 29‐fold (TP53: OR, 29.281; 95%CI, 1.523–1705.506), P/LP variants in the BRCA1 and TP53 genes were discovered to be strongly related to increased lung cancer risk. Additionally, with ORs ranging from 7.322‐fold to infinity, we discovered 23 variations previously categorized as non‐P/LP variants were highly enriched in lung cancer patients. Conclusion Our findings indicated that P/LP variants in BRCA1 and TP53 conferred increased risk of lung cancer in Chinese.

Abstract Argonaute proteins (Agos) bind short nucleic acids as guides and are directed by them to recognize target complementary nucleic acids. Diverse prokaryotic Agos (pAgos) play potential functions in microbial defense. The functions and mechanisms of a group of full-length yet catalytically inactive pAgos, long-B pAgos, remain unclear. Here, we show that most long-B pAgos are functionally connected with distinct associated proteins, including nucleases, Sir2-domain-containing proteins and trans-membrane proteins, respectively. The long-B pAgo-nuclease system (BPAN) is activated by guide RNA-directed target DNA recognition and performs collateral DNA degradation in vitro. In vivo, the system mediates genomic DNA degradation after sensing invading plasmid, which kills the infected cells and results in the depletion of the invader from the cell population. Together, the BPAN system provides immunoprotection via abortive infection. Our data also suggest that the defense strategy is employed by other long-B pAgos equipped with distinct associated proteins.

Abstract Seawater electrolysis is a viable method for producing hydrogen on a large scale and low-cost. However, the catalyst activity during the seawater splitting process will dramatically degrade as salt concentrations increasing. Herein, CoP is discovered that could reject chloride ions far from catalyst in electrolyte based on molecular dynamic simulation. Thus, a binder-free electrode is designed and constructed by in-situ growth of homogeneous CoP on rGO nanosheets wrapped around the surface of Ti fiber felt for seawater splitting. As expected, the as-obtained CoP/rGO@Ti electrode exhibits good catalytic activity and stability in alkaline electrolyte. Especially, benefitting from the highly effective repulsive Cl− intrinsic characteristic of CoP, the catalyst maintains good catalytic performance with saturated salt concentration, and the overpotential increasing is less than 28 mV at 10 mA cm−2 from 0 M to saturated NaCl in electrolyte. Furthermore, the catalyst for seawater splitting performs superior corrosion-resistance with a low solubility of 0.04%. This work sheds fresh light into the development of efficient HER catalysts for salinity tolerance hydrogen evolution.