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Abstract Among over 2,000 species of mealybugs (Hemiptera: Pseudococcidae), only 13 genomes have been published so far, seriously limiting the researches on the phylogeny and adaptive evolution of this group. The continuous publication of mealybug genomes will significantly facilitate our exploration of the biological characteristics, detrimental attributes, and control strategies of the Pseudococcidae family. Jack Beardsley mealybug (Pseudococcus jackbeardsleyi) as one of the hazardous invasive pests, it could cause enormous losses to the fruit and vegetable industries worldwide. Herein, we combined Nanopore long-read, short-read Illumina and Hi-C sequencing, generating a high-quality chromosome-level genome assembly of P. jackbeardsleyi. The genome size was determined to be 334.818 Mb, which was assembled into 5 linkage groups with a N50 of 67.233 Mb. The BUSCO analysis demonstrated the completeness of the genome assembly and annotation are 95.7% and 92.8%, respectively. The developed high-quality genome will serve as an asset for delving into the genetic mechanisms underlying the invasiveness of P. jackbeardsleyi, thereby offering a crucial theoretical foundation for the prevention and management of Pseudococcidae pests.

Abstract Background Changes in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS. Methods Gene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRT‒PCR, western blot, and IHC assays in a PCOS mouse model. Results 19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968–1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice (P

Abstract The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for antiviral agents and provides a new strategy for the treatment of HBV-related HCC. Here, we identified a novel anti‐HBc compound—colchicine, an alkaloid compound—that promoted selective autophagic degradation of HBc through the AMPK/mTOR/ULK1 signalling pathway. We further confirmed that colchicine promoted the selective autophagy of HBc by enhancing the binding of HBc to the autophagy receptor p62. Finally, we evaluated the effects of colchicine on HBV replication and HBc-mediated HCC metastasis in vitro and in vivo. Our research indicated that the inhibitory effects of colchicine on HBV and HBV-related HCC depend on the selective autophagic degradation of HBc. Thus, colchicine is not only a promising therapeutic strategy for chronic hepatitis B but also a new treatment for HBV-related HCC.

Abstract Background The rapid growth of artificial intelligence (AI) technologies has been driven by the latest advances in computing power. Although, there exists a dearth of research on the application of AI in medical education. Methods this study is based on the TAM-ISSM-UTAUT model and introduces STARA awareness and chilling effect as moderating variables. A total of 657 valid questionnaires were collected from students of a medical university in Dalian, China, and data were statistically described using SPSS version 26, Amos 3.0 software was used to validate the research model, as well as moderated effects analysis using Process (3.3.1) software, and Origin (2021) software. Results The findings reveal that both information quality and perceived usefulness are pivotal factors that positively influence the willingness to use AI products. It also uncovers the moderating influence of the chilling effect and STARA awareness. Conclusions This suggests that enhancing information quality can be a key strategy to encourage the widespread use of AI products. Furthermore, this investigation offers valuable insights into the intersection of medical education and AI use from the standpoint of medical students. This research may prove to be pertinent in shaping the promotion of Medical Education Intelligence in the future.

Abstract Background Individuals with osteoarthritis present with comorbidities, and the potential causal associations remain incompletely elucidated. The present study undertook a large-scale investigation about the causality between osteoarthritis and variable traits, using the summary-level data of genome-wide association studies (GWAS). Methods The present study included the summary-level GWS data of knee osteoarthritis, hip osteoarthritis, hip or knee osteoarthritis, hand osteoarthritis, and other 1355 traits. Genetic correlation analysis was conducted between osteoarthritis and other traits through cross-trait bivariate linkage disequilibrium score regression. Subsequently, latent causal variable analysis was performed to explore the causal association when there was a significant genetic correlation. Genetic correlation and latent causal variable analysis were conducted on the Complex Traits Genomics Virtual Lab platform ( https://vl.genoma.io/ ). Results We found 133 unique phenotypes showing causal relationships with osteoarthritis. Our results confirmed several well-established risk factors of osteoarthritis, such as obesity, weight, BMI, and meniscus derangement. Additionally, our findings suggested putative causal links between osteoarthritis and multiple factors. Socioeconomic determinants such as occupational exposure to dust and diesel exhaust, extended work hours exceeding 40 per week, and unemployment status were implicated. Furthermore, our analysis revealed causal associations with cardiovascular and metabolic disorders, including heart failure, deep venous thrombosis, type 2 diabetes mellitus, and elevated cholesterol levels. Soft tissue and musculoskeletal disorders, such as hallux valgus, internal derangement of the knee, and spondylitis, were also identified to be causally related to osteoarthritis. The study also identified the putative causal associations of osteoarthritis with digestive and respiratory diseases, such as Barrett’s esophagus, esophagitis, and asthma, as well as psychiatric conditions including panic attacks and manic or hyperactive episodes. Additionally, we observed osteoarthritis causally related to pharmacological treatments, such as the use of antihypertensive medications, anti-asthmatic drugs, and antidepressants. Conclusion Our study uncovered a wide range of traits causally associated with osteoarthritis. Further studies are needed to validate and illustrate the detailed mechanism of those causal associations.

Abstract Background Medical diagnostics is a pivotal bridge curriculum that receives much less attention from undergraduates in non-clinical medicine health profession programs with less student engagement and poor performance. Mind mapping is an active learning strategy for graphically presenting radiant thinking to culture clinical reasoning. The purpose of this study was to explore whether students’ comprehensive diagnostic skills are enhanced through increased student engagement by employing mind mapping. Methods We implemented mind mapping in small-grouped workshops with 86 junior undergraduates from preventive medicine program, for physical diagnostic sessions including physical examination (PE) maneuver, electrocardiogram (ECG) interpretation and medical history collection. We also conducted assessments of the above skills, as well as online surveys regarding their expectation on this course, self-evaluation of mind mapping in teaching and the learning process of all the modules. Results Group members employing mind mapping in all PE sessions obtained higher scores in the heart and lung systems during the PE maneuver exam. Similarly, groups that made more in-depth mind maps achieved higher scores on the ECG quiz. In addition, groups displaying mind maps for history taking from normal classes and reformed class exhibited greater completeness of medical history with both standardized patients and real patients, which was consistent with increased collection of accompanying symptoms. Mind mapping was valued by the majority of students for its benefits in terms of acquiring PE maneuver, theoretical knowledge, medical history collection and medical records writing, clinical reasoning, communication skills, sense of teamwork and cooperation, professionalism and humanistic literacy. Discussion The visual feature of mind mapping evoked extensive behavioral engagement in all groups, as did cognitive and emotional engagement, as the majority of students expressed their willingness and affective reactions. In the short term, the positive feedbacks encourage growing engagement. The continuous benefits of mind mapping require long-term observation.

Summary: Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while in situ injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells in vivo remains poorly understood, and there is a lack of suitable in vitro models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

Abstract Rock strength criteria are the theoretical grounding of geotechnical design and stability estimation, the Mohr–Coulomb (MC) and Hoek–Brown (HB) criteria are the widely accepted criteria at present, due to their reasonability and unambiguous concept, however they overlook the effect of intermediate principal stress, and contain six singular corners in π plane. Aimed at overcoming those limitations, the MC and normal parabolic criterion (NPC) were improved to their 3D versions that lead to smooth and convex for a wide range of strength parameters. The extended 3D strength criteria coincide with corresponding original forms in the triaxial compression and triaxial extension states, which not only take intermediate principal stress into account, but also provide great convenient in numerical calculation. Multigroup of poly-axial strength datasets gathered from the references are used to check the prediction accuracy of the proposed 3D criteria by the least absolute deviation method. Research proved that the 3D NPC criterion has a relatively larger deviation on poly-axial strength data prediction, but the proposed 3D MC criterion can describe peak strength with low misfit for soft or hard rocks. Peak strength σ1 increases first and then decreases with the increase of σ2, whether increasing or decreasing σ2, both will result in rock failure. Moreover, the 3D MC can fit the poly-axial strength data well for lower or higher values of σ3, which strongly suggests the proposed 3D MC criterion is adequate. Applicability of the proposed strength criterion will be discussed in further research.

Abstract Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device’s soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

Abstract. Background:. Highly expressed in various human cancers, circular RNA Protein Kinase C Iota (circPRKCI) has been reported to play an important role in cancer development and progression. Herein, we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers. Methods:. We searched the Pubmed, Web of Science, and the Cochrane Library databases from inception until May 16, 2021. The relationship between circPRKCI expression and cancer patients' survival, including overall survival (OS) and disease-free survival (DFS), was assessed by pooled hazard ratios (HR) with corresponding 95% confidence interval (CI). The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios (OR) with corresponding 95% CI. The data were analyzed by STATA software (version 12.0) or Review Manager (RevMan 5.3). Results:. A total of 15 studies with 1109 patients were incorporated into our meta-analysis. The results demonstrated that high circPRKCI expression was significantly related to poor OS (HR = 1.96, 95% CI: 1.61, 2.39, P

The development of China’s superhard industry in the first half of 2023 is analyzed according to statistical data, as well as the import & export data of customs and the national macroeconomic indicators. It is found that the industry falls short of development expectations due to the structural adjustment of the manufacturing industry. The main indicators, including the total industrial output value, the sales revenue, the total profit and the export delivery, all in a negative growth, especially the total profit who decreases 39.5% year-on-year. Against the backdrop of relative weak global markets, the export destinations are increasingly concentrated due to the rapid development of emerging economies. For example, the markets in the Middle East and Russia hava shown higher vitality. It is suggested that the companies take active decisions and explore emerging markets for breakthroughs in products and vitality in development.

Summary: Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids.For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ABSTRACT BACKGROUND: Osteoporosis, characterized by decreased bone density and increased fracture risk, imposes significant physical, psychosocial, and financial burdens. Early detection and prevention are crucial for managing osteoporosis and reducing the risk of fractures. OBJECTIVES: To investigate the relationship between Hepatitis A seropositivity and bone mineral density (BMD) in adolescents and adults and to explore the potential link between Hepatitis A infection and osteoporosis risk. DESIGN AND SETTING: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 to evaluate the association between hepatitis A seropositivity and BMD in 15,693 participants. METHODS: Multivariable regression analysis was used to calculate the mean BMD and standard error for adolescents and adults, followed by an independent z-test to determine whether there was a significant difference between the seropositive and seronegative groups. RESULTS: Hepatitis A seropositive adolescents and adults had lower BMD than their seronegative counterparts, with significant differences in lumber spine (mean difference = -0.03 g/cm2, P < 0.01 for both age groups) and pelvis BMDs (mean difference = -0.02 g/cm2, P < 0.01 for the adult age groups), after adjusting for various covariates. CONCLUSIONS: This study confirmed that both adolescent and adult individuals seropositive for Hepatitis A antibodies had reduced BMD among both adolescents and adults, especially in the adult group. This finding suggests a possible link between Hepatitis A infection and risk of osteoporosis.

The Sanjiang Plain is an important base of commodity grain production and contains lots of marsh wetlands in China. In the past 60 years, with the continuous increase of farmland area and the adjustment of planting structure, the decline of wetland and groundwater level has attracted great attention, whether the over-exploited groundwater is controversial. The remote sensing image data from 1956 to 2019 were selected to the analyze the evolution process characteristics of wetland and farmland using single land use dynamic degree. Based on the simultaneous measurement data in 1980 and 2019−2021 and the national groundwater monitoring project data, the influence of wetland reclamation on the groundwater level was explored. The results show that: (1) From 1956 to 2019, the marsh wetland presented a decreasing trend, while the dry land showed a trend of increasing first and then decreasing, and the paddy field had a trend of increasing first and then stabilizing. Sanjiang Plain was characterized by “wetland turning into dry land” with the area of 2.36×104 km2 from 1956 to 1996, while it presented “dry land turning into paddy field” with the area of 1.15×104 km2 from 1996 to 2019. (2) The decrease in groundwater level in the area of 36 546 km2 in the Sanjiang Plain from 1980 to 2021 was less than 5 m, and more than 10 m in the eastern area with 3 669 km2. The groundwater in the Jiansanjiang area is being over-exploited. (3) Compared with the groundwater level in the dry season in 1980, the groundwater depression cone area was 3 669 km2 in 2021 with the depth of 10 m as the standard, which was 269 km2 larger than that in 2019, and slightly expanded to the northeast direction. (4) In 2019, it was difficult to reach the natural regulation of “abundance to make up for deficiency” under the condition of heavy rainfall in the Jiansanjiang reclamation area, and the groundwater storage decreased by 5.81×108 m3. The results of this study provide a foundation for the study on regional water balance and are of great significance to the scientific understanding of the rational development and utilization of water and soil resources.

Introduction: The oriental fruit fly Bactrocera dorsalis is one of the most destructive agricultural pests worldwide, with highly debated species delimitation, origin, and global spread routes. Objectives: Our study intended to (i) resolve the taxonomic uncertainties between B. dorsalis and B. carambolae, (ii) reveal the population structure and global invasion routes of B. dorsalis across Asia, Africa, and Oceania, and (iii) identify genomic regions that are responsible for the thermal adaptation of B. dorsalis. Methods: Based on a high-quality chromosome-level reference genome assembly, we explored the population relationship using a genome-scale single nucleotide polymorphism dataset generated from the resequencing data of 487 B. dorsalis genomes and 25 B. carambolae genomes. Genome-wide association studies and silencing using RNA interference were used to identify and verify the candidate genes associated with extreme thermal stress. Results: We showed that B. dorsalis originates from the Southern India region with three independent invasion and spread routes worldwide: (i) from Northern India to Northern Southeast Asia, then to Southern Southeast Asia; (ii) from Northern India to Northern Southeast Asian, then to China and Hawaii; and (iii) from Southern India toward the African mainland, then to Madagascar, which is mainly facilitated by human activities including trade and immigration. Twenty-seven genes were identified by a genome-wide association study to be associated with 11 temperature bioclimatic variables. The Cyp6a9 gene may enhance the thermal adaptation of B. dorsalis and thus boost its invasion, which tended to be upregulated at a hardening temperature of 38 °C. Functional verification using RNA interference silencing against Cyp6a9, led to the specific decrease in Cyp6a9 expression, reducing the survival rate of dsRNA-feeding larvae exposed to extreme thermal stress of 45 °C after heat hardening treatments in B. dorsalis. Conclusion: This study provides insights into the evolutionary history and genetic basis of temperature adaptation in B. dorsalis.

Abstract Climate change and biological invasions of insect pests are interlinked global concerns that drive shifts in the distribution of invasive insects. The peach fruit fly, Bactrocera zonata Saunders, is one of the most economically important Tephritidae species that attack several host plants and causes serious damage in Asia and Africa. Currently, B. zonata is absent from many countries and regions but has a risk of invasion. Therefore, it is crucial to investigate the impact of climate change on the global potential distribution of B. zonata. In this study, we used MaxEnt and CLIMEX models to estimate the risk area for B. zonata under near current and future climate conditions. The MaxEnt and CLIMEX results showed that the south of North and Central America was suitable for B. zonata. The European countries were slightly suitable for B. zonata. In Asia, the highly suitable regions of B. zonata included Saudi Arabia, United Arab Emirates, Oman, Iran, Pakistan, India, Nepal, Bangladesh, Bhutan, Myanmar, Thailand, Vietnam, and Laos. Moreover, China, Philippines, Indonesia, and Japan showed highly climate suitability for B. zonata. The climate suitability of B. zonata was increasingly high in the projection under climate change. The result of the two models showed that the climatic suitability for B. zonata will increase under climate change in China. Taken together, these predictive results support the quarantine of B. zonata for high-risk countries and provide in-depth information on how climatic changes may affect its possible geographic range.

Abstract Background Time-restricted eating (TRE), a feasible form of intermittent fasting, has been proven to benefit metabolic health in animal models and humans. To our knowledge, specific guidance on the appropriate period for eating during TRE has not yet been promoted. Therefore, to compare and assess the relative effectiveness estimates and rankings of TRE with different eating windows on human metabolic health, we conducted a systematic review and network meta-analysis (NMA). Method PubMed, EMBASE and the Cochrane Library were searched for randomized controlled trials that compared different eating windows on human metabolic health for adults. A Bayesian NMA was used to compare direct and indirect effects to determine the best different eating windows, and scientific evidence using GRADE. Results Twenty-seven RCTs comparing TRE with different eating windows on human metabolic health were reviewed, and all were included in the NMA. Compared with the normal diet group (non-TRE), the TRE group has certain benefits in reducing weight and fasting insulin. In terms of reducing fasting insulin, the 18:6 group (eating time = 6 h) was better than the 14:10 group (eating time = 10 h) and 16:8 group (eating time = 8 h) (P 0.05). Conclusions Our research showed that no particular metabolic advantages of various eating windows were found. Therefore, our results suggested that different eating windows could promote similar benefits for metabolic parameters.

Abstract Tephritidae pests are significant agricultural pests with a notable impact on the economy, with a wide range of species and most having broad host ranges and strong reproductive abilities. However, the wolfberry fruit fly, Neoceratitis asiatica (Becker), is a Tephritidae fly which only harms wolfberry. Here, we assembled and annotated N. asiatica genome at the chromosome level and compared it with the genomic and transcriptomic information from other Tephritidae flies. The assembled genome of N. asiatica had a size of 563.8 Mb and achieved a completeness level of 99.1%, 18,387 genes were annotated totally. All contigs were assembled into 7 linkage groups with an N50 of 93.166 Mb assisted by the Hi-C technique. The high-quality genome developed here will provide a significant resource for exploring the genetic basis of the adaptive and reproductive differences among various Tephritidae pests, and provides an important theoretical basis for the prevention and control of Tephritidae pests.

Abstract Background Changes in population heterozygosity and genetic diversity play important roles in mediating life history traits of organisms; these changes often lead to phenotypic evolution in offspring, which become superior to their parents. In the present study, we examined phenotypic differentiation, the intestinal microbiome composition, and metabolism shift in the oriental fruit fly (Bactrocera dorsalis) by comparing an inbred (monophyletic) original population and an outbred (mixed) invasive population. Results The results showed that the outbred population of B. dorsalis had significantly higher biomass, adult longevity, and fecundity than the inbred population. Additionally, intestinal microflora analysis revealed that both Diutina rugosa and Komagataeibacter saccharivorans were significantly enriched in the outbred population with higher genetic heterozygosity. D. rugosa enrichment altered amino acid metabolism in the intestinal tract, and supplementing essential amino acids (e.g. histidine and glutamine) in the diet led to an increase in pupal weight of the outbred population. Additionally, transcriptome analysis revealed that the HSPA1S gene was significantly downregulated in the outbred population. HSPA1S was involved in activation of the JNK-MAPK pathway through negative regulation, caused the upregulation of juvenile hormone (JH), and led to an increase in biomass in the outbred flies. Conclusion In conclusion, the outbred population had an altered intestinal microbe composition, mediating metabolism and transcriptional regulation, leading to phenotypic differentiation; this may be a potential mechanism driving the global invasion of B. dorsalis. Thus, multiple introductions could lead to invasiveness enhancement in B. dorsalis through population mixing, providing preliminary evidence that changes in the intestinal microbiome can promote biological invasion. Video Abstract

Abstract Background Osteoarthritis (OA) is a common degenerative joint disease and causes chronic pain and disability to the elderly. Several risk factors are involved, such as aging, obesity, genetic susceptibility, and environmental factors. We conducted a transcriptome-wide association study (TWAS) and chemical-related gene set enrichment analysis (CGSEA) to investigate the susceptibility genes and environmental factors. Methods TWAS analysis was conducted to identify the susceptibility genes by integrating the summary-level genome-wide association study data of knee OA (KOA) and hip OA (HOA) with the precomputed expression weights from the Genotype-Tissue Expression Project (Version 8). The FUSION software was used for both single-tissue and cross-tissue TWAS, which were combined using an aggregate Cauchy association test. The biological function and pathways of the TWAS genes were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases, and the human cartilage mRNA expression profiles were utilized to validate the TWAS genes. CGSEA analysis was performed to scan the OA-associated chemicals by integrating the TWAS results with the chemical-related gene sets. Results There were 44 and 93 unique TWAS genes identified in 7 and 11 chromosomes for KOA and HOA, respectively, fourteen and four of which showed significantly differential expression in the mRNA profiles, such as CRHR1, LTBP1, WWP2, LMX1B, and PTHLH. OA-related pathways were found in the KEGG and GO analysis, such as TGF-beta signaling pathway, MAPK signaling pathway, hyaluronan metabolic process, and chondrocyte differentiation. Forty-five OA-associated chemicals were identified, including quercetin, bisphenol A, and cadmium chloride. Conclusions Several candidate OA-associated genes and chemicals were identified through TWAS and CGSEA analysis, which expanded our understanding of the relationship between genes, chemicals, and their impact on OA.

Abstract Development and regeneration in biological tissues are fundamentally affected by stem‐cell‐fate commitment. Bioelectricity is heterogeneous between different tissues and crucially regulates cell behaviors, including cell differentiation. However, the effects of heterogeneous bioelectricity on stem‐cell differentiation remain poorly understood. Herein, it is shown that providing stem cells with electrical stimulation matching the endogenous membrane potentials of cells derived from different tissues (osteogenic‐related: −55.05 ± 4.22 mV, neurogenic‐related: −84.8 ± 7.48 mV) can induce their osteogenic or neurogenic lineage commitment. Molecular dynamics simulations indicated that the osteogenic‐related surface potential favors the adsorption of fibronectin, while the neurogenic‐related surface potential enhances the adsorption of FGF‐2. These different protein adsorptions trigger either downstream Wnt or Erk signaling, which direct stem‐cell differentiation. Surface‐potential‐mediated lineage‐specification of stem cells using bioelectrical intensity has enormous potential application value in tissue regenerative therapy.

Abstract Background Lung adenocarcinoma (LUAD) has a high mortality rate. Ferroptosis is linked to tumor initiation and progression. Aims This study aims to develop prognostic models of ferroptosis‐related lncRNAs, evaluate the correlation between differentially expressed genes and tumor microenvironment, and identify prospective drugs for managing LUAD. Methods and Results In this study, transcriptomic and clinical data were downloaded from the TCGA database, and ferroptosis‐related genes were obtained from the FerrDb database. Through correlation analysis, Cox analysis, and the LASSO algorithm for constructing a prognostic model, we found that ferroptosis‐related lncRNA‐based gene signatures (FLncSig) had a strong prognostic predicting ability in the LUAD patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments reconfirmed that ferroptosis is related to receptor‐ligand activity, enzyme inhibitor activity, and the IL‐17 signaling pathway. Next, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) algorithms, and pRRophetic were used to predict immunotherapy response and chemotherapy sensitivity. The IMvigor210 cohort was also used to validate the prognostic model. In the tumor microenvironment, Type_II_IFN_Response and HLA were found to be a group of low‐risk pathways, while MHC_class_I was a group of high‐risk pathways. Patients in the high‐risk subgroup had lower TIDE scores. Exclusion, MDSC, CAF, and TAMM2 were significantly and positively correlated with risk scores. In addition, we found 15 potential therapeutic drugs for LUAD. Finally, differential analysis of stemness index based on mRNA expression (mRNAsi) indicated that mRNAsi was correlated with gender, primary tumor (T), distant metastasis (M), and the tumor, node, and metastasis (TNM) stage in LUAD patients. Conclusions In conclusion, the prognostic model based on FLncSig can alleviate the difficulty in predicting the prognosis and immunotherapy of LUAD patients. The identified FLncSig and the screened drugs exhibit potential for clinical application and provide references for the treatment of LUAD.

BackgroundSoft tissue sarcoma (STS) is a highly heterogeneous musculoskeletal tumor with a significant impact on human health due to its high incidence and malignancy. Long non-coding RNA (lncRNA) and Neutrophil Extracellular Traps (NETs) have crucial roles in tumors. Herein, we aimed to develop a novel NETsLnc-related signature using machine learning algorithms for clinical decision-making in STS.MethodsWe applied 96 combined frameworks based on 10 different machine learning algorithms to develop a consensus signature for prognosis and therapy response prediction. Clinical characteristics, univariate and multivariate analysis, and receiver operating characteristic curve (ROC) analysis were used to evaluate the predictive performance of our models. Additionally, we explored the biological behavior, genomic patterns, and immune landscape of distinct NETsLnc groups. For patients with different NETsLnc scores, we provided information on immunotherapy responses, chemotherapy, and potential therapeutic agents to enhance the precision medicine of STS. Finally, the gene expression was validated through real-time quantitative PCR (RT-qPCR).ResultsUsing the weighted gene co-expression network analysis (WGCNA) algorithm, we identified NETsLncs. Subsequently, we constructed a prognostic NETsLnc signature with the highest mean c-index by combining machine learning algorithms. The NETsLnc-related features showed excellent and stable performance for survival prediction in STS. Patients in the low NETsLnc group, associated with improved prognosis, exhibited enhanced immune activity, immune infiltration, and tended toward an immunothermal phenotype with a potential immunotherapy response. Conversely, patients with a high NETsLnc score showed more frequent genomic alterations and demonstrated a better response to vincristine treatment. Furthermore, RT-qPCR confirmed abnormal expression of several signature lncRNAs in STS.ConclusionIn conclusion, the NETsLnc signature shows promise as a powerful approach for predicting the prognosis of STS. which not only deepens our understanding of STS but also opens avenues for more targeted and effective treatment strategies.

ABSTRACT Insect sepsis is a severe consequence that arises from the invasion of the hemocoel by symbionts of entomopathogenic nematodes and bacteria. In the present study, we unveiled the heightened virulence of the entomopathogenic nematode Steinernema feltiae and the entomopathogenic bacteria Xenorhabdus bovienii, which operate symbiotically, against the wax moth Galleria mellonella. Maximum mortality was observed at 25°C while the optimal infestation efficiency was 20 nematodes per host. After infestation, G. mellonella displayed rapid darkening and softening, accompanied by an escalated esterase activity at 9 h. The X. bovienii, released by S. feltiae, underwent substantial proliferation and discharged toxins that attacked hemocytes, thus triggering extensive hemolysis and sepsis. The host G. mellonella was usually killed within 24 h due to disseminated septicemia. Additionally, X. bovienii infestation led to the upregulation of metabolites like 3-hydroxyanthranilic acid. Strikingly, we identified the perilous actinomycin D, generated through kynurenine metabolites, representing a novel biomarker of insect sepsis. Furthermore, a comprehensive transcriptomic analysis unveiled a noteworthy upregulation of gene expression associated with actinomycin D. Overall, X. bovienii induced apoptosis and sepsis through actinomycin D production, indicating its pivotal role in infestation activity. These findings open up new avenues for studying the mechanism of sepsis and developing innovative biotic pesticides. IMPORTANCE As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential to promote sustainable pest management. In this study, we found Steinernema feltiae and Xenorhabdus bovienii were highly virulent against the insects. After infective juvenile injection, Galleria mellonella quickly turned black and softened with increasing esterase activity. Simultaneously, X. bovienii attacked hemocytes and released toxic components, resulting in extensive hemolysis and sepsis. Then, we applied high-resolution mass spectrometry-based metabolomics and found multiple substances were upregulated in the host hemolymph. We found extremely hazardous actinomycin D produced via 3-hydroxyanthranilic acid metabolites. Moreover, a combined transcriptomic analysis revealed that gene expression of proteins associated with actinomycin D was upregulated. Our research revealed actinomycin D might be responsible for the infestation activity of X. bovienii, indicating a new direction for exploring the sepsis mechanism and developing novel biotic pesticides.

IntroductionThe primary metabolism of plants, which is mediated by nitrogen, is closely related to the defense response to insect herbivores.MethodsAn experimental system was established to examine how nitrogen mediated tomato resistance to an insect herbivore, the oriental fruit fly (Bactrocera dorsalis). All tomatoes were randomly assigned to the suitable nitrogen (control, CK) treatment, nitrogen excess (NE) treatment and nitrogen deficiency (ND) treatment.ResultsWe found that nitrogen excess significantly increased the aboveground biomass of tomato and increased the pupal biomass of B. dorsalis. Metabolome analysis showed that nitrogen excess promoted the biosynthesis of amino acids in healthy fruits, including γ-aminobutyric acid (GABA), arginine and asparagine. GABA was not a differential metabolite induced by injury by B. dorsalis under nitrogen excess, but it was significantly induced in infested fruits at appropriate nitrogen levels. GABA supplementation not only increased the aboveground biomass of plants but also improved the defensive response of tomato.DiscussionThe biosynthesis of GABA in tomato is a resistance response to feeding by B. dorsalis in appropriate nitrogen, whereas nitrogen excess facilitates the pupal weight of B. dorsalis by inhibiting synthesis of the GABA pathway. This study concluded that excess nitrogen inhibits tomato defenses in plant-insect interactions by inhibiting GABA synthesis, answering some unresolved questions about the nitrogen-dependent GABA resistance pathway to herbivores.

Chronic hepatitis B virus (HBV) infection remains one of the major global public health concerns, and it develop into liver fibrosis, cirrhosis, and hepatocellular carcinoma. Recent evidence suggests that endosomal and autophagic vesicles are beneficial for HBV replication. However, it has not been well elucidated how HBV exploits such intracellular vesicle systems for its replication. RAB5A, a member of small GTPase family, plays crucial roles in early endosome biogenesis and autophagy initiation. We observed that RAB5A mRNA and protein levels were significantly increased in HBV-expressing hepatoma cell lines as well as in liver tissue samples from chronic HBV-infected patients. Moreover, RAB5A silencing inhibited HBV replication and subviral particle (SVP) expression significantly in HBV-transfected and -infected hepatoma cells, whereas RAB5A overexpression increased them. Mechanistically, RAB5A increases HBV replication through enhancement of early endosome (EE) – late endosome (LE) activation by interacting with EEA1, as well as enhancing autophagy induction by interacting with VPS34. Additionally, HBV infection enhances RAB5A-mediated dual activation of EE-LE system and autophagy. Collectively, our findings highlight that HBV utilizes RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways for its own replication and persistence. Therefore, RAB5A is a potential target for chronic HBV infection treatment.

Heavy metals, notably Pb2+ and Cu2+, are some of the most persistent contaminants found in groundwater. Frequent monitoring of these metals, which relies on efficient, sensitive, cost-effective, and reliable methods, is a necessity. We present a nanocomposite-based miniaturized electrode for the concurrent measurement of Pb2+ and Cu2+ by exploiting the electroanalytical technique of square wave voltammetry. We also propose a facile in situ hydrothermal calcination method to directly grow binder-free mesoporous NiO on a three-dimensional nickel foam, which is then electrochemically seeded with gold nanoparticles (AuNPs). The meticulous design of a low-barrier Ohmic contact between mesoporous NiO and AuNPs facilitates target-mediated nanochannel-confined electron transfer within mesoporous NiO. As a result, the heavy metals Pb2+ (0.020 mg·L−1 detection limit; 2.0–16.0 mg·L−1 detection range) and Cu2+ (0.013 mg·L−1 detection limit; 0.4–12.8 mg·L−1 detection range) can be detected simultaneously with high precision. Furthermore, other heavy metal ions and common interfering ions found in groundwater showed negligible impacts on the electrode’s performance, and the recovery rate of groundwater samples varied between 96.3% ± 2.1% and 109.4% ± 0.6%. The compactness, flexible shape, low power consumption, and ability to remotely operate our electrode pave the way for onsite detection of heavy metals in groundwater, thereby demonstrating the potential to revolutionize the field of environmental monitoring.

A survey on main economic indicators of Chinese superhard industry is conducted to reflect its development. Considering China’s macroeconomic data and the import and export trade of superhard commodities, the development situation of Chinese superhard industry is concluded. It is found that the overall development of the industry is benign, with 23.8% increase in operating revenue and 52.8% increase in operating profit, which are the highest in the past decade. The sales profit margin has reached 23.7, obviously higher than the average one of national enterprises above designated size. As with the imports and exports, the superhard industry has lower increase rates than the national average, more manifesting an internal circulation.

In view of the long process route of high-precision gear machining, a method of creep feed deep profile grinding of small-module gears was proposed. The experiments of creep feed deep profile grinding of small-module gears were carried out. The effects of different feed speeds on the grinding power, the workpiece grinding burn and the grinding wheel wear were analyzed. The wear process of grinding wheels was studied by replica method. The results show that the grinding power peak increases with the increase of feed speed. When the feed speed exceeds 150 mm/min, the grinding burns occur on the workpiece surface. Besides, the hardness of the grinding surface is significantly higher than that of the initial hardness, and the martensitic phase transformation occurs on the workpiece surface. As the depth from the grinding surface increases, the hardness values show a downward trend, and the depth of the hardness layer at the tooth bottom is smaller than that at the both sides of the tooth profile. The wear process of grinding wheels is divided into initial wear stage, stable wear stage and rapid wear stage. The material removal volume of stable wear stage is about 2 000 mm3. Excessive feed rate will cause severe wear of the grinding wheel.

This study utilized bismaleimide (BMI) resin, reinforced with introduced ether bonds, as a binding matrix, in combination with silicon carbide (SiC), for the fabrication of composite materials. A thorough investigation was conducted to assess the influence of diverse processing parameters on the mechanical properties and high-temperature thermo-oxidative stability of these composites. Experimental results indicate a notable improvement in the mechanical properties of the composites upon the incorporation of ether bonds, in contrast to their unmodified counterparts. The variation in performance among composites with different ratios and molding densities is apparent. Within a certain range, an increase in resin content and molding density is correlated with improved bending strength in the composites. With a resin content of 27.5 vol% and a molding density of 2.31 g/cm3, the composite achieved a maximum flexural strength of 109.52 MPa, representing a 24% increase compared to its pre-modification state. Even after exposure to high-temperature heat treatment, the composites displayed commendable mechanical properties compared to their pre-ether bond modification counterparts, maintaining 74.5% of the strength of the untreated composites at 300 °C. The scanning electron microscopy (SEM) microstructures of composite materials correlate remarkably well with their mechanical properties.

Currently, the sol-gel technique is employed in the synthesis of high-performance vitrified bonds; however, its application in the fabrication of stacked abrasives has been minimally explored. Furthermore, the methods utilized in the production of abrasive particles for stacked abrasives are technically challenging and incur high costs, which hinders their actual industrial application. Consequently, this study utilizes the sol-gel approach to synthesize a Na2O-B2O3-SiO2 ternary system vitrified bond powder and employs a molding and crushing method, which offers a lower technological barrier and reduced preparation costs, for the production of abrasive particles subsequently fabricating corundum stacked abrasives. Upon setting the binder composition to a molar ratio of n(SiO2):n(B2O3):n(Na2O) = 65:23:12, it was observed that the crystallization within the glass matrix was minimized and the optimal sintering temperature for the synthesized laminate abrasive to be sustained at 820 °C. At the aforementioned temperature, the binder melt is capable of flowing uniformly amongst the abrasive granules, thereby ensuring a robust encapsulation of the particles. The average single particle compressive strength of the prepared corundum stacked abrasive with a grain size of forty mesh can reach the highest of all composition points at 28.56 N and the average single particle compressive strength of the prepared diamond stacked abrasive is 28.14 N.

The surface oxygen content of low rank coal is high and the surface hydrophobicity is poor. It is difficult for diesel oil to adsorb on the coal surface efficiently. The reagent consumption is large and the flotation effect is not ideal. In this paper, diesel oil and carboxylic acid of oleic acid, lauric acid, decanoic acid and octanoic acid were combined to carry out flotation test on Datong Jurassic low rank coal. The results show that the addition of oleic acid, lauric acid and decanoic acid can effectively improve the flotation effect, and oleic acid and lauric acid have the most obvious effect. Compared with diesel oil alone, the oil rate can reach 50%. In addition, the addition of oleic acid and lauric acid can effectively increase the contact angle of coal sample surface and make the coal sample more hydrophobic. The effect of n-decanoic acid is weaker than that of oleic acid and lauric acid. Among the four carboxylic acids with 10% mass fraction and diesel oil, oleic acid has the smallest particle size in slurry, followed by lauric acid; and through XPS analysis, it is found that oleic acid can effectively increase the C-C, C-H hydrophobic oxygen-containing functional groups of coal samples, and reduce the C-O hydrophilic oxygen-containing functional groups. The dispersion of the reagent is improved effectively, and the hydrophilicity of the coal sample is weakened, and the hydrophobicity is enhanced, which improves the flotation effect.

Abstract N6-methyladenosine (m6A) is considered as the most common and important internal transcript modification in several diseases like type 2 diabetes, schizophrenia and especially cancer. As a main target of m6A methylation, long non-coding RNAs (lncRNAs) have been proved to regulate cellular processes at various levels, including epigenetic modification, transcriptional, post-transcriptional, translational and post-translational regulation. Recently, accumulating evidence suggests that m6A-modified lncRNAs greatly participate in the tumorigenesis of cancers. In this review, we systematically summarized the biogenesis of m6A-modified lncRNAs and the identified m6A-lncRNAs in a variety of cancers, as well as their potential diagnostic and therapeutic applications as biomarkers and therapeutic targets, hoping to shed light on the novel strategies for cancer treatment.

Objective: The edible fungi with high calcium enrichment rate and calcium organic degree were screened from sulfur fungus, Poria cocos, Monascus and Armillaria, and the effect of calcium enrichment on the content of the main active ingredient, dentate acid, was studied when the sulfur fungus with high calcium enrichment were cultured in liquid. Methods: The bioaccumulation method was used to study the effect of inorganic calcium on the growth of four edible fungi. The organic degree of calcium in mycelia was analyzed by static leaching method, and the content of the main active ingredient, dentate acid, was analyzed by HPLC. Results: In solid culture, the growth of sulfur fungus was better than that of Poria cocos, Armillaria and Monascus at the right amount of calcium addition. When the calcium addition amount was 100 mg/L in liquid culture, the calcium enrichment rate of sulfur fungus was significantly higher than those of Poria cocos, Armillaria and Monascus. When the calcium concentration of sulfur fungus liquid culture was 100 mg/L, the calcium enrichment rate was 93.51%, the degree of calcium organization was 85.85%, and the content of the dentate acid was 18.34 mg/g. Therefore, sulfur fungus has the potential to become a new functional calcium supplement product.

Background: Peptic ulcer disease has been a major threat to the world’s population, which remains a significant cause of hospitalization worldwide and healthcare resource utilization. Objectives: We aimed to describe the global burden, trends, and inequalities of peptic ulcer disease. Design: An observational study was conducted. Methods: In this secondary analysis of the Global Burden of Disease, Injuries, and Risk Factors Study 2019, we extracted data for age-standardized incidence rates (ASIRs), disability-adjusted life year rates (ASDRs), and mortality rates (ASMRs); then, we stratified by age, level of regionals, and country; subsequently, we calculated estimated annual percentage changes (EAPC) of ASIR, ASDR, ASMR, and quantified cross-country inequalities in peptic ulcer disease mortality. Results: Globally, ASIR showed a continuous downward trend, from 63.84 in 1990 to 44.26 per 100,000 population in 2019, with an annual decrease of 1.42% [EAPC = −1.42 (95% CI: −1.55 to −1.29)]. ASDR showed a continuing downward trend, and the EAPC was −3.47% (−3.58 to −3.37). ASMR showed a persistent decline, declining by nearly half in 2019 compared to 1990 (3.0 versus 7.39 per 100,000 population), with an annual decrease of 2.55% [EAPC = −3.36 (95% CI: −3.47 to −3.25)]. A significant reduction in sociodemographic index (SDI)-related inequality, from an excess of 190.43 disability-adjusted life years (DALY) per 100,000 (95% CI: −190.83 to −190.02) between the poorest and richest countries in 1990 to 62.85 DALY per 100,000 (95% CI −62.81 to −62.35) in 2019. Conclusion: Global peptic ulcer disease morbidity and mortality rates decreased significantly from 1990 to 2019. These health gains were in accordance with a substantial reduction in the magnitude of SDI-related inequalities across countries, which is paired with overall socioeconomic and health improvements observed in the region.

Abstract Despite the numerous unique properties revealed through tribology research on graphene, the development of applications that utilize its rich tribological properties remains a long‐sought goal. In this article, a novel approach for reversible patterning of graphene's frictional properties using out‐of‐plane mechanical tapping is presented. The friction force between the atomic force microscopy (AFM) tip and the graphene film is increased by up to a factor of two, which can be attributed to variations in the interfacial binding strength between the graphene and substrate through the tapping process. The reversible and repeatable frictional properties of graphene make it a promising material for information storage applications with a high storage capacity of ≈1600 GB inch−2, allowing for direct writing and erasing of information, akin to a blackboard. These findings highlight the potential for friction tuning in lamellar materials and emphasize the significance of understanding nanoscale friction on graphene surfaces.

Abstract Soft tissue sarcoma (STS) is an uncommon malignancy that often carries a grim prognosis. Trophinin‐associated protein (TROAP) is augmented in a variety of tumors and can affect tumor proliferation. Nevertheless, the prognostic value and specific functions of TROAP in STS are still vague. Herein, we display that TROAP exhibits an augmented trend in STS, and its elevation correlates with a poor prognosis of STS. Furthermore, its reduction is related to increased immune cell infiltration, enhanced stroma, and elevation of immune activation. Meanwhile, the TROAP‐derived genomic signature is validated to predict patient prognosis, immunotherapy, and drug response reliably. A nomogram constructed based on age, metastatic status, and a TROAP‐derived risk score of an STS individual could be used to quantify the survival probability of STS. In addition, in vitro experiments have demonstrated that TROAP is overexpressed in STS, and the downregulation of TROAP could affect the proliferation, migration, metastasis, and cell cycle of STS cells. In summary, the TROAP expression is elevated in STS tissues and cells, which is related to the poor prognosis and malignant biological behaviors of STS. It could act as a potential prognostic biomarker for diagnosis and treatment of STS.

IntroductionErigeron philadelphicus and Erigeron annuus are two ecologically destructive invasive plants from the Asteraceae family. Predicting the potential distribution pattern of two invasive alien Erigeron weeds can provide a scientific basis for prevent the further spread of these two weeds in China under climate change.MethodsBased on historical occurrence datasets and environmental variables, we optimized a MaxEnt model to predict the potential suitable habitats of E. philadelphicus and E. annuus. We also analyzed the shifts of distribution centroids and patterns under climate change scenarios.ResultsThe key variables that affect the potential geographical distribution of E. annuus and E. philadelphicus, respectively, are temperature seasonality and precipitation of the driest month. Moreover, topsoil sodicity and topsoil salinity also influence the distribution of E. philadelphicus. Under climate change, the overall suitable habitats for both invasive alien Erigeron weeds are expected to expand. The potential geographical distribution of E. annuus exhibited the highest expansion under the SSP245 climate scenario (medium forcing scenarios), whereas E. philadelphicus had the highest expansion under the SSP126 climate scenario (lower forcing scenarios) globally. The future centroid of E. annuus is projected to shift to higher latitudes specifically from Hubei to Hebei, whereas E. philadelphicus remains concentrated primarily in Hubei Province. The overlapping suitable areas of the two invasive alien Erigeron plants mainly occur in Jiangsu, Zhejiang, Fujian, Jiangxi, Hunan, Guizhou, and Chongqing, within China.DiscussionClimate change will enable E. annuus to expand into northeastern region and invade Yunnan Province whereas E. philadelphicus was historically the only suitable species. E. annuus demonstrates a greater potential for invasion and expansion under climate change, as it exhibits higher environmental tolerance. The predictive results obtained in this study can serve as a valuable reference for early warning systems and management strategies aimed at controlling the spread of these two invasive plants.

Abstract An increasing number of invasive fruit fly pests are colonizing new grounds. With this study, we aimed to uncover the invasion pathways of the oriental fruit fly, Bactrocera dorsalis into the islands of the Indian Ocean. By using genome‐wide SNP data and a multipronged approach consisting of PCA, ancestry analysis, phylogenetic inference, and kinship networks, we were able to resolve two independent invasion pathways. A western invasion pathway involved the stepping‐stone migration of B. dorsalis from the east African coast into the Comoros, along Mayotte and into Madagascar with a decreasing genetic diversity. The Mascarene islands (Reunion and Mauritius), on the contrary, were colonized directly from Asia and formed a distinct cluster. The low nucleotide diversity suggests that only a few genotypes invaded the Mascarenes. The presence of many long runs of homozygosity (ROH) in the introduced populations is indicative of population bottlenecks, with evidence of a more severe bottleneck for populations along the western migration pathway than on the Mascarene islands. More strict phytosanitary regulations are recommended in order to prevent the further spread of B. dorsalis.

Abstract Skin infections caused by drug-resistant Staphylococcus aureus occur at high rates nationwide. Mouse primary epidermal organoids (mPEOs) possess stratified histological and morphological characteristics of epidermis and are highly similar to their derived tissue at the transcriptomic and proteomic levels. Herein, the susceptibility of mPEOs to methicillin-resistant S. aureus USA300 infection was investigated. The results show that mPEOs support USA300 colonization and invasion, exhibiting swollen epithelial squamous cells with nuclear necrosis and secreting inflammatory factors such as IL-1β. Meanwhile mPEOs beneficial to observe the process of USA300 colonization with increasing infection time, and USA300 induces mPEOs to undergo pyroptosis and autophagy. In addition, we performed a drug screen for the mPEO infection model and showed that vancomycin restores cell viability and inhibits bacterial internalization in a concentration-dependent manner. In conclusion, we establish an in vitro skin infection model that contributes to the examination of drug screening strategies and antimicrobial drug mechanisms.

Based on the Purchasing Managers' Index, the relevant data of the superhard material industry, the import and the export data of superhard commodities of China Customs, and the import data of United States and Japan Customs, 6 tables and 8 charts are summarized in this study to analyze the economic operation of the superhard industry in the first half of 2022. The data shows that the growth rate of industrial added value of superhard industry is 27.4%, which is 23.0 percentage points higher than that of enterprises above the national size. The profit growth rate is 65.0%, which is 64.0 percentage points higher than that of enterprises above the national scale (74.4 percentage points higher than the 10.4% decline in manufacturing). The growth rate of export delivery value is 10.2% (the export value of superhard goods according to the statistics of the General Administration of Custom increases by 20.6% year on year, which is 7.4 percentage points higher than the national exports value). China dominates the imported market of superhard goods in United States and Japan. In the dilemma of national macroeconomic development, the main economic indicators of the superhard material industry are far higher than the corresponding national indicators, which shows the trend of vigorous development of the superhard industry.

Abstract Pyroptosis is a controlled form of inflammatory cell death characterized by inflammasome activation, pore formation, and cell lysis. According to different caspases, pyroptosis can be divided into canonical, non-canonical, and other pathways. The role of pyroptosis in disease development has been paid more attention in recent years. The trigger factors of pyroptosis are often related to oxidative stress and proinflammatory substances, which coincide with the pathological mechanism of some diseases. Pyroptosis directly leads to cell lysis and death, and the release of cytosolic components and proinflammatory cytokines affects cell activity and amplifies the inflammatory response. All the above are involved in a series of basic pathological processes, such as matrix degradation, fibrosis, and angiogenesis. Since these pathological changes are also common in musculoskeletal diseases (MSDs), emerging studies have focused on the correlations between pyroptosis and MSDs in recent years. In this review, we first summarized the molecular mechanism of pyroptosis and extensively discussed the differences and crosstalk between pyroptosis, apoptosis, and necrosis. Next, we elaborated on the role of pyroptosis in some MSDs, including osteoarthritis, rheumatoid arthritis, osteoporosis, gout arthritis, ankylosing spondylitis, intervertebral disc degeneration, and several muscle disorders. The regulation of pyroptosis could offer potential therapeutic targets in MSDs treatment. Herein, the existing drugs and therapeutic strategies that directly or indirectly target pyroptosis pathway components have been discussed in order to shed light on the novel treatment for MSDs.

The spectral matching algorithm based on the discrete particle swarm optimization algorithm (SMDPSO) sometimes overestimates extracted surface water areas. Here we constructed a new method (MEDPSO) by coupling discrete particle swarm optimization algorithm with maximum entropy model (MaxEnt) to extract water bodies using Landsat 8 Operational Land Imager (OLI) images. To compare the accuracy of the modified normalized difference water index (MNDWI), SMDPSO, and MEDPSO, we selected six areas , i.e. thermokarst lakes, Coongie Lakes National Park, the Amazon River, urban water bodies mixed with buildings, Erhai Lake that is surrounded by mountains, and high-altitude lakes. Our results show that the average overall accuracy of the MEDPSO for the six areas is 97.4%, which is higher than those of MNDWI and SMDPSO. The average commission errors and omission errors of MEDPSO (6.4% and 0.8%) are lower than those of MNDWI and SMDPSO. The MEDPSO has a higher accuracy because the maximum entropy model is a machine learning method that uses all the bands of Landsat imagery and four surface water indices in the calculation of the probability of surface water. Our study established a novel, high-precision water extraction method.

The seismic source release by fault slip under the influence of mining is an important factor to induce rock burst. In this study, the normal fault and reverse fault with different horizontal stress are constructed by numerical simulation and the fault slip law and stope dynamic response characteristics when mining the panel through the faults are compared and analyzed. Studies show that compared with mining the panel through the normal fault, the normal stress level of the reverse fault is higher, so the shear strength of the reverse fault is greater. When the fault coal pillar is small and the mining disturbance to the reverse fault is severe, the slip displacement of fault increases significantly, the shear stress drops suddenly, and the fault slip seismic source is greater. Under the influence of reverse fault slip dynamic load, the vibration velocity of coal and rock mass near the mining space, the reduction value of advanced abutment pressure and the affected range are larger, and fault slip rock burst is more likely to occur. The on-site statistical of fault slip rock burst cases are consistent with the numerical simulation results, verifying the reliability of the numerical simulation methods and conclusions.

Bactrocera dorsalis and Bactrocera correcta are two invasive species that can cause major economic damage to orchards and the fruit import and export industries. Their distribution is advancing northward due to climate change, which is threatening greater impacts on fruit production. This study tested the rapid cold-hardening ability of the two species and identified the temperature associated with the highest survival rate. Transcriptome data and survival data from the two Bactrocera species’ larvae were obtained after rapid cold-hardening experiments. Based on the sequencing of transcripts, four Hsp genes were found to be affected: Hsp68 and Hsp70, which play more important roles in the rapid cold hardening of B. dorsalis, and Hsp23 and Hsp70, which play more important roles in the rapid cold hardening of B. correcta. This study explored the adaptability of the two species to cold, demonstrated the expression and function of four Hsps in response to rapid cold hardening, and explained the occurrence and expansion of these two species of tephritids, offering information for further studies.

Abstract Although great advances have been made over the past decades, therapeutics for osteosarcoma are quite limited. We performed long‐read RNA sequencing and tandem mass tag (TMT)‐based quantitative proteome on osteosarcoma and the adjacent normal tissues, next‐generation sequencing (NGS) on paired osteosarcoma samples before and after neoadjuvant chemotherapy (NACT), and high‐throughput drug combination screen on osteosarcoma cell lines. Single‐cell RNA sequencing data were analyzed to reveal the heterogeneity of potential therapeutic target genes. Additionally, we clarified the synergistic mechanisms of doxorubicin (DOX) and HDACs inhibitors for osteosarcoma treatment. Consequently, we identified 2535 osteosarcoma‐specific genes and several alternative splicing (AS) events with osteosarcoma specificity and/or patient heterogeneity. Hundreds of potential therapeutic targets were identified among them, which showed the core regulatory roles in osteosarcoma. We also identified 215 inhibitory drugs and 236 synergistic drug combinations for osteosarcoma treatment. More interestingly, the multiomic analysis pointed out the pivotal role of HDAC1 and TOP2A in osteosarcoma. HDAC inhibitors synergized with DOX to suppress osteosarcoma both in vitro and in vivo. Mechanistically, HDAC inhibitors synergized with DOX by downregulating SP1 to transcriptionally modulate TOP2A expression. This study provided a comprehensive view of molecular features, therapeutic targets, and synergistic drug combinations for osteosarcoma.

Abstract Microneedles, especially hollow microneedles (HMNs), play an important role in drug delivery, but most of the current HMNs are manufactured based on silicon microfabrication (lithography, etching, etc.), which are slightly conservative due to the lack of low‐cost, batch‐scale and customized preparation approach, especially for the HMNs with flexible substrate. For the first time, we propose the use of a high‐precision 3D printed master mold followed by a dual‐molding process for the preparation of HMNs with different shapes, heights, and inner and outer diameters to satisfy different drug delivery needs. The 3D printed master mold and negative mold can be reused, thereby significantly reducing the cost. HMNs are based on biocompatible materials, such as heat‐curing polymers or light‐curing resins. The thickness and rigidity/flexibility characteristics of the substrate can be customized for different applications. The drug delivery efficiency of the fabricated HMNs was verified by the in situ treatment of psoriasis on the backs of mice, which required only a 0.1‐fold oral dose to achieve similar efficacy, and the associated side effects and drug toxicity were reduced. Thus, this dual‐molding process can reinvigorate HMNs development.

Background: Soft tissue sarcoma (STS) is the malignancy that exhibits remarkable histologic diversity. The diagnosis and treatment of STS is currently challenging, resulting in a high lethality. Chronic inflammation has also been identified as a key characteristic of tumors, including sarcomas. Although senescence plays an important role in the progression of various tumors, its molecular profile remains unclear in STS.Methods: We identified the senescence-related genes (SRGs) in database and depicted characteristics of genomic and transcriptomic profiling using cohort within TCGA and GEO database. In order to investigate the expression of SRGs in different cellular subtypes, single-cell RNA sequencing data was applied. The qPCR and our own sequencing data were utilized for further validation. We used unsupervised consensus clustering analysis to establish senescence-related clusters and subtypes. A senescence scoring system was established by using principal component analysis (PCA). The evaluation of clinical and molecular characteristics was conducted among distinct groups.Results: These SRGs showed differences in SCNV, mutation and mRNA expression in STS tissues compared to normal tissues. Across several cancer types, certain shared features of SRGs were identified. Several SRGs closely correlated with immune cell infiltration. Four clusters related to senescence and three subtypes related to senescence, each with unique clinical and biological traits, were established. The senescence scoring system exhibited effectiveness in predicting outcomes, clinical traits, infiltrations of immune cells and immunotherapy responses.Conclusion: Overall, the current study provided a comprehensive review of molecular profiling for SRGs in STS. The SRGs based clustering and scoring model could help guiding the clinical management of STS.

Background: Soft-tissue sarcomas (STSs) are a rare type of cancer, accounting for about 1% of all adult cancers. Treatments for STSs can be difficult to implement because of their diverse histological and molecular features, which lead to variations in tumor behavior and response to therapy. Despite the growing importance of NETosis in cancer diagnosis and treatment, researches on its role in STSs remain limited compared to other cancer types.Methods: The study thoroughly investigated NETosis-related genes (NRGs) in STSs using large cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and Support Vector Machine Recursive Feature Elimination (SVM-RFE) were employed for screening NRGs. Utilizing single-cell RNA-seq (scRNA-seq) dataset, we elucidated the expression profiles of NRGs within distinct cellular subpopulations. Several NRGs were validated by quantitative PCR (qPCR) and our proprietary sequencing data. To ascertain the impact of NRGs on the sarcoma phenotype, we conducted a series of in vitro experimental investigations. Employing unsupervised consensus clustering analysis, we established the NETosis clusters and respective NETosis subtypes. By analyzing DEGs between NETosis clusters, an NETosis scoring system was developed.Results: By comparing the outcomes obtained from LASSO regression analysis and SVM-RFE, 17 common NRGs were identified. The expression levels of the majority of NRGs exhibited notable dissimilarities between STS and normal tissues. The correlation with immune cell infiltration were demonstrated by the network comprising 17 NRGs. Patients within various NETosis clusters and subtypes exhibited different clinical and biological features. The prognostic and immune cell infiltration predictive capabilities of the scoring system were deemed efficient. Furthermore, the scoring system demonstrated potential for predicting immunotherapy response.Conclusion: The current study presents a systematic analysis of NETosis-related gene patterns in STS. The results of our study highlight the critical role NRGs play in tumor biology and the potential for personalized therapeutic approaches through the application of the NETosis score model in STS patients.

BackgroundHypermethylated in Cancer 1 (HIC1) was originally confirmed as a tumor suppressor and has been found to be hypermethylated in human cancers. Although growing evidence has supported the critical roles of HIC1 in cancer initiation and development, its roles in tumor immune microenvironment and immunotherapy are still unclear, and no comprehensive pan-cancer analysis of HIC1 has been conducted.MethodsHIC1 expression in pan-cancer, and differential HIC1 expression between tumor and normal samples were investigated. Immunohistochemistry (IHC) was employed to validate HIC1 expression in different cancers by our clinical cohorts, including lung cancer, sarcoma (SARC), breast cancer, and kidney renal clear cell carcinoma (KIRC). The prognostic value of HIC1 was illustrated by Kaplan-Meier curves and univariate Cox analysis, followed by the genetic alteration analysis of HIC1 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was conducted to illustrate the signaling pathways and biological functions of HIC1. The correlations between HIC1 and tumor mutation burden (TMB), microsatellite instability (MSI), and the immunotherapy efficacy of PD-1/PD-L1 inhibitors were analyzed by Spearman correlation analysis. Drug sensitivity analysis of HIC1 was performed by extracting data from the CellMiner™ database.ResultsHIC1 expression was abnormally expressed in most cancers, and remarkable associations between HIC1 expression and prognostic outcomes of patients in pan-cancer were detected. HIC1 was significantly correlated with T cells, macrophages, and mast cell infiltration in different cancers. Moreover, GSEA revealed that HIC1 was significantly involved in immune-related biological functions and signaling pathways. There was a close relationship of HIC1 with TMB and MSI in different cancers. Furthermore, the most exciting finding was that HIC1 expression was significantly correlated with the response to PD-1/PD-L1 inhibitors in cancer treatment. We also found that HIC1 was significantly correlated with the sensitivity of several anti-cancer drugs, such as axitinib, batracylin, and nelarabine. Finally, our clinical cohorts further validated the expression pattern of HIC1 in cancers.ConclusionsOur investigation provided an integrative understanding of the clinicopathological significance and functional roles of HIC1 in pan-cancer. Our findings suggested that HIC1 can function as a potential biomarker for predicting the prognosis, immunotherapy efficacy, and drug sensitivity with immunological activity in cancers.