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Abstract Background Anesthetic drugs may alter exosomal microRNA (miRNA) contents and mediate cancer progression and tumor microenvironment remodeling. Our study aims to explore how the anesthetics (sevoflurane and propofol) impact the miRNA makeup within exosomes in hepatocellular carcinoma (HCC), alongside the interconnected signaling pathways linked to the tumor immune microenvironment. Methods In this prospective study, we collected plasma exosomes from two groups of HCC patients (n = 5 each) treated with either propofol or sevoflurane, both before anesthesia and after hepatectomy. Exosomal miRNA profiles were assessed using next-generation sequencing (NGS). Furthermore, the expression data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) was used to pinpoint the differentially expressed exosomal miRNAs (DEmiRNAs) attributed to the influence of propofol or sevoflurane in the context of HCC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to dissect the signaling pathways and biological activities associated with the identified DEmiRNAs and their corresponding target genes. Results A total of 35 distinct DEmiRNAs were exclusively regulated by either propofol (n = 9) or sevoflurane (n = 26). Through TCGA-LIHC database analysis, 8 DEmiRNAs were associated with HCC. These included propofol-triggered miR-452-5p and let-7c-5p, as well as sevoflurane-induced miR-24-1-5p, miR-122-5p, miR-200a-3p, miR-4686, miR-214-3p, and miR-511-5p. Analyses revealed that among these 8 DEmiRNAs, the upregulation of miR-24-1-5p consistently demonstrated a significant association with lower histological grades (p

Abstract This paper studies the input‐to‐state stability of an uncertain switched linear system with external disturbances, whose feedback loop is closed over a digital communication network. In the network, only a finite bit rate can be provided to transmit the feedback signal and unknown network delay always exists. By using reachable set approximation and propagation methods, it can well handle with the effects of model uncertainty, external disturbances and network delay on the stability of the system. To save network resources, event‐triggered sampling is taken here. Under the event‐triggered sampling strategies, a new encoder is proposed, which consumes less feedback bits than the conventional time‐triggered encoders. It is proven that even in the existence of model uncertainty, external disturbances and network delay, the proposed event‐triggered sampling strategies require a lower feedback bit rate to stabilize the switched system than conventional periodic sampling methods.

Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn2+ ions in ABL@ZnTA can act as zinc finger motif to co-stabilize the configuration of ABL through multiple molecular interactions, enabling high bioactivity, high loading capacity (1.36 times), and long-term release (>7 days) of ABL. Our results showed that ABL@ZnTA can modulate macrophage polarization from the pro-inflammatory M1 towards the anti-inflammatory M2 phenotype, promoting immune osteogenesis with increased OCN, ALP, and SOD 1 expression. Furthermore, the ABL@ZnTA significantly reduces inflammatory fibrous tissue encapsulation and enhances the long-term stability of the implants, indicated by enhanced binding strength (6 times) and functional connectivity (1.5−3 times) in the rat bone defect model infected by S. aureus. Overall, our research offers a nano-enabled synergistic strategy that balances infection defense and osteogenesis promotion in orthopedic and dental implantations.

Abstract The outbreak of the coronavirus pandemic in 2019 has profoundly affected public health and the global economy. Policymakers face the challenge of evolving virus mutations and one key measure involves the use of Health Code to classify the public and enforce quarantine policies. Despite widespread adoption, its effectiveness in mitigating the epidemic is not well understood. Here, we proposed an infection component model to assess the Health Code’s effectiveness. We found that “Precise control” using Health Code can strike a balance between economic growth and public health, reducing 97% of deaths and improving 1% of GDP compared to “No control” or city shutdown policies. Moreover, its medical costs are only 43% of the latter. However, its effectiveness diminishes if the basic reproductive number ( $${R}_{0}$$ R 0 ) exceeds 16.5, indicating the end of this epidemic with “Precise control”. These findings have important implications for policymakers in developing effective strategies to combat the pandemic.

In view of the large-scale and efficient coal mining in ecologically fragile areas, which causes a large scope, long cycle and high intensity of ecological impacts, and the lack of a systematic technology that integrates the whole cycle of mining, source reduction and ecological elements, which leads to high costs, low efficiency and poor results in the ecological restoration of mining areas. This paper puts forward the concept of ecological protection coal mining, the damage conduction pathway of surface mining and the damage conduction model of shaft mining, the quantitative analysis method of ecological damage and the decision-making method of ecological restoration in mining areas. It has developed land-saving and loss-reducing mining for open pit mines, ecological stratigraphic reconstruction, distributed water resources collection, storage and use, and synergistic restoration technologies based on the "ecological restoration window period". It has researched and developed technologies for damage conduction control in well mining, ecological function restoration of aquifers, construction of assembled wedge-shaped groundwater reservoir dams, and ecological restoration of subsidence zones in time zones. An ecologically protected open pit mining demonstration project has been completed in the mengdong mining area, with the vegetation cover in the baorixile open pit mine demonstration area increasing from 30% to 59% of the pre-exploitation area, and that in the shengli open pit mine demonstration area from 5% to 39% of the pre-exploitation area. A demonstration project for ecologically protected coal mining in the shengdong wells has been completed, with vegetation cover increasing from less than 10% to 70 % of the pre-exploitation area. The research results provide scientific and technological support for eco-protective coal mining and have wide application and promotion value.

Abstract Background Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. Methods We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. Results During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44–1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44–1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (P trend

BackgroundMigraine is a common primary headache that has a significant impact on patients’ quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background.ObjectiveThe aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort.MethodsIn this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom’s MALDI-TOF iPLEX platform.ResultsIn univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS).ConclusionThe study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients.

Abstract Outdated coal mining technologies involve considerable mine water resource waste. For coal mines located in water-starved western regions of China, this jeopardizes the sustainable coal mining development, local eco-environment, and agricultural production. Coal mine underground reservoirs furnish conservation and cyclic utilization of water resources in the coal mining process. The weakest links of underground reservoirs are artificial dams that are prone to frequent occurrence of water seepage and instability failures. Aiming to explore the deformation rules of artificial dams under fluid–solid coupling action, this study developed a nested multi-coupling test system comprising a model shelf, a mine pressure simulation device, a water pressure simulation device, and a monitoring system, The maximum size of the model shelf is 1400 mm * 1300 mm * 200 mm. The mine pressure simulation device was composed of static-load and vibration-load oil cylinders of various sizes. A servo motor mainly controlled the water pressure device; with a water pressure sensor and high-precision flowmeter, water pressure could be accurately adjusted. By taking the underground reservoir in the Wulanmulun Coal Mine as an example, the deformation failure characteristics of the MB-1 dam under fluid–solid coupling conditions were simulated to validate the reasonability and feasibility of the developed system. The obtained experimental results indicated that the artificial dam damage was induced by increased mine pressure, leading to shear compression failure. The artificial dam underwent plastic deformation at a water pressure of 11.43 kPa, accompanied with the generation of microfractures, which rapid propagation under vibration loading violated the dam’s stability.

The northern sand-proof belt is the key zone for preventing and controlling desertification and sandification in China, and it is the core area of the “Three Norths” project, which is characterized by infertile soil, high wind speed, drought and water shortage, sparse vegetation, and low ecological resilience, and the contradiction between large-scale open-pit coal mining and ecological protection is prominent, which directly affects the regional ecological security and the national energy security, and there is an urgent need to carry out the research on the ecological protection and restoration of large-scale open-pit mining areas. The study of ecological protection and restoration of large-scale open-pit mining area is urgently needed. To address the problems of land destruction, dust and sand, falling water level, soil sanding, and vegetation degradation caused by large-scale open-pit coal mining in the northern sand belt, the study is based on the area of the northern sand belt and the size of the open-pit coal mine. Taking the large-scale surface coal mining area in Inner Mongolia, which has the largest area and proportion of surface coal production in the northern sand belt, as the research area, the research idea of “loss-reducing mining - three-dimensional water preservation - soil creation and soil revitalization - systematic restoration - integrated supervision and management” is revealed. Adhering to the research idea of “loss-reducing mining - three-dimensional water conservation - soil creation and living soil - system restoration - integrated supervision”, the research area reveals the transmission mechanism of geotechnical damage and ecological degradation of large-scale surface mines, the mechanism of ecological loss-reducing mining, the mechanism of ecological self-sustainability, and develops key technologies such as loss-reducing mining with ecological protection, ecological design, water resource protection and comprehensive utilization, erosion-resistant geomorphological remodeling, fine reconstruction of the living soil layer in the discharge site, soil improvement, and quality enhancement and capacity increase, and joint restoration of fungus-algae-grass, ecosystem degradation supervision and other key technologies, form an ecological protection and restoration technology system suitable for the open-pit coal mine area in the northern sand-proof belt, and build a large-scale integrated demonstration area for ecological protection and restoration of the open-pit mine area. We will create a low-cost, high-efficiency, sustainable and replicable ecological protection and restoration model for large-scale open-pit coal mining areas, provide support for scientific mining and ecological safety in large-scale open-pit coal mining areas in the northern sand-proof belt of China, and realize the goal of coordinating energy supply and ecological protection in coal development and the goal of “developing the gold and silver mountains and recreating the green mountains and green water”.

Parkinson’s disease (PD) is a common neurodegenerative disorder with no cure. Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity. The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A. membranaceus (TFA) and their protective mechanisms. TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse model of Parkinsonism, by improving behavior performance in the gait analysis and pole test, and inhibiting the decline of tyrosine hydroxylase (TH) positive neurons and TH protein expression in substantia nigra of mice. TFA also prevented 1-methyl-4-phenylpyridinium (MPP+) induced neurotoxicity in SH-SY5Y cells, by increasing GSH and GSH/GSSG ratio, and reducing reactive oxygen species. In addition, the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+ induced downregulation of SLC7A11 and glutathione peroxidase 4 (GPX-4). In conclusion, we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+ induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis, suggesting the use of TFA as a possible food supplement in the prevention of PD.

BackgroundIncreasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them has yet to be established.MethodsFrom the published genome-wide association study (GWAS) summary statistics, we obtained data on the gut microbiota and three autoimmune neurologic disorders (Multiple Sclerosis, Guillain-Barré Syndrome, and Myasthenia Gravis). We then implemented a two-sample Mendelian Randomization (MR) to determine the causal relationship between the gut microbiota and the diseases. To validate the results, we conducted a series of sensitivity analyses. Finally, to verify the direction of causality, a reverse-causality analysis was done.ResultsWe discovered that a higher relative abundance of the genus Ruminococcus2 (OR: 1.213, 95% CI: 1.006–1.462, p = 0.043, PFDR = 0.048) and the genus Roseburia (OR: 1.255, 95% CI: 1.012–1.556, p = 0.038, PFDR = 0.048) were associated with a higher risk of MS. Furthermore, the higher the abundance of the class Mollicutes (OR: 3.016, 95% CI: 1.228–7.411, p = 0.016, PFDR = 0.021), the genus Eubacterium (hallii group) (OR: 2.787, 95% CI: 1.140–6.816, p = 0.025, PFDR = 0.025), and the phylum Tenericutes (OR: 3.016, 95% CI: 1.228–7.411, p = 0.016, PFDR = 0.021) was linked to a greater probability of GBS. Additionally, the higher the abundance of the genus Ruminococcaceae UCG005 (OR: 2.450, 95% CI: 1.072–5.598, p = 0.034, PFDR = 0.036), the genus Holdemania (OR: 2.437, 95% CI: 1.215–4.888, p = 0.012, PFDR = 0.024), genus Lachnoclostridium (OR: 3.681, 95% CI: 1.288–10.521, p = 0.015, PFDR = 0.025) and the genus Eubacterium (ruminantium group) (OR: 2.157, 95% CI: 1.211–3.843, p = 0.003, PFDR = 0.016) correlated with a greater chance of MG occurrence. No SNPs were identified as outliers through sensitivity analysis. Then, the results of the reverse MR analysis did not indicate any reverse causality.ConclusionOur findings demonstrate a causal relationship between the gut microbiota and three autoimmune neurologic disorders, providing novel insights into the mechanisms of these autoimmune neurologic disorders that are mediated by gut microbiota.

Dysregulated pre-mRNA splicing and metabolism are two hallmarks of MYC-driven cancers. Pharmacological inhibition of both processes has been extensively investigated as potential therapeutic avenues in preclinical and clinical studies. However, how pre-mRNA splicing and metabolism are orchestrated in response to oncogenic stress and therapies is poorly understood. Here, we demonstrate that jumonji domain containing 6, arginine demethylase, and lysine hydroxylase, JMJD6, acts as a hub connecting splicing and metabolism in MYC-driven human neuroblastoma. JMJD6 cooperates with MYC in cellular transformation of murine neural crest cells by physically interacting with RNA binding proteins involved in pre-mRNA splicing and protein homeostasis. Notably, JMJD6 controls the alternative splicing of two isoforms of glutaminase (GLS), namely kidney-type glutaminase (KGA) and glutaminase C (GAC), which are rate-limiting enzymes of glutaminolysis in the central carbon metabolism in neuroblastoma. Further, we show that JMJD6 is correlated with the anti-cancer activity of indisulam, a ‘molecular glue’ that degrades splicing factor RBM39, which complexes with JMJD6. The indisulam-mediated cancer cell killing is at least partly dependent on the glutamine-related metabolic pathway mediated by JMJD6. Our findings reveal a cancer-promoting metabolic program is associated with alternative pre-mRNA splicing through JMJD6, providing a rationale to target JMJD6 as a therapeutic avenue for treating MYC-driven cancers.

Abstract Purpose Serum neurofilament light chain (sNfL) can reflect nerve damage. Whether migraine can cause neurological damage remain unclear. This study assesses sNfL levels in migraine patients and explores whether there is nerve damage in migraine. Methods A case–control study was conducted in Xiamen, China. A total of 138 migraine patients and 70 healthy controls were recruited. sNfL (pg/mL) was measured on the single-molecule array platform. Univariate, Pearson correlation and linear regression analysis were used to assess the relationship between migraine and sNfL levels, with further subgroup analysis by migraine characteristics. Results Overall, 85.10% of the 208 subjects were female, with a median age of 36 years. sNfL levels were higher in the migraine group than in the control group (4.85 (3.49, 6.62) vs. 4.11 (3.22, 5.59)), but the difference was not significant (P = 0.133). The two groups showed an almost consistent trend in which sNfL levels increased significantly with age. Subgroup analysis showed a significant increase in sNfL levels in patients with a migraine course ≥ 10 years (β = 0.693 (0.168, 1.220), P = 0.010). Regression analysis results show that age and migraine course are independent risk factors for elevated sNfL levels, and there is an interaction between the two factors. Patients aged

Abstract Combination chemotherapy is crucial for successfully treating cancer. However, the enormous number of possible drug combinations means discovering safe and effective combinations remains a significant challenge. To improve this process, we conduct large-scale targeted CRISPR knockout screens in drug-treated cells, creating a genetic map of druggable genes that sensitize cells to commonly used chemotherapeutics. We prioritize neuroblastoma, the most common extracranial pediatric solid tumor, where ~50% of high-risk patients do not survive. Our screen examines all druggable gene knockouts in 18 cell lines (10 neuroblastoma, 8 others) treated with 8 widely used drugs, resulting in 94,320 unique combination-cell line perturbations, which is comparable to the largest existing drug combination screens. Using dense drug-drug rescreening, we find that the top CRISPR-nominated drug combinations are more synergistic than standard-of-care combinations, suggesting existing combinations could be improved. As proof of principle, we discover that inhibition of PRKDC, a component of the non-homologous end-joining pathway, sensitizes high-risk neuroblastoma cells to the standard-of-care drug doxorubicin in vitro and in vivo using patient-derived xenograft (PDX) models. Our findings provide a valuable resource and demonstrate the feasibility of using targeted CRISPR knockout to discover combinations with common chemotherapeutics, a methodology with application across all cancers.

The weak bedding plane and the water-softening coal will lead to the decrease in mechanical properties, which has an important influence on the stability of underground reservoirs and the prevention and control of water inrush accidents in coal mine. To study the comprehensive influence of bedding and soaking on the mechanical properties of coal, the uniaxial compression deformation and failure characteristics of coal under different soaking conditions were analyzed through a non-destructive soaking test and uniaxial compression test and based on the Digital image correlation method (DIC). The mechanical property parameters and surface strain field information of axial parallel and vertical bedded coal samples in the natural state, natural water absorption and forced water absorption were obtained. The results shown that the water absorption characteristics of coal shown obvious stratification differences, and the mechanical properties were affected by the combined effects of stratification and soaking. The specific results were as follows, ① Capillary action led to stronger water adsorption in axial parallel-bedded coal than in axial vertical-bedded coal, and the natural limiting water absorption rate of axial parallel-bedded coal was 2.2 times higher than that of axial vertical-bedded coal. ② The uniaxial compressive strength and elastic modulus of coal were mainly affected by bedding and supplemented by soaking. The failure mode was related to the direction of bedding. The failure mode of axial vertical coal was shear failure, while that of axial parallel coal was split failure. ③ The coal failure was a process of transformation from uniform to non-uniform deformation. After water soaking, the coal appeared strain concentration area earlier, its compaction stage was prolonged, and the elastic deformation stage was shortened. The research results were helpful to further understand the water soaking characteristics, mechanical properties, and rupture evolution of axial parallel and vertical bedded coals, and can be used as a reference for the protection and stability analysis of reserved coal pillars in underground reservoirs.

Abstract Background Osteoarthritis (OA) is the most common chronic joint disease and how ferroptosis contributes to OA has garnered much attention recently. Bioinformatics promoted the discovery of ferroptosis-related biomarkers for OA. But since OA is a whole-joint disease, sensitive biomarkers for OA are still limited. We herein focused on subchondral bone, a joint component often-ignored by existing bioinformatic reports, to identify ferroptosis-related diagnostic biomarkers for OA. Method Microarray datasets GSE51588 and GSE55457 were downloaded from Gene Expression Omnibus database. Ferroptosis-related differential expression genes (Ferr-DEGs) between OA and normal samples were identified and their functional enrichment was analyzed. Common genes for OA diagnosis were selected from Ferr-DEGs using the combination of SVM-RFE, LASSO regression, and RandomForest machine learning algorithms. Common genes' diagnostic value was verified by receiver operating characteristic (ROC) curve and their association with immune infiltration was analyzed by CIBERSORT. Finally, candidate gene’s expression was verified in chondrocytes from OA patients and in an in vitro IL-1β-induced OA model, by RT-PCR. Results Two ferroptosis-related genes, LPCAT3 and PGD, were identified as OA diagnostic biomarkers and confirmed by ROC diagnostic test. The association of LPCAT3 and PGD with the infiltration of several types of immune cells was identified. The decreased expression of LPCAT3 and PGD was both confirmed in OA chondrocytes and IL-1β-induced OA condition. Conclusions We identified ferroptosis-related genes LPCAT3 and PGD as potential diagnostic biomarkers for OA, which may offer insight into the role of ferroptosis in OA and provides useful information for the diagnosis and treatment of OA.

Coronaviruses (CoVs), the largest positive-sense RNA viruses, have caused infections in both humans and animals. The cross-species transmission of CoVs poses a serious threat to public health. Rodents and bats, the two largest orders of mammals, serve as significant natural reservoirs for CoVs. It is important to monitor the CoVs carried by bats and rodents. In this study, we collected 410 fecal samples from bats and 74 intestinal samples from rats in Yunnan Province, China. Using RT-PCR, we identified one positive sample for alphacoronavirus (TC-14) from Rhinolophus sinicus (Chinese rufous horseshoe bat) and two positive samples for betacoronavirus (GS-53, GS-56) from Apodemus ilex (Rodentia: Muridae). We successfully characterized the complete genomes of TC-14 and GS-56. Phylogenetic analysis revealed that TC-14 clustered with bat CoV HKU2 and SADS-CoV, while GS-56 was closely related to rat CoV HKU24. The identification of positive selection sites and estimation of divergence dates further helped characterize the genetic evolution of TC-14 and GS-56. In summary, this research reveals the genetic evolution characteristics of TC-14 and GS-56, providing valuable references for the study of CoVs carried by bats and rodents in Yunnan Province.

Gravity measurements have important applications in geophysics, resource exploration, geodesy, and inertial navigation. The range of classical gravimetry includes laser interferometer (LI)-based absolute gravimeters, spring relative gravimeters, superconducting gravimeters, airborne/marine gravimeters, micro-electromechanical-system (MEMS) gravimeters, as well as gravity satellites and satellite altimetry. Atomic gravimetry is a new absolute gravity measurement technology based on atom interferometers (AIs) and features zero drift, long-term stability, long-term continuous measurements, and high precision. Atomic gravimetry has been used to measure static, marine, and airborne gravity; gravity gradient; as well as acceleration to test the weak equivalence principle at the China Space Station. In this paper, classical gravimetry is introduced, and the research progress on static and airborne/marine atomic gravimeters, space AIs, and atomic gravity gradiometers is reviewed. In addition, classical and atomic gravimetry are compared. Future atomic gravimetry development trends are also discussed with the aim of jointly promoting the further development of gravity measurement technologies alongside classical gravimetry.

The coal mining might cause the disturbance to the vegetation and the disturbance impacts might exist the differences for different areas, and few literatures compared and analyzed different disturbed areas based on the location of the mining face, and paid attention to the post mining self-healing effects of vegetation. Here, this paper selected the GaoFen multispectral images during 2017-2021 to study different areas of Shangwan Mine which includes the old mining area more than 5 years after mining, the new working face underground mined in 2018 and 2019, the natural growth control area and the open-pit mining affected area. The spatiotemporal changes of the surface fraction vegetation coverage (FVC) were analyzed in each area and the correlation between vegetation coverage and climatic factors was studied. The results showed that: (1) The overall vegetation coverage showed a moderate decrease trend in fluctuation from 2017 to 2021. The Open-pit mining affected areas showed the largest decline, reaching 68.3%. The FVC in the underground mining areas had a downward trend, but self-healing effect after mining was also observed. (2) The overall FVC in the study area was positively correlated with the number of precipitation days. (3) There were differences in the sensitivity to mining disturbance for different landform in the underground mining areas. (4) Although the FVC in the Old mining areas had recovered to the level of Natural growth control area, but the annual fluctuation was larger, which might mean lower ecological stability.

Abstract Background Clostridium piliforme (causative agent of Tyzzer disease) infects various animals, including primates, and hence a threat to animal and human health worldwide. At present, it is detected using traditional methods, such as path morphology, polymerase chain reaction and enzyme‐linked immunosorbent assay. Therefore, it is necessary to develop convenient, efficient visual molecular biological methods for detecting C. piliforme. Objectives To establish a method with good specificity, high sensitivity and simple operation for the detection of C. piliforme. Methods In this study, we designed internal and external primers based on the conserved 23S rRNA region of C. piliforme to develop a biotin‐labelled diarrhoea‐suffered loop‐mediated isothermal amplification (LAMP) system for detecting of C. piliforme and assessed the specificity, sensitivity and repeatability of the LAMP system. Results The LAMP system did not exhibit cross‐reactivity with 24 other common pathogenic species, indicating that it had good specificity. The minimum concentration of sensitivity was 1 × 10−7 ng/μL. Mouse models (Meriones unguiculatus) of Tyzzer disease were established and a LAMP−lateral flow dipstick (LAMP–LFD) was developed for detecting C. piliforme. The detection rate of C. piliforme was 5.08% in clean‐grade animals and 9.96% in specific‐pathogen‐free‐grade animals from Jiangsu, Zhejiang and Shanghai. In addition, the detection rates of C. piliforme were 10.1%, 8.6% and 20%, in animals from Hangzhou, Wenzhou and Shaoxing, respectively. The detection rate of C. piliforme was higher in experimental animals used in schools than in those used in companies and research institutes. Conclusions The LAMP–LFD method established in this study can be used to detect C. piliforme in animals handled in laboratory facilities of universities, pharmaceutical enterprises and research and development institutions.

AbstractBackground End-stage renal disease (ESRD) patients have functional and structural brain abnormalities. The cerebellum also showed varying degrees of damage. However, no studies on cerebellar-cerebral functional connectivity (FC) have been conducted in ESRD patients. This study aimed to investigate the changes in cerebellar-cerebral FC in ESRD patients and its relationship with neuropsychological and clinical indexes.Methods Resting-state functional magnetic resonance imaging and neuropsychological assessment were performed on 37 ESRD patients and 35 control subjects. Seed-based FC analysis was performed to investigate inter-group differences in cerebellar-cerebral FC. In addition, the relations of altered FC with the neuropsychological function and clinical indicators were analyzed in ERSD patients.Results ESRD patients exhibited alterations in cerebellar-cerebral FC involving the executive control network, default mode network, and affective-limbic network compared to control subjects (False discovery rate-corrected, p

Abstract Investigating gene function relies on the efficient manipulation of endogenous gene expression. Currently, a limited number of tools are available to robustly manipulate endogenous gene expression between “on” and “off” states. In this study, we insert a 63 bp coding sequence of T3H38 ribozyme into the 3’ untranslated region (UTR) of C. elegans endogenous genes using the CRISPR/Cas9 technology, which reduces the endogenous gene expression to a nearly undetectable level and generated loss-of-function phenotypes similar to that of the genetic null animals. To achieve conditional knockout, a cassette of loxP-flanked transcriptional termination signal and ribozyme is inserted into the 3’ UTR of endogenous genes, which eliminates gene expression spatially or temporally via the controllable expression of the Cre recombinase. Conditional endogenous gene turn-on can be achieved by either injecting morpholino, which blocks the ribozyme self-cleavage activity or using the Cre recombinase to remove the loxP-flanked ribozyme. Together, our results demonstrate that these ribozyme-based tools can efficiently manipulate endogenous gene expression both in space and time and expand the toolkit for studying the functions of endogenous genes.

Abstract The precision of the weak equivalence principle (WEP) test using atom interferometers (AIs) is expected to be extremely high in microgravity environment. The microgravity scientific laboratory cabinet (MSLC) in the China Space Station (CSS) can provide a higher-level microgravity than the CSS itself, which provides a good experimental environment for scientific experiments that require high microgravity. We designed and realized a payload of a dual-species cold rubidium atom interferometer. The payload is highly integrated and has a size of $$460\,{\rm{mm}}\times 330\,{\rm{mm}}\times 260\,{\rm{mm}}$$ 460 mm × 330 mm × 260 mm . It will be installed in the MSLC to carry out high-precision WEP test experiment. In this article, we introduce the constraints and guidelines of the payload design, the compositions and functions of the scientific payload, the expected test precision in space, and some results of the ground test experiments.

Abstract A lack of relevant genetic models and cell lines hampers our understanding of hepatoblastoma pathogenesis and the development of new therapies for this neoplasm. Here, we report an improved MYC-driven hepatoblastoma-like murine model that recapitulates the pathological features of embryonal type of hepatoblastoma, with transcriptomics resembling the high-risk gene signatures of the human disease. Single-cell RNA-sequencing and spatial transcriptomics identify distinct subpopulations of hepatoblastoma cells. After deriving cell lines from the mouse model, we map cancer dependency genes using CRISPR-Cas9 screening and identify druggable targets shared with human hepatoblastoma (e.g., CDK7, CDK9, PRMT1, PRMT5). Our screen also reveals oncogenes and tumor suppressor genes in hepatoblastoma that engage multiple, druggable cancer signaling pathways. Chemotherapy is critical for human hepatoblastoma treatment. A genetic mapping of doxorubicin response by CRISPR-Cas9 screening identifies modifiers whose loss-of-function synergizes with (e.g., PRKDC) or antagonizes (e.g., apoptosis genes) the effect of chemotherapy. The combination of PRKDC inhibition and doxorubicin-based chemotherapy greatly enhances therapeutic efficacy. These studies provide a set of resources including disease models suitable for identifying and validating potential therapeutic targets in human high-risk hepatoblastoma.

The Baiyun gold deposit is a medium-sized deposit in northeastern Hubei around the southern margin of the Tongbai-Dabie metallogenic belt. However, its genesis has not been determined. The metallogenic process of the Baiyun gold deposit can be divided into three stages: quartz + feldspar, quartz + native gold + electrum + polymetallic sulfides, and quartz + pyrite + calcite + iron dolomite + illite. In this study, LA-ICP-MS was used for in situ trace element and isotope analyses in the main and late ore stage hydrothermal sulfides to evaluate the genesis and evolution of ore-forming fluids. Gold is positively correlated with Ag, Cu, Pb, Zn, and Te and the Co/Ni ratio is greater than 1. The S isotope values of Py1 and Py2 are −0.23–3.04‰ and 1.27–6.09‰, respectively. As mineralization progressed, S isotope values increased. In situ S isotope values of the two types of galena symbiotic with pyrite in the main metallogenic stage are 2.97–3.47‰. In situ Fe isotopic values of pyrite are −0.05–0.82‰; values in the two stages are similar without significant fractionation. We inferred that the Baiyun gold deposit formed via magmatic mineralization related to the subduction of the Pacific Plate during the Yanshanian.

The corrosion of steel materials has become a global issue, causing significant socio-economic losses and safety concerns. Hot-dip galvanizing is currently one of the most widely used steel anti-corrosion processes. With the rapid advancement of science and technology and emerging industries, the performance of pure galvanized products struggles to meet the demands of practical applications in various environments. Consequently, researchers have begun introducing various metals into the zinc solution to form high-performance alloy coatings. This article primarily explains the process flow of hot-dip galvanizing and the impact of metal elements such as Al, Mg, Sn, and Bi on the coating, as well as outlining the major issues currently faced by the hot-dip galvanizing process. The objective is to offer a more comprehensive introduction to those new to the field of hot-dip galvanizing and to provide theoretical insights for addressing production issues.

Acute myeloid leukemia (AML) is a hematological malignancy that is characterized by an expansion of immature myeloid precursors. Despite therapeutic advances, the prognosis of AML patients remains poor and there is a need for the evaluation of promising therapeutic candidates to treat the disease. The objective of this study was to evaluate the efficacy of duocarmycin Stable A (DSA) in AML cells in vitro. We hypothesized that DSA would induce DNA damage in the form of DNA double-strand breaks (DSBs) and exert cytotoxic effects on AML cells within the picomolar range. Human AML cell lines Molm-14 and HL-60 were used to perform 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), DNA DSBs, cell cycle, 5-ethynyl-2-deoxyuridine (EdU), colony formation unit (CFU), Annexin V, RNA sequencing and other assays described in this study. Our results showed that DSA induced DNA DSBs, induced cell cycle arrest at the G2M phase, reduced proliferation and increased apoptosis in AML cells. Additionally, RNA sequencing results showed that DSA regulates genes that are associated with cellular processes such as DNA repair, G2M checkpoint and apoptosis. These results suggest that DSA is efficacious in AML cells and is therefore a promising potential therapeutic candidate that can be further evaluated for the treatment of AML.

Abstract Purpose The purpose of this study was to explore the feasibility and evaluate the clinical outcomes of treatment for phalangeal and metacarpal segmental defects with the induced membrane technique and autologous structural bone grafting. Methods Sixteen patients who sustained phalangeal or metacarpal bone segmental defects were treated by the induced membrane technique and autologous structural bone grafting from June 2020 to June 2021 at our center. Results The average follow-up was 24 weeks (range, 12–40 weeks). Radiography demonstrated union of all bone grafts after an average of 8.6 weeks (range, 8–12 weeks). All incisions at donor and recipient sites demonstrated primary heal without infection complications. The mean visual analog scale score of the donor site was 1.8 (range, 0–5), with a good score in 13 cases and a fair score in 3. The mean total active motion of the fingers was 179.9°. Conclusions The feasibility of the induced membrane technique and structural treatment with a cylindrical bone graft for segmental bone defects of the metacarpal or phalanx is demonstrated by follow-up radiography results. The bone graft provided much more stability and structural support in the bone defects, and the bone healing time and bone union rate were ideal.

In the finite control set model predictive control (FCS-MPC) strategy of the grid-tied inverter, the current ripple (CR) affects the selection of optimal voltage vectors, which leads to the increase of output current ripples. In order to solve this problem, this paper proposes a CR reduction method based on reference current compensation (RCC) for the FCS-MPC strategy of grid-tied inverters. Firstly, the influence of the CR on optimal voltage vector selection is analyzed. The conventional CR prediction method is improved, which uses inverter output voltage and grid voltage to calculate current ripples based on the space state equation. It makes up for the shortcomings that the conventional CR prediction method cannot predict in some switching states. The improved CR method is more suitable for the FCS-MPC strategy. In addition, the differences between the two cost functions are compared through visual analysis. It is found that the sensitivity of the square cost function to small errors is better than that of the absolute value function. Finally, the predicted CR is used to compensate the reference current. The compensated reference current is substituted into the square cost function to reduce the CR. The experimental results show that the proposed method reduces the CR by 47.3%. The total harmonic distortion (THD) of output current is reduced from 3.86% to 2.96%.

Introduction: Preeclampsia (PE), a notable pregnancy-related disorder, leads to 40,000+ maternal deaths yearly. Recent research shows PE divides into early-onset (EOPE) and late-onset (LOPE) subtypes, each with distinct clinical features and outcomes. However, the molecular characteristics of various subtypes are currently subject to debate and are not consistent.Methods: We integrated transcriptomic expression data from a total of 372 placental samples across 8 publicly available databases via combat algorithm. Then, a variety of strategies including Random Forest Recursive Feature Elimination (RF-RFE), differential analysis, oposSOM, and Weighted Correlation Network Analysis were employed to identify the characteristic genes of the EOPE and LOPE subtypes. Finally, we conducted in vitro experiments on the key gene HK2 in HTR8/SVneo cells to explore its function.Results: Our results revealed a complex classification of PE placental samples, wherein EOPE manifests as a highly homogeneous sample group characterized by hypoxia and HIF1A activation. Among the core features is the upregulation of glycolysis-related genes, particularly HK2, in the placenta-an observation corroborated by independent validation data and single-cell data. Building on the pronounced correlation between HK2 and EOPE, we conducted in vitro experiments to assess the potential functional impact of HK2 on trophoblast cells. Additionally, the LOPE samples exhibit strong heterogeneity and lack distinct features, suggesting a complex molecular makeup for this subtype. Unsupervised clustering analysis indicates that LOPE likely comprises at least two distinct subtypes, linked to cell-environment interaction and cytokine and protein modification functionalities.Discussion: In summary, these findings elucidate potential mechanistic differences between the two PE subtypes, lend support to the hypothesis of classifying PE based on gestational weeks, and emphasize the potential significant role of glycolysis-related genes, especially HK2 in EOPE.

Abstract Background and objective Protease-activated receptor 1 (PAR1) is crucial in individuals with acute myocardial infarction (AMI). The continuous and prompt PAR1 activation mainly dependent on PAR1 trafficking is essential for the role of PAR1 during AMI in which cardiomyocytes are in hypoxia. However, the PAR1 trafficking in cardiomyocytes specially during the hypoxia is still unclear. Methods and result A rat AMI model was created. PAR1 activation with thrombin-receptor activated peptide (TRAP) had a transient effect on cardiac function in normal rats but persistent improvement in rats with AMI. Cardiomyocytes from neonatal rats were cultured in a normal CO2 incubator and a hypoxic modular incubator chamber. The cells were then subjected to western blot for the total protein expression and staining with fluorescent reagent and antibody for PAR1 localization. No change in total PAR1 expression following TRAP stimulation was observed; however, it led to increased PAR1 expression in the early endosomes in normoxic cells and decreased expression in the early endosomes in hypoxic cells. Under hypoxic conditions, TRAP restored the PAR1 expression on both cell and endosomal surfaces within an hour by decreasing Rab11A (8.5-fold; 179.93 ± 9.82% of the normoxic control group, n = 5) and increasing Rab11B (15.5-fold) expression after 4 h of hypoxia. Similarly, Rab11A knockdown upregulated PAR1 expression under normoxia, and Rab11B knockdown downregulated PAR1 expression under both normoxic and hypoxic conditions. Cardiomyocytes knocked out of both Rab11A, and Rad11B lost the TRAP-induced PAR1 expression but still exhibited the early endosomal TRAP-induced PAR1 expression under hypoxia. Conclusions TRAP-mediated activation of PAR1 in cardiomyocytes did not alter the total PAR1 expression under normoxic conditions. Instead, it triggers a redistribution of PAR1 levels under normoxic and hypoxic conditions. TRAP reverses the hypoxia-inhibited PAR1 expression in cardiomyocytes by downregulating Rab11A expression and upregulating Rab11B expression.

Abstract To provide evidence-based medicine references for formulating prevention and control policies in plateau areas, we explore the characteristics of anemia patients in Tibet (the plateau areas of China), especially those located at an altitude above 4500 m. We collected clinical data from 379 Tibetan anemia patients over the age of 18 years. We found those female patients accounted for the majority of Tibetan anemia patients. Almost half of the anemia patients aged from 28 to 47 years. The percentage of severe anemia and extremely severe anemia was 45.4% and 2.4%, respectively. 88.7% of patients are engaged in agriculture and animal husbandry, and 81.5% of patients just graduated from primary school or below. The most common causes of anemia were nutritional anemia, especially iron-deficiency anemia. At high-altitude localities, folic acid-deficiency anemia needs more attention. Overall, this study showed that altitude influences the incidence, severity, and cause of anemia. Peasants and herdsmen, low education levels, young and middle-aged women, and nutrition status should be paid attention to in future anemia control.

Abstract Background Gestational diabetes Mellitus (GDM) is a common pregnancy-specific disease with high morbidity, which is linked to a high risk of obesity and diabetes in offspring. N6-methyladenosine modification of RNA is emerging as an important epigenetic mechanism that is widely manifested in many diseases. This study aimed to investigate the mechanism of m6A methylation in metabolic syndrome in offspring result from intrauterine hyperglycemia. Methods GDM mice were established by feeding a high-fat diet 1 weeks before pregnancy. The m6A RNA methylation quantification kit was used to detect liver tissue methylation levels. PCR array was used to determine the expression of the m6A methylation modification enzyme. Immunohistochemistry, qRT-PCR, and western blot were used to examine the expression of RBM15, METTL13, IGF2BP1, and IGF2BP2. Subsequently, methylated RNA immunoprecipitation sequencing combined with mRNA sequencing, followed by dot blot and glucose uptake tests, were performed. Results In this study, we found that offspring from a GDM mother were more vulnerable to glucose intolerance and insulin resistance. GC–MS revealed significant metabolic changes including saturated fatty acids and unsaturated fatty acids in liver of GDM offspring. We also demonstrated that global mRNA m6A methylation level was significantly increased in the fetal liver of GDM mice, indicating epigenetic change may have a strong relationship with the mechanism of metabolism syndrome. Concordantly, RBM15, the RNA binding methyltransferase, was upregulated in the liver. In vitro, RBM15 suppressed insulin sensitivity and increased insulin resistance through m6A-regulated epigenetic inhabitation of CLDN4. Moreover, MeRIP-sequencing and mRNA-sequencing revealed that differently regulated genes with differential m6A peaks were enriched in metabolic pathways. Conclusion Our study revealed the essential role of RBM15 in insulin resistance and the effect of RBM15-regulated m6A modification in the metabolic syndrome of offspring of GDM mice.

Thangka murals hold significant cultural value in Tibet, but unfortunately, many of these precious murals have sustained damage over time. Therefore, the restoration of Thangka murals is crucial in preserving Tibet’s cultural heritage. The potential of Gated Convolution for Thangka mural restoration is significant due to its impressive performance. However, existing Gated Convolution-based approaches for Thangka restoration face two challenges: 1) restoration results using Gated Convolution still show blurring at the pixel level, and 2) Gated Convolution remains dependent on the perceptual field of the convolution during image inpainting. To address two challenges, we propose a novel Thangka mural inpainting method that incorporates two key components: 1) an Edge-assisted Feature Fusion (EFF) method that leverages edge information to assist in inpainting the texture details of the image and enhance the consistency of textures and edges; and 2) a Self Attention based Local Refine (SALR) network that effectively enhances the perceptual field of the convolution and captures long-distance dependencies. The experimental results demonstrate that our proposed method is effective in repairing broken areas of Thangka murals, even on a small dataset (N = 5605). To validate the effectiveness of our proposed architecture and its components, we conduct a series of ablation experiments. The results demonstrate the necessity of our approach and highlight the contributions of each component. Moreover, the proposed end-to-end approach exhibits broad applicability and can be extended to other profiling tasks based on small datasets.

Platelets are multifunctional effectors of inflammatory responses and inseparable from the occurrence and development of various inflammatory diseases. The platelet membrane (PM) is integrated onto the surface of a nano-drug delivery system to form the PM-cloaked nanoparticles (PM@NPs), which can increase the biocompatibility of the nano-drug delivery system and mitigate adverse drug reactions. Owing to the strong affinity of immune regulation and adhesion-related antigens on the surface of PM to the focal sites of inflammatory diseases, which endows PM@NPs with the potential to actively target lesions and improve the therapeutic efficacy of drugs for inflammatory diseases. Based on latest developments in PM biomimetic technique and nanomedicine for the treatment of inflammatory diseases, this paper mainly elaborates three aspects: advantages of PM@NPs, experimental foundation of PM biomimetic nanotechnology, and applications of PM@NPs to the treatment of inflammatory diseases. The aim is to provide reference for the development and application of PM@NPs and novel insights into the treatment of inflammatory diseases.

A dynamic gravimeter with an atomic interferometer (AI) can perform absolute gravity measurements with high precision. AI-based dynamic gravity measurement is a type of joint measurement that uses an AI sensor and a classical accelerometer. The coupling of the two sensors may degrade the measurement precision. In this study, we analyzed the cross-coupling effect and introduced a recovery vector to suppress this effect. We improved the phase noise of the interference fringe by a factor of 1.9 by performing marine gravity measurements using an AI-based gravimeter and optimizing the recovery vector. Marine gravity measurements were performed, and high gravity measurement precision was achieved. The external and inner coincidence accuracies of the gravity measurement were ±0.42 mGal and ±0.46 mGal after optimizing the cross-coupling effect, which was improved by factors of 4.18 and 4.21 compared to the cases without optimization.

Abstract Background Atopy varies in people of different ages owing to different physical conditions and exposure to allergens. We aimed to cluster ages based on atopic severity using K‐means cluster analysis and identify atopic incidence, severity, as well as the association among peripheral eosinophils, IgE and sensitisation. Methods Consecutive patients (n = 7654) with allergic symptoms and undergoing allergen‐specific IgE tests were included from 2013 to 2017. Age, sex, specific‐IgE, peripheral eosinophil counts and total‐IgE were collected. Results Five age categories were identified: 1–17, 18–36, 37–52, 53–69 and 70–100 years. The incidences of atopy and poly‐sensitisation decreased with increasing age. Similar trend was observed for aeroallergens, egg and milk but not for peanuts, soy or seafood. Dust mites remain the crucial factor bothering patients with allergic symptoms, especially for children and adolescents. In patients aged

PurposeTo evaluate the significance of magnetic resonance (MR) intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters in predicting early efficacy of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids before treatment.Method64 patients with 89 uterine fibroids undergoing HIFU ablation (51 sufficient ablations and 38 insufficient ablations) were enrolled in the study and completed MR imaging and IVIM-DWI before treatment. The IVIM-DWI parameters, including D (diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction) and relative blood flow (rBF) were calculated. The logistic regression (LR) model was constructed to analyze the predictors of efficacy. The receiver operating characteristic (ROC) curve was drawn to assess the model’s performance. A nomograph was constructed to visualize the model.ResultsThe D value of the sufficient ablation group (931.0(851.5-987.4) × 10−6 mm2/s) was significantly lower than that of the insufficient ablation group (1052.7(1019.6-1158.7) × 10−6 mm2/s) (p0.05). The LR model was constructed with D value, fibroid position, ventral skin distance, T2WI signal intensity, and contrast enhanced degree. The area under the ROC curve, specificity, and sensitivity of the model were 0.858 (95% confidence interval: 0.781, 0.935), 0.686, and 0.947. The nomogram and calibration curves confirmed that the model had excellent performance.ConclusionThe IVIM-DWI quantitative parameters can be used to predict early effects of HIFU ablation on uterine fibroids. A high D value before treatment may indicate that the treatment will be less effective in the early stages.

Abstract MicroRNAs (miRNAs) are a class of small non-coding RNAs ranging from 17 to 25 nt in length. miR-637 is down-regulated in most cancers and up-regulated only in clear cell renal cell carcinoma (ccRCC). miR-637 can target 21 protein-coding genes, which are involved in the regulation of cell growth, cell cycle, cell proliferation, epithelial-mesenchymal transition (EMT), cancer cell invasion and metastasis, etc. In glioma, the transcription factor ZEB2 can bind to the miR-637 promoter region and inhibit miR-637 expression. Besides, miR-637 could be negatively regulated by competing endogenous RNA (ceRNAs) comprising 13 circular RNA (circRNAs) and 9 long non-coding RNA (lncRNAs). miR-637 is involved in regulating five signaling pathways, including the Jak/STAT3, Wnt/β-catenin, PI3K/AKT, and ERK signaling pathways. Low miR-637 expression was significantly associated with larger tumors and later tumor node metastasis (TNM) staging in cancer patients. Low miR-637 expression was also associated with poorer overall survival (OS) in cancer patients such as glioblastoma and low-grade gliomas (GBM/LGG), non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and ovarian cancer (OV). Low expression of miR-637 increases the resistance of colorectal cancer (CRC) and human cholangiocarcinoma (CHOL) cancer cells to three anticancer chemotherapeutics (gemcitabine (dFdC), cisplatin (DDP), and oxaliplatin (OXA)). Our work summarizes the abnormal expression of miR-637 in various cancers, expounds on the ceRNA regulatory network and signaling pathway involved in miR-637, and summarizes the effect of its abnormal expression on the biological behavior of tumor cells. At the same time, the relationship between the expression levels of miR-637 and its related molecules and the prognosis and pathological characteristics of patients was further summarized. Finally, our work points out the insufficiency of miR-637 in current studies and is expected to provide potential clues for future miR-637-related studies.

Objective To evaluate the appropriate optimal capacity and matching probability of the platelet donor database with known HLA/HPA genotype in Shaanxi aera, and provide data support for subsequent construction, maintenance and application of the local platelet donor database. Methods A total of 11 755 individuals from the Shaanxi Branch of China Marrow Donor Program, 401 and 249 unrelated random platelet donors in Shaanxi aera were enrolled to the population study of HLA-A, -B polymorphisms, HPA genotyping and CD36 antigen expression, respectively. The frequencies of HLA-A, -B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software; matching probability and capacity evaluation of platelet donor database was conducted according to the phenotypic frequencies. Results The population genetic and phenotypic polymorphisms data of HLA-A, -B and HPA1-6, 10, 15, 21 in Shaanxi aera were obtained. The frequency of CD36 type Ⅰ or Ⅱ deficiency was 0.40%(1/249). According to the subsequent calculating and deriving, with a database size of 194 donors, the patient having approximate 95% probability could achieve matching of HPA1-6, 10, 15, 21 genotype. With a database size of 1500 donors, there is a 95% probability of matching at least one donor with HLA-A-B phenotype frequency >0.002 or haplotype frequency >0.001; meanwhile, the probability of matching a cross-reactive group donor should be 44.95%-97.57%. Based on database size of 8 856 and 15 033, the probabilities of matching HLA-A, -B phenotype were about 80% and 90%, respectively. Conclusion The differences in the distribution of HLA/HPA polymorphism in different regions make the establishment mode and optimal capacity of platelet donor database different. It is necessary to apply a variety of platelet matching transfusion strategies to expand the range of donor selection, thereby effectively reducing the database construction cost and resource requirements.

Abstract Background Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality rates. However, extant investigations have mainly focused on gray matter injury within the primary injury site after ICH rather than on white matter (WM) injury in the brain and spinal cord. This focus partly accounts for the diminished therapeutic discovery. Recent evidence suggests that chondroitin sulphate proteoglycans (CSPG), which can bind to the neural transmembrane protein tyrosine phosphatase-sigma (PTPσ), may facilitate axonal regrowth and remyelination by ameliorating neuroinflammation. Methods A clinically relevant ICH model was established using adult C57BL/6 mice. The mice were then treated systemically with intracellular sigma peptide (ISP), which specifically targets PTPσ. Sensorimotor function was assessed by various behavioral tests and electrophysiological assessment. Western blot was used to verify the expression levels of Iba-1 and different inflammatory cytokines. The morphology of white matter tracts of brain and spinal cord was evaluated by immunofluorescence staining and transmission electron microscopy (TEM). Adeno-associated virus (AAV) 2/9 injection was used to assess the ipsilateral axonal compensation after injury. Parallel in vitro studies on the effects of CSPG interference on oligodendrocyte–DRG neuron co-culture explored the molecular mechanism through which ISP treatment promoted myelination capability. Results ISP, by targeting PTPσ, improved WM integrity and sensorimotor recovery via immunomodulation. In addition, ISP administration significantly decreased WM injury in the peri-hematomal region as well as cervical spinal cord, enhanced axonal myelination and facilitated neurological restoration, including electrophysiologically assessed sensorimotor functions. Parallel in vitro studies showed that inhibition of PTPσ by ISP fosters myelination by modulating the Erk/CREB signaling pathway. Conclusions Our findings revealed for the first time that manipulation of PTPσ signaling by ISP can promote prolonged neurological recovery by restoration of the integrity of neural circuits in the CNS through modulation of Erk/CREB signaling pathway.

Concomitant fractures of the hook of hamate and scaphoid are rare injuries to the wrist. Whenever these fractures cannot be effectively managed, nonunion or osteonecrosis is encountered. Subsequent treatment is thus much more challenging for a hand surgeon or orthopedist. Minimally invasive percutaneous internal fixation is an optimal treatment with the potential to minimize injury and reduce fractures. However, the control of iatrogenic injuries, including possible damage to the adjacent vital tissue, is a challenge that needs to be addressed. Herein, we describe the case of a 26-year-old man who presented with fractures to the scaphoid and hook of hamate in his left wrist. Minimally invasive treatment—with closed reduction and percutaneous fixation of the scaphoid, wrist arthroscopy, and closed reduction and percutaneous fixation of the hook of hamate—was performed at our institution. The Mayo score of the wrist, visual analog scale (VAS) for pain, grip strength, pinch strength, and wrist motion in radial/ulnar and flexion/extension deviation were recorded. Primary healing was achieved in both fractures. At the final follow-up, the Mayo score of the wrist was 100 (excellent), the VAS score was 0 (no pain), and the grip and pinch strength of his injured hand were 90.9% and 83.3%, respectively, compared with the contralateral hand (grip strength: left, 50 kg; right, 55 kg. Pinch strength: left, 20 kg; right, 24 kg). The radial-ulnar, flexion-extension, and forearm pronation-supination directions were 30°, 140°, and 90°, respectively. Minimally invasive closed reduction with percutaneous internal fixation is an optimal technique with satisfactory outcomes for simultaneous fractures of the hook of hamate and scaphoid. Provided in this paper are details of the technique and technical suggestions for performing the procedure.

As a new type of computing paradigm closer to service terminals, mobile edge computing (MEC), can meet the requirements of computing-intensive and delay-sensitive applications. In addition, it can also reduce the burden on mobile terminals by offloading computing. Due to cost issues, results in the deployment density of mobile edge servers (MES) is restricted in real scenario, whereas the suitable MES should be chosen for better performance. Therefore, this article proposes a task offloading strategy under the sparse MES density deployment scenario. Commonly, mobile terminals may reach MES through varied access points (AP) based on multi-hop transmitting mode. The transmission delay and processing delay caused by the selection of AP and MES will affect the performance of MEC. For the purpose of reducing the transmission delay due to system load balancing and superfluous multi-hop, we formulated the multi-objective optimization problem. The optimization goals are the workload balancing of edge servers and the completion delay of all task offloading. We express the formulated system as an undirected and unweighted graph, and we propose a hybrid genetic particle swarm algorithm based on two-dimensional genes (GA-PSO). Simulation results show that the hybrid GA-PSO algorithm does not outperform state-of-the-art GA and NSA algorithms in obtaining all task offloading delays. However, the workload by standard deviation approach is about 90% lower than that of the GA and NSA algorithms, which effectively optimizes the performance of load balancing and verifies the effectiveness of the proposed algorithm.

Aiming at high accuracy of dissolved gas content prediction in transformer oil, a novel method based on gated recurrent unit and adaptive graph convolution network (GRU-AGCN) is proposed. For gated recurrent unit (GRU) can selectively choose the feature of time series, it is used to extract time series information of the gas content. Correlation among gases are extracted to improve the accuracy. The original adjacency matrix of the model is constructed according to the grey relational analysis (GRA), and the dynamic relation information between gases is extracted by adaptive graph convolution network (AGCN). The experimental result shows that the GRU-AGCN model can efficiently extract the temporal features and perceive the dynamic relationship of gases. The predictions error of the proposed method is lower than that of RNN, LSTM network and GRU network. The proposed method provides a reliable and accurate result for the prediction of dissolved gas content in transformer oil.

As a highly valued and multiple function tree species, the leaves of Cyclocarya paliurus are enriched in diverse bioactive substances with healthy function. To meet the requirement for its leaf production and medical use, the land with salt stress would be a potential resource for developing C. paliurus plantations due to the limitation of land resources in China. The basic helix-loop-helix (bHLH) transcription factor protein family, the second largest protein family in plants, has been found to play essential roles in the response to multiple abiotic stresses, especially salt stress. However, the bHLH gene family in C.paliurus has not been investigated. In this study, 159 CpbHLH genes were successfully identified from the whole-genome sequence data, and were classified into 26 subfamilies. Meanwhile, the 159 members were also analyzed from the aspects of protein sequences alignment, evolution, motif prediction, promoter cis-acting elements analysis and DNA binding ability. Based on transcriptome profiling under a hydroponic experiment with four salt concentrations (0%, 0.15%, 0.3%, and 0.45% NaCl), 9 significantly up- or down-regulated genes were screened, while 3 genes associated with salt response were selected in term of the GO annotation results. Totally 12 candidate genes were selected in response to salt stress. Moreover, based on expression analysis of the 12 candidate genes sampled from a pot experiment with three salt concentrations (0%, 0.2% and 0.4% NaCl), CpbHLH36/68/146 were further verified to be involved in the regulation of salt tolerance genes, which is also confirmed by protein interaction network analysis. This study was the first analysis of the transcription factor family at the genome-wide level of C. paliurus, and our findings would not only provide insight into the function of the CpbHLH gene family members involved in salt stress but also drive progress in genetic improvement for the salt tolerance of C. paliurus.

A 54-years-old man presented with a plaque on his right knee for 10 years, with ulceration and scabs for 2 years. Dermatological examination revealed a demarcated, intact, keratinized plaque with tenderness, covered by thick scabs, on the right medial knee. Histopathology showed hyperkeratosis, parakeratosis, acanthosis, downward projection of rete ridges, and koilocytes in the epidermis. Other features included dermal papillomatous hyperplasia, granule cells between the papillary projections, disorganized atypical cells and dyskeratosis, with normal basal layer, in the epidermis. The upper dermis was infiltrated by mixed inflammatory cells. The diagnosis was squamous cell carcinoma arising from giant verruca vulgaris.

Improving the job satisfaction of vocational education teachers (VET) is necessary for maintaining the stability of the vocational education teaching force and is an essential support for enhancing the professional attractiveness and ensuring the quality of VET. Unlike previous studies, firstly, in terms of groups, the particular group of teachers in this study focuses on VET, which in reality is often overlooked compared to other groups of teachers due to the low level of recognition of vocational education (VE) in China. Secondly, this phenomenon is more prominent and less researched regionally in economically underdeveloped areas due to the uneven and disparate economic development between the East and West of China. In terms of sample size, previous studies have lacked large samples, making it difficult to obtain convincing and realistic results. Finally, most previous studies considered teachers' job satisfaction (TJS) in terms of external or internal factors alone. However, this study considers a combination of the external factor of the school climate (SC) in which VET works and the internal factor of teachers' self-efficacy (TSE) to explore the relationship with TJS and its impact. Based on data from a survey of 1035 teachers in China, a structural equation model estimation method was used to explore and analyze the impact of SC and TSE on their TJS and the specific role of the relationship. The research found that VET-perceived SC is positively predicting TJS; VET-perceived SC is positively predicting TSE; TSE is positively predicting TJS; TSE significantly mediates the relationship between SC and TJS. This study provides a theoretical perspective that integrates the external organizational influences of SC and introduces the internal psychological factor of TSE as a mediating variable to understand TJS. In practice, it helps raise the importance of VET and provides empirical data and intellectual support to the relevant government departments in improving TJS.

In view of the problems of A∗ algorithm in path planning, such as collision risk, the path is not necessarily optimal, and there are numerous turning nodes. Therefore, this study proposes an improved A∗ algorithm to improve the quality of the planned path. First, the 8-neighborhood children of the parent node are generated, and the security of the planned path is improved by further investigating the properties of the neighbors of these children one by one to reasonably set virtual obstacles. Second, the heuristic function of A∗ algorithm is ameliorated to make it closer to the actual cost, so as to enhance the accuracy of the planned path; finally, the planned path is smoothed by using the cubic uniform B-spline curve to eliminate corner sharp points in the path. The simulation results show that the improved A∗ algorithm can not only ensure the safety and smoothness of the planned path but also obtain the shortest planned path in the static environment with different obstacle rates. In addition, we combine the improved A∗ algorithm with the dynamic window algorithm to enable mobile robots to realize real-time dynamic obstacle avoidance while ensuring the optimality of global path planning.

As a branch of the two-dimensional (2D) optimal blanking problem, rectangular strip packing is a typical non-deterministic polynomial (NP-hard) problem. The classical packing solution method relies on heuristic and metaheuristic algorithms. Usually, it needs to be designed with manual decisions to guide the solution, resulting in a small solution scale, weak generalization, and low solution efficiency. Inspired by deep learning and reinforcement learning, combined with the characteristics of rectangular piece packing, a novel algorithm based on deep reinforcement learning is proposed in this work to solve the rectangular strip packing problem. The pointer network with an encoder and decoder structure is taken as the basic network for the deep reinforcement learning algorithm. A model-free reinforcement learning algorithm is designed to train network parameters to optimize the packing sequence. This design can not only avoid designing heuristic rules separately for different problems but also use the deep networks with self-learning characteristics to solve different instances more widely. At the same time, a piece positioning algorithm based on the maximum rectangles bottom-left (Maxrects-BL) is designed to determine the placement position of pieces on the plate and calculate model rewards and packing parameters. Finally, instances are used to analyze the optimization effect of the algorithm. The experimental results show that the proposed algorithm can produce three better and five comparable results compared with some classical heuristic algorithms. In addition, the calculation time of the proposed algorithm is less than 1 second in all test instances, which shows a good generalization, solution efficiency, and practical application potential.