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The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Abstract Background Childbirth pain is a physiological phenomenon during the delivery process, the intense pain of childbirth could bring harmful effects to pregnant women and their babies. Assessment of childbirth pain is the first step in childbirth pain intervention. Some pain assessment scales have shortcomings such as interfering in the birthing process and affecting pain perception during delivery, while the Rating Scale of Pain Expression during Childbirth (ESVADOPA) could be used as an auxiliary scale to compensate for these shortcomings. The purpose of this study was to introduce the ESVADOPA and adapt it among Chinese pregnant women to check on the psychometric properties of the translated version of ESVADOPA. Methods A new translation model based on Brislin’s classical back translation model was used to translate and cross-cultural adapt the ESVADOPA. During June 2021 and June 2022, pregnant women at Shandong Provincial Hospital Affiliated to Shandong First Medical University were invited. In the stage of translation and cross-culturally adaptation, 18 midwives and 30 pregnant women were invited to participate in the first round of pre-experiment. And in the second round of pre-experiment, 15 midwives and 20 pregnant women were invited to participate. The Chinese version of ESVADOPA was tested on a group of pregnant women (N = 487). Construct validity was evaluated by exploratory factor analysis, confirmatory factor analysis and criterion-related validity. Reliability was assessed by Cronbach’s α coefficient, McDonald Omega, Spearman-Brown split-half reliability and Guttman split-half reliability. Results The item statistical analysis and construct validity resulted in six items and one factor that explained 61.064% of the total variance. Confirmatory factor analysis showed that the data fit the one-factor structure. Criterion-related validity indicated that the scale is significantly and positively correlated with the Numeric Rating Scale (NRS). Cronbach’s α coefficient, McDonald Omega, Spearman-Brown split-half reliability, and Guttman split-half reliability of the Chinese version of ESVADOPA were 0.868, 0.896, 0.845, 0.842, respectively. Conclusion The Chinese version of the ESVADOPA with good reliability and validity data could be used to assess the pain rating of pregnant women during childbirth without interfering in the birthing process.

Abstract The evolution and mechanism of ground collapse caused by underground water pipeline leakage have become increasingly significant as more urban areas experience collapses. Based on the principle of similarity, and considering the engineering context of road collapses in Anqing City, Anhui Province, this study designed a 3 m × 2 m × 2 m rupture-collapse model test device. Digital Image Correlation (DIC) technology was employed to investigate the erosion process and collapse mechanisms caused by underground pipeline leakage. The results indicate that groundwater seepage provides the driving force for collapses, combined with the migration space provided by defects, collectively triggering the collapses. When groundwater seepage is minimal, the cohesive forces between soil particles maintain soil stability. As groundwater seepage increases, the soil particle framework is eroded, leading to soil structure destabilization and collapse initiation. The depth of collapse significantly influences stress evolution: stress evolution intensity beneath and above the collapse pit is positively correlated with the distance from the collapse pit bottom, but negatively correlated with the distance from the defect. The research provides insights for the early warning and management of ground collapse.

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

Objective(s): Salidroside (SAL), an active ingredient purified from the medicinal plant Rhodiola rosea, has anti-inflammatory, anti-oxidant, anticancer, and neuroprotective properties. The study aims to examine SAL’s protective role in liver damage brought on by lipopolysaccharide (LPS). Materials and Methods: Six to eight-week-old male C57BL/6 wild-type mice were intraperitoneally treated with 10 mg/kg LPS for 24 hr and 50 mg/kg SAL two hours before LPS administration. Mice were categorized into control, LPS, and LPS + SAL groups. To evaluate liver injury, biochemical and TUNNEL staining test studies were performed. The Elisa assay analyzed interleukin- 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) pro-inflammatory cytokine expression levels. RT-qPCR and western blotting measured mRNA and protein expression of SIRT1, NF-кB, NLRP3, cleaved caspase-1, and GSDMD, respectively.Results: Analysis of the serum alanine/aspartate aminotransferases (ALT/AST), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) revealed that SAL protected against hepatotoxicity induced by LPS. The pathological evaluation of the liver supported the protection provided by SAL. SAL treatment reversed IL-1β, TNF-α, and IL-6 pro-inflammatory cytokines after being induced by LPS (all, P

Bartter syndrome (BS) is a rare, inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism, hypokalemia, hypochloremia, metabolic alkalosis, and low-to-normal blood pressure. Classic BS, or BS Type 3, the most common subtype in the Asian population, is caused by a molecular defect in ClC-Kb, a voltage-gated chloride channel in renal tubules, due to CLCNKB gene mutation. Because the onset of BS is more common in children than in adults, the diagnosis, treatment outcomes, genotype/phenotype association, and follow-up of adult-onset BS Type 3 are limited. This case report describes the findings in a 20-year-old man who was admitted with hypokalemic paralysis, with clinical manifestations were similar to those of Gitelman syndrome (GS); however, the patient was later diagnosed to have BS Type 3 through genetic testing (NM_000085.4 (CLCNKB): c.1052G>T). A literature review showed that no homozygous mutations have been reported to date. After 5 years of treatment and follow-up, we found that this genotype requires high levels of potassium and is prone to urinary protein and metabolic syndrome. Distinguishing adult-onset BS from GS is challenging in clinical practice. However, genetic diagnosis can help solve this problem effectively, and genotypes play a guiding role in treatment planning.

Copper-based azide (Cu(N3)2 or CuN3, CA) chips synthesized by in-situ azide reaction and utilized in miniaturized explosive systems has become a hot research topic in recent years. However, the advantages of in-situ synthesis method, including small size and low dosage, bring about difficulties in quantitative analysis and differences in ignition capabilities of CA chips. The aim of present work is to develop a simplified quantitative analysis method for accurate and safe analysis of components in CA chips to evaluate and investigate the corresponding ignition ability. In this work, Cu(N3)2 and CuN3 components in CA chips were separated through dissolution and distillation by utilizing the difference in solubility and corresponding content was obtained by measuring N3− concentration through spectrophotometry. The spectrophotometry method was optimized by studying influencing factors and the recovery rate of different separation methods was studied, ensuring the accuracy and reproducibility of test results. The optimized method is linear in range from 1.0–25.0 mg/L, with a correlation coefficient R2 = 0.9998, which meets the requirements of CA chips with a milligram-level content test. Compared with the existing ICP method, component analysis results of CA chips obtained by spectrophotometry are closer to real component content in samples and have satisfactory accuracy. Moreover, as its application in miniaturized explosive systems, the ignition ability of CA chips with different component contents for direct ink writing CL-20 and the corresponding mechanism was studied. This study provided a basis and idea for the design and performance evaluation of CA chips in miniaturized explosive systems.

Abstract To explore the relationship between miR-373 and the occurrence and development of colorectal cancer. Additionally, it aims to predict the potential cellular signaling pathways and regulatory mechanisms in which miR-373 may be involved and provides a theoretical basis and experimental evidence for the clinical application of miR-373 as a potential biomarker, molecular target, and prognostic indicator in colorectal cancer. Real-time quantitative PCR is used to analyze the expression of miR-373 in human colorectal cancer cell lines and normal human colonic epithelial cells. Further validation of the differential expression of miR-373 in colorectal cancer cell lines is being performed. Biological functions such as cell proliferation, invasion and apoptosis are being detected by MTT, CCK-8, transwell, cell cycle analysis, and flow cytometry experiments to verify the changes in the biological behavior of colon cancer cells after overexpression and interference of miR-373 in SW-480 cells and to explore the effects of miR-373 on cell proliferation, invasion, and apoptosis in colon cancer cells. Proteomic analysis is being conducted on proteins extracted from miR-373 overexpressing SW480 cells, and mass spectrometry is used for protein identification. GO, KEGG, and enrichment analysis are being employed to analyze the significantly differentially expressed proteins. The expression levels of pathway-related proteins are being verified using Western blot. Overexpression of miR-373 increased the invasive and metastatic ability of SW-480 cells; knockdown of miR-373 decreased the invasive and metastatic ability of SW-480 cells. However, there was no statistically significant effect on cell proliferation and apoptosis in SW-480 cells. Proteomic analysis identified 78 differentially expressed proteins based on fold change (FC) > 1.2 and P

Flower organ identity in rice is mainly determined by the A-, B-, C- and E-class genes, with the majority encoding MADS-box transcription factors. However, few studies have investigated how the expression of these floral organ identity genes is regulated during flower development. In this study, we identified a gene named SUPER WOMAN 2 (SPW2), which is necessary for spikelet/floret development in rice by participating in the regulation of the expression of pistil identity genes such as OsMADS3, OsMADS13, OsMADS58 and DL. In the spw2 mutant, ectopic stigma/ovary-like tissues were observed in the non-pistil organs, including sterile lemma, lemma, palea, lodicule, and stamen, suggesting that the identities of these organs were severely affected by mutations in SPW2. SPW2 was shown to encode a plant-specific EMF1-like protein that is involved in H3K27me3 modification as an important component of the PRC2 complex. Expression analysis showed that the SPW2 mutation led to the ectopic expression of OsMADS3, OsMADS13, OsMADS58, and DL in non-pistil organs of the spikelet. The ChIP-qPCR results showed significant reductions in the levels of H3K27me3 modification on the chromatin of these genes. Thus, we demonstrated that SPW2 can mediate the process of H3K27me3 modification of pistil-related genes to regulate their expression in non-pistil organs of spikelets in rice. The results of this study expand our understanding of the molecular mechanism by which SPW2 regulates floral organ identity genes through epigenetic regulation.

In the context of global warming, the habitats of Ephedra, including Ephedra sinica Stapf, Ephedra intermedia Schrenk ex Mey, and Ephedra equisetina Bunge, have been substantially threatened and deteriorated in recent years. Little is known about the potential geographic dynamics of economically renowned species, including those used in sand fixation and traditional Chinese medicine, under climate change. Therefore, evaluating their potential habitat and determining the crucial environmental variables affecting E. sinica, E. intermedia and E. equisetina under the driving force of global warming are extremely important. In this study, an optimized MaxEnt model in the kuenm package on the basis of occurrence records (a total of 103, 101 and 97 points for E. sinica, E. intermedia and E. equisetina, respectively) and 37 environmental factors were utilized to simulate the distribution of the three species. Two representative concentration pathways (SSP2.6 and SSP8.5) at 2041–2060 and 2061–2080, respectively, were used to establish a future distribution model of the three species. The results indicated that approximately 6.92 × 105 km2, 2.95 × 105 km2, and 11.5 × 105 km2 of suitable regions for E. sinica, E. intermedia and E. equisetina were obtained, which were mostly distributed in central and eastern Inner Mongolia, eastern and southern Gansu, and northern Xinjiang, respectively. Critical environmental variables, such as land cover and annual precipitation, were regarded as critical parameters for the three species. Future assessment revealed that over 60 % of the potential distribution area was affected, and the stability of E. sinica under the SSP8.5 scenario was the greatest. The spatial dynamic changes in suitable areas for E. intermedia were smaller than those for E. equisetina and E. sinica in the future. The comprehensive analysis revealed that the fluctuations in the distributions of the three Ephedra species under climate change are small and provide useful information for future conservation. Therefore, target conservation and management measures should be implemented in combination with the suitability thresholds of different environmental parameters. Our results provide useful recommendations for the current and future protection of Ephedra populations.

Abstract The morphological variation in Schizothorax oconnori, Schizothorax waltoni, and their natural hybrids was examined using conventional and image‐based analysis approaches. In total, 38 specimens of S. oconnori, 35 of S. waltoni, and 37 natural hybrids were collected from the Shigatse to the Lhasa section of the Yarlung Zangbo River during June and July 2021. A total of 21 morphometric, 4 meristic, and 27 truss variables were employed for the classification of S. oconnori, S. waltoni, and natural hybrids. Principal component analysis (PCA) and factor analysis (FA), as well as discriminant function analysis (DFA) and cluster analysis (CA), were conducted to identify differences based on traditional and truss measurements. Four principal components explained 75.92% of the variation among the morphometric characters, while five principal components accounted for 79.69% of the variation among the truss distances. FA results showed that factor 1 was associated with head shape, and factor 2 was associated with fins based on morphometric characters. Among the truss characters, factor 1 was related to head shape, and factor 2 was related to chest shape. In DFA, morphometric measurements achieved higher accuracy (100%) compared to truss distances (94.55%). The head morphology of hybrids exhibited intermediate traits between S. oconnori and S. waltoni. Both morphometry‐based and truss‐based clustering indicated that the morphology of natural hybrids leaned toward S. oconnori. In conclusion, the combination of morphometric and truss analysis is beneficial for classifying S. oconnori, S. waltoni, and their natural hybrids. The presence of natural hybrids could be considered an evolutionary response to the differentiation of nutritional and spatial niches in the middle Yarlung Zangbo River.

Abstract. Background:. Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. Methods:. First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. Results:. A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. Conclusions:. A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.

The popularization of intelligent healthcare devices and big data analytics significantly boosts the development of Smart Healthcare Networks (SHNs). To enhance the precision of diagnosis, different participants in SHNs share health data that contain sensitive information. Therefore, the data exchange process raises privacy concerns, especially when the integration of health data from multiple sources (linkage attack) results in further leakage. Linkage attack is a type of dominant attack in the privacy domain, which can leverage various data sources for private data mining. Furthermore, adversaries launch poisoning attacks to falsify the health data, which leads to misdiagnosing or even physical damage. To protect private health data, we propose a personalized differential privacy model based on the trust levels among users. The trust is evaluated by a defined community density, while the corresponding privacy protection level is mapped to controllable randomized noise constrained by differential privacy. To avoid linkage attacks in personalized differential privacy, we design a noise correlation decoupling mechanism using a Markov stochastic process. In addition, we build the community model on a blockchain, which can mitigate the risk of poisoning attacks during differentially private data transmission over SHNs. Extensive experiments and analysis on real-world datasets have testified the proposed model, and achieved better performance compared with existing research from perspectives of privacy protection and effectiveness.

In the process of promoting China’s rural energy reform, there will be a power gap problem, and the power companies will reduce the policy effect in disguise from their interests. To promote clean power supply in rural areas, this paper constructs an evolutionary game model between electric power companies and solar investment companies under the background of energy reform in rural areas, systematically deduces the possible different strategy combinations of both parties, and uses real data to conduct simulation and parameter sensitivity analysis. The results show that: (1) Under the current market mechanism, the system will evolve into (0,0), and there may be four different strategy combinations when government regulation is introduced. (2) Under the condition that the system evolves into the optimal state in the initial state, the local government’s subsidy to the investment company is no less than ¥0.11/kW h, and the penalty to the power company is ¥0.18/ kW h. (3) Compared with power companies, investment companies are more sensitive to government subsidies, so it is suggested that the government pay more attention to subsidies to investment companies. This study can provide theoretical support and policy references for promoting rural energy reform.

Abstract Assembly of nanoparticles into macroscopic materials with mechanical robustness, green processability, and recastable ability is an important and challenging task in materials science and nanotechnology. As an emerging nanoparticle with superior properties, macroscopic materials assembled from carbon dots will inherit their properties and further offer collective properties; however, macroscopic materials assembled from carbon dots solely remain unexplored. Here we report macroscopic films assembled from carbon dots modified by ureido pyrimidinone. These films show tunable fluorescence inherited from carbon dots. More importantly, these films exhibit collective properties including self-healing, re-castability, and superior mechanical properties, with Young’s modulus over 490 MPa and breaking strength over 30 MPa. The macroscopic films maintain original mechanical properties after several cycles of recasting. Through scratch healing and welding experiments, these films show good self-healing properties under mild conditions. Moreover, the molecular dynamics simulation reveals that the interplay of interparticle and intraparticle hydrogen bonding controls mechanical properties of macroscopic films. Notably, these films are processed into diverse shapes by an eco-friendly hydrosetting method. The methodology and results in this work shed light on the exploration of functional macroscopic materials assembled from nanoparticles and will accelerate innovative developments of nanomaterials in practical applications.

Abstract At different time scales, a species will experience diverse distribution changes. For Epimedium brevicornum Maxim, the phenomenon is obvious, but the understanding of the spatial dynamics of E. brevicornum under distinct time scales is poor. In this study, we modeled the potential distribution for E. brevicornum for five time scales, 1970–1979, 1980–1989, 1990–1999, 2000–2009, and 2010–2019, with different occurrence data, and the Kuenm package was used to optimize the parameter combination. Then, SDM tools and a Venn diagram were utilized to simulate the changes in highly suitable areas and spatial dynamics, respectively. Comprehensive results show that temperature seasonality (BIO4, 37.54%) has the greatest effect on the distribution of E. brevicornum, followed by minimum temperature (TMIN, 21.42%). The areas of distribution for E. brevicornum are 35.06 × 105 km2, 25.7 × 105 km2, 67.64 × 105 km2, 27.29 × 105 km2, and 9.87× 105 km2, which are mainly concentrated in Gansu, Shaanxi, Shanxi, and Henan, respectively. In addition, the largest regions for expansion, stability, and contraction under various time scales are 5.6 × 105 km2, 3.54 × 105 km2, and 3.47 × 105 km2, respectively. These changes indicate that approximately 7.96% of the regions are highly stable, and three critical counties, Wanyuan, Chenggu, and Hechuan, and Xixiang, have become significant areas for migration. Overall, our results indicate that there are different spatial distribution patterns and dynamics for E. brevicornum for different time scales. Given these results, this study also proposes comprehensive strategies for the conservation and management of E. brevicornum, which will further improve the current resource utilization status.

Mouth ulcers, a highly prevalent ailment affecting the oral mucosa, leading to pain and discomfort, significantly impacting the patient’s daily life. The development of innovative approaches for oral ulcer treatment is of great importance. Moreover, a deeper and more comprehensive understanding of mouth ulcers will facilitate the development of innovative therapeutic strategies. The oral environment possesses distinct traits as it serves as the gateway to the digestive and respiratory systems. The permeability of various epithelial layers can influence drug absorption. Moreover, oral mucosal injuries exhibit distinct healing patterns compared to cutaneous lesions, influenced by various inherent and extrinsic factors. Furthermore, the moist and dynamic oral environment, influenced by saliva and daily physiological functions like chewing and speaking, presents additional challenges in local therapy. Also, suitable mucosal adhesion materials are crucial to alleviate pain and promote healing process. To this end, the review comprehensively examines the anatomical and structural aspects of the oral cavity, elucidates the healing mechanisms of oral ulcers, explores the factors contributing to scar-free healing in the oral mucosa, and investigates the application of mucosal adhesive materials as drug delivery systems. This endeavor seeks to offer novel insights and perspectives for the treatment of oral ulcers.

To investigate the longitudinal gradient patterns and the factors influencing fish taxonomic and functional groups, a survey involving 28 sampling sites was conducted in the Anning River in November 2020 and April 2021. A total of 60 fish species were collected, and these species were classified into 4 locomotor groups and 4 trophic groups, resulting in 11 combined functional groups based on locomotor and trophic characteristics. The results of two-way cross similarity analysis (ANOSIM) revealed significant changes in both the fish taxonomic and functional groups along the longitudinal gradient, while no significant seasonal variation was observed in either group. Spatial changes in taxonomic and functional groups along the river were primarily due to turnover processes, as indicated by the similarity percentage analysis. Variance partitioning analysis demonstrated that local habitat conditions and land use/cover explained 37.56% and 41.33% of the spatial variation in taxonomic and functional organizations, respectively. Notably, the influence of landscape features on taxonomic organization was less significant than that of local habitat variables. Nevertheless, landscape conditions played a more important role than local environmental factors in explaining variations associated with functional organization. Our study helps in understanding the spatial patterns and formation mechanisms of taxonomic and functional groups driven by multiple-scale environmental factors in mountain rivers. In addition, our results showed that the response of functional groups to different scale environmental factors differ from taxonomic groups.

Summary: N-methyl-D-aspartate receptor (NMDAR)-mediated glutamate excitotoxicity significantly contributes to ischemic neuronal death and post-recanalization infarction expansion. Despite tremendous efforts, targeting NMDARs has proven unsuccessful in clinical trials for mitigating brain injury. Here, we show the discovery of an interaction motif for transient receptor potential melastatin 2 (TRPM2) and protein kinase Cγ (PKCγ) association and demonstrate that TRPM2-PKCγ uncoupling is an effective therapeutic strategy for attenuating NMDAR-mediated excitotoxicity in ischemic stroke. We demonstrate that the TRPM2-PKCγ interaction allows TRPM2-mediated Ca2+ influx to promote PKCγ activation, which subsequently enhances TRPM2-induced potentiation of extrasynaptic NMDAR (esNMDAR) activity. By identifying the PKCγ binding motif on TRPM2 (M2PBM), which directly associates with the C2 domain of PKCγ, an interfering peptide (TAT-M2PBM) is developed to disrupt TRPM2-PKCγ interaction without compromising PKCγ function. M2PBM deletion or TRPM2-PKCγ dissociation abolishes both TRPM2-PKCγ and TRPM2-esNMDAR couplings, resulting in reduced excitotoxic neuronal death and attenuated ischemic brain injury.

Background Systemic chemotherapy or chemoradiation therapy has proven to be effective in treating advanced biliary tract carcinoma (BTC). However, its efficacy in the adjuvant setting remains controversial. Therefore, this study aimed to determine the prognostic significance of genomic biomarkers in resected BTC and their potential role in stratifying patients for adjuvant treatment. Methods We retrospectively reviewed 113 BTC patients who underwent curative‐intent surgery and had available tumor sequencing data. Disease‐free survival (DFS) was the primary outcome examined and univariate analysis was used to identify gene mutations with prognostic value. Favorable and unfavoratble gene subsets were distinguished from the selected genes through grouping, respectively. Multivariate Cox regression was used to identify independent prognostic factors of DFS. Results Our results indicated that mutations in ACVR1B, AR, CTNNB1, ERBB3, and LRP2 were favorable mutations, while mutations in ARID1A, CDKN2A, FGFR2, NF1, NF2, PBRM1, PIK3CA, and TGFBR1 were unfavorable mutations. In addition to age, sex, and node positive, favorable genes (HR = 0.15, 95% CI = 0.04–0.48, p = 0.001) and unfavorable genes (HR = 2.86, 95% CI = 1.51–5.29, p = 0.001) were identified as independent prognostic factors for DFS. Out of the 113 patients, only 35 received adjuvant treatment whereas the majority (78) did not. For patients with both favorable and unfavorable mutations undetected, adjuvant treatment showed negative effect on DFS (median DFS: S441 vs. 956 days, p = 0.010), but there was no significant difference in DFS among those in other mutational subgroups. Conclusions Genomic testing might be useful in guiding the decisions regarding adjuvant treatment in BTC.

Abstract Background The exact optimal timing of dialysis for ESKD patients remains unknown. This study systematically reviewed the available evidence with regard to the optimal initiation of maintenance dialysis in ESKD patients. Methods An electronic search was performed in Embase, PubMed and the Cochrane Library in order to find studies investigating associations between variables reference to “start of dialysis” and outcomes. Quality assessment and bias assessment were performed by the Newcastle–Ottawa scale and the ROBINSI tool. Due to the heterogeneity of studies, a meta-analysis could not be performed. Results Thirteen studies were included; four studies included only haemodialysis patients, three peritoneal dialysis, six both; study outcomes included mortality, cardiovascular events, technique failure, quality of life and others. Nine studies mainly focused on the optimal GFR of maintenance dialysis initiation; five studies showed none association between GFR and mortality or other adverse outcomes, two studies showed dialysis initiation at higher GFR levels were with poor prognosis, and 2 studies showed higher GFR levels with better prognosis. Three studies paid attention to comprehensive assessment of uremic signs and/or symptoms for optimal dialysis initiation; uremic burden based on 7 uremic indicators (hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate) were not associated with mortality; another equation (combination of sex, age, serum creatinine, blood urea nitrogen, serum albumin, haemoglobin, serum phosphorus, diabetes mellitus, and heart failure) based on fuzzy mathematics to assess the timing of haemodialysis initiation was accuracy to prognose 3-year survival; the third study found that volume overload or hypertension was associated with the highest risk for subsequent mortality. Two studies compared urgent or optimal start in dialysis, a study reported increased survival in optimal start patients, another reported no differences between Urgent-Start-PD and Early-Start-PD regarding 6-month outcomes. Limitations: Heterogeneity among the studies was quite high, with differences in sample size, variable and group characteristics; no RCT studies were included, which weakened the strength of evidences. Conclusions The criteria for dialysis initiation were varied. Most studies proved that GFR at dialysis initiation was not associated with mortality, timing of dialysis initiation should not be based on GFR, assessments of volume load and patient’s tolerance to volume overload are prospective approaches.

Titanium (Ti) alloys have been widely used as bone implants, but challenges such as the stress shielding effect still compromise long-term clinical successes. To improve the mechanical properties of Ti, non-toxic alloying elements zirconium (Zr) and molybdenum (Mo) were added either alone or in combination to produce Ti–Mo–Zr alloys. The influence of Zr or Mo addition on the alloy properties, such as the microstructure and the corrosion resistance, were investigated. The cytocompatibility and osteointegration of prepared alloys were evaluated to determine the potential for bone repair. The results showed that Ti–10Zr displayed an acicular α′ phase, while Ti–12Mo and Ti–12Mo–10Zr comprised a metastable β phase. Due to the solid solution and phase precipitation strengthening effect of Zr and Mo elements, the prepared alloys showed higher microhardness and compressive yield strength when compared with commercially pure Ti (CP–Ti). Ti–12Mo–10Zr possessed the lowest Young's modulus, while CP-Ti and Ti–10Zr showed a comparable Young's modulus. The corrosion resistance was in the order of Ti–12Mo–10Zr > Ti–12Mo > CP-Ti > Ti–10Zr. Notably, all alloys showed good cytocompatibility and osteointegration, which were similar to those of CP-Ti. Taken together, due to excellent material and biological performance, Ti–12Mo–10Zr presents a promising material for bone repair.

Abstract Objects Colorectal cancer (CRC) is one of the most common cancers in the world. Approximately two-thirds of patients with CRC will develop colorectal cancer liver metastases (CRLM) at some point in time. In this study, we aimed to construct a prognostic model of CRLM and its competing endogenous RNA (ceRNA) network. Methods RNA-seq of CRC, CRLM and normal samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Limma was used to obtain differential expression genes (DEGs) between CRLM and CRC from sequencing data and GSE22834, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed, respectively. Univariate Cox regression analysis and lasso Cox regression models were performed to screen prognostic gene features and construct prognostic models. Functional enrichment, estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) algorithm, single-sample gene set enrichment analysis, and ceRNA network construction were applied to explore potential mechanisms. Results An 8-gene prognostic model was constructed by screening 112 DEGs from TCGA and GSE22834. CRC patients in the TCGA and GSE29621 cohorts were stratified into either a high-risk group or a low-risk group. Patients with CRC in the high-risk group had a significantly poorer prognosis compared to in the low-risk group. The risk score was identified as an independent predictor of prognosis. Functional analysis revealed that the risk score was closly correlated with various immune cells and immune-related signaling pathways. And a prognostic gene-associated ceRNA network was constructed that obtained 3 prognosis gene, 14 microRNAs (miRNAs) and 7 long noncoding RNAs (lncRNAs). Conclusions In conclusion, a prognostic model for CRLM identification was proposed, which could independently identify high-risk patients with low survival, suggesting a relationship between local immune status and prognosis of CRLM. Moreover, the key prognostic genes-related ceRNA network were established for the CRC investigation. Based on the differentially expressed genes between CRLM and CRC, the prognosis model of CRC patients was constructed.

Abstract Background The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40–45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. Methods The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1β and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. Results Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1β-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. Conclusions CD8+ T cells and IL-1β were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1β-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1β antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.

The film mulched drip irrigation (FMDI) in severe drought and salinity areas makes the transport of water, heat, and salt in the soil more complicated. In this paper, two-year field experiments were carried out in southern Xinjiang from 2020 to 2021 (Salt levels: 0.2%, 0.4%, and 0.6%; Irrigation levels: 30 mm and 45 mm (2020). 22.5 mm, 30 mm, 37.5 mm, and 45 mm (2021)). Using the measured data of soil moisture, heat, and salinity, the HYDRUS-2D model was calibrated and validated, and the effects of soil adsorption on the simulation results were compared. Meanwhile, six irrigation scenarios were designed (The three levels of irrigation times were 8 times, 10 times, and 12 times. The total irrigation amounts were 360 mm and 450 mm). The results indicate that the simulated results of salt transport under the condition of kinetic adsorption matched accurately with the observed data (the maximum of RMSE was 0.293 ds m−1, and the minimum values of R2 and d were 0.923 and 0.934, respectively); similarly, the simulation results of soil water and heat transport were acceptable (the maximum values of RMSE were 0.033 cm cm−1 and 1.897 °C, and the minimum values of R2 and d were 0.877, 0.99 and 0.915, 0.807, respectively). The scenario simulation indicate that salt leaching mainly occurred under plastic film, the desalination in the 0–40 cm soil layer was obvious (The rate range of salt leaching is 29.8∼58.8%), and salt accumulation appeared in the 40–100 cm layer under plastic film in the specific scenarios. Considering the optimal desalination in the cotton root zone, the irrigation mode with 8 irrigation times (The irrigation interval of 12 d during the budding period, 2 times; the irrigation interval of 8 d, 6 times) with a total irrigation amount of 450 mm was recommended, which provides a reference for the regulation of water, heat, and salt in severe drought and salinity areas.

ABSTRACTDietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95–1.05 in group A to D (all P

Film mulching is widely used as an agronomic practice to counteract water scarcity in arid and semi-arid areas. Although crop models have emerged as powerful tools for system studies and scenarios analysis, they have been rarely used in areas with severe drought and salinization and where mulching is being used as a management practice. An earlier study shown great modelling potential under severe salinity in southern Xinjiang, China. The model is WAVES (the WAter Vegetation Energy and Solute), while evaporation was overestimated in the earlier study without considering the mulching effect. In this study, we used a modified WAVES model by incorporating three functions working on potential evaporation, underlying surface albedo, and soil resistance into it to represent the mulching effect. Calibration and validation were conducted using cotton field experiments from 2 different years. Of the 3 functions evaluated, the one representing potential evaporation reduction exerted the highest modification effect on soil water status. The modified model better simulated evaporation, soil-water content, soil-salt content, leaf area index (LAI), and yield than the original model, decreasing normalized root mean square error (NRMSE) by 173%, 15%, 14%, 9%, and 35%, respectively. The modification effects were most significant during the seedling stage. In addition, the modified model produced a higher realistic evaporation (E)/evapotranspiration (ET) under the film mulching environment. These findings suggest that the modified WAVES model can be applied for crop management under film mulching, particularly in areas with low rainfall and high salinization.

Abstract Replication of the coronavirus genome starts with the formation of viral RNA-containing double-membrane vesicles (DMV) following viral entry into the host cell. The multi-domain nonstructural protein 3 (nsp3) is the largest protein encoded by the known coronavirus genome and serves as a central component of the viral replication and transcription machinery. Previous studies demonstrated that the highly-conserved C-terminal region of nsp3 is essential for subcellular membrane rearrangement, yet the underlying mechanisms remain elusive. Here we report the crystal structure of the CoV-Y domain, the most C-terminal domain of the SARS-CoV-2 nsp3, at 2.4 Å-resolution. CoV-Y adopts a previously uncharacterized V-shaped fold featuring three distinct subdomains. Sequence alignment and structure prediction suggest that this fold is likely shared by the CoV-Y domains from closely related nsp3 homologs. NMR-based fragment screening combined with molecular docking identifies surface cavities in CoV-Y for interaction with potential ligands and other nsps. These studies provide the first structural view on a complete nsp3 CoV-Y domain, and the molecular framework for understanding the architecture, assembly and function of the nsp3 C-terminal domains in coronavirus replication. Our work illuminates nsp3 as a potential target for therapeutic interventions to aid in the on-going battle against the COVID-19 pandemic and diseases caused by other coronaviruses.

Abstract Competency is closely related to the occurrence of the behavior. Breastfeeding competence is the mastery of different breastfeeding factors which intervene in breastfeeding behavior. Breastfeeding competence could improve the breastfeeding behavior. However, few studies have paid attention to the status and the influencing factors of breastfeeding competency. The breastfeeding competency of pregnant women in third trimester pregnancy has the greatest impact on breastfeeding behavior after childbirth. Therefore, the objective of this study were to investigate the breastfeeding competency level and independent risk factors for breastfeeding competency among pregnant women in third trimester pregnancy. A cross-sectional survey method and convenience sampling method was used in the study. The general information questionnaire including age, gestational week, educational background, and so on were used to investigate the general information of pregnant women and their husbands. A breastfeeding competency scale (BCS) was used to investigate the breastfeeding competency of pregnant women. The total score of the BCS ranges from 38 to 190, with higher scores indicating greater breastfeeding competency. Lower level, medium level and higher level are 38–89, 90–140 and 141–190 respectively. Type-D Scale-14 (DS14) was used to investigate the type D personality of pregnant women. A multivariable linear regression was used to examine the independent predictors of breastfeeding competency. A total of 550 questionnaires were collected and finally 525 effective questionnaires were collected. The age of 525 pregnant women is (30.24 ± 3.954) years old. The breastfeeding competency score of pregnant women was (134 ± 19.741). Multivariable linear regression analysis showed that higher breastfeeding competency in pregnant women were reported among pregnant women who gestational age ≥ 256 days (37 weeks) (B = 8.494, p

A subset of Sec14 domain proteins use their gated hydrophobic pocket to bind and transport lipids. Here the authors provide structural and biochemical data revealing how the Sec14-fold of a Rho-GEF forms a surface groove that interacts with lysolipids.

An appropriate water supply strategy is imperative for obtaining tomatoes of a high yield and quality; the lack of one has caused resource wastage and quality deterioration. To determine the suitable irrigation amount and simulate daily transpiration under these optimal irrigation conditions, a two-year greenhouse cultivation experiment was conducted over 2022–2023. Commencing at anthesis, three distinct irrigation gradients were triggered and designated as irrigation controls with the lower limits set at 80% (T1), 70% (T2), and 60% (T3) of the substrate water-holding capacity. We determined the optimal irrigation amount by ranking the treatments using the TOPSIS method, balancing the tomato yield and quality. A segmented daily transpiration model under optimal irrigation conditions driven by crop and environmental factors was established using the Marquardt method and data from 2022, and the model was validated using data from 2023. The results indicated that T2 was the optimal irrigation amount, with the water use efficiency increased by 18.0%, but with a 10.9% decrease in yield, while the quality indices improved significantly. The R2 values of the segmented model in the flowering and fruit-setting stage and the picking stage were 0.92 and 0.86, respectively, which could provide support for optimized water management for tomato planting in greenhouse substrate cultivation.

Abstract Structure self‐modification of graphitic carbon nitride (g‐C3N4) without the assistance of other species has attracted considerable attention. In this study, the structure vacancy defect modified diatomic‐layered g‐C3N4 nanosheet (VCN) is synthesized by thermal treatment of bulk g‐C3N4 in a quartz tube with vacuum atmosphere that will generate a pressure‐thermal dual driving force to boost the exfoliation and formation of structure vacancy for g‐C3N4. The as‐prepared VCN possesses a large specific surface area with a rich pore structure to provide more active centers for catalytic reactions. Furthermore, the as‐formed special defect level in VCN sample can generate a higher exciton density at photoexcitation stage. Meanwhile, the photogenerated charges will rapidly transfer to VCN surface due to the greatly shortened transfer path resulting from the ultrathin structure (≈1.5 nm), which corresponds to two graphite carbon nitride atomic layers. In addition, the defect level alleviates the drawback of enlarged bandgap caused by the quantum size effect of nano‐scaled g‐C3N4, resulting in a well visible‐light utilization. As a result, the VCN sample exhibits an excellent photocatalytic performance both in hydrogen production and photodegradation of typical antibiotics.

Suillus luteus is a widespread edible ectomycorrhizal fungus that holds significant importance in both ecological and economic value. Mycoviruses are ubiquitous infectious agents hosted in different fungi, with some known to exert beneficial or detrimental effects on their hosts. However, mycoviruses hosted in ectomycorrhizal fungi remain poorly studied. To address this gap in knowledge, we employed next-generation sequencing (NGS) to investigate the virome of S. luteus. Using BLASTp analysis and phylogenetic tree construction, we identified 33 mycovirus species, with over half of them belonging to the phylum Lenarviricota, and 29 of these viruses were novel. These mycoviruses were further grouped into 11 lineages, with the discovery of a new negative-sense single-stranded RNA viral family in the order Bunyavirales. In addition, our findings suggest the occurrence of cross-species transmission (CST) between the fungus and ticks, shedding light on potential evolutionary events that have shaped the viral community in different hosts. This study is not only the first study to characterize mycoviruses in S. luteus but highlights the enormous diversity of mycoviruses and their implications for virus evolution.

Carbon fibre (CF) reinforced H62 brass matrix composites were fabricated by friction stir process (FSP). The influence of CF compound amount and welding speed on the microstructure and properties of CF-H62 brass matrix composites was investigated by variable orthogonal experiments by drilling CF filled holes in H62 brass plates. Under the set experimental process parameters, the stirred friction processed composites with good surface formation, all without macroscopic defects, no loosening or holes. Optical microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the microstructure of the joints. The microstructure is a fine isometric crystal that is the result of dynamic recrystallisation. As the welding speed increased from 20 mm/min to 60 mm/min, the average grain size at the weld in the weld zone decreased from 5 μm to 2 μm. When the hole depth of the filled CF was 1.5 mm and the welding speed was 40 mm/min, the CF was most uniformly distributed in the composite area. This paper uses the orthogonal test method to optimise the formulation design of a variety of reinforcement fibre contents. The friction and wear properties as well as the physical properties of the two friction material samples were tested using a constant speed friction tester, a shear strength tester and a Rockwell hardness tester. The influence of each fibre and content on the friction material properties was investigated by extreme difference analysis; The best fibre ratio formulation was selected by combining a fuzzy comprehensive evaluation method. ANOVA was used to investigate the changes in friction material properties after the addition of graphene.

Abstract Background: miR-145-5P is generally considered as a tumor suppressor at early stage of colorectal cancer, but up-regulation occurs in the progressive and later stages which is associated with metastasis, indicating miR-145-5p may play dual role in colorectal cancer (CRC). To explore the detailed mechanism of miR-145-5p in carcinogenic is of importance. Methods: The expression pattern of miR-145-5p in CRC patients was downloaded from TCGA database, and the probable mechanism involved in the carcinogenic effect of miR-145-5p was predicted by bioinformatics analysis. Then, interference of miR-145-5p on SW480 and SW620 cells was conducted, and the influences on tumor cell viability, invasion ability, epithelial-mesenchymal transition (EMT), anoikis, and relative protein expression were examined respectively. Results: A total of 522 CRC patients’ data indicated that miR-145-5p expression was significantly higher in metastatic CRC than that in non-metastatic CRC, and higher expression of miR-145-5p was correlate with worse prognosis. Overexpression of miR-145-5P-5p enhanced the proliferation and invasion ability of SW620, but inhibited them in SW480. EMT was induced in SW620 after miR-145-5p overexpression and mesenchymal–epithelial transition (MET) was induced in SW480, resulted in the decreased apoptotic rate in SW620 and elevated apoptotic rate in SW480 respectively. Western blot results showed that AKT signaling pathway was involved in the miR-145-5p evoked EMT-mediated anoikis process in SW620 and SW480 cells. Conclusion: miR-145-5p is a tumor suppressor at early stage of CRC, and an oncogene at advanced stage of CRC. AKT signaling evoked EMT-mediated anoikis might be the pathway by which miR-145-5P regulates CRC cell invasion and metastasis.

Abstract In vivo imaging has been widely used for investigating the structure and function of neurons typically located within ~ 800 μm below the cortical surface. Due to light scattering and absorption, it has been difficult to perform in-vivo imaging of neurons in deep cortical and subcortical regions of large animals with two-photon microscopy. Here, we combined a thin-wall quartz capillary with a GRIN lens attached to a prism for large-volume structural and calcium imaging of neurons located 2 mm below the surface of rabbit and monkey brains. The field of view was greatly expanded by rotating and changing the depth of the imaging probe inside a quartz capillary. Calcium imaging of layer 5/6 neurons in the rabbit motor cortex revealed differential activity of these neurons between quiet wakefulness and slow wave sleep. The method described here provides an important tool for studying the structure and function of neurons located deep in the brains of large animals.

Abstract Background High temperature induces early bolting in lettuce (Lactuca sativa L.), which affects both quality and production. However, the molecular mechanism underlying high temperature-induced bolting is still limited. Results We performed systematical analysis of morphology, transcriptome, miRNAs and methylome in lettuce under high temperature treatment. Through a comparison of RNA-Seq data between the control and the high temperature treated lettuces at different time points totally identified 2944 up-regulated genes and 2203 down-regulated genes, which cover three floral pathways including photoperiod, age and gibberellin (GA) pathways. Genome wide analysis of miRNAs and methylome during high temperature treatment indicated miRNAs and DNA methylation might play a role controlling gene expression during high temperature-induced bolting. miRNA targets included some protein kinase family proteins, which potentially play crucial roles in this process. Conclusions Together, our results propose a possible regulation network involved in high temperature-induced bolting.

ObjectiveExamine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).MethodsLARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded.ResultsTwenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs.ConclusionNeoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT.

2Duf, named after the presence of a transmembrane (TM) Duf421 domain and a small Duf1657 domain in its sequence, is likely located in the inner membrane (IM) of spores in some Bacillus species carrying a transposon with an operon termed spoVA2mob. These spores are known for their extreme resistance to wet heat, and 2Duf is believed to be the primary contributor to this trait. In this study, we found that the absence of YetF or YdfS, both Duf421 domain-containing proteins and found only in wild-type (wt) B. subtilis spores with YetF more abundant, leads to decreased resistance to wet heat and agents that can damage spore core components. The IM phospholipid compositions and core water and calcium-dipicolinic acid levels of YetF-deficient spores are similar to those of wt spores, but the deficiency could be restored by ectopic insertion of yetF, and overexpression of YetF increased wt spore resistance to wet heat. In addition, yetF and ydfS spores have decreased germination rates as individuals and populations with germinant receptor-dependent germinants and increased sensitivity to wet heat during germination, potentially due to damage to IM proteins. These data are consistent with a model in which YetF, YdfS and their homologs modify IM structure to reduce IM permeability and stabilize IM proteins against wet heat damage. Multiple yetF homologs are also present in other spore forming Bacilli and Clostridia, and even some asporogenous Firmicutes, but fewer in asporogenous species. The crystal structure of a YetF tetramer lacking the TM helices has been reported and features two distinct globular subdomains in each monomer. Sequence alignment and structure prediction suggest this fold is likely shared by other Duf421-containing proteins, including 2Duf. We have also identified naturally occurring 2duf homologs in some Bacilli and Clostridia species and in wt Bacillus cereus spores, but not in wt B. subtilis. Notably, the genomic organization around the 2duf gene in most of these species is similar to that in spoVA2mob, suggesting that one of these species was the source of the genes on this operon in the extremely wet heat resistant spore formers.

As space resources become increasingly constrained, the major space-faring nations are establishing large space target monitoring systems. There is a demand for both the number and the detection capability of space-based optical monitoring equipment. The detection range (i.e., field of view) and parasitic capability (lightweight and small size) of a single optical payload will largely reduce the scale and cost of the monitoring system. Therefore, in this paper, the optic-mechanical system of an ultra-lightweight and ultra-compact space camera and the optical alignment method are investigated around a fully freeform off-axis triple-reversal large field of view (FOV) optical system. The optic-mechanical system optimisation design is completed by adopting the optic-mechanical integration analysis method, and the weight of the whole camera is less than 10 kg. In addition, to address the mounting problems caused by the special characteristics of the freeform surface optical system, a dual CGH coreference alignment method is innovatively proposed. The feasibility of the method is verified by the mounting and testing test, and the test results show that the system wavefront difference is better than 1/10 λ. The imaging test of the space camera and the magnitude test results meet the design requirements of the optical system. The optic-mechanical system design method and alignment method proposed in this paper are instructive for the design and engineering of large field of view full freeform optical loads.

Background: Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of death worldwide. Seriously threatens human life and health. Previous studies have identified that inhibin βA (INHBA) could induce tumorgenesis and progression of CRC through the regulation of the TGF-β/Smad signal axis. The abnormal expression of INHBA is related to the poor prognosis of patients. The aim of this study was to identify the molecular mechanism of HNF1A-AS1 and miR-214 regulating INHBA and carcinogenesis through bioinformatics combined with experiments. Methods: The expression of HNF1A-AS1, miRNA-214-5p, INHBA in pan-cancer and CRC were investigated in the Cancer Genome Atlas (TCGA). The correlation between HNF1A-AS1 and immune-related genes or miRNAs was explored via the Gene Expression Profiling Interactive Analysis (GEPIA) and volcano plots, respectively. The association between HNF1A-AS1 and differentially expressed miRNAs was constructed by TargetScan. The miRDB, miRWalk, and TargetScan databases were utilized to predict the target genes of hsa-miR-214. The expression of INHBA in tissues and cell lines of CRC was examined by RT-qPCR and western blot assay. Results: The INHBA and HNF1A-AS1 expressions were increased in Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) of the TCGA database. Hsa-miR-214 was relatively less expressed in CRC tissues compared with para-cancer tissues. The expression of HNF1A-AS1 was negatively correlated with hsa-miR-214. INHBA was one of the target genes of hsa-miR-214 based on miRDB, miRWalk, and TargetScan databases. The specific binding sites of INHBA-3’UTR and miR-214-5p were identified by starBase. The expression level of INHBA was positively correlated with the T stage of tumor and negatively correlated with overall survival (OS) and disease-free survival (DFS) in CRC patients. The results of RT-qPCR and western blot indicated that the expression of INHBA in tissues and cell lines in CRC was higher than those in para-carcinoma tissues and normal colon cell lines, respectively. Conclusions: These findings suggested that HNF1A-AS1 and miRNA-214-5p were key upstream non-coding RNAs of INHBA. The HNF1A-AS1/miR-214/INHBA signal axis plays a significant role in the tumorgenesis and progression of CRC. By interfering with HNF1A-AS1 and INHBA genes on HT29 and SW480 cells, it was found that HNF1A-AS1 and INHBA genes may be important target genes in CRC.

Creatine deficiency disorders are inborn errors of creatine metabolism, an energy homeostasis molecule. One of these, guanidinoacetate N-methyltransferase (GAMT) deficiency, has clinical characteristics that include features of autism, self-mutilation, intellectual disability, and seizures, with approximately 40% having a disorder of movement; failure to thrive can also be a component. Along with low creatine levels, guanidinoacetic acid (GAA) toxicity has been implicated in the pathophysiology of the disorder. Present-day therapy with oral creatine to control GAA lacks efficacy; seizures can persist. Dietary management and pharmacological ornithine treatment are challenging. Using an AAV-based gene therapy approach to express human codon-optimized GAMT in hepatocytes, in situ hybridization, and immunostaining, we demonstrated pan-hepatic GAMT expression. Serial collection of blood demonstrated a marked early and sustained reduction of GAA with normalization of plasma creatine; urinary GAA levels also markedly declined. The terminal time point demonstrated marked improvement in cerebral and myocardial creatine levels. In conjunction with the biochemical findings, treated mice gained weight to nearly match their wild-type littermates, while behavioral studies demonstrated resolution of abnormalities; PET-CT imaging demonstrated improvement in brain metabolism. In conclusion, a gene therapy approach can result in long-term normalization of GAA with increased creatine in guanidinoacetate N-methyltransferase deficiency and at the same time resolves the behavioral phenotype in a murine model of the disorder. These findings have important implications for the development of a new therapy for this abnormality of creatine metabolism.

Studies of the confinement of filamentous hydrogels such as fibrin, a major component of blood clots, can shed light on the resistance of strained occlusive clots to lysis with therapeutic agents. Here, the authors show the mechanism of the response of fibrous hydrogels to confinement.

IntroductionSoil pollution by heavy metals and climate change pose substantial threats to the habitat suitability of cash crops. Discussing the suitability of cash crops in this context is necessary for the conservation and management of species. We developed a comprehensive evaluation system that is universally applicable to all plants stressed by heavy metal pollution.MethodsThe MaxEnt model was used to simulate the spatial distribution of Ligusticum chuanxiong Hort within the study area (Sichuan, Shaanxi, and Chongqing) based on current and future climate conditions (RCP2.6, RCP4.5, RCP6.0, and RCP8.5 scenarios). We established the current Cd pollution status in the study area using kriging interpolation and kernel density. Additionally, the three scenarios were used in prediction models to simulate future Cd pollution conditions based on current Cd pollution data. The current and future priority planting areas for L. chuanxiong were determined by overlay analysis, and two levels of results were obtained.ResultsThe results revealed that the current first- and secondary-priority planting areas for L. chuanxiong were 2.06 ×103 km2 and 1.64 ×104 km2, respectively. Of these areas, the seven primary and twelve secondary counties for current L. chuanxiong cultivation should be given higher priority; these areas include Meishan, Qionglai, Pujiang, and other regions. Furthermore, all the priority zones based on the current and future scenarios were mainly concentrated on the Chengdu Plain, southeastern Sichuan and northern Chongqing. Future planning results indicated that Renshou, Pingwu, Meishan, Qionglai, Pengshan, and other regions are very important for L. chuanxiong planting, and a pessimistic scenario will negatively impact this potential planting. The spatial dynamics of priority areas in 2050 and 2070 clearly fluctuated under different prediction scenarios and were mainly distributed in northern Sichuan and western Chongqing.DiscussionGiven these results, taking reasonable measures to replan and manage these areas is necessary. This study provides. not only a useful reference for the protection and cultivation of L. chuanxiong, but also a framework for analyzing other cash crops.

Objective. To investigate the oncogenic effect and clinical significance of RAC2 in pancarcinoma from the perspective of tumor immunity and cancer stem cell. Methods. After in-depth mining of TCGA, GEO, UCSC, and other databases, basic information of the RAC2 gene and its expression in tumor tissues as well as the relationship between RAC2 and tumor were analyzed based on survival, mutation, immune microenvironment, tumor stemness, and enrichment analysis on related pathways. Results. RAC2 mRNA expression was increased in most tumor tissues and was associated with their prognosis. Compared to normal tissues, the RAC2 mutation rate was higher in patients with skin melanoma, uterine sarcoma, and endometrial cancer. RAC2 had a strong relation with immune cell infiltration, immunomodulators, immunotherapy markers, cancer stem cell of THYM, and immune-related pathways. Conclusions. This study explored the potential importance of RAC2 in the prognosis, immunotherapy, and cancer stem cell of 33 cancers, laying the foundation for mechanistic experiments and its future application in clinical practice. However, the results using bioinformatics methods could be affected by the differences in patients across databases. Thus, the present results were preliminary and required further experimental validation.

ObjectiveThis study aims to explore the association between the frailty index and chronic heart failure (CHF).MethodsWe collected data from the National Health and Nutrition Examination Survey (NHANES) (1998–2018) database to assess the association between CHF and frailty. Demographic, inquiry, laboratory examinations, and characteristics were gathered to compare CHF and non-CHF groups. Multiple logistic regression analysis was performed to explore the relationship between frailty and CHF. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence interval (CI) for mortality from all causes and cardiovascular disease (CVD).ResultsA total of 16,175 participants with cardiac and cerebrovascular disease were categorized into CHF (n = 1,125) and non-CHF (n = 15,050) groups. In patients with CHF, the prevalence of frailty, pre-frailty, and non-frailty were 66.31, 30.93, and 2.75%, respectively. In multiple logistic regression, patients with CHF who were male (OR = 0.63, 95% CI: 3.11–5.22), whose annual family income was over $20,000 (OR = 0.52, 95% CI: 0.37–0.72, p < 0.001), or with normal hemoglobin level (OR = 0.77, 95% CI: 0.68–0.88, P < 0.001) had a lower likelihood of frailty. CHF patients with hypertension (OR = 3.60, 95% CI: 2.17–5.99, P < 0.0001), coronary heart disease (OR = 1.76, 95% CI: 1.10–2.84, P = 0.02), diabetes mellitus (OR = 1.89, 95% CI: 1.28–2.78, P < 0.001), and stroke (OR = 2.52, 95% CI: 1.53–4.15, P < 0.001) tended to be frail. Survival analysis suggested that pre-frailty and frailty were related to poor all-cause deaths (HR = 1.48, 95% CI: 1.36–1.66; HR = 2.77, 95% CI: 2.40–3.18) and CVD mortality (HR = 1.58, 95% CI: 1.26–1.97; HR = 2.55, 95% CI: 2.02–3.21). CHF patients with frailty were strongly connected with all-cause death (HR = 2.14, 95% CI: 1.27–3.62).ConclusionFrailty was positively associated with CHF. Patients with CHF who were male, whose annual family income was over $20,000, or with normal hemoglobin level were negatively correlated to frailty. For patients with cardiac and cerebrovascular disease as well as CHF, frailty was strongly connected with all-cause death.

ObjectiveThe aim of this study was to compare the efficacy and safety of a novel percutaneous pedicle screw fixation and vertebral reconstruction (PPSR) vs. that of open pedicle screw fixation (OPSF) in the treatment of thoracolumbar fractures.MethodsThis retrospective study enrolled 153 patients who underwent PPSR and 176 patients who received OPSF. Periprocedural characteristics, radiographic parameters, and clinical outcomes were compared between the two groups.ResultsThe operation duration was 93.843 ± 20.611 in PPSR group and 109.432 ± 11.903 in OPSF group; blood loss was 131.118 ± 23.673 in PPSR group and 442.163 ± 149.701 in OPSF group, incision length was 7.280 ± 1.289 in PPSR group and 14.527 ± 2.893 in OPSF group, postoperative stay was 8.732 ± 1.864 in PPSR group and 15.102 ± 2.117 in OPSF group, and total hospitalization costs were 59027.196 ± 8687.447 in PPSR group and 73144.432 ± 11747.567 in OPSF group. These results indicated that these parameters were significantly lower in PPSR compared with those in OPSF group. No significant difference was observed in the incidence of complications between the two groups. The radiographic parameters including height of the anterior vertebra, Cobb angle, and vertebral wedge angle were better in PPSR group than in OPSF group. Recovery rate of AVH was 0.449 ± 0.079 in PPSR group and 0.279 ± 0.088 in OPSF group. Analysis of clinical results revealed that during postoperative period, the VAS and ODI scores in PPSR group were lower than those in OPSF group.ConclusionsCollectively, these results indicated that PPSR more effectively restored the height of anterior vertebra and alleviated local kyphosis compared with OPSF. Moreover, the VAS and ODI scores in PPSR group were better than those of OPSF group.

Signal source number detection is an essential issue for the direction of arrival (DOA) estimation in satellite communication systems. The performances of conventional and deep-learning-based signal source number detection methods will deteriorate when the signal-to-noise ratio is low or coherent signals exist. This paper proposes a DOA detection network (DTN) combined with the root weighted subspace fitting (root-WSF) method to tackle this challenge. The DTN uses the constructed deep neural networks (DNN) to denoise the received signals and captures the nonlinear mapping relationship between the received signals and the number of signal sources. The received signals in the complex-valued domain are directly treated as DTN’s input, and the label of DTN is the one-hot encoding of the source number. It solves the issue that the classifier cannot well-handle the coherent signals and extends the values of discrete features to Euclidean space. Accordingly, the trained DTN can detect the signal source numbers with an average detection accuracy of 96.6%, and the root-WSF algorithm is applied as the rear stage of DOA estimation. Compared with the traditional DOA methods, the proposed DTN incorporated with the root-WSF algorithm features superior robustness, high DOA estimation accuracy, and enhanced resolution.

Abstract R. esculentum is a popular seafood in Asian countries and an economic marine fishery resource in China. However, the genetic linkage map and growth-related molecular markers are still lacking, hindering marker assisted selection (MAS) for genetic improvement of R. esculentum. Therefore, we firstly used 2b-restriction site-associated DNA (2b-RAD) method to sequence 152 R. esculentum specimens and obtained 9100 single nucleotide polymorphism (SNP) markers. A 1456.34 cM linkage map was constructed using 2508 SNP markers with an average interval of 0.58 cM. Then, six quantitative trait loci (QTLs) for umbrella diameter and body weight were detected by QTL analysis based on the new linkage map. The six QTLs are located on four linkage groups (LGs), LG4, LG13, LG14 and LG15, explaining 9.4% to 13.4% of the phenotypic variation. Finally, 27 candidate genes in QTLs regions of LG 14 and 15 were found associated with growth and one gene named RE13670 (sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1-like) may play an important role in controlling the growth of R. esculentum. This study provides valuable information for investigating the growth mechanism and MAS breeding in R. esculentum.