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Abstract The ecological significance of secondary metabolites is to improve the adaptive ability of plants. Secondary metabolites, usually medicinal ingredients, are triggered by unsuitable environment, thus the quality of medicinal materials under adversity being better. The quality of the cultivated was heavily declined due to its good conditions. Radix Saposhnikoviae, the dried root of Saposhnikovia divaricata (Turcz.) Schischk., is one of the most common botanicals in Asian countries, now basically comes from cultivation, resulting in the market price being only 1/10 to 1/3 of its wild counterpart, so improving the quality of cultivated Radix Saposhnikoviae is of urgency. Nitric oxide (NO) plays a crucial role in generating reactive oxygen species and modifying the secondary metabolism of plants. This study aims to enhance the quality of cultivated Radix Saposhnikoviae by supplementing exogenous NO. To achieve this, sodium nitroprusside (SNP) was utilized as an NO provider and applied to fresh roots of S. divaricata at concentrations of 0.03, 0.1, 0.5, and 1.0 mmol/L. This study measured parameters including the activities of antioxidant enzymes, secondary metabolite synthesis enzymes such as phenylalanine ammonia-lyase (PAL), 1-aminocyclopropane-1-carboxylic acid (ACC), and chalcone synthase (CHS), as well as the contents of NO, superoxide radicals (O2 ·−), hydrogen peroxide (H2O2), malondialdehyde (MDA), and four secondary metabolites. The quality of Radix Saposhnikoviae was evaluated with antipyretic, analgesic, anti-inflammatory effects, and inflammatory factors. As a result, the NO contents in the fresh roots were significantly increased under SNP, which led to a significant increase of O2 ·− , H2O2, and MDA. The activities of important antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were found to increase as well, with their peak levels observed on the 2nd and 3rd days. PAL, ACC, and CHS activities were also significantly enhanced, resulting in the increased secondary metabolite contents of Radix saposhnikoviae in all groups, especially the 0.5 mmol/L SNP. The four active ingredients, prim-O-glucosylcimifugin, cimifugin, 4′-O-β-d-glucosyl-5-O-methylvisamminol, and sec-O-glucosylhamaudol, increased by 88.3%,325.0%, 55.4%, and 283.8%, respectively, on the 3rd day. The pharmaceutical effects of Radix Saposhnikoviae under 0.5 mmol/L SNP were significantly enhanced. Exogenous SNP can induce the physiological response of S. divaricata under adverse conditions and significantly improve the quality of Radix Saposhnikoviae.

Abstract Teleost fish have evolved various adaptations that allow them to tolerate cold water conditions. However, the underlying mechanism of this adaptation is poorly understood in Tibetan Plateau fish. RNA-seq combined with liquid chromatography‒mass spectrometry (LC‒MS/MS) metabolomics was used to investigate the physiological responses of a Tibetan Plateau-specific teleost, Gymnocypris przewalskii, under cold conditions. The 8-month G. przewalskii juvenile fish were exposed to cold (4 ℃, cold acclimation, CA) and warm (17 ℃, normal temperature, NT) temperature water for 15 days. Then, the transcript profiles of eight tissues, including the brain, gill, heart, intestine, hepatopancreas, kidney, muscle, and skin, were evaluated by transcriptome sequencing. The metabolites of the intestine, hepatopancreas, and muscle were identified by LC‒MS/MS. A total of 5,745 differentially expressed genes (DEGs) were obtained in the CA group. The key DEGs were annotated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The DEGs from the eight tissues were significantly enriched in spliceosome pathways, indicating that activated alternative splicing is a critical biological process that occurs in the tissues to help fish cope with cold stress. Additionally, 82, 97, and 66 differentially expressed metabolites were identified in the intestine, hepatopancreas, and muscle, respectively. Glutathione metabolism was the only overlapping significant pathway between the transcriptome and metabolome analyses in these three tissues, indicating that an activated antioxidative process was triggered during cold stress. In combination with the multitissue transcriptome and metabolome, we established a physiology-gene‒metabolite interaction network related to energy metabolism during cold stress and found that gluconeogenesis and long-chain fatty acid metabolism played critical roles in glucose homeostasis and energy supply.

Dielectrophoresis (DEP) is an advanced microfluidic manipulation technique that is based on the interaction of polarized particles with the spatial gradient of a non-uniform electric field to achieve non-contact and highly selective manipulation of particles. In recent years, DEP has made remarkable progress in the field of microfluidics, and it has gradually transitioned from laboratory-scale research to high-throughput manipulation in practical applications. This paper reviews the recent advances in dielectric manipulation and separation of microparticles and biological cells and discusses in detail the design of chip structures for the two main methods, direct current dielectrophoresis (DC-DEP) and alternating current dielectrophoresis (AC-DEP). The working principles, technical implementation details, and other improved designs of electrode-based and insulator-based chips are summarized. Functional customization of DEP systems with specific capabilities, including separation, capture, purification, aggregation, and assembly of particles and cells, is then performed. The aim of this paper is to provide new ideas for the design of novel DEP micro/nano platforms with the desired high throughput for further development in practical applications.

Dental caries (DC) is one of the most common oral diseases and is mainly caused by Streptococcus mutans (S. mutans). The use of antibiotics against S. mutans usually has side effects, including developing resistance. N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC), a natural product, has great potential utility in antibacterial agents owing to its low toxicity and good biocompatibility. Thus, the purpose of the present study was to explore the antimicrobial activity of N-2-HACC against S. mutans through the permeability of the cell wall, integrity of cell membrane, protein and nucleic acid synthesis, respiratory metabolism, and biofilm formation. Our results confirmed that the MIC of N-2-HACC against S. mutans was 0.625 mg/mL with a 90.01 ± 1.54% inhibition rate. SEM observed the formation of cavities on the surface of S. mutans after 12 h N-2-HACC treatment. The level of alkaline phosphatase (AKP) activity was higher in the N-2-HACC treatment group than in the control group, indicating that N-2-HACC can improve the permeability of the cell wall. Also, N-2-HACC treatment can destroy the cell membrane of S. mutans by increasing conductivity and absorbance at 260 nm, decreasing cell metabolic activity, and enhancing the fluorescence at 488 nm. Respiratory metabolism revealed that the activities of the Na+-K+-ATP enzyme, pyruvate kinase (PK), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were decreased after N-2-HACC treatment, revealing that N-2-HACC can inhibit glycolysis and the tricarboxylic acid cycle (TCA cycle) of S. mutans. Moreover, N-2-HACC can also decrease the contents of the nucleic acid and solution protein of S. mutans, interfere with biofilm formation, and decrease the mRNA expression level of biofilm formation-related genes. Therefore, these results verify that N-2-HACC has strong antibacterial activity against S. mutans, acting via cell membrane integrity damage, increasing the permeability of cell walls, interfering with bacterial protein and nucleic acid synthesis, perturbing glycolysis and the TCA cycle, and inhibiting biofilm formation. It is suggested that N-2-HACC may represent a new potential synthetically modified antibacterial material against S. mutans.

Cymbidium ensifolium, a prominent orchid species, is both highly valued for its ornamental qualities and commercially cultivated. However, the species has a considerable challenge in its breeding efforts due to the lengthy period of 7–8 years required for it to transition from seed germination to flowering. BBXs are multifunctional proteins that modulate the actions of critical regulators including HY5 and COP1 in response to blue light, ultimately impacting photomorphogenic processes. In this study, BBX proteins, known for their essential roles in regulating developmental processes under various light conditions, were chosen as the main subject of investigation. The outcome reveals the presence of 19 BBX genes in their genome. The genes are classified into four separate clades and dispersed among 12 out of the 20 chromosomes. Located in the nuclear, physicochemical properties of proteins, analysis of the promoter region reveals the existence of almost 800 cis-acting elements, highlighting the complex regulatory mechanisms that control the expression of the CeBBXs in various organs, as well as their response to light and hormone inputs. Moreover, the examination of differential expression under blue light therapy reveals their involvement in photomorphogenic reactions. The expression of CeBBXs exhibits substantial alterations as the duration of exposure to blue light increases. These findings contribute to a deeper understanding of the roles that BBX genes serve in C. ensifolium, providing a basis for future studies on the functions and regulatory mechanisms of BBX members in the context of floral initiation and development within this species.

The Chang 6 sandstone reservoir of the Upper Triassic Yanchang Formation in the Ordos Basin is one of the tight-oil-rich intervals in the basin. Owing to the strong heterogeneity and complex lithology of the Chang 6 reservoir, lithology and fluid identification have become more challenging, hindering exploration and development. This study focused on the Chang 6 member in the Qingcheng area of the Ordos Basin to systematically analyze the lithology, physical properties, and oil-bearing properties of the Chang 6 reservoir. We adopted the method of normalized superposition of neutron and acoustic time-difference curves, the method of induced conductivity–porosity–density intersection analysis, the method of superposition of difference curves (Δφ), and the induced conductivity curve. Our results indicated that the method of normalized superposition of neutron and acoustic wave time-difference curves could quickly and effectively identify the lithologies of tight fine sandstone, silty mudstone, mudstone, and carbonaceous mudstone. The induced conductivity–porosity–density cross-plot could be used to effectively identify oil and water layers, wherein the conductivity of tight oil layers ranged from 18 to 28.1 mS/m, the density ranged from 2.42 to 2.56 g/cm3, the porosity was more than 9.5%, and the oil saturation was more than 65%. Based on the identification of tight fine sandstone using the dual-curve normalized superposition method, the oil layer thickness within the tight fine sandstone could be effectively identified using the superposition of difference curves (Δφ) and induced conductivity curves. Verified by oil-bearing reservoir data from the field test, the overall recognition accuracy of the plots exceeded 90%, effectively enabling the identification of reservoir lithology and fluid types and the determination of the actual thickness of oil layers. Our results provide a reference for predicting favorable areas in the study area and other tight reservoirs.

Naringenin (NRG) is widely found in citrus fruits and has anti-inflammatory, hypoglycemic, and immunomodulatory effects. Previous studies have shown that NRG promotes gastrointestinal motility in mice constipation models, but there are few systematic evaluations of its effects on normal animals. This study first clarified the promotive effects of NRG on gastric emptying and small intestine propulsion (p < 0.01). NRG can also regulate the release of gastrointestinal hormones, including enhancing gastrin (GAS) and motilin (MTL) (p < 0.01), while reducing vasoactive intestinal peptide (VIP) secretion (p < 0.01). Using NRG to stimulate the isolated stomach, duodenum, and colon showed similar promotive effects to those observed in vivo (p < 0.01). A Western blot analysis indicated that this effect may be mediated by increasing the expression of stem cell factor (SCF) and its receptor (c-Kit) in these three segments, thus regulating their downstream pathways. It is worth noting that NRG can also increase the proportion of beneficial bacteria (Planococcaceae, Bacteroides acidifaciens, Clostridia_UCG-014) in the intestine and reduce the quantity of harmful bacteria (Staphylococcus). These findings provide a new basis for the application of NRG.

Numerous researchers have endeavored to amalgamate critical transit-oriented development (TOD) indicators, such as development density, walkability, and diversity, into a single TOD index to assess TOD performance. However, implementing TOD in megacities necessitates a more comprehensive selection of indicators, an objective calculation methodology, and accessible calculation data for the TOD index. This study introduces a method based on multi-indicator TOD performance assessment using multi-source urban big data; it uses Shanghai as a case study to evaluate and analyze the impact of site characteristics on performance. The method constructs the Comprehensive Socio-Economic Development Index (CSEDI) based on four indicators of TOD site operations. It establishes a multivariate regression model utilizing principal component analysis to extract 22 leading component indicators as independent variables from 71 indicators associated with TOD. Within the sample space of 77 rail transit TOD sites in Shanghai, the CSEDI exhibited a robust correlation with the independent variables. The evaluation results of the case study demonstrate consistency with the development characteristics of the city and the sites, indicating that the evaluation method can guide the renovation of existing sites and the development of new sites.

The heterogeneity of natural rocks complicates the study of carbon sequestration within these materials and raises concerns about the reproducibility of experimental results. Consequently, identifying appropriate rock-like materials has become critical. This research examined the impact of various factors—humidity, binder content, curing period, and cold pressure—on the bond strength of magnesium oxychloride cement (MOC) through orthogonal testing. The tests utilized a molar ratio of MgO to MgCl2-6H2O to H2O of 7:1:18. Both X-ray diffraction (XRD) and scanning electron microscopy (SEM) were employed to analyze the hydration reactions of MOC and to explore the correlation between the microstructure of the SiO2-MgO-MgCl2 system and its bonding characteristics. The findings indicated that a 5% relative humidity enhances the 7-day bond strength of MOC. Moreover, increasing the curing humidity to 60% relative humidity supports the ongoing hydration of the strength-contributing phases. A binder content ranging from 15% to 25% proved optimal, yielding samples with superior strength and stiffness. While cold pressing initially enhances the bonding properties of MOC, solution loss during the process adversely affects its long-term bonding characteristics. From a mechanical standpoint, the silica-magnesium oxide-magnesium chloride system demonstrates exceptional early strength and resilience, positioning it as a promising rock-like material system.

The Bou Dahar Pb-Zn district, located in the Moroccan High Atlas, is a typical carbonate-hosted Pb-Zn ore district (>30 Mt at 4 wt.% Pb, 4 wt.% Zn). In situ trace element analysis was performed using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) on galena and cerussite from different ore types. The galena is generally enriched in Ag and Sb, secondarily enriched in Cu, with a trace amount of Cd and As, but extremely depleted in Bi and Tl. The main substitution mechanism in galena is (Ag, Cu)+ + Sb3+ ↔ 2Pb2+, and at high Sb concentrations, the further substitution of 2Sb3+ + □ ↔ 3Pb2+ (where □ represents a vacancy) took place. Micro-inclusions of Cu-Sb-bearing minerals (such as tetrahedrite) and Ag-bearing minerals (such as acanthite) may exist in some situations. The features of trace elements in galena show the existence of different coupled substitutions in vein-related ore, breccia-related ore, and strata-bound ore. This suggests that the Bou Dahar district experienced multistage mineralization. The MVT model alone cannot fully explain the ore-forming process. The cerussite replacing strata-bound galena is enriched in Sr, Ba, Ag, and Cu, with minor Sb, As, and Tl. Strontium and Ba are directly substituted with Pb in the cerussite lattice. Copper and Ag are likely present in cerussite as nano-inclusions, which differs from the coupled substitution mechanism of the original galena. High concentrations of Ag may occur due to minor electrum inclusions. The enrichment of Ag, Cu, and Au in cerussite during the oxidation process may guide the optimization of ore processing, especially in extracting valuable trace/minor elements.

The types and morphology of sheep horns have been extensively researched, yet the genetic foundation underlying the emergence of diverse horn characteristics during the breeding of polled Tibetan sheep has remained elusive. Genome-wide association analysis (GWAS) was performed on 103 subtypes (normal large horn, scurs, and polled) differentiated from G2 (offspring (G2) of parent (G1) of polled) of the polled core herd. Six single nucleotide polymorphisms (SNPs) located on chromosome 10 of the relaxin family peptide receptor 2 (RXFP2) gene exhibited positive correlations with horn length, horn base circumference, and horn base interval. Furthermore, in genotyping 382 G2 individuals, significant variations were observed for each specific horn type. Three additional mutations were identified near the target SNP upstream of the amplification product. Finally, the RXFP2-specific haplotype associated with the horned trait effectively maintained horn length, horn base circumference, and horn base interval in Tibetan sheep, as confirmed by population validation of nine loci in a sample size of 1125 individuals. The present study offers novel insights into the genetic differentiation of the horned type during improvement breeding and evolution, thereby establishing a robust theoretical foundation for polled Tibetan sheep breeding and providing valuable guidance for practical production.

Biochar is regarded as a soil improvement material possessing superior physical and chemical properties that can effectively enhance plant growth. However, there exists a paucity of research examining the efficacy of biochar in supplanting traditional materials and its subsequent impact on the growth of Ardisia crenata, which is currently domesticated as fruit ornamentals. In this study, the mechanism of biochar’s effect on Ardisia crenata was analyzed by controlled experiments. For 180 days, their growth and development were meticulously assessed under different treatments through the measurement of various indices. Compared with the references, the addition of biochar led to an average increase in soil nutrient content, including a 14.1% rise in total nitrogen, a 564.1% increase in total phosphorus, and a 63.2% boost in total potassium. Furthermore, it improved the physical and chemical properties of the soil by reducing soil bulk density by 6.2%, increasing total porosity by 6.33%, and enhancing pore water by 7.35%, while decreasing aeration porosity by 1.11%. The growth and development of Ardisia crenata were better when the appending ratio of biochar was in the range of 30% to 50%, with the root parameters, such as root length, root surface area, and root volume, 48.90%, 62.00%, and 24.04% higher to reference. At the same time, the biomass accumulation of roots in the best group with adding biochar also increased significantly (55.80%). The addition of biochar resulted in a significant improvement in the content of chlorophyll a and chlorophyll b (1.947 mg g−1) and the net photosynthetic rate (5.6003 µmol m−2 s−1). This study’s findings underpinned the addition of biochar in soil improvement and plant response. Therefore, biochar can favor the cultivation and industrial application of Ardisia crenata in the future, leading to an efficient and environmentally friendly industrial development.

As pH is a key factor affecting the quality of maize silage, its accurate detection is essential to ensuring product quality. Although traditional methods for testing the pH of maize silage feed are widely used, the procedures are often complex and time-consuming and may damage the sample. This study presents a non-destructive hyperspectral imaging (HSI) technology that provides a more efficient and cost-effective method of monitoring pH by capturing the spectral information of samples and analyzing their chemical and physical properties rapidly and without contact. We applied four spectral preprocessing methods, among which the multiplicative scatter correction (MSC) preprocessing method yielded the best results. To minimize model redundancy and enhance predictive performance, we utilized six feature extraction methods for characteristic wavelength extraction, integrating these with partial least squares (PLS), non-linear support vector machine regression (SVR), and extreme learning machine (ELM) algorithms to construct a quantitative pH value prediction model. The results showed that the model based on the bootstrapping soft shrinkage (BOSS) feature wavelength extraction method outperformed the other feature extraction methods, selecting 20 pH value-related feature wavelengths from 256 bands and building a stable BOSS–ELM model with prediction set determination coefficient (RP2), root-mean-square error of prediction (RMSEP), and relative percentage deviation (RPD) values of 0.9241, 0.4372, and 3.6565, respectively. To further optimize the model for precisely predicting pH at each pixel in hyperspectral images, we employed three algorithms: the genetic algorithm (GA), whale optimization algorithm (WOA), and bald eagle search (BES). These algorithms optimized and compared the BOSS–ELM model to obtain the best model for predicting maize silage pH: the BOSS–BES–ELM model. This model achieved a determination coefficient (RP2) of 0.9598, an RMSEP of 0.3216, and an RPD of 5.1448. We generated a visualized distribution map of pH value variation in maize silage using the BOSS–BES–ELM model. This study provides strong technical support and a reference for the rapid, non-destructive detection of maize silage pH from an image, an advancement of great significance to ensuring the quality of maize silage.

Hydro-viscous clutch has already become an inevitable choice for special vehicle transmission in the present and future. As a nonlinear system with a large hysteresis loop, its speed control performance is affected by input rotational speed, lubricating oil temperature, lubrication pressure, and other factors. The traditional control method cannot adjust the temperature and rotational speed, which will lead to problems of narrow speed range, poor rotational speed stability, and large dynamic load impact. In order to solve the above problems, this paper studies the control method of an integrated multi-parameter hydro-viscous speed control system (HSCS) in a controlled environment. Through the mechanism analysis of the law of HSCS, the influence law of speed and temperature during the system operation is found. The temperature closed loop based on model predictive control (MPC) is introduced to control the rotational speed, and then the traditional PID control results are compensated according to the speed closed loop. Next, a novel double closed loop control method of temperature and rotational speed for HSCS is formed. Finally, the simulating verification is carried out. Compared with the traditional control method, the design method in this paper can adjust the control parameters according to the temperature of the lubricating oil and the input rotational speed and effectively expand the domain of HSCS and the speed control stability. The effective transmission ratio is extended to 0.2~0.8, and the hydro-viscous torque and speed fluctuation under the engine rotational speed fluctuation are reduced by more than 30%. The novel control method of HSCS designed in this paper can effectively improve the influence of input rotational speed and lubricating oil temperature on the speed control performance of HSCS and can be widely used in nonlinear HSCS such as hydro-viscous clutch.

Field effect transistors based on few-layered van der Waals transition metal halide (TMH) Nb3Cl8 are studied in this work. Few-layered Nb3Cl8 exhibits typical N-type semiconducting behavior controlled by a Si gate, with the electrical signal enhancing as the thickness increases from 4.21 nm to 16.7 nm. Moreover, we find that the tunability of few-layered Nb3Cl8 FETs’ electrical transport properties can be significantly augmented through the use of an ionic liquid gate (or electrical double layer, EDL). This enhancement leads to a substantial increase in the on–off ratio by approximately a factor of 102, with the transfer curve modulated into a bipolar fashion. The emergence of such bipolar tunable characteristics in Nb3Cl8 FETs serves to enrich the electronic properties within the transition metal halide family, positioning Nb3Cl8 as a promising candidate for diverse applications spanning transistors, logic circuits, neuromorphic computing and spintronics.

Hepatitis A virus (HAV), a member of the genus Hepatovirus (Picornaviridae HepV), remains a significant viral pathogen, frequently causing enterically transmitted hepatitis worldwide. In this study, we conducted an epidemiological survey of HepVs carried by small terrestrial mammals in the wild in Yunnan Province, China. Utilizing HepV-specific broad-spectrum RT-PCR, next-generation sequencing (NGS), and QNome nanopore sequencing (QNS) techniques, we identified and characterized two novel HepVs provisionally named EpMa-HAV and EpLe-HAV, discovered in the long-tailed mountain shrew (Episoriculus macrurus) and long-tailed brown-toothed shrew (Episoriculus leucops), respectively. Our sequence and phylogenetic analyses of EpMa-HAV and EpLe-HAV indicated that they belong to the species Hepatovirus I (HepV-I) clade II, also known as the Chinese shrew HepV clade. Notably, the codon usage bias pattern of novel shrew HepVs is consistent with that of previously identified Chinese shrew HepV. Furthermore, our structural analysis demonstrated that shrew HepVs differ from other mammalian HepVs in RNA secondary structure and exhibit variances in key protein sites. Overall, the discovery of two novel HepVs in shrews expands the host range of HepV and underscores the existence of genetically diverse animal homologs of human HAV within the genus HepV.

Abstract Endoscopic evaluation is the key to the management of ulcerative colitis (UC). However, there is interobserver variability in interpreting endoscopic images among gastroenterologists. Furthermore, it is time‐consuming. Convolutional neural networks (CNNs) can help overcome these obstacles and has yielded preliminary positive results. We aimed to develop a new CNN‐based algorithm to improve the performance for evaluation tasks of endoscopic images in patients with UC. A total of 12,163 endoscopic images from 308 patients with UC were collected from January 2014 to December 2021. The training set and test set images were randomly divided into 37,515 and 3191 after excluding possible interference and data augmentation. Mayo Endoscopic Subscores (MES) were predicted by different CNN‐based models with different loss functions. Their performances were evaluated by several metrics. After comparing the results of different CNN‐based models with different loss functions, High‐Resolution Network with Class‐Balanced Loss achieved the best performances in all MES classification subtasks. It was especially great at determining endoscopic remission in UC, which achieved a high accuracy of 95.07% and good performances in other evaluation metrics with sensitivity 92.87%, specificity 95.41%, kappa coefficient 0.8836, positive predictive value 93.44%, negative predictive value 95.00% and area value under the receiver operating characteristic curve 0.9834, respectively. In conclusion, we proposed a new CNN‐based algorithm, Class‐Balanced High‐Resolution Network (CB‐HRNet), to evaluate endoscopic activity of UC with excellent performance. Besides, we made an open‐source dataset and it can be a new benchmark in the task of MES classification.

Abstract Purpose This study aimed to investigate the prevalence of antimicrobial de-escalation (ADE) strategy and assess its effect on 14-day mortality among intensive care unit patients. Methods A single-center retrospective cohort study was conducted on patients admitted to the intensive care unit (ICU) with infectious diseases between January 2018 and December 2020. Patients were stratified into three groups based on the initial treatment regimen within 5 days of antimicrobial administration: ADE, No Change, and Other Change. Confounders between groups were screened using one-way ANOVA and Chi-square analysis. Univariate and multivariate analyses were performed to identify risk factors for 14-day mortality. Potential confounders were balanced using propensity score inverse probability of treatment weighting (IPTW), followed by multivariate logistic regression analysis to evaluate the effect of ADE strategy on 14-day mortality. Results A total of 473 patients met the inclusion criteria, with 53 (11.2%) in the ADE group, 173 (36.6%) in the No Change group, and 247 (52.2%) in the Other Change group. The 14-day mortality rates in the three groups were 9.4%, 11.6%, and 21.9%, respectively. After IPTW, the adjusted odds ratio for 14-day mortality comparing No Change with ADE was 1.557 (95% CI 1.078–2.247, P = 0.0181) while comparing Other Change with ADE was 1.282(95% CI 0.884–1.873, P = 0.1874). Conclusion The prevalence of ADE strategy was low among intensive care unit patients. The ADE strategy demonstrated a protective effect or no adverse effect on 14-day mortality compared to the No Change or Other Change strategies, respectively. These findings provide evidence supporting the implementation of the ADE strategy in ICU patients.

Urban vitality is the comprehensive characterization of the activities and processes in the city, which is influenced not only by environmental factors but also by the vitality of surrounding areas. Thus, the spatial effect of urban vitality can be understood under the constraint of the built environment. Taking Xiamen Island as a case, multisource big data are used to measure urban vitality, development intensity, and functional diversity. Spatial weight matrices with different distances are constructed. Through the spatial autoregressive threshold model, the threshold values of development intensity and functional diversity are estimated, and the spatial nonlinear effects of urban vitality based on different spatial weight matrices are analyzed. Results show that: (1) There is a significant spatial spillover effect of urban vitality. The spatial spillover effect is influenced by the built environment conditions and shows the characteristics of nonlinear growth with the change in development intensity and functional diversity; (2) the spatial spillover effect of urban vitality is significantly enhanced with the expansion of influence distance; (3) The development intensity has double thresholds. With the improvement of development intensity, the spatial spillover effect of urban vitality becomes stronger and more significant. The functional diversity has a significant single threshold value. The discussion of functional diversity should be carried out on the premise of density. The conclusion provides a theoretical basis for the optimization of urban vitality and built environment.

In this paper, we consider a Schrödinger operator $ L = -\Delta_{\mathbb{H}}+V $ on the stratified Lie group $ \mathbb{H} $. First, we establish fractional heat kernel estimates related to $ L^{\beta} $, $ \beta\in(0, 1) $. By utilizing kernel estimations and the fractional Carleson measure, we are able to derive a characterization of the Campanato type space $ BMO_{L}^{v}(\mathbb{H}) $. Second, we demonstrate that both Littlewood-Paley $ {\bf g} $-functions and area functions are bounded on $ BMO^{v}_{L}(\mathbb{H}) $. Finally, we also obtain that the above square functions are bounded on the Morrey space $ L^{\gamma, \theta}_{p, \kappa}(\mathbb{H}) $ and the weak Morrey space $ WL^{\gamma, \theta}_{1, \kappa}(\mathbb{H}) $, respectively.

Objective: The novel coronavirus (severe acute respiratory syndrome coronavirus 2) has been spreading worldwide since December 2019, posing a serious danger to human health and socioeconomic development. A large number of clinical trials have revealed that coronavirus disease 2019 (COVID-19) results in multi-organ damage including the urogenital system. This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis. Methods: We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and CD147 in major organs in the healthy and disease-specific populations, particularly the genitourinary organs. Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2, TMPRSS2, CD147, cytokine receptors, and cytokine interacting proteins in genitourinary organs, such as the bladder, kidney, prostate, and testis. Additionally, gene set enrichment analysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer. Results: The results revealed that ACE2, TMPRSS2, and CD147 were highly expressed in normal urogenital organs. Then, they were also highly expressed in multiple tumors and chronic kidney diseases. Additionally, ACE2, TMPRSS2, and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing. Cytokine receptors and cytokine interacting proteins, especially CCL2, JUN, and TIMP1, were commonly highly expressed in urogenital organs. Finally, gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19. Conclusion: Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives, which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

Abstract The enhanced geothermal system (EGS) is the key to improving the heat production efficiency of hot dry rock (HDR). Due to the existence of EGS, the reservoir produces significant heterogeneity, so the optimal design of well location and injection rate has an important influence on the heat recovery effect of an EGS. To solve this problem, a calculation model for the heat output of an EGS under multifield coupling is established in this paper, and the influence of well location and injection rate on the heat recovery effect under different scales of EGS is deeply analyzed. The results show that the production well location and injection well displacement have a great influence on the heat recovery effect under different fracture‐network scales. The larger the size of the fracture network, the larger the effective utilization area of reservoir heat recovery and the better the effect of heat recovery. The closer the production well is to the fracture network and in the direction of the fracture network, the larger the effective utilization area of reservoir heat recovery is, and the better the effect of heat recovery is. The higher the injection well displacement is, the larger the effective utilization area of reservoir heat recovery is, and the better the heat recovery effect is. The research results have important guiding significance for the optimization of the scale, well placement, and water injection displacement of the EGS in the HDR reservoir.

Abstract Background N6-methyladenosine (m6A) and 5-methylcytosine (m5C) are the main RNA methylation modifications involved in the oncogenesis of cancer. However, it remains obscure whether m6A/m5C-related long non-coding RNAs (lncRNAs) affect the development and progression of low grade gliomas (LGG). Methods We summarized 926 LGG tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas and Chinese Glioma Genome Atlas. 105 normal brain samples with RNA-seq data from the Genotype Tissue Expression project were collected for control. We obtained a molecular classification cluster from the expression pattern of sreened lncRNAs. The least absolute shrinkage and selection operator Cox regression was employed to construct a m6A/m5C-related lncRNAs prognostic signature of LGG. In vitro experiments were employed to validate the biological functions of lncRNAs in our risk model. Results The expression pattern of 14 sreened highly correlated lncRNAs could cluster samples into two groups, in which various clinicopathological features and the tumor immune microenvironment were significantly distinct. The survival time of cluster 1 was significantly reduced compared with cluster 2. This prognostic signature is based on 8 m6A/m5C-related lncRNAs (GDNF-AS1, HOXA-AS3, LINC00346, LINC00664, LINC00665, MIR155HG, NEAT1, RHPN1-AS1). Patients in the high-risk group harbored shorter survival times. Immunity microenvironment analysis showed B cells, CD4 + T cells, macrophages, and myeloid-derived DC cells were significantly increased in the high-risk group. Patients in high-risk group had the worse overall survival time regardless of followed TMZ therapy or radiotherapy. All observed results from the TCGA-LGG cohort could be validated in CGGA cohort. Afterwards, LINC00664 was found to promote cell viability, invasion and migration ability of glioma cells in vitro. Conclusion Our study elucidated a prognostic prediction model of LGG by 8 m6A/m5C methylated lncRNAs and a critical lncRNA regulation function involved in LGG progression. High-risk patients have shorter survival times and a pro-tumor immune microenvironment.

Objective This study aimed to elucidate the underlying gene regions responsible for productive, phenotypic or adaptive traits in different ecological types of Tibetan sheep and the discovery of important genes encoding valuable traits. Methods We used whole-genome resequencing to explore the genetic relationships, phylogenetic tree, and population genetic structure analysis. In addition, we identified 28 representative Tibetan sheep single-nucleotide polymorphisms (SNPs) and genomic selective sweep regions with different traits in Tibetan sheep by fixation index (Fst) and the nucleotide diversity (θπ) ratio. Results The genetic relationships analysis showed that each breed partitioned into its own clades and had close genetic relationships. We also identified many potential breed-specific selective sweep regions, including genes associated with hypoxic adaptability (MTOR, TRHDE, PDK1, PTPN9, TMTC2, SOX9, EPAS1, PDGFD, SOCS3, TGFBR3), coat color (MITF, MC1R, ERCC2, TCF25, ITCH, TYR, RALY, KIT), wool traits (COL4A2, ERC2, NOTCH2, ROCK1, FGF5, SOX9), and horn phenotypes (RXFP2). In particular, a horn-related gene, RXFP2, showed the four most significantly associated SNP loci (g. 29481646 A>G, g. 29469024 T>C, g. 29462010 C>T, g. 29461968 C>T) and haplotypes. Conclusion This finding demonstrates the potential for genetic markers in future molecular breeding programs to improve selection for horn phenotypes. The results will facilitate the understanding of the genetic basis of production and adaptive unique traits in Chinese indigenous Tibetan sheep taxa and offer a reference for the molecular breeding of Tibetan sheep.

AIM: To study the effects of long-term use of clozapine on tear film stability and ocular surface tissue structure.METHODS: Case-control study was conducted on 45 patients(group 1)who were diagnosed with schizophrenia and treated with clozapine for 3.45±0.72a between March 2021 and December 2021. Another 45 healthy subjects(group 2)served as controls, whose demographic characteristics were similar to those of group 1. Patients' dry eye symptoms were investigated using OSDI questionnaire, tear secretion was detected by the Schirmer I test, ocular surface damage was assessed by the ocular surface staining score, and comprehensive ophthalmic examination was performed on all patients through LipiView ocular surface interferometer, ocular surface integrated analyzer, corneal confocal microscope and slit lamp photographic system.RESULTS: Slit-lamp photography showed diffuse grayish-white spot-like opacification in the corneal stroma of group 1, accompanied by brown star-like opacification in the center of the anterior capsule of the lens. OSDI scores were 38.00(31.50, 48.50)and 15.00(9.00, 19.50)in the two groups respectively. Schirmer test showed that the group 1 was 5.27±2.18mm/5min, while group 2 was 15.62±3.05mm/5min. Corneal fluorescein staining score: 4.00(2.50, 5.00)for group 1 and 1.00(0.00, 1.50)for group 2. The lissamine green staining score for the conjunctiva was 9.00(6.50, 10.00)and 3.00(2.00, 3.50)for the two groups, respectively. LipiView detected lipid layer thickness(LLT), suggesting that the results of group 1 and group 2 were similar, respectively 75.91±15.51 and 77.24±12.11nm; and the results were similar for the lid gland deficiency score, with 1.37±0.26 and 1.29±0.31 points, respectively. The mean tear meniscus height in group 1 was 0.13±0.06mm, which was lower than 0.23±0.04mm of group 2. Non-invasive breakup time(NIBUT)was 6.04±2.62 and 11.4±2.74s in group 1 and group 2 respectively. OSDI score, Schirmer Ⅰ test, ocular surface staining score, tear meniscus height and NIBUT were significantly different between the two groups(P

Phalaenopsis was the genus with the highest ornamental and commercial values among orchids. Phalaenopsis with fragrance were rarely distributed in the market due to selection constraints, such as affinity, ploidy and breeding age. Therefore, research on transferring aroma traits into commercial Phalaenopsis are of great significance to the breeding of Phalaenopsis. In order to investigate the key aroma-causing components among different varieties of Phalaenopsis, the floral fragrance components of the eight new hybrid varieties in full blooming period were examined by headspace solid-phase microextraction and gas chromatography-mass spectrometry. The principal components, clustering and aroma quality analysis were performed based on the identification of floral substance components. The results were as follows: (1) 96 substances were detected in eight varieties of Phalaenopsis, mainly divided into eight categories of terpenes, aldehydes, esters, alcohols, ketones, ethers, phenols and aromatic compounds, among which terpenes were dominant in quantity and content and were the main volatile substances of Phalaenopsis. (2) Principal component analysis showed that eight varieties were divided into three quadrants, F2 had the most volatile components and the most quantity, terpenes were mainly 1,8-cineole, α-bergamotene, linalool and (+)-calarene; F1, F4, F5 and F8 were divided into a group without ketones, ethers or phenols, and they had the least volatile components and terpenes were mainly linalool; F3, F6 and F7 were divided into a group with more volatile components and the terpenes were mainly α-bergamotene. (3) The results of cluster analysis were consistent with the principal component analysis, and the eight varieties were clustered into three categories, F1, F4, F5 and F8 were more closely related to each other as floral odor types; F3, F6 and F7 were more closely related to each other as woody floral quality; F2 showed a long genetic distance from the other seven varieties, with complex floral components and relatively average contribution of volatile substances, and both woody, minty and fruity types. This study shows that floral fragrance substances can be used as potential trait markers to distinguish between groups of varieties with different fragrance characteristics and provide a theoretical basis for further development and utilization research through cross selection to achieve specific floral fragrance Phalaenopsis selection and product processing and production.

Abstract Poplar is one of the main urban and rural greening and shade tree species in the northern hemisphere, but its growth and development is always restricted by salt stress. R2R3-MYB transcription factor family is commonly involved in many biological processes during plant growth and stress endurance. In this study, PagMYB151 (Potri.014G035100) one of R2R3-MYB members related to salt stress and expressed in both nucleus and cell membrane was cloned from Populus alba × P. glandulosa to perfect the salt tolerance mechanism. Morphological and physiological indexes regulated by PagMYB151 were detected using the PagMYB151 overexpression (OX) and RNA interference (RNAi) transgenic poplar lines. Under salt stress conditions, compared with RNAi and the non-transgenic wild-type (WT) plants, the plant height, both aboveground and underground part fresh weight of OX was significantly increased. In addition, OX has a longer and finer root structure and a larger root surface area. The root activity of OX was also enhanced, which was significantly different from RNAi but not from WT under salt treatment. Under normal conditions, the stomatal aperture of OX was larger than WT, whereas this phenotype was not obvious after salt stress treatment. In terms of physiological indices, OX enhanced the accumulation of proline but reduced the toxicity of malondialdehyde to plants under salt stress. Combing with the transcriptome sequencing data, 6 transcription factors induced by salt stress and co-expressed with PagMYB151 were identified that may cooperate with PagMYB151 to function in salt stress responding process. This study provides a basis for further exploring the molecular mechanism of poplar PagMYB151 transcription factor under abiotic stress.

This is a paper in the field of metallurgical engineering. As a technical method to effectively improve the permeability of charge column and reduce the coke ratio, mixed charging of ore and coke is widely used to improve the forward process of blast furnace. In this paper, the reduction and migration behavior of vanadium at different temperatures in the mixed charging process of vanadium titanium ore and coke in blast furnace are studied. The results show that when the temperature is lower than 1350℃, the reduction condition of vanadium in the layer loading area is better than that in the mixed loading area; In the melting zone, vanadium is mainly concentrated at the interface between slag and iron; The formation of magnesium ferrite in the soft melt zone can promote the vanadium to gather near the molten iron, and the basic oxide MgO can promote the migration of V to Fe.

The Genhe River Basin is an ecological barrier and water conservation area in northern China, but its hydrological process has undergone significant changes due to climate change and human activities, endangering ecosystem functions and water resource security. Systematic research on the influencing mechanisms and laws of hydrological processes in different ecosystems in this region remains lacking. Therefore, this study analyzed the effects of different anthropogenic factors on the hydrological processes of typical ecosystems in the Genhe River Basin. The Soil and Water Assessment Tool distributed hydrological model was used to simulate the surface runoff, evapotranspiration, and soil water content of the three ecosystems of forest, grassland, and farmland in four different periods of 1980, 1990, 2000, and 2010. The spatial and temporal changes in water resources in typical ecosystems under the influence of historical climate change were demonstrated. Results showed that under different land use scenarios, the surface runoff of the farmland ecosystem increased, the evapotranspiration remained unchanged, and the soil water content decreased. The surface runoff of forest and grassland ecosystems did not change significantly, the evapotranspiration increased, and the soil water content decreased. This study reveals the influence of different human factors on the hydrological processes of typical ecosystems in the Genhe River Basin and provides a scientific basis for water resources management and ecological protection in the region.

Particle engulfment plays a vital role in the application of particulate reinforced metal matrix composites fabricated by ingot metallurgy. During solidification, particles are nevertheless pushed by an advancing front. As a model system, TiB2p/Al composites were used to investigate the particle engulfment facilitated by acoustic cavitation. The implosion of bubbles drives the particles plunging towards the solid/liquid interface, which increases the engulfment probability. The secondary dendrite arms are refined from 271.2 μm to 98.0 μm as a result of the forced movements of TiB2 particles. Owing to the particle engulfment and dendrite refinement, the composite with ultrasound vibration treatment shows a more rapid work-hardening rate and higher strength.

The tunnel construction by the drill-and-blast method can have a significant impact on the adjacent buildings, especially the historical buildings with poor structural performances. Based on a special explosive case of Nanjing Metro Line 4, an in-situ blasting test for vibration safety evaluation on the Nanjing Drum Tower was carried out. According to the site geological investigation, the location of the blasting test was selected near the planned tunnel. 6 blasting was carried out in terms of sing-hole blasting and millisecond-delay blasting. The attenuation of the ground vibration and the structural vibration responses of the historical Drum Tower were analyzed. The test results also showed that the Nanjing Drum Tower was not damaged by this blasting test. For single-hole blasting tests, the peak particle velocity increased with the increasing of the explosive charge, but decreased remarkably when using the millisecond-delay blasting technology. The horizontal and vertical ground vibration attenuation patterns were consistent, which can be described by the Sadowski formula. The ground vibration response was dominated by the horizontal vibration, and the velocity amplification factor in the case of the single-hole test with a charge quantity of 400 g reached 2.4, which was observed the most remarkable amplification effect.

In numerous developing nations, the pervasive practice of crop residue incineration is a principal contributor to atmospheric contamination in agricultural operations. This study examines the repercussions of such biomass combustion on air quality during the autumnal harvest season, utilizing data acquired from satellite-based remote sensing of fire events and air pollution measurements. Employing wind direction information alongside difference-in-difference and fixed-effects methodologies, this investigation rectifies estimation inaccuracies stemming from the non-random distribution of combustion occurrences. The empirical findings reveal that agricultural residue burning precipitates an elevation in average PM2.5 and PM10 concentrations by approximately 27 and 22 μg/m3 during the autumnal incineration period, respectively. Furthermore, air pollution attributed to residue burning in prominent grain-producing regions exceeds the national average by approximately 40%. By integrating economic paradigms into agri-environmental inquiries, this study offers novel insights and substantiation of the environmental expenditures engendered by crop residue burning, juxtaposed with extant meteorological and ecological research findings.

Abstract Subduction leads to voluminous arc magmatism at active continental margins; however, the potential far‐field geodynamic connections with coeval magmatism along opposing passive margins, are rarely investigated. Here we report large‐scale and parallel mafic dike swarms on the South Qinling passive margin, whose geochemical features record the thick and cold subcontinental lithospheric mantle beneath passive margin was gradually replaced by thin and hot one during the early Paleozoic. The subduction of the Proto‐Tethys oceanic lithosphere led to arc magmatism along the active margin, shortly after the rift‐related mafic dike swarms occurred along the passive margin. Subsequent to the continuous oceanic subduction including the ridge‐margin collision, mantle upwelling and slab rollback eventually triggered large‐scale rift‐related magmatism and the opening of new ocean basin at passive margin, and also back‐arc magmatism on the active margin. We highlight slab subduction and pull link the geodynamic processes at active and passive continental margins, which improves our understanding of plate tectonics.

Background and purposeThe differential diagnosis between solid glioma and brain inflammation is necessary but sometimes difficult. We assessed the effectiveness of multiple diffusion metrics of diffusion-weighted imaging (DWI) in differentiating solid glioma from brain inflammation and compared the diagnostic performance of different DWI models.Materials and methodsParticipants diagnosed with either glioma or brain inflammation with a solid lesion on MRI were enrolled in this prospective study from May 2016 to April 2023. Diffusion-weighted imaging was performed using a spin-echo echo-planar imaging sequence with five b values (500, 1,000, 1,500, 2000, and 2,500 s/mm2) in 30 directions for each b value, and one b value of 0 was included. The mean values of multiple diffusion metrics based on diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), mean apparent propagator (MAP), and neurite orientation dispersion and density imaging (NODDI) in the abnormal signal area were calculated. Comparisons between glioma and inflammation were performed. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of diffusion metrics were calculated.Results57 patients (39 patients with glioma and 18 patients with inflammation) were finally included. MAP model, with its metric non-Gaussianity (NG), shows the greatest diagnostic performance (AUC = 0.879) for differentiation of inflammation and glioma with atypical MRI manifestation. The AUC of DKI model, with its metric mean kurtosis (MK) are comparable to NG (AUC = 0.855), followed by NODDI model with intracellular volume fraction (ICVF) (AUC = 0.825). The lowest value was obtained in DTI with mean diffusivity (MD) (AUC = 0.758).ConclusionMultiple diffusion metrics can be used in differentiation of inflammation and solid glioma. Non-Gaussianity (NG) from mean apparent propagator (MAP) model shows the greatest diagnostic performance for differentiation of inflammation and glioma.

Introduction: Short Tandem Repeats (STRs) are highly valuable genetic markers in forensic science. However, the conventional PCR-CE technique has limitations, and the emergence of massively parallel sequencing (MPS) technology presents new opportunities for STR analysis. Yet, there is limited research on Chinese population diversity using MPS.Methods: In this study, we obtained genotype data for 52 A-STRs and 81 Y-STRs from the Hakka population in Meizhou, Guangdong, China, using the Forensic Analysis System Multiplecues SetB Kit on the MGISEQ-2000 platform.Results: Our findings demonstrate that these 133 STRs are highly efficient for forensic applications within the Meizhou Hakka population. Statistical analysis revealed Hobs values ranging from 0.61306 to 0.91083 and Hexp values ranging from 0.59156 to 0.91497 for A-STRs based on length polymorphism. For sequence polymorphism, Hobs values ranged from 0.61306 to 0.94586, and Hexp values fluctuated between 0.59156 and 0.94487. The CPE values were 1-5.0779620E-21 and 1-3.257436E-24 for length and sequence polymorphism, respectively, while the CPD values were 1-1.727007E-59 and 1-5.517015E-66, respectively. Among the 80 Y-STR loci, the HD values for length and sequence polymorphism were 0.99764282 and 0.99894195, respectively. The HMP values stood at 0.00418102 and 0.00288427, respectively, and the DC values were 0.75502742 and 0.83363803, respectively. For the 52 A-STR loci, we identified 554 and 989 distinct alleles based on length and sequence polymorphisms, respectively. For the 81 Y-STR loci, 464 and 652 unique alleles were detected at the length and sequence level, respectively. Population genetic analysis revealed that the Meizhou Hakka population has a close kinship relationship with the Asian populations THI and KOR based on length polymorphism data of A-STRs. Conversely, based on length polymorphism data of Y-STRs, the Meizhou Hakka population has the closest kinship relationship with the Henan Han population.Discussion: Overall, the variation information of repeat region sequences significantly enhances the forensic identification efficacy of STR genetic markers, providing an essential database for forensic individual and paternity testing in this region. Additionally, the data generated by our study will serve as a vital resource for research into the genetic structure and historical origins of the Meizhou Hakka population.

A synthetic organic substance called bisphenol A (BPA) is used to make polyester, epoxy resin, polyacrylate, and polycarbonate plastic. BPA exposure on a regular basis has increased the risk of developing cancer. Recent research has shown that there is a strong link between BPA exposure and a number of malignancies. We want to investigate any connections between BPA and prostate cancer in this work. The scores of bisphenols in the prostate cancer cohort were obtained using the ssGSEA algorithm. The analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was used to investigate probable pathways that are closely related to the genes tied to BPA. The BPA-based risk model was built using regression analysis. Additionally, the molecular docking method was employed to assess BPA's capacity to attach to important genes. Finally, we were able to successfully get the BPA cohort ratings for prostate cancer patients. Additionally, the KEGG enrichment study showed that of the malignancies linked to BPA, prostate cancer is the most highly enriched. In a group of men with prostate cancer, the BPA-related prognostic prediction model exhibits good predictive value. The BPA demonstrated strong and efficient binding to the androgen receptor, according to the molecular docking studies. According to cell proliferation and invasion experiments, exposing prostate cancer cells to BPA at a dosage of 10–7 uM could greatly enhance their ability to proliferate and invade.

BackgroundThe performance of existing image-based training models in evaluating bowel preparation on colonoscopy videos was relatively low, and only a few models used external data to prove their generalization. Therefore, this study attempted to develop a more precise and stable AI system for assessing bowel preparation of colonoscopy video.MethodsWe proposed a system named ViENDO to assess the bowel preparation quality, including two CNNs. First, Information-Net was used to identify and filter out colonoscopy video frames unsuitable for Boston bowel preparation scale (BBPS) scoring. Second, BBPS-Net was trained and tested with 5,566 suitable short video clips through three-dimensional (3D) convolutional neural network (CNN) technology to detect BBPS-based insufficient bowel preparation. Then, ViENDO was applied to complete withdrawal colonoscopy videos from multiple centers to predict BBPS segment scores in clinical settings. We also conducted a human-machine contest to compare its performance with endoscopists.ResultsIn video clips, BBPS-Net for determining inadequate bowel preparation generated an area under the curve of up to 0.98 and accuracy of 95.2%. When applied to full-length withdrawal colonoscopy videos, ViENDO assessed bowel cleanliness with an accuracy of 93.8% in the internal test set and 91.7% in the external dataset. The human-machine contest demonstrated that the accuracy of ViENDO was slightly superior compared to most endoscopists, though no statistical significance was found.ConclusionThe 3D-CNN-based AI model showed good performance in evaluating full-length bowel preparation on colonoscopy video. It has the potential as a substitute for endoscopists to provide BBPS-based assessments during daily clinical practice.

BackgroundDespite advancements in hepatocellular carcinoma (HCC) treatments, the prognosis for patients remains suboptimal. Cumulative evidence suggests that programmed cell death (PCD) exerts crucial functions in HCC. PCD-related genes are potential predictors for prognosis and therapeutic responses.MethodsA systematic analysis of 14 PCD modes was conducted to determine the correlation between PCD and HCC. A novel machine learning-based integrative framework was utilized to construct the PCD Index (PCDI) for prognosis and therapeutic response prediction. A comprehensive analysis of PCDI genes was performed, leveraging data including single-cell sequencing and proteomics. GBA was selected, and its functions were investigated in HCC cell lines by in vitro experiments.ResultsTwo PCD clusters with different clinical and biological characteristics were identified in HCC. With the computational framework, the PCDI was constructed, demonstrating superior prognostic predictive efficacy and surpassing previously published prognostic models. An efficient clinical nomogram based on PCDI and clinicopathological factors was then developed. PCDI was intimately associated with immunological attributes, and PCDI could efficaciously predict immunotherapy response. Additionally, the PCDI could predict the chemotherapy sensitivity of HCC patients. A multilevel panorama of PCDI genes confirmed its stability and credibility. Finally, the knockdown of GBA could suppress both the proliferative and invasive capacities of HCC cells.ConclusionThis study systematically elucidated the association between PCD and HCC. A robust PCDI was constructed for prognosis and therapy response prediction, which would facilitate clinical management and personalized therapy for HCC.

Optical nano sources play important roles in optical communications, photonic integrated circuits, and quantum information. However, integratable, multi-color and directionally controllable nanoscale optical sources remain a challenge. This work presents a design of a two-channel upconversion nanosource based on phase coupling between metal-dielectric-metal (MDM) cavities. The resonant cavities embedded with upconversion nanoparticles (UCNPs) couple with each other by phase modulation in the bus waveguide, which enables simultaneous excitation and fluorescence enhancement of the UCNPs in cavities. Benefiting from inherent ability of MDM structure, the emitted light can be manipulated directionally for subsequent multi-channel applications. In addition, the relevant optical properties can be accurately described by a theoretical model. The excitation field strength in cavities was found to be sensitive to the coupling phase, and the derived theoretical model can predict the optimal coupling distance for an efficient dual-channel upconversion nano-emitter. This nano-emitter combines the unique fluorescence advantages of UCNPs with the easy preparation of MDM nanocavities for easy integration and nanoscale optical control, promising major applications in photonic chips, optical sensors, and complex energy optoelectronic devices.

The synergistic anti-tumor therapy based on chemotherapeutic drugs and gene drugs has become a new direction of tumor treatment. However, the significantly distinct physicochemical properties and the unbalanced coordinate proportion of chemotherapeutic and genetic drugs limit the actual therapeutic efficiency of the combined drug delivery strategy. Herein, we developed a simple method to self-assemble the fluorine atom-modified antisense oligonucleotide (2′F-G1319) with chemotherapeutic pirarubicin (THP) to form the carrier-free nanomedicines (2′F-G1319/THP NMs), which could efficaciously achieve the synergistic gene therapy and chemotherapy. In this study, 2′F-G1319 and THP could be self-assembled to form uniform nanoparticles through enhanced intermolecular interactions after G1319 was modified with the fluorine atom. Both in-vitro and in-vivo experiments verified that 2′F-G1319/THP NMs exhibited significant synergistic anti-tumor effects with high biostability and biocompatibility. Owing to the simple and universal synthesis process, our constructed self-assembled nanomedicine provides a promising opportunity for the wide applications of nanomedicines and is expected to realize more effective synergistic anti-tumor therapy without the addition of non-therapeutic excipients

Disco Interacting Protein 2 Homolog A (DIP2A) is expressed throughout the body and abundantly expressed in the brain tissue. It is activated by Follistatin-like 1 (FSTL1). Activated DIP2A interacts with several pathways, such as AMPK/mTOR and AKT pathways, to contribute to many biological processes, such as oxidative stress, transcriptional regulation, and apoptosis. Dysregulated DIP2A activation has been implicated in numerous processes in the brain. If the upstream pathways of DIP2A remain globally unexplored, many proteins, including cortactin, AMPK, and AKT, have been identified as its downstream targets in the literature. Recent studies have linked DIP2A to a variety of mechanisms in many types of brain disorders, suggesting that regulation of DIP2A could provide novel diagnostic and therapeutic approaches for brain disorders. In this review, we comprehensively summarized and discussed the current research on DIP2A in various brain disorders, such as stroke, autism spectrum disorders (ASD), Alzheimer’s disease (AD), dyslexia, and glioma.

Abstract Background The use of artificial intelligence (AI) assisted white light imaging (WLI) detection systems for superficial esophageal squamous cell carcinoma (SESCC) is limited by training with images from one specific endoscopy platform. Methods In this study, we developed an AI system with a convolutional neural network (CNN) model using WLI images from Olympus and Fujifilm endoscopy platforms. The training dataset consisted of 5892 WLI images from 1283 patients, and the validation dataset included 4529 images from 1224 patients. We assessed the diagnostic performance of the AI system and compared it with that of endoscopists. We analyzed the system's ability to identify cancerous imaging characteristics and investigated the efficacy of the AI system as an assistant in diagnosis. Results In the internal validation set, the AI system's per-image analysis had a sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 96.64%, 95.35%, 91.75%, 90.91%, and 98.33%, respectively. In patient-based analysis, these values were 90.17%, 94.34%, 88.38%, 89.50%, and 94.72%, respectively. The diagnostic results in the external validation set were also favorable. The CNN model’s diagnostic performance in recognizing cancerous imaging characteristics was comparable to that of expert endoscopists and significantly higher than that of mid-level and junior endoscopists. This model was competent in localizing SESCC lesions. Manual diagnostic performances were significantly improved with the assistance by AI system, especially in terms of accuracy (75.12% vs. 84.95%, p = 0.008), specificity (63.29% vs. 76.59%, p = 0.017) and PPV (64.95% vs. 75.23%, p = 0.006). Conclusions The results of this study demonstrate that the developed AI system is highly effective in automatically recognizing SESCC, displaying impressive diagnostic performance, and exhibiting strong generalizability. Furthermore, when used as an assistant in the diagnosis process, the system improved manual diagnostic performance.

A novel heat-resistant Al matrix composite was fabricated, reinforced by a combination of nano-AlN and submicron TiN particles, i.e., (5TiN+6.4AlN)/Al composite, using the liquid–solid reaction method, and followed by an extrusion process. According to scanning electron microscopy and transmission electron microscopy results, AlN particles with an average size of 45 nm were mainly distributed along the intergranular grain and partially distributed in the grains, and TiN particles with an average size of 300 nm were uniformly distributed in the Al matrix. The novel composites exhibited excellent tensile strength at both room temperature (RT), especially at high temperature (350 °C, HT), reaching 400 and 195 MPa, respectively. The TiN particles were found to further generate the effect of dispersion strengthening, while the AlN particles were effective in stabilizing the grain boundaries and pinning dislocations at HT. The enhancement of grain boundary stability by the intergranular particles and dislocation pinning by the intragranular particles were the main strengthening mechanisms of the composites at 350 °C. Based on the critical roles of the dispersive reinforcement particles and theoretical calculations at RT, the Orowan strengthening of AlN plays a dominant role at RT. This work may provide new ideas for the development of high-strength heat-resistant Al matrix composites.

By means of direct current electrodeposition, Cu foil with columnar grain growth and equiaxed grain growth with different average grain sizes were prepared. Electron backscatter diffraction (EBSD), X-ray diffraction (XRD), atomic force microscopy (AFM), and transmission electron microscope (TEM) were employed to elucidate the correlation between the microstructures and properties of Cu foil after a certain relaxation time under different grain growth methods. A remarkable preferential ratio of {220} orientation was exhibited in the columnar-grown copper. However, as the copper layer transitions to equiaxed grain growth, the superiority altered to {200} crystal orientation. This variability in grain orientation makes the copper layer profile of columnar crystal growth higher than that of equiaxed crystal formation. The twin boundary density in copper foil increases as the grain growth mode changes from columnar to equiaxed, and grain refinement is beneficial to increase the twin boundary density in the samples. And columnar crystal copper and equiaxed crystal copper show different twin characteristics. There are a few single-stage twin steps in columnar crystal copper and more multi-stage twin steps in equiaxed crystal copper. With an increase of twin boundary density, both the tensile strength and the ductility increase remarkably.

Abstract Background The identification of disease-related genes is of great significance for the diagnosis and treatment of human disease. Most studies have focused on developing efficient and accurate computational methods to predict disease-causing genes. Due to the sparsity and complexity of biomedical data, it is still a challenge to develop an effective multi-feature fusion model to identify disease genes. Results This paper proposes an approach to predict the pathogenic gene based on multi-head attention fusion (MHAGP). Firstly, the heterogeneous biological information networks of disease genes are constructed by integrating multiple biomedical knowledge databases. Secondly, two graph representation learning algorithms are used to capture the feature vectors of gene-disease pairs from the network, and the features are fused by introducing multi-head attention. Finally, multi-layer perceptron model is used to predict the gene-disease association. Conclusions The MHAGP model outperforms all of other methods in comparative experiments. Case studies also show that MHAGP is able to predict genes potentially associated with diseases. In the future, more biological entity association data, such as gene-drug, disease phenotype-gene ontology and so on, can be added to expand the information in heterogeneous biological networks and achieve more accurate predictions. In addition, MHAGP with strong expansibility can be used for potential tasks such as gene-drug association and drug-disease association prediction.

Abstract Most existing template matching algorithms are global matching between the template target and the search region, which makes the matching process retain a lot of unfavourable background information and ignore the structure and local information of the template target. To address this problem, a template matching algorithm based on bipartite graph and graph attention mechanism is proposed in this paper. The algorithm models the similarity matching problem between template features and search region features as a complete bipartite graph, realises local‐to‐local information transfer between the two, and uses the graph attention mechanism to apply weights between local information to obtain a learnable embedding network module. In addition, in terms of feature representation, a multi‐level feature fusion module based on CNN is introduced, which improves the representation of a target by fusing features with different representational meanings of the target. Experimental results on several typical datasets show that the proposed algorithm achieves leading performance in terms of accuracy and efficiency compared to the two state‐of‐the‐art CNN‐based template matching algorithms, Deep‐DIM and QATM.

AIM: To evaluate the clinical efficacy of P2Y2 agonist diquafosol sodium(DQS)eye drops in the treatment of diabetic dry eye.METHODS: A total of 80 patients(160 eyes)with diabetic dry eye who admitted to our hospital from January 2022 to March 2022 were selected. They were randomly divided into study group and control group. A total of 40 patients(80 eyes)in the study group were treated with 3% DQS eye drops and 40 patients(80 eyes)in the control group were treated with 0.3% sodium hyaluronate eye drops. The ocular surface disease index(OSDI)score, non-invasive tear meniscus height(NITMH), first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tarsal gland loss score, lipid layer thickness grade and bulbar redness analysis(including conjunctival grade and ciliary grade), were examined before treatment and at 1wk, 1 and 3mo after treatment, respectively. Furthermore, corneal fluorescence staining and conjunctival lissamine green staining were analyzed based on the ocular surface staining score(OSS), and the conjunctival impression cytology and confocal microscopy were evaluated before and 3mo after treatment, respectively.RESULTS: There were no differences in OSDI score, tarsal gland loss score, conjunctival grade score and ciliary grade score between the two groups before and after treatment(P>0.05). OSS scores in the study group were lower than those in the control group, while NITMH, NIBUTf and NIBUTav were higher than those in the control group at 1 and 3mo after treatment(P0.05).CONCLUSION: 3% DQS eye drops were effective in treating diabetic dry eye without serious complications.

In order to understand the connotation and substantive relationship among oil and gas resources, reserves and production on a deeper level, this paper made an in-depth analysis and elaboration on the relationship among the three from the perspectives of theoretical logic and practical transformation, and presented suggestions for the development direction of resource assessment based on the analysis of application status. Resources, reserves and production are estimated quantities of oil and gas mineral resources under different levels of understanding. In China's classification system, reserves and resources are in a parallel relationship, and reserves and production are in an inclusive relationship. Both resources and reserves are geological meanings. The transformation from resources to reserves is affected by factors such as national spatial planning, mining right setting, theoretical technical and economic conditions, and the transformation from reserves to production is affected by factors such as reserves upgrading and transformation, whether to convert to mining, recovery factor, etc. China still has some deficiencies in resource assessment and release, as well as quantitative prediction of resources, reserves and production, which is also an important reason for the cognitive confusion of "China has rich resource potential but it is difficult to increase reserves and production". The enrichment and development of resource assessment contents and results application analysis will help to form a comprehensive and in-depth understanding of the current situation of oil and gas resources. It should be further explored and developed in the future from the following respects: mobility classification of assessment results, assessment of (undiscovered) recoverable resources and application analysis of results.

Abstract Reasonable volumetric fracturing effect evaluation is the key to effective stimulation of fractured reservoir. Traditional fracturing effect evaluation is mainly conducted by the SRV (stimulated reservoir volume), fracture length, fracture width and other indicators, ignoring the influence of failure mode on fracturing performance. In this paper, the different fracture modes including main fractures, branch fractures and self-supporting fractures contained in the fracture network and their contributions to fracturing effect were studied in depth by numerical simulation. The results show that the main fracture formed by tensile failure has the largest width but simple shape and relatively small distribution range, while the branch fracture has a slightly smaller width but effectively expands the main fracture. Although the self-supporting fracture by shear failure is not connected, it can still improve the overall flow conductivity. The angle and number of natural fractures in fractured reservoir have a significant effect on fracture network scale and fracturing effect. When the number of natural fractures is larger, both of the number and proportion of branching fractures and self-supported fractures are larger, although the isolated self-supported fractures account for a larger proportion, the overall flow conductivity of the final fracture network is stronger. When the angle of natural fractures is larger, the natural fractures in uniform stress field are easier to be connected by hydraulic fractures and the final fracturing effect is better. The research methods and results have a certain guiding significance for the evaluation of volumetric fracturing effect in fractured reservoirs and are conducive to the reasonable selection of favorable fracturing areas and engineering parameters.

A porous ceramic support is designed as a multi-functional independent catalyst layer for solid oxide fuel cells (SOFCs) running on liquid hydrocarbon fuel. The layer consists of a highly porous Ce0.9Ca0.1O2−δ ceramic backbone and active NiMo catalysts, which could be integrated into the conventional Ni metal containing the anode for internal reforming of the hydrocarbon fuel. Compared to conventional catalyst layers sintered on the anodes, this independent catalyst layer could be simply assembled on top of the anode without additional sintering, thereby avoiding the mismatch of the thermal expansion coefficient between the catalyst layer and the anode and improving stability of a single cell. Moreover, a current collector layer could be inserted between the catalyst and the anode to enhance current collection efficiency and electrochemical performance of the single cell. At 750 ℃, the independent catalyst layer displays high activity towards the catalytic decomposition of methanol, and the single cell could achieve the maximum power density of 400–500 mW·cm−2 in dry methanol. Furthermore, by employing the independent catalyst layer, the single cell offers additional in-situ catalyst regeneration capability under the methanol operation mode. Feeding 10 mL·min−1 air into an anode channel for 5 min is found to be effective to burn out carbon species in the catalyst layer, which reduces the degradation rate of the cell voltage by orders of magnitude from 2.6 to 0.024 mV·h−1 during the operation of 360 h in dry methanol. The results demonstrate the significance of the independent catalyst layer design for direct internal reforming methanol fuel cells.