Search

ABSTRACT A scraper conveyor is one of the important equipment to ensure reliable, efficient and stable mining and transportation of coal. As the most important transmission system of the scraper conveyor, the gearbox takes the role of transmitting power and torque. Due to the influence of working conditions in underground coal mines, the gear transmission system is often subject to the impact of nonuniform large loads, which is very prone to failures, and affected by environmental interference, it is difficult to detect the early abnormal signals of the scraper conveyor gearbox in the conventional industrial scenarios of fault monitoring methods. To ensure the stability and reliability of its work, this paper carries out the research on the multi‐parameter fusion of gearbox early fault diagnosis method under strong background noise interference. Aiming at the problem that the change of fluid physical and chemical characteristic parameters can reflect the early health condition of the gear transmission system and the single vibration signal is difficult to be extracted under the strong background noise, a model based on the fluid physical and chemical characteristic parameters and vibration signals is constructed by utilizing the RBF neural network and the Random Forest algorithm, and the body of evidence of the two models is fused at the decision‐making level through the DS evidence theory, which forms the fluid‐vibration multi‐parameter fusion judgment of the early fault diagnosis method of scraper conveyor gearbox. Through comparison, it is found that compared with the fusion methods, such as high‐dimensional variational self‐encoder, and single diagnosis methods, such as the Random Forest Algorithm, the method researched in this paper is more suitable for the early fault warning of the scraper conveyor gearbox of the well coal mine, and the experimental validation finds that the average accuracy rate of the early fault recognition can be up to 96.6%.

With the gradual depletion of shallow coal resources, the most serious threat restricting the safe mining of Group A coal seams in Huainan Mining Area has changed from gas to floor confined water. According to the production and geological conditions of 12123 working face in Pan’er Mine, a micro-seismic monitoring system was established for the coal floor. Through mining and interpreting micro-seismic data, a micro-seismic identification method for floor failure and conduction induced by mining was proposed. An inversion method of mining fractures evolution was defined based on micro-fractures conductivity. The failure conduction evolution characteristics of grouted rock around collapse column were revealed. The results show that, affected by the advance grouting reinforcement, micro-seismic events show a phenomenon of detour distribution around the grouted collapse column. There was a longitudinal through zone for floor conductivity in the interface and shallow layer, and other areas were sporadically isolated due to the barrier of grouting veins.

With continuous growth in scale, topology complexity, mission phases, and mission diversity, challenges have been placed for efficient capability evaluation of modern combat systems. Aiming at the problems of insufficient mission consideration and single evaluation dimension in the existing evaluation approaches, this study proposes a mission-oriented capability evaluation method for combat systems based on operation loop. Firstly, a combat network model is given that takes into account the capability properties of combat nodes. Then, based on the transition matrix between combat nodes, an efficient algorithm for operation loop identification is proposed based on the Breadth-First Search. Given the mission-capability satisfaction of nodes, the effectiveness evaluation indexes for operation loops and combat network are proposed, followed by node importance measure. Through a case study of the combat scenario involving space-based support against surface ships under different strategies, the effectiveness of the proposed method is verified. The results indicated that the ROI-priority attack method has a notable impact on reducing the overall efficiency of the network, whereas the O-L betweenness-priority attack is more effective in obstructing the successful execution of enemy attack missions.

Environmental parameter data collected by sensors for monitoring the environment of agricultural facility operations are usually incomplete due to external environmental disturbances and device failures. And the missing of collected data is completely at random. In practice, missing data could create biased estimations and make multivariate time series predictions of environmental parameters difficult, leading to imprecise environmental control. A multivariate time series imputation model based on generative adversarial networks and multi-head attention (ATTN-GAN) is proposed in this work to reducing the negative consequence of missing data. ATTN-GAN can capture the temporal and spatial correlation of time series, and has a good capacity to learn data distribution. In the downstream experiments, we used ATTN-GAN and baseline models for data imputation, and predicted the imputed data, respectively. For the imputation of missing data, over the 20%, 50% and 80% missing rate, ATTN-GAN had the lowest RMSE, 0.1593, 0.2012 and 0.2688 respectively. For water temperature prediction, data processed with ATTN-GAN over MLP, LSTM, DA-RNN prediction methods had the lowest MSE, 0.6816, 0.8375 and 0.3736 respectively. Those results revealed that ATTN-GAN outperformed all baseline models in terms of data imputation accuracy. The data processed by ATTN-GAN is the best for time series prediction.

Abstract Background Viola diffusa is used in the formulation of various Traditional Chinese Medicines (TCMs), including antiviral, antimicrobial, antitussive, and anti-inflammatory drugs, due to its richness in flavonoids and triterpenoids. The biosynthesis of these compounds is largely mediated by cytochrome P450 enzymes, which are primarily located in the membranes of mitochondria and the endoplasmic reticulum. Results This study presents the complete assembly of the mitogenome and plastome of Viola diffusa. The circular mitogenome spans 474,721 bp with a GC content of 44.17% and encodes 36 unique protein-coding genes, 21 tRNA, and 3 rRNA. Except for the RSCU values of 1 observed for the start codon (AUG) and tryptophan (UGG), the mitochondrial protein-coding genes exhibited a codon usage bias, with most estimates deviating from 1, similar to patterns observed in closely related species. Analysis of repetitive sequences in the mitogenome demonstrated potential homologous recombination mediated by these repeats. Sequence transfer analysis revealed 24 homologous sequences shared between the mitogenome and plastome, including nine full-length genes. Collinearity was observed among Viola diffusa species within the other members of Malpighiales order, indicated by the presence of homologous fragments. The length and arrangement of collinear blocks varied, and the mitogenome exhibited a high frequency of gene rearrangement. Conclusions We present the first complete assembly of the mitogenome and plastome of Viola diffusa, highlighting its implications for pharmacological, evolutionary, and taxonomic studies. Our research underscores the multifaceted importance of comprehensive mitogenome analysis.

Background: The emergence and transmission of the multidrug resistance gene cfr have raised public health concerns worldwide. Objectives: Multidrug-resistant Staphylococcus equorum isolates can pose a threat to public health. In this study, we have characterised the whole-genome of one Staphylococcus equorum isolate harbouring two distinct cfr-carrying plasmids. Methods: Antimicrobial susceptibility testing was performed by broth microdilution. Genomic DNA was sequenced using both the Illumina HiSeq X Ten and Nanopore MinION platforms. De novo hybrid assembly was performed by Unicycler. Genomic data were assessed by in silico prediction and bioinformatic tools. Results: Staphylococcus equorum isolate SN42 exhibited resistance or high MICs to linezolid, erythromycin, tetracycline, oxacillin, clindamycin, virginiamycin, tiamulin, chloramphenicol and florfenicol. It carried two cfr-harbouring plasmids: the RepA N-family plasmid pSN42–51 K and the Inc18-family plasmid pSN42–50 K. These two plasmids exhibited low structural similarities to the so far reported cfr-carrying plasmids. Both plasmids harboured an arsenic resistance operon, copper and cadmium resistance genes as well as the lincosamide-pleuromutilin-streptogramin A resistance gene lsa(B). In addition, plasmid pSN42–51 K carried two erm(B) genes for macrolide-lincosamide-streptogramin B resistance, the streptomycin resistance gene ant(6)-Ia as well as mercury resistance genes while pSN42–50 K was associated with the heavy metal translocating P-type ATPase gene hmtp. The co-carriage and co-existence of these antimicrobial resistance and heavy metal resistance genes increases the likelihood of co-selection of the cfr-carrying plasmids. Conclusion: This is the first report of S. equorum carrying two distinct cfr-carrying plasmids, underscoring the need for ongoing surveillance to address the potential dissemination of multi-drug resistance in bacteria from food-producing animals to ensure food safety and public health.

In object segmentation, the existence of hard-classified-pixels limits the segmentation performance. Focusing on these hard pixels through assigning different weights to pixel loss can guide the learning of segmentation model effectively. Existing loss weight assignment methods perceive pixels hardness by current predicted information, pay less attention to past predicted information. While current studies show that samples with less improvement in predicted probability compared to the past are difficult to learn. To define hard pixels more accurately, a hardness-aware loss for object segmentation is proposed. Firstly, the metric of pixel hardness degree is defined, and a mapping function is proposed to quantitatively evaluate the hardness degree which is defined on the difference between current and past predicted probabilities. Then a new compound metric, hardness value, is defined based on hardness degree and the uncertainty. Based on the compound metric, a new loss function is proposed. Experiment results on four datasets using convolutional neural network and Transformer as the backbone models demonstrate that the proposed method effectively improves the accuracy of object segmentation. Especially, in the segmentation model based on ResNet-50, the proposed method improves mean Intersection over Union (mIoU) by almost 4.3 % compared to cross entropy on DUT-O dataset.

Cervical cancer remains a significant global public health concern, often exhibits cisplatin resistance in clinical settings. Hypoxia, a characteristic of cervical cancer, substantially contributes to cisplatin resistance. To evaluate the therapeutic efficacy of cisplatin in patients with cervical cancer and to identify potential effective drugs against cisplatin resistance, we established a hypoxia-inducible factor-1 (HIF-1)-related risk score (HRRS) model using clinical data from patients treated with cisplatin. Cox and LASSO regression analyses were used to stratify patient risks and prognosis. Through qRT-PCR, we validated nine potential prognostic HIF-1 genes that successfully predict cisplatin responsiveness in patients and cell lines. Subsequently, we identified fostamatinib, an FDA-approved spleen tyrosine kinase inhibitor, as a promising drug for targeting the HRRS-high group. We observed a positive correlation between the IC50 values of fostamatinib and HRRS in cervical cancer cell lines. Moreover, fostamatinib exhibited potent anticancer effects on high HRRS groups in vitro and in vivo. In summary, we developed a hypoxia-related gene signature that suggests cisplatin response prediction in cervical cancer and identified fostamatinib as a potential novel treatment approach for resistant cases.

Objective To investigate the spatial-temporal variations in landslide susceptibility due to human engineering activities in resettled urban areas. Methods This study focuses on the new urban area of Yunyang County in the Three Gorges Reservoir region. Landslide susceptibility time-varying index factors were introduced to map spatial-temporal susceptibility differences and explore the spatial-temporal evolution of landslide disasters during urbanization in resettled urban areas. First, the stacking ensemble model was selected as the static susceptibility evaluation model. Then, the InSAR deformation rates and land use types over three distinct time spans (namely, January 16, 2017, to August 27, 2018 (T1), September 20, 2018, to July 30, 2021 (T2), and August 23, 2021, to November 17, 2023 (T3)) were selected as time-varying factors. Last, the time-varying factors were combined with the static evaluation results to create susceptibility difference distribution maps for the different periods. Results The study revealed that introducing time-varying factors in the analysis of spatial-temporal susceptibility differences effectively reflects the impact of urbanization on landslide disasters. When the land type in the study area changed from non-engineering land to engineering land, the landslide susceptibility level generally increased, with grid shares of 61.3% and 67.1% in the two change stages, respectively. The temporal trends of the InSAR displacement time series curves for selected typical landslides in urban areas showed high spatial-temporal correlations with land type changes, further validating the reliability of this method. Conclusion The proposed research approach provides the basis for disaster prevention, mitigation, and regional planning during the urbanization process in resettled urban areas of the Three Gorges Reservoir region.

Using first principles, a systematic investigation of interface bonding nature and tensile behaviour of Ti2AlC(0001)/TiC(111) interface has been carried out at the atomic scale. The results show that Ti(Al)-on-top-C2 has the largest work of adhesion (13.1160 J/m2), the smallest interface energy (−2.6161 J/m2), and the largest interface fracture toughness (3.9660–4.9372 MPa⋅m1/2). Its interfacial bond is Ti–C covalent bond. And its tensile properties (critical strain of 12% and ideal tensile strength of 26.32 GPa) are second only to the best tensile properties (13% and 28.73 GPa). Except for Ti(Al)-fcc-hollow-Ti3, the fracture locations of seven interface models in the tensile simulation correspond to Griffith theory and work of interface separation. The inconsistency arises from the mutual repulsion of two Ti atoms in the Ti2–Ti3 bond in Ti(Al)-fcc-hollow-Ti3. And movement of C atoms on Ti2AlC bulk of C1–C2 bond changes stacking site from “hcp-hollow” to “on-top”, which leads to a decrease in stress of C-hcp-hollow-C2 before inflection point. The fracture process of the interface is summarized as follows: tiny electron holes form at lower strains, followed by electron microcrack as strain increases, and finally fracture failure due to the breakage of the chemical bond allowing the charge depletion region to form.

Cu–12Fe-0.42Si-0.008B alloy was formed by twin-roll strip casting. Studied the strengthening mechanism after adding Si and B elements and the effect of single/double stage cold rolling aging on its microstructure and properties. The solidification structure of the two alloys was dominated by equiaxed grains, with a “sandwich” structure formed by the Cu and the central Fe-rich phases. The tensile strength of the alloy increases with the increase of aging time. The maximum strength at 16 h of two-stage cold rolling and aging (450 °C) is 682.2 MPa, 52% higher than that of the Cu–12Fe alloy, and the saturation magnetic field strength increased by 29.4 %. This is attributed to the addition of Si and B elements to increase the number of primary iron-rich phases in the alloy and promote the precipitation of nano-α-Fe phase during aging. The finer nano-Fe-rich phase particles are generated with a coherent relationship between the precipitated Fe phase and the Cu bas, that is (1-1-1)Cu//(10-1)Fe. The strength of the alloy after two-stage cold rolling aging is always better than that of single-stage cold rolling. This is because the two-stage cold rolling treatment reduces the content of fibrous α - Fe phase in the alloy and increases the nanoscale spherical α-Fe phase. Confirming that the spherical α-Fe phase has a better strengthening effect. The relative conductivity of alloy increases with the increased aging time, with the highest relative conductivity of 53.9% IACS and 54.9% IACS obtained after 16 h of two-stage cold rolling aging.

Abstract Background TgMIC1, a soluble adhesion protein that typically facilitates parasite invasion, exhibited varying expression levels among distinct virulence strains of Chinese 1 Toxoplasma. This study aims to explore its role in immunological regulation and its association with diverse postinfection outcomes in Toxoplasma infection. Methods First, the mic1 knockout strain Wh3Δmic1 was generated and assessed for its virulence and proliferative capacity. Subsequently, the serum inflammation levels were examined in mice infected with Wh3Δmic1, Wh3, and Wh6. Furthermore, rMIC1 and rMIC1-T126A/T220A, which lack binding sites to N-glycan in TLR4, were produced for coculture with bone marrow-derived macrophages (BMDMs) to investigate their impact on pyroptosis. Results Our data showed Wh3Δmic1 exhibited a significant reduction in invasion efficiency, limited growth, and attenuated inflammatory responses in mice. Additionally, it displayed a decreased capacity to induce pyroptosis when compared with Wh3-infected BMDMs. Moreover, rMIC1 but not rMIC1-T126A/T220A was found to be able to upregulate NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and activate GSDMD and caspase-1 in BMDMs but not in TLR4−/− and NLRP3−/− BMDMs. Conclusions TgMIC1 is implicated in both parasite invasion and the modulation of macrophage pyroptosis via the TLR4/NLRP3 pathway. This investigation indicates that TgMIC1 serves diverse functions in Toxoplasma gondii infection, thereby enhancing comprehension of the immune regulatory mechanisms of the parasite. Graphical Abstract

Abstract Background Haff disease is a condition that has emerged in China in recent years, primarily associated with the consumption of crayfish. Despite its increasing incidence, the exact cause of Haff disease remains unknown, prompting further investigation into its potential triggers and risk factors. The purpose of this system review is to investigate and summarize the current understanding of Haff disease and provide insights into the etiology and pathogenesis of Haff disease by collecting and analyzing data from a large number of patients. Method Systematic searches were conducted in PubMed, CNKI, and Wanfang Databases to investigate and summarize Haff disease by crayfish consumption in China over recent years. The search included observational studies published up to May 1, 2024. Result This review collected data from 1437 patients and conducted a comprehensive analysis of symptoms. In-depth examinations of patient symptoms revealed that nearly all patients exhibited abnormally elevated serum creatine kinase levels and muscular pain, while some also experienced changes in urine color, abdominal discomfort, and chest pain. Risk factors associated with Haff disease from crayfish consumption included high crayfish consumption, alcohol use, the consumption of specific crayfish organs such as the head, liver, and pancreas, and the consumption of wild crayfish. Conclusion Haff disease is indeed related to the consumption of crayfish, which may be due to the presence of an unknown heat stable toxin in crayfish. During the research process, many risk factors were identified, and it is recommended that people who consume crayfish pay attention to these risk factors and take appropriate preventive measures to minimize the risk of illness.

Abstract The gamut and EOTF (Electro-Optical Transfer Function) of a display together determine its color performance. Gamut determines the range of displayable colors, and the EOTF determines the color accuracy and depth. Image reproduction often comprises two parts: the image source and the display terminal. To ensure the universality of different terminals, the image source is generally produced in a standardized gamut standard, while the terminal pursues a wider gamut and more spectacular color performance. As a widely welcomed form of display, WCGDs (Wide Color Gamut Displays) boast stunning color performance. However, certain colors in WCGDs displays are oversaturated, which is unacceptable to the human eye. This paper analyzes the oversaturation problem of WCGDs. Firstly, a display model based on EOTF and gamut parameters is established. Then the color point vector field varies with EOTF is derived and the drift of luminance and chromaticity are analyzed separately. Finally, two strategies are present to optimize the color oversaturation problem of WCGDs based on the analysis conclusions and verify its effectiveness. This paper presents a detailed analysis and possible strategy for color oversaturation in WCGDs, providing a theoretical basis for the accurate color reproduction and efficient color management of WCGDs.

Abstract Murals carry cultural significance and historical information, and are an important channel for understanding ancient social norms, artistic styles, and religious beliefs. At present, the digitization of murals is an important technical means for the protection of cultural heritage. Orthogonal images of murals play a vital role in high-precision recording, preservation, academic research, educational expansion, mural protection, digital exhibition and dissemination. At present, orthogonal images of murals are mostly realized by plane projection, but this method is not suitable for making orthogonal images of arched and dome-shaped murals. To address this problem, this paper proposes a method for generating orthogonal expansion images of arched and dome-shaped murals. This method combines a three-dimensional virtual space simulation model with an RTT virtual camera and adopts a spatial reference orthogonal ray scanning model. First, the detailed three-dimensional color model is fitted to the geometric reference of cylindrical and spherical objects to determine its parameters. Next, for the cylindrical murals on the arch, the orientation of the model is initialized using quaternions, and the viewport matrix is adjusted to obtain the required resolution. Then, the RTT camera is used to perform line orthogonal projection in the viewport, and the fringe projection image is generated by rotating around the cylinder axis according to the inversely calculated rotation angle. For the murals on the dome ceiling, this method is used to segment them according to a certain longitude, and the circumscribed cylinder of the fitted sphere is rotated to perform cylindrical orthogonal line scanning in the segmented area. These individual orthogonal line scan images are carefully spliced together to form a complete orthogonal unfolded image. Finally, a fringe projection image is generated with the central meridian of the unfolded part as the center line, and the fringe projection images are spliced together to obtain the final orthogonal unfolded image. Experiments show that compared with existing methods, this method can generate two-dimensional orthogonal unfolded images with high texture fidelity, minimal texture deformation, and uniform deformation distribution. This study provides a novel perspective on the orthogonal unfolding of quasi-cylindrical and quasi-spherical painted objects, and provides an accurate and diverse data basis for the digitization of murals.

Abstract Background Cisplatin resistance is the leading cause of mortality in muscle-invasive bladder cancer (MIBC) cases. Previous evidence suggests that abnormal epitranscriptome modifications are associated with reduced chemotherapy responses. However, the exact underlying mechanism remains largely unknown. Methods Insulin-like growth factor-2 mRNA-binding protein 2 (IMP2) was identified by clustered regularly interspaced short palindromic repeats (CRISPR) data screening, single-cell RNA-sequencing and sample analysis. To evaluate the regulatory role of IMP2, functional studies were conducted both in vitro and in vivo. To elucidate the underlying mechanisms, various techniques including immunofluorescence, fluorescent in situ hybridization, RNA pull-down, coimmunoprecipitation, and RNA immunoprecipitation were used. Results Our study revealed that IMP2 was overexpressed in chemoresistant MIBC and lung metastasis tissues. IMP2 inhibition markedly enhanced the sensitivity of BC cells to cisplatin both in vitro and in vivo. Mechanistically, IMP2 enhanced the mRNA stability of IPO4 and SLC7A11 in a m6A-dependent manner, augmenting the nuclear translocation of C/EBPδ to activate PRKDC-mediated DNA damage repair in response to cisplatin. Moreover, IMP2 upregulated SLC7A11 levels and suppressed cisplatin-induced ferroptosis. Combining ferroptosis and apoptosis inhibitors completely reversed cisplatin resistance caused by IMP2 overexpression. LINC00941, which was induced by HIF-1α-mediated transcriptional activation, specifically bound IMP2 and protects it from degradation. Conclusions This work demonstrated a novel mechanism involving the IMP2-IPO4/SLC7A11 pathway as a promising treatment target for cisplatin-resistant bladder cancer.

Abstract Background The unilateral biportal endoscopic (UBE) technique has garnered significant attention for its little paraspinal iatrogenic damage, expedited recovery, and low complication rates. This method is also applicable to open transforaminal lumbar interbody fusion (TLIF). Therefore, this study aimed to conduct a comparative analysis of the outcomes associated with unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF), minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), and TLIF for Meyerding grade I lumbar spondylolisthesis. Methods The study examined the outcomes of 79 patients with Meyerding grade I lumbar spondylolisthesis who underwent single-level intervertebral fusion. Clinical assessments included the measurement of pain levels using the Visual Analogue Scale (VAS) for low back and leg pain, the Oswestry Disability Index (ODI), surgical data, and demographic information. Imaging techniques were utilized to evaluate the fusion rate. Results The VAS-Back demonstrated a statistically significant improvement in Group UBE-TLIF compared to the other groups at the one-week postoperative evaluation (p

Abstract Since the discovery of antibiotics, they have served as a potent weapon against bacterial infections; however, natural evolution has allowed bacteria to adapt and develop coping mechanisms, ultimately leading to the concerning escalation of multidrug resistance. Bacterial persisters are a subpopulation that can survive briefly under high concentrations of antibiotic treatment and resume growth after lethal stress. Importantly, bacterial persisters are thought to be a significant cause of ineffective antibiotic therapy and recurrent infections in clinical practice and are thought to contribute to the development of antibiotic resistance. Therefore, it is essential to elucidate the molecular mechanisms of persister formation and to develop precise medical strategies to combat persistent infections. However, there are many difficulties in studying persisters due to their small proportion in the microbiota and their non-heritable nature. In this review, we discuss the similarities and differences of antibiotic resistance, tolerance, persistence, and viable but non-culturable cells, summarize the molecular mechanisms that affect the formation of persisters, and outline the emerging technologies in the study of persisters.

Abstract We conducted a retrospective study of 1055 patients with urinary stones who attended our single center from September 2017 to June 2024. Clinical data and laboratory indicators of patients were evaluated and compared with stone components. The most common type in our study was calcium oxalate (CaOx) stones (76.6%), followed by infection stones (13.2%) and uric acid (UA) stones (7.8%). Among the 1055 specimens, 899 (85.2%) cases were mixed component stones, of which calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) mixture were the most frequent (34.8%). There were only 156 cases (14.8%) of pure-component stones, of which anhydrous UA was the most frequent (7.0%). There were 738 males and 317 females, with a male-to-female ratio of 2.33:1. Male dominance was evident in CaOx stones (79.0 vs. 71.0%, P = 0.005). Female dominance was noted in infection stones (21.1 vs. 9.8%, P

Abstract Dysregulation of SMAD4 (i.e. somatic mutation) is strongly associated with poor pancreatic ductal adenocarcinoma (PDAC) prognosis, yet the molecular mechanisms remain underlying this relationship obscure. Previously, we discovered that SMAD4 mutation renders pancreatic cancer resistant to radiotherapy via promotion of autophagy. In the current work, we observed a downregulation of the protein level of SMAD4 in PDAC as compared with adjacent normal tissue, and that such SMAD4low PDAC failed to benefit from chemotherapy. Furthermore, we observed that SMAD4 depletion dramatically enhanced DNA repair capacity in response to irradiation (IR) or a radiomimetic chemical. Interestingly, we found the radiomimetic chemical having induced a robust translocation of SMAD4 into the nucleus, where a direct interaction was shown to occur between the MH1 domain of SMAD4 and the DBD domain of PARP1. Functionally, the SMAD4-PARP1 interaction was found to perturb the recruitment of PARP1 to DNA damage sites. Accordingly, the combination of olaparib and radiotherapy was indicated in vivo and in vitro to specifically reduce the growth of SMAD4-deficient PDAC by attenuating PARP1 activity. Collectively, our results revealed a novel molecular mechanism for the involvement of the SMAD4-PARP1 interaction in DNA repair with a vital role in radiotherapy response in PDAC. Based on our set of findings, our findings offer a new combined therapeutic strategy for SMAD4 deficient PDAC that can significantly reduce pancreatic cancer radiotherapy resistance.

Abstract Previous studies have suggested a potential association between the gut microbiota and arthritis. However, the causal links between the gut microbiota and various types of arthritis, as well as the potential mediating role of inflammatory proteins, remain unclear. Mendelian randomization was used to explore the causal relationships between gut microbiota, inflammatory proteins, and various forms of arthritis (osteoarthritis, rheumatoid and psoriatic arthritis, and ankylosing spondylitis [AS]). The inverse variance-weighted method was the primary analytical approach used. Furthermore, we examined the mediating role of inflammatory proteins in the pathway linking the gut microbiota to arthritis. Sensitivity analyses were performed to verify the robustness of the findings, and enrichment analyses were conducted to investigate the biological functions and pathways involved. We identified 11 positive and 14 negative causal effects linking the genetic liability of the gut microbiota to arthritis. Similarly, 9 positive and 8 negative causal effects between inflammatory proteins and arthritis were identified. Notably, an increased abundance of the order Bacillales (odds ratio [OR] = 1.199, 95% confidence interval [CI] = 1.030–1.394, P = 0.019) and higher interleukin-7 levels (OR = 1.322, 95% CI = 1.004–1.741, P = 0.046) significantly elevated the risk of AS. Furthermore, interleukin-7 mediated 13.8% of the effect caused by the order Bacillales, with a mediation effect size of β = 0.025 (95% CI = 0.001–0.064). Sensitivity and supplementary analyses revealed no significant evidence of horizontal pleiotropy or heterogeneity. Overall, our findings demonstrate causal links between the gut microbiota, inflammatory proteins, and four arthritis types, highlighting the gut microbiota as a potential therapeutic target. Crucially, interleukin-7 not only strongly correlated with AS but also partially mediated the effect exerted by the gut microbiota on AS, suggesting that managing the gut microbiota to modulate inflammatory proteins could serve as an effective therapeutic strategy for arthritis.

Abstract The pig is an important model for studying human diseases and is also a significant livestock species, yet its testicular development remains underexplored. Here, we employ single-cell RNA sequencing to characterize the transcriptomic landscapes across multiple developmental stages of Bama pig testes from fetal stage through infancy, puberty to adulthood, and made comparisons with those of humans and mice. We reveal an exceptionally early onset of porcine meiosis shortly after birth, and identify a distinct subtype of porcine spermatogonia resembling transcriptome state 0 spermatogonial stem cells identified in humans, which were previously thought to be primate specific. We also discover the persistent presence of proliferating progenitors for myoid cells in postnatal testes. The regulatory roles of Leydig cell steroidogenesis and estrogen synthesis in supporting cell lineages are also explored, including the potential impact of estrogen on Sertoli cell maturation and spermatogenesis. Overall, this study offers valuable insights into porcine testicular development, paving the way for future research in reproductive biology, advancements in agricultural breeding, and potential applications in translational medicine.

Abstract Current academic research on fitting the volume of urban theft crimes at a macro size is limited, especially from the urban functionality perspective. Given this gap, this study utilizes a Bayesian model to conduct a fitting analysis of theft crime data from 674 cities in China from 2018 to 2020. This research aims to explore novel pathways for theft crime fitting. Results indicate that the size of urban functionality, particularly points of interest (POIs), exhibits excellent performance in fitting theft crimes, with POIs related to public services and commercial activities demonstrating the most significant fitting effects. This research successfully identifies effective indicators for crime fitting, thereby offering a new perspective and supplement to theft crime research. This study holds significant value for gaining a profound understanding of criminal phenomena and explaining the causes and mechanisms underlying the differences in theft crimes among various cities in China.

Abstract This study aims to develop machine learning (ML)-assisted models for analyzing datasets related to Gleason scores in prostate cancer, conducting statistical analyses on the datasets, and identifying meaningful features. We retrospectively collected data from 717 hormone-sensitive prostate cancer (HSPC) patients at Yunnan Cancer Hospital. Of these, data from 526 patients were used for modeling. Seven auxiliary models were established using Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Decision Tree (DT), Extreme gradient boosting tree (XGBoost), Adaptive Boosting (Adaboost), and artificial neural network (ANN) based on 21 clinical biochemical indicators and features. Evaluation metrics included accuracy (ACC), precision (PRE), specificity (SPE), sensitivity (SEN) or regression rate(Recall), and f1 score. Evaluation metrics for the models primarily included ACC, PRE, SPE, SEN or Recall, f1 score, and area under the curve(AUC). Evaluation metrics were visualized using confusion matrices and ROC curves. Among the ensemble learning methods, RF, XGBoost, and Adaboost performed the best. RF achieved a training dataset score of 0.769 (95% CI: 0.759—0.835) and a testing dataset score of 0.755 (95% CI: 0.660—0.760) (AUC: 0.786, 95%CI: 0.722—0.803), while XGBoost achieved a training dataset score of 0.755 (95% CI: 95%CI: 0.711—0.809) and a testing dataset score of 0.745 (95% CI: 0.660—0.764) (AUC: 0.777, 95% CI: 0.726—0.798). Adaboost scored 0.789 on the training dataset (95% CI: 0.782—0.857) and 0.774 on the testing dataset (95% CI: 0.651—0.774) (AUC: 0.799, 95% CI: 0.703—0.802). In terms of feature importance (FI) in ensemble learning, Bone metastases at first visit, prostatic volume, age, and T1-T2 have significant proportions in RF’s FI. fPSA, TPSA, and tumor burden have significant proportions in Adaboost’s FI, while f/TPSA, LDH, and testosterone have the highest proportions in XGBoost. Our findings indicate that ensemble learning methods demonstrate good performance in classifying HSPC patient data, with TNM staging and fPSA being important classification indicators. These discoveries provide valuable references for distinguishing different Gleason scores, facilitating more accurate patient assessments and personalized treatment plans.

Abstract Background The safety and efficacy of combination of gefitinib with chemotherapy and bevacizumab in treatment patients with epidermal growth factor receptor (EGFR) mutations are currently unknown. This study was designed to evaluate the safety and preliminary efficacy of a combination therapy consisting of gefitinib, bevacizumab, pemetrexed, and carboplatin in patients with advanced non-squamous non–small cell lung cancer (NSCLC) harboring EGFR mutations. Methods Eligible patients with EGFR-mutated advanced non-squamous NSCLC were recruited and received gefitinib combination with bevacizumab plus pemetrexed and carboplatin treatment. The primary endpoints were safety and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS). Results From June 2019 to June 2021, 20 patients were enrolled in this study. The median follow-up was 33.8 months (95% CI, 31.0-36.6). Grade ≥ 3 adverse events was 65%, including neutropenia (30%), thrombocytopenia (20%), nausea (20%), skin rash (20%), bleeding (10%), and increased ALT (10%). There was no death related to toxicity occurred. The median PFS was 28 months (95% CI, 20.4–35.6). the ORR was 95% (95% CI, 75.1-99.9%), the DCR was 100% (95% CI, 83.2-100%), and the median DOR was 26.4 months (95% CI, 18.9–33.9). The median OS has not been reached. Conclusion The results of this study demonstrate that the four-drug combination regimen, led by gefitinib, is manageable and tolerated and effective for patients with EGFR-mutated advanced non-squamous NSCLC.

Abstract Chemoresistance remains a major challenge in the effective treatment of colorectal cancer (CRC), contributing to poor patient outcomes. While the molecular mechanisms underlying chemoresistance are complex and multifaceted, emerging evidence suggests that altered mitochondrial function and hormone signaling play crucial roles. In this study, we investigated the role of CYP19A1, a key enzyme in estrogen biosynthesis, in regulating chemoresistance in CRC. Using a combination of in vitro functional assays, transcriptomic analysis, and clinical data mining, we demonstrate that CYP19A1 expression is significantly upregulated in CRC cells and patient-derived samples compared to normal controls. Mechanistically, we found that CYP19A1 regulates chemoresistance through modulation of mitochondrial function and complex I activity, which is mediated by CYP19A1-dependent estrogen biosynthesis. Notably, targeted inhibition of CYP19A1 and complex I using specific inhibitors effectively reversed the chemoresistance of CRC cells to chemotherapeutic drugs. Moreover, analysis of the TCGA CRC dataset revealed that high CYP19A1 expression correlates with poor overall survival in chemotherapy-treated patients. Taken together, our findings uncover a novel role for CYP19A1 in regulating chemoresistance in CRC through modulation of mitochondrial function and estrogen signaling, and highlight the potential of targeting the CYP19A1/estrogen/complex I axis as a therapeutic strategy to overcome chemoresistance and improve patient outcomes.

Abstract The fungi of the human microbiota play important roles in the nutritional metabolism and immunological balance of the host. Recently, research has increasingly emphasised the role of fungi in modulating inflammation in intestinal diseases and maintaining health in this environment. It is therefore necessary to understand more clearly the interactions and mechanisms of the microbiota/pathogen/host relationship and the resulting inflammatory processes, as well as to offer new insights into the prevention, diagnosis and treatment of inflammatory bowel disease (IBD), colorectal cancer (CRC) and other intestinal pathologies. In this review, we comprehensively elucidate the fungal-associated pathogenic mechanisms of intestinal inflammation in IBD and related CRC, with an emphasis on three main aspects: the direct effects of fungi and their metabolites on the host, the indirect effects mediated by interactions with other intestinal microorganisms and the immune regulation of the host. Understanding these mechanisms will enable the development of innovative approaches based on the use of fungi from the resident human microbiota such as dietary interventions, fungal probiotics and faecal microbiota transplantation in the prevention, diagnosis and treatment of intestinal diseases.

Abstract Ferroptosis is a cell death modality in which iron-dependent lipid peroxides accumulate on cell membranes. Cysteine, a limiting substrate for the glutathione system that neutralizes lipid peroxidation and prevents ferroptosis, can be converted by cystine reduction or synthesized from methionine. However, accumulating evidence shows methionine-based cysteine synthesis fails to effectively rescue intracellular cysteine levels upon cystine deprivation and is unable to inhibit ferroptosis. Here, we report that methionine-based cysteine synthesis is tissue-specific. Unexpectedly, we find that rather than inhibiting ferroptosis, methionine in fact plays an essential role during cystine deprivation-induced ferroptosis. Methionine-derived S-adenosylmethionine (SAM) contributes to methylation-dependent ubiquinone synthesis, which leads to lipid peroxides accumulation and subsequent ferroptosis. Moreover, SAM supplementation synergizes with Imidazole Ketone Erastin in a tumor growth suppression mouse model. Inhibiting the enzyme that converts methionine to SAM protects heart tissue from Doxorubicin-induced and ferroptosis-driven cardiomyopathy. This study broadens our understanding about the intersection of amino acid metabolism and ferroptosis regulation, providing insight into the underlying mechanisms and suggesting the methionine-SAM axis is a promising therapeutic strategy to treat ferroptosis-related diseases.

Abstract The precise cellular mechanisms underlying heightened proinflammatory cytokine production during coronavirus infection remain incompletely understood. Here we identify the envelope (E) protein in severe coronaviruses (SARS-CoV-2, SARS, or MERS) as a potent inducer of interleukin-1 release, intensifying lung inflammation through the activation of TMED10-mediated unconventional protein secretion (UcPS). In contrast, the E protein of mild coronaviruses (229E, HKU1, or OC43) demonstrates a less pronounced effect. The E protein of severe coronaviruses contains an SS/DS motif, which is not present in milder strains and facilitates interaction with TMED10. This interaction enhances TMED10-oligomerization, facilitating UcPS cargo translocation into the ER-Golgi intermediate compartment (ERGIC)—a pivotal step in interleukin-1 UcPS. Progesterone analogues were identified as compounds inhibiting E-enhanced release of proinflammatory factors and lung inflammation in a Mouse Hepatitis Virus (MHV) infection model. These findings elucidate a molecular mechanism driving coronavirus-induced hyperinflammation, proposing the E-TMED10 interaction as a potential therapeutic target to counteract the adverse effects of coronavirus-induced inflammation.

Abstract SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared with its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated the immune resistance of SARS-CoV-2 JN.1 but additional factors are speculated to contribute to its global dominance, which remain elusive until today. Here, we find that SARS-CoV-2 JN.1 has a higher infectivity than BA.2.86 in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, we demonstrate that the gained infectivity of SARS-CoV-2 JN.1 over BA.2.86 associates with increased entry efficiency conferred by L455S and better spike cleavage in hNECs. Structurally, S455 altered the mode of binding of JN.1 spike protein to ACE2 when compared to BA.2.86 spike at ACE2H34, and modified the internal structure of JN.1 spike protein by increasing the number of hydrogen bonds with neighboring residues. These findings indicate that a single mutation (L455S) enhances virus entry in hNECs and increases immune evasiveness, which contribute to the robust transmissibility of SARS-CoV-2 JN.1. We further evaluate the in vitro and in vivo virological characteristics between SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3, and identify key lineage-specific features of the two Omicron sublineages that contribute to our understanding on Omicron antigenicity, transmissibility, and pathogenicity.

Deep eutectic solvents (DESs) are recognized as an emerging green solvent that can be applied to lignocellulosic biomass fractionation and valorization. A deep understanding of the physicochemical properties of DESs is of great significance to the development of biomass processing technology. Meanwhile, the importance of DESs is manifested by an increasing number of value-added chemicals derived from lignocellulose in DESs. This review focuses on the physicochemical properties of different types of DESs as well as examples of their application to lignocellulosic fractionation. Additionally, recent advancements in research on converting products from DESs fractionation into bio-based materials are highlighted. Potential obstacles and prospects for integrating DESs into biomass processing are also discussed.

Aiming at the problems of complex and diverse influencing factors and insufficient weight analysis in evaluating the hot cracking susceptibility of multi-alloy steel by solidification micro-segregation model, the brittleness temperature range (BTR) and Kou criterion were used as the evaluation indexes for hot cracking susceptibility, and the optimal number of principal components was determined by partial least squares regression (PLSR). Based on the optimal number of principal components, the interrelationships between factors, principal components and dependent variables were elucidated, and the weight of influencing factors of hot cracking susceptibility were analyzed. The results show that the factor weights affected the evaluation of hot cracking susceptibility were, in order, the initial concentration of components, the liquidus correlation coefficient, and the equilibrium distribution coefficient. Their contributions to BTR were 0.43, 0.38, and 0.16, respectively, and to Kou criterion were 0.42, 0.38, and 0.17, respectively. PLSR had good predictive performance for BTR and Kou criterion, with R2 values of 0.898 and 0.975, respectively, effectively capturing the relationship between factors and dependent variables.

The paper addresses the challenges of task migration and resource allocation in heterogeneous cloud–edge environments, where dynamic and stochastic conditions complicate efficient scheduling. To tackle this, the authors propose a novel scheduling algorithm combining soft actor–critic (SAC) agent with masked layer and graph convolutional network (GCN), namely MGSAC algorithm. MGSAC utilizes GCN to extract hidden structural features from the environment, enabling better adaptation to dynamic changes. Additionally, a learnable mask layer filters out ineffective actions, refining the selection of scheduling strategies and improving overall performance. By evaluating MGSAC on the real-world Bit-Brain dataset and simulating it using Cloud-Sim, experimental results demonstrate its superiority over existing algorithms in energy consumption, task response time, task migration time, and task Service-Level-Agreement violations rate, showcasing its effectiveness in real-world scenarios.

As a fundamental tool in synthetic biology, promoters are pivotal in regulating gene expression, enabling precise genetic control and spurring innovation across diverse biotechnological applications. However, most advances in engineered genetic systems rely on host-specific regulation of the genetic portion. With the burgeoning diversity of synthetic biology chassis cells, there emerges a pressing necessity to broaden the universal promoter toolkit spectrum, ensuring adaptability across various microbial chassis cells for enhanced applicability and customization in the evolving landscape of synthetic biology. In this study, we analyzed and validated the primary structures of natural endogenous promoters from Escherichia coli, Bacillus subtilis, Corynebacterium glutamicum, Saccharomyces cerevisiae, and Pichia pastoris, and through strategic integration and rational modification of promoter motifs, we developed a series of cross-species promoters (Psh) with transcriptional activity in five strains (prokaryotic and eukaryotic). This series of cross species promoters can significantly expand the synthetic biology promoter toolkit while providing a foundation and inspiration for standardized development of universal components The combinatorial use of key elements from prokaryotic and eukaryotic promoters presented in this study represents a novel strategy that may offer new insights and methods for future advancements in promoter engineering.

Abstract The growing prevalence of mental health issues underscores the need for innovative screening methods. Large-scale, internet-based psychological screening has emerged as a vital tool to accurately determine morbidity rates and facilitate early diagnosis of mental disorders. However, conventional psychological screening methods often struggle with non-genuine responses and lack objective metrics. To bridge this gap, we have compiled a novel dataset derived from an expansive screening initiative at Xinxiang Medical University. The study, conducted from February 27 to March 17, 2021, yielded a dataset comprising responses from 24,292 students to four well-established psychological scales—PHQ-9, GAD-7, ISI, and PSS. A distinctive feature of this dataset is the inclusion of response time data, which captures the temporal dynamics of participants’ interactions with the scales, offering valuable insights into their response behaviour. The release of this dataset offers a substantial opportunity for researchers in the domains of psychology and public health to explore new insights into mental health, scale reliability, and the dynamics of psychological assessment.

Abstract Background Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.

Abstract Given the surpassing of the Shockley-Quiesser efficiency limit in conventional p-n junction photovoltaic effect, bulk photovoltaic effect (BPVE) has garnered significant research interest. However, the BPVE primarily focuses on a narrow wavelength range, limiting its potential applications. Here we report a giant infrared bulk photovoltaic effect in tellurene (Te) for broad-spectrum neuromodulation. The generated photocurrent in uniformly illuminated Te excludes other photoelectric effects and is attributed to the BPVE. The bulk photovoltaic wavelength in Te spans a wide range from the ultraviolet (390 nm) to the mid-infrared (3.8 µm). Moreover, the photocurrent density of 70.4 A cm−2 under infrared light simulation outperforms that in previous ultraviolet and visible semiconductors as well as infrared semimetals. Te attached to the dendrites or somata of the cortical neurons successfully elicit action potentials under broad-spectrum light irradiation. This work lays the foundation for the further development of infrared BPVE in narrow bandgap materials.

Purpose: This study aimed to investigate the efficacy of orthopedic insoles, specifically three-dimensional (3D)-printed orthopedic insoles, for treatment of symptomatic flexible flatfoot in school-age children. Methods: A systematic review of PubMed and China National Knowledge Infrastructure (CNKI) from database inception to March 2024 was conducted to determine additional studies. This single-center study included 38 participants, including 20 who chose ordinary orthopedic insoles and 18 who chose 3D printed orthopedic insoles, presented from January 2021 to December 2022. Pain symptom relief was compared between the two groups after 1 year of follow-up. Results: A systematic review identified an additional six publications, involving 206 samples, and meta-analysis indicated that the force-bearing area, arch index, and heel valgus angle after treatment were 0.74 (95 ​% confidence interval [CI]: 0.65–1.01), 0.20 (95 ​% CI: 0.03–1.35), and 0.10 (95 ​% CI: 0.03–0.28) of those before treatment, respectively. The 1-year follow-up study revealed that because of its good comfort, 3D printed orthopedic insole can significantly improve the wearing time of both male (P ​

Abstract The plastic flow behavior of soft rock exhibits non-coaxial features under complex stress paths, while traditional plasticity theories are ill-equipped to adequately represent this, which leads to the mechanism of soft rock failure still unclear. To investigate the evolution law of strain increments and non-coaxial characteristics of weakly cemented soft rock, the directional shear tests are conducted using the hollow cylinder apparatus (HCA). The results show that non-coaxiality does not occur when α is distinct from 0° or 90°. The oscillation of the non-coaxial angle is significantly more variable in soft rock experiencing combined tension–torsion (45°

Abstract The direct synthesis of light aromatics, especially para-xylene (p-X), from syngas/CO2 is drawing strong interest, but improving the space-time yield (STY) of p-X is a significant challenge. Here, a dynamic “dual-engine-driven” (DED) catalytic system is designed by combining two partners of ZnCr and FeMn (named “dual-engine”) with Z5@SiO2 capsule zeolite. The DED catalyst of 1.0%FeMn&[ZnCr&Z5@SiO2] shows an extremely higher p-X STY of 36.1 g p-x·kgcat -1·h-1, about eight times higher than that of [ZnCr&Z5]. DED manipulates ZnCr engine for methanol formation and drives FeMn engine for light olefins generation together, and then the formed methanol and light olefins are coordinately converted in situ into p-X-rich aromatics over Z5@SiO2. The DED model boosts the driving force for syngas/CO2 conversion, simultaneously concerting the cooperation of “dual-engine” for p-X generation, resulting in extremely high STY of p-X. This study achieves non-petroleum p-X production at industrial-relevant level and advances knowledge in designing innovative heterogeneous catalysts.

Abstract Background Thyroid disorders(TD) poses a significant health threat to Americans due to its high incidence rate. Obesity, a common factor linked to thyroid disorders, has garnered increasing attention. While Body mass index (BMI) is a widely used obesity index, it fails to account for the distribution of muscle and fat in the body. Recently, tMFR has emerged as a crucial obesity index in clinical research, warranting further investigation into its association with TD. Objective Exploring the association between tMFR and thyroid disorders. Method A comprehensive survey and data analysis were conducted using the NHANES database to investigate the relationship between tMFR and the risk of TD. This study utilized multiple logistic regression, smooth curve fitting, and subgroup analysis across four periods from 2011 to 2018. Result A total of 11,912 subjects were included in the study, showing a prevalence of 7.14% for TD. The research indicated that tMFR had an inverse correlation with the risk of TD in a comprehensive model (OR = 0.90, 95% CI 0.82 to 1.00). When tMFR was divided into quartiles (Q1-Q4), individuals in the highest quartile had a 28% lower risk of TD than those in Q1 (OR = 0.72, 95% CI 0.57 to 0.91). Analysis using smoothed curve fitting demonstrated a nonlinear relationship between tMFR and TD risk, with the inflection point for tMFR saturation effect identified as 1.5. Subgroup analysis further confirmed the strong association between tMFR and TD risk. Receiver operating characteristic (ROC) curve analysis indicated that tMFR exhibited superior predictive ability for TD relative to BMI. Conclusion The study found a negative association between tMFR and the risk of TD; however, additional prospective studies are required to validate these findings.

The effect of a tilted-dipole three-dimensional corotating interaction region (CIR) on the transport and acceleration of solar energetic particles (SEPs) is studied. In this work, we discussed how the particle intensity longitudinal and radial dependence might be influenced by the background structures. Moreover, we investigate how the spectral index distribution is modulated by the CIR structure. We use the focused transport equation (FTE) to describe the propagation and acceleration of SEPs in a tilt-dipole 3D CIR, generated by the high-resolution 3D magnetohydrodynamic (MHD) model. The forward stochastic differential method is used to solve the FTE. The protons with the \begin{document}$ E^{-4.4} $\end{document} spectrum from 0.5 to 15 MeV are injected uniformly at the heliographic equator of 0.15 AU. Physical quantities are extracted along each interplanetary magnetic field (IMF) line to show the results. In the tilted-dipole CIR background, if injected from the solar equator at the inner boundary, particles in the slow flow are transported to higher latitudes due to the extension of the IMF lines to higher latitudes. The longitudinal patterns of the particles are dominated by the density of IMF lines. The focusing effect modulates the longitudinal variation of the particle intensity and gives rise to new longitudinal intensity peaks. The adiabatic effect largely increases the intensity fluctuation along the longitude. The structure of the solar wind can also lead to the difference of the index \begin{document}$ \alpha $\end{document} in the empirical function \begin{document}$ I_{{\mathrm{max}}}=kR^{-\alpha} $\end{document}, describing the radial variation of peak intensity according to our simulation. Under the influence of the CIR structure, the index \begin{document}$ \alpha $\end{document} varies from 1.9 to 3.4 at 0.3−1.0 AU. The variation of the solar wind speed should be considered when estimating the radial dependence of the SEP peak intensity. The spectra indices rise near the CIR boundaries and drop near the stream interface (SI). The adiabatic effect makes the spatial variability of the spectral index larger. The spectral index could be similar at different radial distances in the CIR structure.

Soybean protein has high nutritional value, but its functional properties are easily affected by external factors, which limits its application in food industry. In the study, soybean protein isolate (SPI) was modified by dry heat glycation of galactooligosaccharides (GOS). The gel properties, antioxidant properties and structural changes of SPI-GOS conjugates were investigated. The application of SPI-GOS conjugates in noodles was also explored. The results observed that the glycation degree of SPI increased with the increasing reaction time. SDS-PAGE and spectral analysis showed the changes of spatial conformation of SPI after glycation. The antioxidant activity of SPI increased after glycation and DPPH radical scavenging activity of SPI-GOS peaked at 48 h of reaction. The hardness, elasticity and resilience of soybean protein gel reached their relative maximum at 48 h, 48 h and 12 h of glycation reaction, respectively. Moreover, the appropriate addition of glycated SPI improved the quality of noodles. The noodles with 4% addition of SPI-GOS had higher hardness, elasticity and tensile properties. This study will provide an effective method to modify soybean protein and expand the use of soybean protein in food industry.

The creation of a dense, convenient, and diverse built environment is a strategic approach for fostering urban development. However, few studies have considered the relationship between a compact built environment and livability. This study seeks to answer the following question: What type of built environment is conducive to long-term residency? Using the Guangzhou urban district in China as a case study, we develop a livability-oriented assessment system for the built environment and integrate it into the hedonic price model. We employ spatial regression methods to analyze the impact of the built environment on housing prices, and findings suggest that (1) livability-oriented built environments are characterized by spaciousness, convenience, and diversity. Environments with a low building density, high building heights, a large plot area, and diverse land use are highly favorable for livability. (2) The built environment is intricate, and different factors can affect livability in diverse areas within an urban space. The impact of POI (Point of Interest) density and road density on livability varies by location. (3) The principles of small-scale blocks, high-density road networks, and compact urban planning are not universally applicable to the construction of livable cities. (4) The spatial heterogeneity of the built environment in the Guangzhou urban district is pronounced. This study addresses the assessment standards dominated by new urbanism. Under a livability-oriented approach, urban planners and managers should not indiscriminately pursue the construction of high-density and compact cities.

Tuned mass dampers (TMDs) are attractive vibration control devices, and their seismic attenuation depends on their frequency and damping coefficient. Structural characteristics are changed by the soil-structure interaction (SSI); therefore, SSI should be considered in the optimization of TMD. A high-rise building with 40 stories, including four different soil conditions, is proposed as a case study. For the objective function, considering the randomness of earthquakes, a stationary white noise stochastic process based on the Kanai-Tajimi spectrum was used as the input. To improve the performance of a TMD in controlling multimodal and overall dynamic responses, three objectives were considered in the objective function: the maximum and root mean square (RMS) displacements of the top story and the maximum displacement of all stories, respectively. The weight coefficient of each objective function was obtained according to the modal mass participation coefficient. To clearly observe the damping effect of the TMD with different parameter combinations, an ergodic parameter calculation is used. The TMD optimization parameters for each benchmark model with different soil conditions were proposed. Far-field ground motions were considered, and four optimized TMDs from reference were compared. The results show that the proposed TMDs can significantly mitigate earthquake oscillations in a great degree. They performed better than contrastively optimized TMDs under several earthquakes.

Abstract Introduction There remains a critical need for precise localization of the epileptogenic foci in individuals with drug-resistant epilepsy (DRE). 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging can reveal hypometabolic regions during the interval between seizures in patients with epilepsy. However, visual-based qualitative analysis is time-consuming and strongly influenced by physician experience. CortexID Suite is a quantitative analysis software that helps to evaluate PET imaging of the human brain. Therefore, we aimed to evaluate the efficacy of CortexID quantitative analysis in the localization of the epileptogenic zone in patients with temporal lobe epilepsy (TLE). Methods A total of 102 patients with epilepsy who underwent 18F-FDG-PET examinations were included in this retrospective study. The PET visual analysis was interpreted by two nuclear medicine physicians, and the quantitative analysis was performed automatically using CortexID analysis software. The assumed epileptogenic zone was evaluated comprehensively by two skilled neurologists in the preoperative assessment of epilepsy. The accuracy of epileptogenic zone localization in PET visual analysis was compared with that in CortexID quantitative analysis. Results The diagnostic threshold for the difference in the metabolic Z-score between the right and left sides of medial temporal lobe epilepsy (MTLE) was calculated as 0.87, and that for lateral temporal lobe epilepsy (LTLE) was 2.175. In patients with MTLE, the area under the curve (AUC) was 0.922 for PET visual analysis, 0.853 for CortexID quantitative analysis, and 0.971 for the combined diagnosis. In patients with LTLE, the AUC was 0.842 for PET visual analysis, 0.831 for CortexID quantitative analysis, and 0.897 for the combined diagnosis. These results indicate that the diagnostic efficacy of CortexID quantitative analysis is not inferior to PET visual analysis (p > 0.05), while combined analysis significantly increases diagnostic efficacy (p

Abstract Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects.

Abstract A variety of therapeutic possibilities have emerged for skillfully regulating protein function or conformation through intermolecular interaction modulation to rectify abnormal biochemical reactions in diseases. Herein, a devised strategy of enzyme coordinators has been employed to alleviate postoperative pancreatic fistula (POPF), which is characterized by the leakage of digestive enzymes including trypsin, chymotrypsin, and lipase. The development of a dextrorotary (D)-peptide supramolecular gel (CP-CNDS) under this notion showcases its propensity for forming gels driven by intermolecular interaction. Upon POPF, CP-CNDS not only captures enzymes from solution into hydrogel, but also effectively entraps them within the internal gel, preventing their exchange with counterparts in the external milieu. As a result, CP-CNDS completely suppresses the activity of digestive enzymes, effectively alleviating POPF. Remarkably, rats with POPF treated with CP-CNDS not only survived but also made a recovery within a mere 3-day period, while mock-treated POPF rats had a survival rate of less than 5 days when experiencing postoperative pancreatic fistula, leak or abscess. Collectively, the reported CP-CNDS provides promising avenues for preventing and treating POPF, while exemplifying precision medicine-guided regulation of protein activity that effectively targets specific pathogenic molecules across multiple diseases.

Abstract Adversarial patches, a type of adversarial example, pose serious security threats to deep neural networks (DNNs) by inducing erroneous outputs. Existing gradient stabilization methods aim to stabilize the optimization direction of adversarial examples through accumulating gradient momentum to enhance attack transferability on black-box models. However, they are not fully effective for adversarial patches. The accumulated momentum during optimization often misaligns with the optimization direction, reducing their efficacy in black-box scenarios. We introduce an optimization method called Alternating Minimization for Adversarial Patch (AMAP). This method decomposes the original AP into multiple sub-patches and utilizes their update direction to stabilize the optimization of the original AP. Additionally, we propose an adaptive step size optimization method that accelerates convergence and boosts the attack performance. In face recognition tasks, AMAP outperforms baseline methods by a remarkable 5.21% and exceeds the second-best method by 1.4%. Furthermore, AMAP demonstrates practical feasibility in the physical domain, highlighting its potential for robust computer security testing applications.

Objective(s): The combination of TNF-α inhibitors and vitamin D in colitis remains to be elucidated. In the present study, we revealed the benefit of infliximab (IFX) and vitamin D in a mouse model of Ulcerative colitis (UC). Materials and Methods: A dextran sulfate sodium-induced colitis model was used. The therapeutic effect of the combination was evaluated by symptom and histopathology analysis. The synergistic mechanism was explored by detecting the regulatory effect of the combined therapy on Regulatory T cell (Treg) differentiation.Results: IFX and 1,25-dihydroxyvitamin D3 (VitD3) synergistically prevented the development of colitis by improving clinical signs, pathological and hematological manifestation, and inhibiting intestinal inflammation (decreasing TNF-α, IL-1β, and IL-6). Coadministration of IFX (2.5 mg/kg) with VitD3 or IFX (5.0 mg/kg) with VitD3 was more effective than administration of IFX (2.5 mg/kg, 5.0 mg/kg). There was no difference in therapeutic effect between IFX (5.0 mg/kg) and VitD3+ IFX (2.5 mg/kg) groups or between the VitD3+IFX (5.0 mg/kg) and VitD3+ Azathioprine (AZA) groups. VitD3 or combination therapy showed more powerful regulation of splenetic Treg differentiation and IL-10 production than IFX alone. Moreover, VitD3 alone or in combination induced higher levels of Foxp3 and IL-10 than IFX in colon tissue. In ulcerative colitis patients, serum VitD3 levels positively correlated with Treg levels.Conclusion: VitD3 and IFX synergistically inhibit colitis based on their powerful regulation of Treg differentiation. VitD3 combined with IFX is an alternative therapy for patients who are intolerant to standard doses of IFX or combination of IFX and AZA.