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Abstract Background The efficiency of medical services directly impacts the economic burden of healthcare, making it crucial to analyze the input-output efficiency of various types of medical institutions. However, while hospitals had been extensively analyzed for their efficiency, other types of medical institutions had received limited attention in this regard. Methods In this study, we employed data envelopment analysis (DEA) methods based on time series and internal benchmarks to autonomously assess the efficiency of 18 distinct categories of healthcare facilities in China over the past decade. The verification was conducted through the utilization of the critical incident technique (CIT). Additionally, we utilized the Delphi process (AHP) method to evaluate suppliers of medical consumables, implemented a multi-population genetic algorithm for managing these consumethod and analytic hierarchymables efficiently, and applied stakeholder theory to manage medical personnel efficiency. Results Our findings indicated that medical institutions capable of providing clinical services exhibited higher levels of efficiency compared to those unable to do so. Multiple indicators suggested redundancy within these institutions. Notably, comprehensive benefit evaluation revealed that clinical laboratory had performed poorly over the past decade. We selected an inefficient medical institution for intervention in reagent management and the work efficiency of medical staff. After implementing the Delphi method and multi-population genetic algorithm for consumable replenishment, the reagent cost was reduced by 40%, 39% and 31% respectively in each of the three experimental groups, compared to the control group. By applying stakeholder theory and process reengineering methods, we were able to shorten quality control management time for medical staff in the experimental group by 41 min per day, reduce clinical service time by 25 min per day, and extend rest time by 70 min per day, while the quality indicators were all meeting the targets. Conclusion By employing various mathematical models as described above, we were able to reduce costs associated with medical consumables and enhance medical personnel work efficiency without compromising quality objectives.

Chlorogenic acid (CGA) is a natural product that effectively inhibits tumor growth, demonstrated in many preclinical models, and phase II clinical trials for patients with glioma. However, its direct proteomic targets and anticancer molecular mechanisms remain unknown. Herein, we developed a novel bi-functional photo-affinity probe PAL/CGA and discovered mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) was one of the main target proteins of CGA by using affinity-based protein profiling (AfBPP) chemical proteomic approach. We performed in-depth studies on ACAT1/CGA interactions via multiple assays including SPR, ITC, and cryo-EM. Importantly, we demonstrated that CGA impaired cancer cell proliferation by inhibiting the phosphorylation of tetrameric ACAT1 on Y407 residue through a novel mode of action in vitro and in vivo. Our study highlights the use of AfBPP platforms in uncovering unique druggable modalities accessed by natural products. And identifying the molecular target of CGA sheds light on the future clinical application of CGA for cancer therapy.

Abstract Rice grown in cadmium (Cd)-contaminated soil, is a potential threat to human health, but exogenous selenium (Se) application on rice can mitigate Cd toxicity. However, the mechanisms underlying Se mitigation of Cd stress in ratoon rice (RR) are still poorly understood. We conducted a pot experiment with moderate Cd-contaminated yellow–brown paddy soil on two rice varieties ‘Taoyouxiangzhan’ (TX) and ‘Liangyou 6326’(LY). For all treatments, 1.0 mg kg−1 sodium selenite solution was added to soil. Treatment T1 was sodium selenite only, and in the other treatments 100 mg L−1 Se solution was sprayed on the leaves at seedling stage (T2), at tillering stage (T3), and in early anthesis stage (T4). Se treatments decreased Cd accumulation in rice grains and herbage. Under foliar spraying 100 mg L−1 Se at the seedling + 1.0 mg kg−1 Se in soil (T2), leaf Cd content decreased 16.95% in the current season and grains content decreased 46.67% in the subsequent season. Furthermore, grain Se content increased 0.94 mg kg−1 for the TX variety combined with the analysis of Cd bio-accumulation factor in grains, and Se treatments effectively decreased Cd grain concentrations due to reduced Cd translocation from roots to grains. TX variety rice showed a more pronounced response to Se treatments than LY.

Most directed energy deposition (DED) implementations employ a rigid end effector to deposit material layer-by-layer, which is insufficient in cases with space constraints. To enhance the flexibility, this paper proposes a novel soft-robotic gun (SRG) based DED technology. The ideology is to replace the rigid weld gun with a tendon-driven omnidirectional-steering continuum manipulator, which a computer can numerically control. To this end, both requirements and concepts of the SRG-DED are introduced. A prototype system is designed and implemented before dedicated kinematic modelling and trajectory planning mechanisms are presented. As demonstrated by the experimental results, the developed trajectory planning algorithm improves the computational efficiency of tendon variables and enhances the consistency of trajectory tracking. The prototype system can deposit a complex path on an inclined substrate and fabricate a thin-wall component within a pipeline. The validation work confirms the feasibility and applicability of the prototype system for metal additive manufacturing applications.

To observe the antitumour efficacy of programmed death 1 (PD-1) inhibitors in the real world and explore the relationship between NRS2002 score or other clinical characteristics and immunotherapy efficacy, we retrospectively analyzed 341 tumor patients who received immune checkpoint inhibitor (ICI) treatment at one center. A total of 341 solid tumor patients treated with ICIs from June 2018 to December 2021 were retrospectively included in this study. Patient characteristics, ICI responses, and survival status were documented, and the relationships between clinical factors and survival were analyzed. Among all patients, the median progression-free survival (PFS) was 5.8 months, and the median overall survival (OS) was 12.5 months. The Performance Status (PS), NRS2002 score, The Naples Prognostic Score (NPS), Lymphocyte and C-reactive protein ratio (LCR), line of therapy, and nutritional support were significantly related to PFS or OS according to univariate analysis. The median PFS and OS were significantly better in the group without nutritional risk (NRS2002 0–2) than those with nutritional risk (NRS2002 ≥ 3) (PFS: HR = 1.82, 95% CI 1.30–2.54, p value

ObjectiveThis study aimed to identify immune states associated with a high risk of preterm birth by immunophenotyping in pregnant populations, and to elucidate the characteristics of immune subtypes and their relationships with preterm birth. Additionally, it sought to uncover the microbial composition and functional characteristics of immune states linked to preterm birth, and to evaluate the impact of bacterial interactions on the initiation of preterm birth.MethodsUtilizing 16S rRNA sequencing data and local immune factor expression data from a publicly available longitudinal pregnancy cohort, we conducted immunophenotyping through unsupervised clustering of the immune factors. We compared the differences in vaginal microbiota richness, diversity, and composition between identified immune subtypes using α and β diversity analysis. Signature microbiotas were identified using LEfSe analysis, and functional pathway enrichment variations were analyzed using PICRUSt2. Bidirectional mediation analysis was employed to construct a network of mediating roles, and preliminary in vitro validation of the Microbial-Cytokine-Preterm Birth pathway was performed to explore the effects of microbial and immune characteristics on vaginal epithelial cell function.ResultsPregnant women were categorized into three immune subtypes based on local immune status. Microbial functional analysis identified 31 distinct functional pathways, six of which were downregulated in the preterm birth and excessive inflammatory response group. Significant differences in vaginal microbial diversity and composition were observed among pregnant women with different immune subtypes. Bidirectional mediation analysis revealed multiple intermediary roles in preterm birth, highlighting C3b/iC3b and IL-8 in mid-pregnancy and IgE and IgM in late pregnancy.ConclusionThis study classified pregnant women into three immune subtypes, with the excessive inflammatory response subtype showing a higher predisposition to preterm birth. Mid-pregnancy immune status emerged as a key indicator of preterm birth risk, associated with the vaginal microbiome composition. Microorganisms affected the occurrence of preterm birth by modulating immune factor levels, with time-specific mediation roles observed. Lactobacillus crispatus demonstrated potential in protecting against preterm birth by modulating vaginal immune status.

The coal-fired power plant (CFPP) coupled with the molten salt thermal energy storage system is a potential way to improve its flexibility and peak-shaving ability. The steam generation system (SGS) is a suitable choice to convert the feed water into hot steam by using the heat from the molten salt. In this paper, the schematic of an SGS coupled with the CFPP is presented. A dynamic model of the SGS basing lump parameter method is established and validated to investigate its dynamic response characteristics. Five different disturbance experiments including feed water inlet parameters, molten salt inlet parameters and medium pressure steam valve, are conducted and analyzed. The dynamic response curves of molten salt and steam are obtained. Moreover, the load adjustment process of SGS with three different load changing rates (3 %, 6 %, 10 % Pe/min) under the rated conditions is compared and its influence on the SGS is analyzed. The temperature changing rates in the thick-wall components of SGS are within 2 °C/min which meets the safe operating standard. Based on the above results, the three elements control strategy with excellent robustness for the SGS safety operation is proposed and demonstrated. The results show that the response time for the SGS load regulation process and the water level fluctuation have been significantly improved as the three elements control strategy is imposed. The water level can be stabilized in 200 s with tiny fluctuation when the SGS loads down 10 % thermal load with 10 % Pe/min load changing rate. These results could provide useful references for the design and control strategy making of the CFPP coupled with the molten salt thermal energy storage system.

BackgroundCurrently developed molecular markers can predict the effectiveness of cancer immunotherapy and screen beneficiaries to some extent, but they are not stable enough. Therefore, there is an urgent need for discovering novel biomarkers. At the same time, sex factor plays a vital role in the response to immunotherapy, so it is particularly important to identify sex-related molecular indicators.MethodsWe integrated a pan-cancer cohort consisting of 2348 cancer patients who received immune checkpoint inhibitors and targeted sequencing. Using somatic mutation profiles, we identified mutational signatures, molecular subtypes, and frequently mutated genes, and analyzed their relationships with immunotherapeutic outcomes. We also explored sex disparities of determined biomarkers in response to treatments.ResultsWe found that male patients exhibited better immunotherapy outcomes and higher tumor mutational burden. A total of seven mutational signatures were identified, among which signatures 1 and 3 were associated with worse immunotherapy outcomes, while signatures 2 and 6 correlated with better outcomes. Gender-based analysis revealed that mutational signature 1 continued to show a worse immunotherapy outcome in female patients, whereas signature 6 demonstrated a better outcome in male patients. Based on mutational activities, we identified four potential molecular subtypes with gender differences and relevance to treatment outcomes. PI3K-AKT, RAS signaling pathways, and 68 significantly mutated genes were identified to be associated with immunotherapy outcomes, with nine genes (i.e., ATM, ATRX, DOT1L, EP300, EPHB1, NOTCH1, PBRM1, RBM10, and SETD2) exhibiting gender differences. Finally, we discovered co-mutated gene pairs and TP53 p.R282W mutations related to treatment outcomes, highlighting their gender-specific differences.ConclusionThis study identified several molecular biomarkers related to cancer immunotherapy outcomes in terms of mutational signatures, molecular subtypes, and mutated genes, and explored their gender-relatedness in order to provide clues and basis for clinical treatment efficacy evaluation and patient selection.

Abstract Background Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that poses a substantial economic burden. The Random forest algorithm is effective in predicting AD; however, the key factors influencing AD onset remain unclear. This study aimed to analyze the key lipoprotein and metabolite factors influencing AD onset using machine-learning methods. It provides new insights for researchers and medical personnel to understand AD and provides a reference for the early diagnosis, treatment, and early prevention of AD. Methods A total of 603 participants, including controls and patients with AD with complete lipoprotein and metabolite data from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database between 2005 and 2016, were enrolled. Random forest, Lasso regression, and CatBoost algorithms were employed to rank and filter 213 lipoprotein and metabolite variables. Variables with consistently high importance rankings from any two methods were incorporated into the models. Finally, the variables selected from the three methods, with the participants’ age, sex, and marital status, were used to construct a random forest predictive model. Results Fourteen lipoprotein and metabolite variables were screened using the three methods, and 17 variables were included in the AD prediction model based on age, sex, and marital status of the participants. The optimal random forest modeling was constructed with “mtry” set to 3 and “ntree” set to 300. The model exhibited an accuracy of 71.01%, a sensitivity of 79.59%, a specificity of 65.28%, and an AUC (95%CI) of 0.724 (0.645–0.804). When Mean Decrease Accuracy and Gini were used to rank the proteins, age, phospholipids to total lipids ratio in intermediate-density lipoproteins (IDL_PL_PCT), and creatinine were among the top five variables. Conclusions Age, IDL_PL_PCT, and creatinine levels play crucial roles in AD onset. Regular monitoring of lipoproteins and their metabolites in older individuals is significant for early AD diagnosis and prevention.

Abstract Sandy Dolomite is a kind of widely distributed rock. The uniaxial compressive strength (UCS) of Sandy Dolomite is an important metric in the application in civil engineering, geotechnical engineering, and underground engineering. Direct measurement of UCS is costly, time-consuming, and even infeasible in some cases. To address this problem, we establish an indirect measuring method based on the convolutional neural network (CNN) and regression analysis (RA). The new method is straightforward and effective for UCS prediction, and has significant practical implications. To evaluate the performance of the new method, 158 dolomite samples of different sandification grades are collected for testing their UCS along and near the Yuxi section of the Central Yunnan Water Diversion (CYWD) Project in Yunnan Province, Southwest of China. Two regression equations with high correlation coefficients are established according to the RA results, to predict the UCS of Sandy Dolomites. Moreover, the minimum thickness of Sandy Dolomite was determined by the Schmidt hammer rebound test. Results show that CNN outperforms RA in terms of prediction the precision of Sandy Dolomite UCS. In addition, CNN can effectively deal with uncertainty in test results, making it one of the most effective tools for predicting the UCS of Sandy Dolomite.

Prostate cancer is a significant contributor to cancer-related mortality, and the tumor typically develops into castration-resistant prostate cancer (CRPC). Hence, few effective clinical strategies are available to patients with advanced disease. Extrachromosomal circular DNA (eccDNA) is a type of circular DNA originating from the chromosomes but is likely independent of them. Because of its unique structural characteristics, eccDNA has extensive applications as a new biomarker for cancer prevention and treatment. Circle-seq obtains a comprehensive picture of the overall landscape of eccDNA sizes and content in cell populations. In this study, we used Circle-seq and studied the distribution pattern and expression level of eccDNA in prostate cancer. We confirmed that eccDNA is derived from every human chromosome and has sequences from all known types of genomic structures, revealing it is a common mutational element in prostate cancer. We also identified an eccDNA-related gene SPOCK1 that promotes drug resistance, proliferation, and metastasis of many cancers through the epithelial-mesenchymal transition (EMT) mechanism. The SPOCK1-associated eccDNA was highly upregulated in various groups of sequencing results, and SPOCK1 was highly expressed in prostate cancer tissues and cells. Therefore, SPOCK1 exists as eccDNA in prostate cancer and encourages its development and drug resistance via the EMT mechanism. Our results suggest that upregulated genes in the form of eccDNA are oncogenes in prostate cancer and play a pivotal role in carcinogenesis.

Background: Type 2 diabetes mellitus (T2DM) significantly contributes to sepsis, with patients suffering from both conditions exhibiting greater severity and higher mortality rates compared to those with sepsis alone. Elderly individuals in the intensive care unit (ICU) are particularly prone to these comorbidities. A nomogram prediction model was developed to accurately assess prognosis and guide treatment for elderly patients with sepsis and T2DM. Methods: Data from 1489 patients with sepsis and T2DM in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were analyzed and categorized into 28-days survival ( n = 1156) and 28-days death groups ( n = 333). The dataset’s clinical characteristics were employed to create a nomogram predicting 28-days mortality in elderly ICU patients with sepsis and T2DM. The least absolute shrinkage and selection operator (LASSO) regression identified candidate predictors, followed by a multivariate logistic regression analysis incorporating variables with p < .05 into the final model. A nomogram was then constructed using these significant risk predictors. The model’s discriminatory power was evaluated through a receiver operating curve (ROC) and the area under the curve (AUC). Additionally, model performance was assessed using a calibration plot and the Hosmer-Lemeshow goodness-of-fit test (HL test), and clinical utility was examined via decision curve analysis (DCA). Results: Risk factors incorporated into the nomogram included age, ICU length of stay, mean blood pressure (MBP), metastatic solid tumor, Sequential Organ Failure Assessment (SOFA) score, Logistic Organ Dysfunction System (LODS) score, blood urea nitrogen (BUN), and vasopressor use. The predictive model demonstrated robust discrimination, with an AUC of 0.802 (95% CI 0.768–0.835) in the training dataset and 0.753 (95% CI 0.697–0.809) in the validation set. Calibration was confirmed with the HL test ( p > .05), and DCA indicated clinical usefulness. Conclusion: This new nomogram serves as a practical tool for predicting 28-days mortality among elderly ICU patients with sepsis and T2DM. Optimizing treatment strategies based on this model could enhance 28-days survival rates for these patients.

Abstract Background Dwarf rootstocks have important practical significance for high-density planting in pear orchards. The shoots of ‘Cuiguan’ grafted onto the dwarf rootstock were shorter than those grafted onto the vigorous rootstock. However, the mechanism of shorter shoot formation is not clear. Results In this study, the current-year shoot transcriptomes and phytohormone contents of ‘CG‒QA’ (‘Cuiguan’ was grafted onto ‘Quince A’, and ‘Hardy’ was used as interstock) and ‘CG‒DL’ (‘Cuiguan’ was grafted onto ‘Duli’, and ‘Hardy’ was used as interstock) were compared. The transcriptome results showed that a total of 452 differentially expressed genes (DEGs) were identified, including 248 downregulated genes and 204 upregulated genes; the plant hormone signal transduction and zeatin biosynthesis pathways were significantly enriched in the top 20 KEGG enrichment terms. Abscisic acid (ABA) was the most abundant hormone in ‘CG‒QA’ and ‘CG‒DL’; auxin and cytokinin (CTK) were the most diverse hormones; additionally, the contents of ABA, auxin, and CTK in ‘CG‒DL’ were higher than those in ‘CG‒QA’, while the fresh shoot of ‘CG‒QA’ accumulated more gibberellin (GA) and salicylic acid (SA). Metabolome and transcriptome co-analysis identified three key hormone-related DEGs, of which two (Aldehyde dehydrogenase gene ALDH3F1 and YUCCA2) were upregulated and one (Cytokinin oxidase/dehydrogenase gene CKX3) was downregulated. Conclusions Based on the results of transcriptomic and metabolomic analysis, we found that auxin and CTK mainly regulated the shoot differences of ‘CG–QA’ and ‘CG–DL’, and other hormones such as ABA, GA, and SA synergistically regulated this process. Three hormone-related genes ALDH3F1, YUCCA2, and CKX3 were the key genes contributing to the difference in shoot growth between ‘CG–QA’ and ‘CG–DL’ pear. This research provides new insight into the molecular mechanism underlying shoot shortening after grafted onto dwarf rootstocks.

Selenium (Se) is an essential trace element that has various beneficial effects for human healthy. However, the effects of different Se forms and concentrations on growth and development, photosynthetic characteristics and antioxidant capacity are still unclear with regard to the dual grain-and-feed dual-use of ratoon rice (RR). In this study, three concentrations of three different Se forms were applied to RR using the foliar spraying method, and the results showed that Se treatment can increase the Se content of rice grain and straw. All the Se treatments improved the photosynthetic indexes and activities of antioxidant enzymes. The Se and trace elements contents, and the percentages of organic Se and protein Se of brown rice were found to be similar in all three Se forms. A higher organic Se content was found in the grain by spraying sodium selenite and Se-Met, in which the resistant starch (RS) content was increased with the increase in amylose content in grains. The main Se species in the grain was SeMet and the SeMeCys was found only with SeMet treatments. The grain quality showed that all three Se forms increased the consistency of gelatinization. Our study indicated that exogenous Se could improve the nutritional quality of both grain and straw by improving photosynthetic traits and antioxidant enzyme activities, especially sodium selenite and Se-Met. These results underscore the potential of foliar biofortification to enhance the functional component contents of RR grains and provide an insight into the Se enrichment of ratoon rice.

The efficient cutting of non-woven fabric shows great significance to the development of the textile industry. In recent years, laser cutting technology has been widely applied in the clothing industry due to its high efficiency and cutting quality. In this work, a UV nanosecond pulsed laser with a wavelength of 355 nm and a max power of 6.5 W is used to cut non-woven fabric with a thickness of 0.15 mm. The variation of kerf width, surface morphology, and chemical contents are investigated under different laser processing parameters, and the optimal processing parameter is determined. The experimental results demonstrate that the degree of crystallization and chemical composition of the kerf on the non-woven fabric surface is significantly influenced by laser cutting parameters such as laser scanning speed (from 100 to 700 mm/s) and frequency (from 20 to 70 kHz). The scanning speed of 500 mm/s and frequency of 30 kHz are considered the best parameters for achieving abundant energy for the complete and efficient cutting of non-woven fabric. In addition, the level of carbonization and oxidation reaches a relatively low value, and the kerf width is 0.214 mm, which is considered a reasonable value under the optimal processing parameters, showing high cutting quality. Furthermore, the effect of different cutting treatments on surface morphology and chemical contents is also studied. The experimental results present that the non-woven fabric cut by laser possesses a flat kerf, showing a similar effect to that of scissor cutting. Moreover, due to the programmability of laser processing patterns, it is possible to create more intricate designs on non-woven fabric. This facilitates the application and promotion of laser-cut non-woven fabrics. These results can provide a certain reference for laser cutting in the textile industry and are expected to allow for the cutting of high-quality kerf with low carbonization and oxidation.

IntroductionAmong clinical healthcare personnel, nurses face the highest proportion of workplace violence, which has a significant impact on their physical and mental well-being as well as their personal and professional lives. However, little is known about the effects of workplace violence on inexperienced breastfeeding nurses and their experiences during and after breastfeeding when they return to work. This study aimed to explore the experiences of inexperienced breastfeeding nurses who encountered workplace violence and its resulting impacts.MethodsThis study employed a descriptive qualitative design. Semi-structured in-depth interviews were conducted with 20 nurses working in various positions and departments at three tertiary hospitals. Purposive and maximum variation sampling techniques were employed. The interview data were analyzed using Colaizzi’s method, and the research findings were reported according to Consolidated Criteria for Reporting Qualitative Studies (COREQ)standards.ResultsInferences regarding workplace violence and risks for inexperienced breastfeeding nurses included physical labor (such as lifting heavy objects and performing cardiopulmonary resuscitation), conflicts, inadequate job skills, role confusion, occupational exposure risks, patient violence, and pressure from older adults. An inductive thematic investigation revealed the “Challenges faced during breastfeeding,” “Conflicting professional and family roles,” “Out of balance,” and “Coping strategies.”ConclusionInexperienced breastfeeding nurses experience several negative consequences due to workplace violence. Therefore, it is essential to plan and implement preventive strategies and management programs that specifically target workplace violence among inexperienced breastfeeding nurses.

BackgroundA burgeoning body of evidence has substantiated the association between alterations in the composition of the gut microbiota and rheumatoid arthritis (RA). Nevertheless, our understanding of the intricate mechanisms underpinning this association is limited.MethodsTo investigate whether the gut microbiota influences the pathogenesis of RA through metabolism or immunity, we performed rigorous synthesis analyses using aggregated statistics from published genome-wide association studies (GWAS) using two-sample Mendelian randomization (MR) and mediated MR techniques, including two-step MR and multivariate MR analyses. Subsequently, we conducted in vitro cellular validation of the analyzed Microbial-Cytokine-RA pathway. We determined the optimal culture conditions through co-culture experiments involving concentration and time. Cell Counting Kit-8 (CCK-8) assays were employed to assess cellular viability, and enzyme-linked immunosorbent assays (ELISA) were performed to assess tumor necrosis factor-inducible gene 6 protein (TSG-6) and tumor necrosis factor-α (TNF-α) levels.ResultsOur univariable MR results confirmed 15 microbial traits, 7 metabolites and 2 cytokines that may be causally associated with RA (PFDR < 0.05). Mediation analysis revealed that microbial traits influence the risk of RA through metabolite or cytokine (proportion mediated: 7.75% - 58.22%). In vitro experiments demonstrated that TSG-6 was highly expressed in the Subdoligranulum variabile treatment group and was correlated with decreased RA severity (reduced TNF-α expression). Silencing the TSG-6 gene significantly increased TNF-α expression, regardless of treatment with S. variabile. Additionally, S. variabile-secreted exosomes exhibited the same effect.ConclusionThe results of this study suggest that S. variabile has the potential to promote TSG-6 secretion, thereby reducing RA inflammation.

ABSTRACT: The objective of this study was to evaluate the effects of different levels of glycerol monolaurate (GML) on laying performance, egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens. A total of 480 Hy-Line Variety Brown hens (age 54 wk) were randomly assigned to 5 treatments: the control group (basal diet) and 4 GML groups (basal diet supplemented with 100, 200, 300, and 400 mg/kg GML). Each treatment consisted of 8 replicates with 12 hens each and the trial lasted for 8 wk. The results showed that dietary inclusion of GML increased the ADFI in the entire experimental period and the average egg weight in wk 5 to 8 and wk 1 to 8 of the experiment (linear, P < 0.05). Dietary GML addition linearly increased albumen height, Haugh unit and yolk color, and quadratically increased eggshell thickness (P < 0.05). The serum SOD activity, T-AOC and IgG concentrations in the 200 mg/kg GML group, and GSH-Px activity in 200 and 300 mg/kg GML groups were increased, while the MDA concentration in 200 and 300 mg/kg GML groups was decreased than those in the control group (P < 0.05). The jejunal villus height and villus height: crypt depth in 300 mg/kg GML group were higher than that in the control group (P < 0.05). The mRNA expression of TLR4, IL-1β and TNF-α in spleen and jejunum decreased with the increase of dietary GML concentration (linear, P < 0.05). In conclusion, dietary GML supplementation could improve egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens, and dietary 300 mg/kg GML inclusion is suggested.

Abstract Wear topography is a significant indicator of tribological behavior for the inspection of machine health conditions. An intelligent in-suit wear assessment method for random topography is here proposed. Three-dimension (3D) topography is employed to address the uncertainties in wear evaluation. Initially, 3D topography reconstruction from a worn surface is accomplished with photometric stereo vision (PSV). Then, the wear features are identified by a contrastive learning-based extraction network (WSFE-Net) including the relative and temporal prior knowledge of wear mechanisms. Furthermore, the typical wear degrees including mild, moderate, and severe are evaluated by a wear severity assessment network (WSA-Net) for the probability and its associated uncertainty based on subjective logic. By integrating the evidence information from 2D and 3D-damage surfaces with Dempster–Shafer (D–S) evidence, the uncertainty of severity assessment results is further reduced. The proposed model could constrain the uncertainty below 0.066 in the wear degree evaluation of a continuous wear experiment, which reflects the high credibility of the evaluation result.

To understand the reservoir property and hydrocarbon accumulation conditions of the Middle and Upper Ordovician intraplatform shoal between ultra-deep main strike-slip faults in Fuman Oilfield of the Tarim Basin, China, the main strike-slip faults in and around well FD1 in the basin were analyzed in terms of sedimentary facies, sequence stratigraphy, intraplatform shoal reservoir property, and oil and gas origins, based on drilling data. The Yingshan Formation intraplatform shoal between the main strike-slip faults is superimposed with low-order faults to form a new type of hydrocarbon play. Firstly, hydrocarbons generated from the Lower Cambrian Yuertusi Formation source rocks vertically migrated into the second member of Yingshan Formation through the main strike-slip faults, and then migrated laterally until they were accumulated. A small amount of oil from Well FD1 came from the Yuertusi Formation source rocks in the mature stage, and a large amount of gas originated from oil cracking in the ultra-deep reservoirs. Therefore, the secondary gas condensate reservoir in Well FD1 is characterized by high gas to oil ratio, dry gas (dryness coefficient being 0.970) and hybrid origin. This new type of hydrocarbon play characterized by intraplatform shoal and low-order fault suggests a prospect of continuous hydrocarbon-bearing area in Fuman Oilfield, which will expand the ultrap-deep oil and gas exploration in the oilfield.

Spermatozoa cryopreservation protocols have been established for yellow catfish (Pelteobagrus fulvidraco), but cryopreservation can still cause cellular damage and affect spermatozoa viability and fertility. Therefore, the aim of this paper was to evaluate the effects of adding or not adding cryoprotectants during low-temperature storage on the ultrastructural damage, oxidative damage, and DNA damage of thawed yellow catfish spermatozoa. The mixed semen of three male yellow catfish was divided into a fresh spermatozoa group, a frozen spermatozoa group (DMSO+) with a cryoprotectant (10% DMSO), and a frozen spermatozoa group without a cryoprotectant (DMSO−). Ultrastructural of the spermatozoa after thawing were observed under an electron microscope and the spermatozoa were assayed for SOD, MDA, and T-AOC enzyme activities, as well as for DNA integrity. In terms of movement parameters, compared with DMSO−, the addition of DMSO has significantly improved sperm motility, curve line velocity (VCL), and straight line velocity (VSL). The ultrastructural results showed that although thawed spermatozoa exhibited increased damage than fresh spermatozoa, 10% DMSO effectively reduced the damage to the plasma membrane, mitochondria, and flagellum of spermatozoa by cryopreservation, and most of the spermatozoa were preserved with intact structure. The results of oxidative damage showed that compared with frozen spermatozoa, 10% DMSO significantly increased the activities of SOD and T-AOC enzymes and clearly reduced the activity of the MDA enzyme. The antioxidant capacity of spermatozoa was improved, lipid peroxidation was reduced, and the oxidative damage caused by cryopreservation was mitigated. The DNA integrity of spermatozoa showed that 10% DMSO clearly reduced the DNA fragmentation rate. In conclusion, 10% DMSO can effectively reduce the ultrastructural damage, oxidative damage, and DNA damage of yellow catfish spermatozoa during cryopreservation; it can also further optimize the cryopreservation protocol for yellow catfish spermatozoa. Meanwhile, it also provides a theoretical basis for the future optimization of the cryopreservation protocols.

The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It is produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia and other anomalies. Importantly, it is associated with chronic pathologies (often age-related) that have an inflammatory component. This includes atherosclerosis, diabetes and Alzheimer’s disease. Its mode of action in these diseases is not well understood, but it inhibits or regulates multiple major pathways. Klotho has a membrane form and a soluble form (s-Klotho). Cytosolic Klotho is postulated but not well characterized. s-Klotho has endocrine properties that are incompletely elucidated. It binds to the FGF receptor 1c (FGFR1c) that is widely expressed (including endothelial cells). It also attaches to soluble FGF23, and FGF23/Klotho binds to FGFRs. Thus, s-Klotho might be a roaming FGF23 coreceptor, but it has other functions. Notably, Klotho (cell-bound or soluble) counteracts inflammation and appears to mitigate related aging (inflammaging). It inhibits NF-κB and the NLRP3 inflammasome. This inflammasome requires priming by NF-κB and produces active IL-1β, membrane pores and cell death (pyroptosis). In accord, Klotho countered inflammation and cell injury induced by toxins, damage-associated molecular patterns (DAMPs), cytokines, and reactive oxygen species (ROS). s-Klotho also blocks the TGF-β receptor and Wnt ligands, which lessens fibrotic disease. Low Klotho is associated with loss of muscle mass (sarcopenia), as occurs in aging and chronic diseases. s-Klotho counters the inhibitory effects of myostatin and TGF-β on muscle, reduces inflammation, and improves muscle repair following injury. The inhibition of TGF-β and other factors may also be protective in diabetic retinopathy and age-related macular degeneration (AMD). This review examines Klotho functions especially as related to inflammation and potential applications.

ObjectivesTo examine the gut microbiota characteristics in children with immunoglobulin A vasculitis and their interrelationships with the host, while evaluate the vertical inheritance of microbiota in the development and progression of IgA vasculitis.MethodsThis study investigated the gut microbiome of 127 IgA vasculitis mother-child pairs and 62 matched healthy mother-child pairs, and compared the gut microbial composition of different groups. The pathway enrichment analysis evaluated potential gut microbiome-mediated pathways involved in the pathophysiology of IgA vasculitis. The Spearman correlation analysis illustrated the relationships between clinical variables and bacterial biomarkers.ResultsThis study identified distinct intestinal microbiome in IgA vasculitis children compared to healthy children, and further pointed out the association in gut microbiota between IgA vasculitis children's and their mother's. The relative abundance of Megamonas and Lactobacillus in IgAV children was positively correlated with that in their mothers. The pathway enrichment analysis found microbial biosynthesis of vitamins and essential amino acids was upregulated in children with IgA vasculitis. Correlation analysis showed bacterial biomarkers were correlated with indicators of blood coagulation.ConclusionChildren with IgA vasculitis have unique bacterial biomarkers and may affect coagulation function, and their gut microbiome was closely associated with that of their mothers. The observed association in gut microbiota between IgA vasculitis children and their mothers suggested a potential intergenerational influence of the maternal microbiota on the development or progression of IgA vasculitis in children.

IntroductionMenstrual blood-derived stem cells (MenSCs) are vital in treating many degenerative and traumatic disorders. However, the underlying molecular mechanisms remain obscure in MenSCs-treating spinal cord injury (SCI) rats.MethodsMenSCs were adopted into the injured sites of rat spinal cords at day 7 post surgery and the tissues were harvested for total RNA sequencing analysis at day 21 after surgery to investigate the expression patterns of RNAs. The differentially expressed genes (DEGs) were analyzed with volcano and heatmap plot. DEGs were sequentially analyzed by weighted gene co-expression network, functional enrichment, and competitive endogenous RNAs (ceRNA) network analysis. Next, expression of selected miRNAs, lncRNAs, circRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics packages and extra databases were enrolled to scoop the genes functions and their interaction relationships.ResultsA total of 89 lncRNAs, 65 circRNAs, 120 miRNAs and 422 mRNAs were significantly upregulated and 65 lncRNAs, 72 circRNAs, 74 miRNAs, and 190 mRNAs were significantly downregulated in the MenSCs treated rats compared to SCI ones. Current investigation revealed that MenSCs treatment improve the recovery of the injured rats and the most significantly involved pathways in SCI regeneration were cell adhesion molecules, nature killer cell mediated cytotoxicity, primary immunodeficiency, chemokine signaling pathway, T cell receptor signaling pathway and B cell receptor signaling pathway. Moreover, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA network of SCI was constructed. Finally, the protein-protein interaction (PPI) network was constructed using the top 100 DE mRNAs. The constructed PPI network included 47 nodes and 70 edges.DiscussionIn summary, the above results revealed the expression profile and potential functions of differentially expressed (DE) RNAs in the injured spinal cords of rats in the MenSCs-treated and SCI groups, and this study may provide new clues to understand the mechanisms of MenSCs in treating SCI.

The aim of this study was to improve the utilization of peanut vines as forage material for ruminants by investigating the degradation pattern of peanut vines in the dairy cow rumen. Samples of peanut vine incubated in cow rumens were collected at various time points. Bacterial diversity was investigated by scanning electron microscopy (SEM) and 16S rRNA gene sequencing. Carbohydrate-active enzymes (CAZymes) were analyzed by metagenomics. The peanut vines degraded rapidly from 2 to 24 h, before slowing from 24 to 72 h. SEM images confirmed dynamic peanut vine colonization. Firmicutes and Bacteroidetes were the two most dominant bacterial phyla throughout. Principal coordinates analysis indicated significant microbial composition changes at 6 and 24 h. This may be because, in the early stage, soluble carbohydrates that are easily degradable were degraded, while in the later stage, fibrous substances that are difficult to degrade were mainly degraded. Glycoside hydrolases (GHs) were the most abundant CAZymes, with peak relative abundance at 6 h (56.7 trans per million, TPM), and reducing at 24 (55.9 TPM) and 72 h (55.3 TPM). Spearman correlation analysis showed that Alistipes_sp._CAG:435, Alistipes_sp._CAG:514, Bacteroides_sp._CAG:1060, Bacteroides_sp._CAG:545, Bacteroides_sp._CAG:709, Bacteroides_sp._CAG:770, bacterium_F082, bacterium_F083, GH29, GH78, and GH92 were important for plant fiber degradation. These findings provide fundamental knowledge about forage degradation in the cow rumen, and will be important for the targeted improvement of ruminant plant biomass utilization efficiency.

Abstract Background In recent years, it has become a research focus to accurately extract key genes influencing the occurrence and development of diseases from massive genomic data and study their regulatory mechanisms. Further exploration of these large databases is beneficial for us to identify key regulatory mechanisms in the occurrence and development of diseases, providing direction and theoretical basis for subsequent experimental design and research. Methods By using data from The Cancer Genome Atlas (TCGA) for lung adenocarcinoma (LUAD), the immune cell content of patients was obtained through deconvolution calculations in CIBERSORTx. Combined with Bayesian network inference methods, the impact of key gene expression on the heterocellular network influencing lung cancer was analyzed. Results We found CD36 and ADRA1A genes were identified as two key mRNA genes influencing lung adenocarcinoma. The sensitivity analysis shows that the model performs well on both the testing set (error rate = 4%, AUC = 0.9804), the training set (error rate = 5.637%, AUC = 0.9746) and the verification set (error rate = 28.85%, AUC = 0.8689). The model has excellent predictive capabilities. Conclusion We found that CD36 and ADRA1A genes may influence the development of lung cancer by affecting regulatory T cell and follicular helper T cell populations. Additionally, plasma cells may affect the expression of the CD36 gene. And the mutual information calculated by the model for these two genes is also the highest, indicating their potential as tumour biomarkers. Combining the network model, it can be inferred that CD36 and ADRA1A are likely to influence the occurrence and development of the disease through follicular helper T cells and regulatory T cells.

BackgroundOsteoporosis (OP) is a systemic skeletal disease characterized by compromised bone strength leading to an increased risk of fracture. There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of OP. The aim of this study was to assess the causal association between NAFLD and OP.MethodsWe performed two‐sample Mendelian randomization (MR) analyses to investigate the causal association between genetically predicted NAFLD [i.e., imaging‐based liver fat content (LFC), chronically elevated serum alanine aminotransferase (cALT) and biopsy-confirmed NAFLD] and risk of OP. The inverse variant weighted method was performed as main analysis to obtain the causal estimates.ResultsImaging-based LFC and biopsy-confirmed NAFLD demonstrated a suggestive causal association with OP ([odds ratio (OR): 1.003, 95% CI: 1.001-1.004, P < 0.001; OR: 1.001, 95% CI: 1.000-1.002, P = 0.031]). The association between cALT and OP showed a similar direction, but was not statistically significant (OR: 1.001, 95% CI: 1.000-1.002, P = 0.079). Repeated analyses after exclusion of genes associated with confounding factors showed consistent results. Sensitivity analysis indicated low heterogeneity, high reliability and low pleiotropy of the causal estimates.ConclusionThe two‐sample MR analyses suggest a causal association between genetically predicted NAFLD and OP.

Glucose oxidase (GOx) can specifically catalyze the conversion of β-d-glucose into gluconic acid and hydrogen peroxide (H2O2) in the presence of oxygen, making it promising for tumor starvation therapy and oxidative therapy. However, GOx's immunogenicity, poor in vivo stability, short half-life, and potential systemic toxicity, limit its application in cancer therapy. Nanocarriers are capable of improving the pharmacological properties of therapeutic drugs (e.g. stability, circulating half-life, and tumor accumulation) and lower toxicity, hence resolving GOx issues and enhancing its efficacy. Although the application of targeted nanocarriers based on GOx has recently flourished, this field has not yet been reviewed and evaluated. Herein, we initially examined the mechanism of GOx-based nanocarriers for enhanced tumor therapy. Also, we present a comprehensive and up-to-date review that highlights GOx-based nanocarriers for tumor targeting therapy. This review expands on GOx-based nano-targeted combination therapies from both passive and active targeting perspectives, meanwhile, active targeting is further classified into ligand-mediated targeting and physical-mediated targeting. Furthermore, this review also emphasizes the present challenges and promising advancements.

Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.

Abstract Chemotherapy-related thrombocytopenia (CIT) is a significant adverse event during chemotherapy, which can lead to reduced relative dose intensity, increased risk of serious bleeding and additional medical expenditure. Herein, we aimed to develop and validate a predictive nomogram model for prediction of CIT in patients with solid tumor. From Jun 1, 2018 to Sep 9, 2021, a total of 1541 patients who received 5750 cycles of chemotherapy were retrospectively enrolled. Cox regression analysis was performed to identify predictive factors to establish the nomogram model for CIT. The incidence of chemotherapy-induced thrombocytopenia was 21.03% for patient-based and 10.26% for cycles of chemotherapy. The top five solid tumors with CIT are cervix, gastric, bladder, biliary systemic, and ovarian. The incidence of chemotherapy dose delays in any cycle because of CIT was 5.39%. Multivariate analysis showed that tumor site, treatment line, AST, oxaliplatin, and capecitabine were significantly associated with CIT. Moreover, we established a nomogram model for CIT probability prediction, and the model was well calibrated (Hosme-Lemeshow P = 0.230) and the area under the receiver operating characteristic curve was 0.844 (Sensitivity was 0.625, Specificity was 0.901). We developed a predictive model for chemotherapy-induced thrombocytopenia based on readily available and easily assessable clinical characteristics. The predictive model based on clinical and laboratory indices represents a promising tool in the prediction of CIT, which might complement the clinical management of thrombocytopenia.

Abstract Background Hippocampal damage caused by status epilepticus (SE) can bring about cognitive decline and emotional disorders, which are common clinical comorbidities in patients with epilepsy. It is therefore imperative to develop a novel therapeutic strategy for protecting hippocampal damage after SE. Mitochondrial dysfunction is one of contributing factors in epilepsy. Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria, we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE. Methods Pilocarpine was used to induced SE in mice. SE‐generated cognitive decline and emotional disorders were determined using novel object recognition, the tail suspension test, and the open field test. SE‐induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes. The metabolites underlying mitochondrial transplantation were determined using metabonomics. Results The results showed that peripheral administration of isolated mitochondria could improve cognitive deficits and depressive and anxiety‐like behaviors. Exogenous mitochondria blunted the production of reactive oxygen species, proliferation of microglia and astrocytes, and loss of neurons in the hippocampus. The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism. Among potential affected metabolites, mitochondrial transplantation decreased levels of sphingolipid (d18:1/18:0) and methylmalonic acid, and elevated levels of D‐fructose‐1,6‐bisphosphate. Conclusion To the best of our knowledge, these findings provide the first direct experimental evidence that artificial mitochondrial transplantation is capable of ameliorating hippocampal damage following SE. These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy‐associated psychiatric and cognitive disorders.

Eighteen sun-dried tea samples were selected from six major tea-producing regions in Yunnan Province, namely Xishuangbanna, Pu'er, Lincang, Baoshan, Dehong and Yuxi to use for this study. In this study, these samples' biochemical components such as moisture, water leachate, caffeine, tea polyphenols and free amino acids were tested and their sensory evaluations were conducted. The quality differences of sun-dried tea from different regions in Yunnan Province were investigated by means of index correlation analysis, principal component analysis, cluster analysis and quality appellation analysis, and high-quality production regions were screened. The results showed that the quality indicators of different regional sun-dried tea had differences and there were some correlations among the quality indicators. Among them, the water leachate content showed correlation with the content of tea polyphenol and leaf base (P

Abstract Chinese hamster ovary (CHO) cell lines are widely used to manufacture biopharmaceuticals. However, CHO cells are not an optimal expression host due to the intrinsic plasticity of the CHO genome. Genome plasticity can lead to chromosomal rearrangements, transgene exclusion, and phenotypic drift. A poorly understood genomic element of CHO cell line instability is extrachromosomal circular DNA (eccDNA) in gene expression and regulation. EccDNA can facilitate ultra-high gene expression and are found within many eukaryotes including humans, yeast, and plants. EccDNA confers genetic heterogeneity, providing selective advantages to individual cells in response to dynamic environments. In CHO cell cultures, maintaining genetic homogeneity is critical to ensuring consistent productivity and product quality. Understanding eccDNA structure, function, and microevolutionary dynamics under various culture conditions could reveal potential engineering targets for cell line optimization. In this study, eccDNA sequences were investigated at the beginning and end of two-week fed-batch cultures in an ambr®250 bioreactor under control and lactate-stressed conditions. This work characterized structure and function of eccDNA in a CHO-K1 clone. Gene annotation identified 1551 unique eccDNA genes including cancer driver genes and genes involved in protein production. Furthermore, RNA-seq data is integrated to identify transcriptionally active eccDNA genes.

Abstract Background Volatile components are important secondary metabolites essential to fruit aroma quality, thus, in the past decades many studies have been extensively performed in clarifying fruit aroma formation. However, aroma components and biosynthesis in the fruit of Binzi (Malus pumila × Malus asiatica), an old local species with attractive aroma remain unknown. Results We investigated two Binzi cultivars, ‘Xiangbinzi’ (here named high-fragrant Binzi, ‘HFBZ’) and ‘Hulabin’ (here named low-fragrant Binzi, ‘LFBZ’) by monitoring the variation of volatiles and their precursors by Gas Chromatography–Mass Spectrometer (GC–MS), as well as their related genes by RNA-seq during post-harvest ripening. We firstly confirmed that ‘HFBZ’ and ‘LFBZ’ fruit showed respiratory climacteric by detecting respiratory rate and ethylene emission during post-harvest; found that esters were the major aroma components in ‘HFBZ’ fruit, and hexyl 2-methylbutyrate was responsible for the ‘fruity’ note and most potent aroma component, followed by ethyl acetate, ethyl butanoate, (E)-2-hexenal, and 1-hexanol. Regarding aroma synthesis, fatty acid metabolism seemed to be more important than amino acid metabolism for aroma synthesis in ‘HFBZ’ fruit. Based on RNA-seq and quantitative reverse transcription PCR (RT-qPCR), LOX2a, LOX5a, ADH1, and AAT1 genes are pointed to the LOX pathway, which may play a vital role in the aroma formation of ‘HFBZ’ fruit. Conclusion Our study firstly investigated the aroma components and related genes of Binzi fruit, and provided an insight into the fragrant nature of Malus species.

Abstract This paper proposes a three‐stage algorithm based on clustering decomposition and task allocation—improved clustering planning algorithm (iK‐iD‐N), aiming at the optimization task allocation problem of drones in actual application to meet the task demand constraints. The algorithm solves the problem of the number of drones demanded and the initial delivery range of each drone by introducing dual‐objective planning into the clustering decomposition. Combining improved Dijkstra algorithm (iK‐D) with neighbourhood insertion algorithm into task allocation, to get high‐quality solutions and solve efficiently. Compared with the existing ant colony algorithm, the iK‐iD‐N algorithm proposed in this paper is more efficient and can obtain the best and stable solutions while evenly distributing tasks. Then it is compared with the improved clustering algorithm combined with the basic iK‐D to get better solutions of the iK‐iD‐N algorithm at any time, and compared with the basic clustering algorithm with the improved task allocation algorithm (K‐iD‐N) that iK‐ iD‐N can get a better solution with high probability. The thesis also simulates and analyzes the impact of uncertainty requirements on the solutions based on drone demand and task allocation models, and discusses the impact of drone load capability and endurance capability constraints on the final solutions.

Objectives To determine the relationship between chemotherapy dose delay/reduction with progression-free survival (PFS) and overall survival (OS) in colorectal cancer patients treated with FOLFIRI based first-line chemotherapy in real-world retrospectively study. Methods We identified 144 eligible patients with advanced CRC who received FOLFIRI as first-line based treatment. The study protocol was submitted to the institutional review board and was exempted. Dose delay was defined as an average delay of more than 3 days (>3 days vs. ≤3 days) from the intended date. Dose reduction (actual dose/standard dose * 100%) ≤85% was considered as chemotherapy reduction in the chemotherapy dose relative to the standard (mg/m2) regimen for all cycles. Relative dose intensity (RDI) ≤80% was described as chemotherapy reduction. OS and PFS were measured using Kaplan–Meier and Cox proportional hazard models. Results There were 114 patients with chemotherapy dose delay (dose delay >3 days). PFS of patients without dose delay had better survival than patients with dose delay (p = 0.002). There were 28.47% patients treated with dose reduction of 5-Fu. PFS and OS were better in patients without 5-Fu dose reduction than in patients with 5-Fu dose reduction with p values of 0.024 and

IntroductionThe aim of this study was to examine the perceptions and experiences of male patients with alcoholic pancreatitis after healing regarding alcohol withdrawal and life management.MethodsThis study used a qualitative descriptive design, and participants were selected by purposive sampling from two tertiary care hospitals in Shandong Province, China. Semi-structured in-depth interviews were conducted with 18 male patients discharged from the gastroenterology department who had recovered from alcoholic pancreatitis. Colaizzi’s method was used to analyze the interview data, and the findings were reported using COREQ criteria.ResultsBy analyzing the interview data, we summarized five themes, (1) the dilemma of sobriety, (2) role change, (3) illness status, (4) family influence, and (5) life management.ConclusionBy profiling the perceptions and experiences of post-healing alcoholic pancreatitis patients’ alcohol cessation and life management in men, it helps to grasp the details of alcohol cessation and health direction of patients’ home management, which provides more directional guidance to help patients maintain positive and good lifestyle habits and active management awareness, followed by targeted personalized interventions to provide patients with knowledge of disease care and health management.

Cancer is one of the important factors threatening human health. Hence, it is essential to create novel potent drugs to treat it. Due to the strong correlation among histone deacetylase1 (HDAC1), speckle-type POZ protein (SPOP) and cancers, dual inhibition of HDAC1 and SPOP may be a promising strategy for cancer treatment. In this study, we successfully identified four potential dual-targeting HDAC1/SPOP candidate compounds with structure-based virtual screening. In vitro inhibition experiments confirmed that the four compounds had dual inhibitory effects on HDAC1 and SPOP. Among them, compound HS-2 had a stronger inhibitory effect on HDAC1 and SPOP than the positive controls. Further molecular dynamics simulations indicated that HS-2 could stably bind to HDAC1 and SPOP. In addition, MTT assay indicated that HS-2 inhibited the growth of tumor cells in the micromolar range. In vivo evaluation showed that HS-2 could obviously inhibit the growth of tumor in nude mice without obvious toxicity. These findings suggest that HS-2 is a novel and potent dual-targeting HDAC1/SPOP inhibitor for cancer treatment.

Sperm cryopreservation is a valuable tool for breeding, conservation, and genetic improvement in aquatic resources, while oxidative damage will cause a decline in sperm quality during this progress. Melatonin (MT), a natural antioxidant hormone, is used as an additive in sperm cryopreservation to reduce cellular damage from oxidative stress. Here, we aimed to investigate the effect of adding MT to the freezing medium in sperm cryopreservation of brown-marbled grouper (Epinephelus fuscoguttatus). Different concentrations of MT (0, 0.1, 0.25, and 0.5 mg/mL) were tested. We evaluated sperm motility, viability, apoptosis, mitochondrial membrane potential (MMP), and fertilization ability to assess the effects of MT supplementation. Our results demonstrated that the addition of MT to the extender improved the post-thaw motility, MMP, and fertilization ability of brown-marbled grouper sperm. The total motility, curvilinear velocity, straight linear velocity, and average path velocity in MT-treated groups (0.1 and 0.25 mg/mL) exhibited significantly higher values than that of the control group. A higher MMP (p < 0.05) was observed in the group treated with 0.25 mg/mL MT, suggesting that supplementation of MT in the extender might be able to protect mitochondrial membrane integrity effectively. Regarding fertilizing ability, 0.25 mg/mL MT yielded a significantly higher hatching rate than the control. An adverse effect was found with the concentration of MT up to 0.5 mg/mL, suggesting the possible toxicity of a high-dose addition. In this study, we optimized the sperm cryopreservation protocol of brown-marbled grouper, which might be valuable for sperm cryopreservation and sample commercialization of groupers and other fish.

African swine fever (ASF) is a lethal contagious viral disease of domestic pigs and wild boars caused by the African swine fever virus (ASFV). The pandemic spread of ASF has caused severe effects on the global pig industry. Whole-genome sequencing provides crucial information for virus strain characterization, epidemiology analysis and vaccine development. Here, we evaluated the performance of next-generation sequencing (NGS) in generating ASFV genome sequences from clinical samples. Thirty-four ASFV-positive field samples including spleen, lymph node, lung, liver and blood with a range of Ct values from 14.73 to 25.95 were sequenced. For different tissue samples collected from the same sick pigs, the proportion of ASFV reads obtained from the spleen samples was 3.69–9.86 times higher than other tissues. For the high-viral-load spleen samples (Ct < 20), a minimum of a 99.8% breadth of ≥10× coverage was revealed for all the samples. For the spleen samples with Ct ≥ 20, 6/12 samples had a minimum of a 99.8% breadth of ≥10× coverage. A high average depth of sequencing coverage was also achieved from the blood samples. According to our results, high-quality ASFV whole-genome sequences could be obtained from the spleen or blood samples with Ct < 20. The high-quality ASFV genome sequence generated in this study was further used for the high-resolution phylogenetic analysis of the ASFV genomes in the early stage of the ASF epidemic in China. Our study demonstrates that NGS may act as a useful tool for efficient ASFV genome characterization, providing valuable information for disease control.

Cracks inside urban underground comprehensive pipe galleries are small and their characteristics are not obvious. Due to low lighting and large shadow areas, the differentiation between the cracks and background in an image is low. Most current semantic segmentation methods focus on overall segmentation and have a large perceptual range. However, for urban underground comprehensive pipe gallery crack segmentation tasks, it is difficult to pay attention to the detailed features of local edges to obtain accurate segmentation results. A Global Attention Segmentation Network (GA-SegNet) is proposed in this paper. The GA-SegNet is designed to perform semantic segmentation by incorporating global attention mechanisms. In order to perform precise pixel classification in the image, a residual separable convolution attention model is employed in an encoder to extract features at multiple scales. A global attention upsample model (GAM) is utilized in a decoder to enhance the connection between shallow-level features and deep abstract features, which could increase the attention of the network towards small cracks. By employing a balanced loss function, the contribution of crack pixels is increased while reducing the focus on background pixels in the overall loss. This approach aims to improve the segmentation accuracy of cracks. The comparative experimental results with other classic models show that the GA SegNet model proposed in this study has better segmentation performance and multiple evaluation indicators, and has advantages in segmentation accuracy and efficiency.

Four full-scale specimens were constructed, including two hybrid precast specimens with a haunch (height: 150 mm, PUT-H) and without a haunch (PUT). Additionally, two cast-in-place (CIP) comparative specimens (referred to as RUT-H and RUT) were included, all of which underwent reversed cyclic loading. The results showed that the four specimens suffered flexural damage at the ends of the sidewall and displayed similar hysteresis loops shapes. The bearing capacity of the PUT specimen was 2.7% higher than that of the RUT, while the bearing capacity of the PUT-H specimen was 8.5% lower than that of the RUT-H. Additionally, the displacement ductility values of the precast specimens PUT and PUT-H were 2.98 and 2.46, respectively, which are 11.3% and 3.53% lower than those of the corresponding CIP specimens. The haunch increases the local stiffness of the component, exerting a notable influence on the bearing capacity and displacement ductility of the specimens, increasing the bearing capacity by 20% and decreasing the ductility by 21%. Moreover, an assessment conducted using the criteria outlined in ACI 374.1-05 indicated that the four specimens exhibit excellent seismic performance.

In order to reveal the main composition of walnut globulin and its antioxidant activity in vitro, defatted walnut meal was used as raw material to separate and purify the globulin. And 2,2'-azido-bis(3-ethylbenzothiazoline-6-sulfonic acid) (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), ABTS) cationic radical scavenging ability was used to evaluate its antioxidant capacity, after further defatting, the crude walnut globulin extract was extracted according to the Osborne fractionation method, and then the main protein components were separated and purified by HiTrapTM CaptoTM Q anion exchange column and SephacrylTM S 100HR gel filtration column. The results showed that the prepared globulin protein content was 51.53%, accounting for 15.3% of the walnut protein, and the isoelectric point was 3.8. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the molecular weight of the purified main protein component was 10.1 kDa. The major protein component in the active state consists of a 7S globulin vicilin Car i 2.0101 and 2S albumin. It was found that both crude globulin extract and purified protein component had good scavenging ability against ABTS+·, with IC50 values of 0.302 and 0.075 mg/mL, respectively, indicating that the scavenging ability of purified protein component was increased by more than 4 times. The research results could provide a theoretical basis for the development and utilization of walnut globulin.

Low temperature inhibits the regeneration of amputated tails of Gekko japonicus by influencing the energy sensory Akt/mTOR pathway, which is also modulated by injury-induced Wnt signal.

Abstract Background Research shows that the clinical learning environment can affect medical learners’ levels of empathy and formation of professional identity. However, few studies examined the impacts of early exposure to the clinical learning environment on first-year nursing students’ empathy levels and professional identity perceptions. Aim This study aimed to explore effects of initial contact with the clinical learning environment on first-year nursing students’ empathy levels and perceptions of professional identity. Methods This is a mixed-methods study conducted in a medical university and its affiliated hospital in Northeast China. For quantitative analysis, 220 first-year nursing students finished Interpersonal Reactivity Index (IRI) twice before and after their five-day clinical placement in the hospital in June, 2021. Paired samples t tests were used to explore the changes in first-year nursing students’ cognitive empathy, affective empathy and total empathy levels as measured by IRI before and after the clinical placement. For qualitative analysis, 15 first-year nursing students’ diary recording their clinical learning experiences were analyzed. An inductive thematic analysis approach was adopted to extract themes from the content on professional identity in nursing students’ diary. Results After the five-day clinical placement, first-year nursing students’ cognitive empathy, affective empathy and total empathy levels all increased. Five themes emerged regarding nursing students’ perceptions of professional identity: (1) Love for the nursing profession; (2) Multiple roles nurses play; (3) Personal characteristics a good nurse needs to have; (4) Deeper understanding of the nursing profession; (5) New understanding of the relationships between patients and nurses, between patients and doctors, and between doctors and nurses. Conclusions First-year nursing students’ initial contact with the clinical learning environment helped them enhance empathy levels and shape professional identity. Nursing educators may consider providing nursing students with opportunities of early exposure to the clinical learning setting to cultivate their empathy and develop their professional identity.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) contributes to the global epidemic of metabolic syndrome and is considered a prelude to end-stage liver diseases such as cirrhosis and hepatocellular carcinoma. During NAFLD pathogenesis, hepatic parenchymal cells (hepatocytes) undergo both morphological and functional changes owing to a rewired transcriptome. The underlying mechanism is not entirely clear. In the present study, we investigated the involvement of early growth response 1 (Egr1) in NAFLD. Methods: Quantitative PCR, Western blotting, and histochemical staining were used to assess gene expression levels. Chromatin immunoprecipitation was used to evaluate protein binding to DNA. NAFLD was evaluated in leptin receptor-deficient (db/db) mice. Results: We report here that Egr1 was upregulated by pro-NAFLD stimuli in vitro and in vivo. Further analysis revealed that serum response factor (SRF) was recruited to the Egr1 promoter and mediated Egr1 transactivation. Importantly, Egr1 depletion markedly mitigated NAFLD in db/db mice. RNA sequencing revealed that Egr1 knockdown in hepatocytes, on the one hand, boosted fatty acid oxidation (FAO) and, on the other hand, suppressed the synthesis of chemoattractants. Mechanistically, Egr1 interacted with peroxisome proliferator-activated receptor α (PPARα) to repress PPARα-dependent transcription of FAO genes by recruiting its co-repressor NGFI-A binding protein 1 (Nab1), which potentially led to promoter deacetylation of FAO genes. Conclusions: Our data identify Egr1 as a novel modulator of NAFLD and a potential target for NAFLD intervention. Impact and Implications: Non-alcoholic fatty liver disease (NAFLD) precedes cirrhosis and hepatocellular carcinoma. In this paper, we describe a novel mechanism whereby early growth response 1 (Egr1), a transcription factor, contributes to NAFLD pathogenesis by regulating fatty acid oxidation. Our data provide novel insights and translational potential for NAFLD intervention.

Colorectal cancer (CRC) is a common digestive tract tumor worldwide. Specific microorganisms, including Fusobacterium nucleatum (F. nucleatum) and Escherichia coli (E. coli), are abundant in colonic mucosa and can promote the cancer progression and malignancy. Therefore, a therapeutic strategy is proposed to deliver effective drugs to colorectum for both anticancer and antibacteria. Here we used thin-film dispersion method to encapsulate hemiprotonic phenanthroline-phenanthroline+ (ph-ph+) into nanomicelle. The results showed that the drug-loading nanomicelle had good dispersion, and the particle size was about 28 nm. In vitro assay indicated that the nanomicelle was active against CRC-related obligate and facultative anaerobes. In human CRC cells, the nanomicelle could effectively inhibit cell proliferation and induce apoptosis. In vivo distribution showed that the nanomicelle could release ph-ph+ mainly in the colorectum. In CRC model mice, the nanomicelle significantly reduced tumor number and volume, and decreased the bacteria load and colorectal inflammation. Together, the study identifies that the ph-ph+nanomicelle has the potential to apply in treating CRC, and also suggests that anticancer combined with antimicrobial therapy would be a feasible way for CRC therapy.

BackgroundAccurate preoperative assessment of surgical difficulty is crucial to the success of the surgery and patient safety. This study aimed to evaluate the difficulty for endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) using multiple machine learning (ML) algorithms.MethodsFrom December 2010 to December 2022, 555 patients with gGISTs in multi-centers were retrospectively studied and assigned to a training, validation, and test cohort. A difficult case was defined as meeting one of the following criteria: an operative time ≥ 90 min, severe intraoperative bleeding, or conversion to laparoscopic resection. Five types of algorithms were employed in building models, including traditional logistic regression (LR) and automated machine learning (AutoML) analysis (gradient boost machine (GBM), deep neural net (DL), generalized linear model (GLM), and default random forest (DRF)). We assessed the performance of the models using the areas under the receiver operating characteristic curves (AUC), the calibration curve, and the decision curve analysis (DCA) based on LR, as well as feature importance, SHapley Additive exPlanation (SHAP) Plots and Local Interpretable Model Agnostic Explanation (LIME) based on AutoML.ResultsThe GBM model outperformed other models with an AUC of 0.894 in the validation and 0.791 in the test cohorts. Furthermore, the GBM model achieved the highest accuracy among these AutoML models, with 0.935 and 0.911 in the validation and test cohorts, respectively. In addition, it was found that tumor size and endoscopists’ experience were the most prominent features that significantly impacted the AutoML model’s performance in predicting the difficulty for ER of gGISTs.ConclusionThe AutoML model based on the GBM algorithm can accurately predict the difficulty for ER of gGISTs before surgery.

African swine fever virus (ASFV), the etiological agent of African swine fever (ASF), causes deadly hemorrhagic fever in domestic pigs. ASF's high mortality and morbidity have had disastrous effects on the world's swine industry. In recent years, the number of African swine virus strains has increased and presented new challenges for detecting classical ASFV-p72-based viruses. In this study, we observed that the ASFV MGF505-7R gene, a member of the multigene family that can enhance ASFV virulence and pathogenesis, has the potential to be a candidate for vaccine formulations. We also developed a real-time PCR assay based on the ASFV MGF505-7R gene and validated it in multiple aspects. The results indicated that the approach could detect standard plasmids with a sensitivity and a specificity of up to 1 × 101 copies/μL. Moreover, the assay had no cross-reactions with other porcine viruses. In laboratory and clinical settings, the assay can detect ASFV-infected samples at an early stage (4 hpi) and show a consistency of 92.56% when compared with classical ASFV detection in clinically ASFV-infected materials. This study's results also indicated that the TaqMan-based quantitative real-time PCR assay we developed for detecting the ASFV MGF505-7R gene is both sensitive and specific. This assay can provide a quick and accurate method for detecting ASFV and has the potential to be used as an optional tool for screening and monitoring ASF outbreaks.