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Cell surface receptors, including erythropoietin-producing hepatocellular A4 (EphA4), are important in regulating hippocampal synapse loss, which is the key driver of memory decline in Alzheimer's disease (AD). However, the cell-specific roles and mechanisms of EphA4 are unclear. Here, we show that EphA4 expression is elevated in hippocampal CA1 astrocytes in AD conditions. Specific knockout of astrocytic EphA4 ameliorates excitatory synapse loss in the hippocampus in AD transgenic mouse models. Single-nucleus RNA sequencing analysis revealed that EphA4 inhibition specifically decreases a reactive astrocyte subpopulation with enriched complement signaling, which is associated with synapse elimination by astrocytes in AD. Importantly, astrocytic EphA4 knockout in an AD transgenic mouse model decreases complement tagging on excitatory synapses and excitatory synapses within astrocytes. These findings suggest an important role of EphA4 in the astrocyte-mediated elimination of excitatory synapses in AD and highlight the crucial role of astrocytes in hippocampal synapse maintenance in AD. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the postoperative safety, long-term survival, and postoperative peritoneal metastases (PPM) rate associated with laparoscopic surgery (LS) for T4 colon cancer. Materials and methods: After propensity score matching, there were 68 patients in each of the LS and Open surgery groups. The primary outcomes were the 3-year OS, DFS, and PPM rates. Results: After matching, 68 patients in each of the groups. The LS group had a higher cumulative 3-year peritoneal metastasis rate (19.8% vs. 6.7%, P =.036), while the 3-year OS (82.3% vs. 83.8%, P =.750) and 2-year DFS (69.0% vs. 75.7%, P =.310) showed no significant difference, compared to the open surgery group. The LS group had a significantly longer operation time (201 ± 85.7 min vs. 164 ± 65.9 min, P =.008) but less postoperative complications (P =.036). Additionally, patients in the LS group removed gastric tube more quickly (1.91 ± 1.18 days vs. 2.69 ± 2.41 days, P =.048). The multivariate analysis revealed that LS (HR = 3.496, 95% CI = 1.108—11.030, P =.033), underweight (HR = 11.650, 95% CI = 2.155—62.990, P =.004), and lymphovascular invasion (HR = 3.123, 95% CI = 1.010—9.664, P =.048) were all predictive factors of PPM. For the pN + subgroup, the 3-year cumulative PPM rate was 29.6% in the LS group, significantly higher than 15.3% in the open group (P =.029), but there was no significant difference after PSM (P =.100). Conclusion: LS offers faster postoperative recovery and comparable long-term survival outcomes. Therefore, it should remain a viable option for locally advanced T4 colon cancer. However, it is crucial to fully recognize the potential risk of increased PPM associated with LS, especially in patients with preoperative suspicion of positive lymph nodes. Further multicenter prospective studies are necessary to validate the potential risks of LS and gain insight into treatment efficacy in different patient populations. In addition, future studies should assess prognosis based on the grade and extent of peritoneal dissemination to provide a more nuanced understanding. [ABSTRACT FROM AUTHOR]

A heparinase III (NsHep-III) from Niabella sp. was identified, cloned, and expressed as soluble form in E. coli BL21 (DE3). With heparin as substrate, the maximum activity of NsHep-III of 90.0 U·mg− 1 was achieved at pH 7.1 Tris-HCl (containing 15 mM Mg2+) and 30oC. The half-life of NsHep-III was determined to be 5 h at 30oC. The interactions between NsHep-III and substrates were studied by molecular docking. The combination of NsHep-III and a heparinase I from Bacteroides eggthii (BeHep-I) was employed to cleave heparin. Analysis of the enzymatic products of NsHep-III by SAX-HPLC showed seven different modified disaccharides, indicating that NsHep-III has a wide range of substrate specificity. The results of GPC analysis demonstrated that the average molecular weight of the product of heparin cleavage by the combination of NsHep-III/BeHep-I was reduced to 3969 Da, which accounted for 90% of all the components, and complied with the requirements of the European Pharmacopoeia. NsHep-III has notable activity and efficiency in cleaving heparin, which is potentially useful for the industrial production of low molecular weight heparin. [ABSTRACT FROM AUTHOR]

Formolase, a thiamine pyrophosphate (TPP)-dependent enzyme, catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. It has many important functions in the biosynthesis of carbon-based compounds and utilization of CO2. However, the enzyme has low activity and stability in the catalytic process, resulting in high cost in the applications. To improve the stability, formolase was immobilized onto magnetic nanoparticles, which were designed to have functional epoxy groups for covalently binding the enzyme. In the immobilization, effects of pH, temperature, and cofactor TPP on the immobilization were investigated and optimized. The results showed that the retention activity of immobilized formolase was highly related to TPP. In the presence of TPP, the specific activity of the immobilized formolase was 6.8 times higher than that without TPP. The optimal immobilization conditions were as follows: a temperature of 20 °C, a pH of 7.0, an immobilization time of 8 h, and an enzyme loading of 20 mg/g. Molecular docking was used to analyze the effect of TPP on the stabilization of the enzyme in the immobilization, which indicated that TTP could stabilize the enzyme structure during the immobilization. The stabilization effect of TPP could be a reference in the immobilization of other enzymes with TPP as the cofactor. [ABSTRACT FROM AUTHOR]

Mexel®432 is a surfactant-like substance that is a biosuppressant against marine fouling organisms. Therefore, to study the toxic effect of Mexel®432 on marine organisms, the wrinkled abalone and echinococcus was exposed to concentrations of 0.175 mg·L-1, 0.350 mg·L-1, 0.700 mg·L-1, 0.275 mg·L-1, 0.550 mg·L-1, 1.100 mg·L-1 Mexel®432 solution, and single-cell gel electrophoresis (comet experiment) was used to detect different exposure times (0, 10, 20 d) DNA damage effect of digestive gland cells and echinococcus pallidae intestinal cells in wrinkled disc abalone, and tail DNA content, tail length, tail distance, and Olive tail distance were used as evaluation indexes. The results showed that different concentrations of Mexel®432 could cause DNA disintegration and tailing in digestive gland cells and intestinal cells in a short period of time (10 d), and with the increase of Mexel®432 concentration and the extension of exposure time, DNA deformation was obvious, the fragmentation increased, and the degree of damage was aggravated. When the concentration of Mexel®432 reaches 0.350 mg·L-1, it produces certain genotoxicity to the digestive gland cells of wrinkled abalone, and when the concentration of Mexel®432 reaches 1.1000 mg·L-1, it also has certain genotoxicity to the intestinal cells of Mesocentrotus nudus. The experimental results showed that Mexel®432 had a significant dose effect relationship on DNA damage in the cells of two biological tissues. [ABSTRACT FROM AUTHOR]

Heat stress poses a significant threat to grain yield. As an α2 subunit of the 26S proteasome, TT1 has been shown to act as a critical regulator of rice heat tolerance. However, the heat tolerance mechanisms mediated by TT1 remain elusive. In this study, we unveiled that small ubiquitin-like modifier (SUMO)-conjugating enzyme 1 (SCE1), which interacts with TT1 and acts as a downstream component of TT1, is engaged in TT1-mediated 26S proteasome degradation. We showed that SCE1 functions as a negative regulator of heat tolerance in rice, which is associated with its ubiquitination modification. Furthermore, we observed that small heat-shock proteins (sHSPs) such as Hsp24.1 and Hsp40 can undergo SUMOylation mediated by SCE1, leading to increased accumulation of sHSPs in the absence of SCE1. Reducing protein levels of SCE1 significantly enhanced grain yield under high-temperature stress by improving seed-setting rate and rice grain filling capacity. Taken together, these results uncover the critical role of SCE1 in the TT1-mediated heat tolerance pathway by regulating the abundance of sHSPs and SUMOylation, and ultimately modulating rice heat tolerance. These findings underscore the great potential of the TT1–SCE1 module in improving the heat tolerance of crops. This study reveals the pivotal role of SCE1, a SUMO E2 enzyme in TT1-mediated thermotolerance by modulating the abundance of small heat-shock proteins and SUMO modification. The findings implicate the great potential of the TT1–SCE1 module in integrating ubiquitination and SUMOylation, thereby serving as a valuable genetic target for enhancing heat tolerance in crops. [ABSTRACT FROM AUTHOR]

The hybrid excitation eddy current damper is a novel principle damper characterized by high reliability, simple structure, and controllable magnetic field. Under intensive impact loads, hybrid excitation electromagnetic damping can induce demagnetization effects, resulting in significant fluctuations of the electromagnetic damping force at 6-8 ms. To mitigate this phenomenon, this study established a finite element model of the hybrid excitation damper using COMSOL and developed a control module based on a BP neural network in Simulink. Through co-simulation of COMSOL and Simulink, the difference between the maximum and minimum electromagnetic damping force at 6-8ms is reduced from 45 kN to 5 kN. This research provides valuable technical references for the optimization and practical application of eddy current dampers. [ABSTRACT FROM AUTHOR]

Rice grain number is a crucial agronomic trait impacting yield. In this study, we characterized a quantitative trait locus (QTL), GRAIN NUMBER 1.1 (GN1.1), which encodes a Flowering Locus T‐like1 (FT‐L1) protein and acts as a negative regulator of grain number in rice. The elite allele GN1.1B, derived from the Oryza indica variety, BF3‐104, exhibits a 14.6% increase in grain yield compared with the O. japonica variety, Nipponbare, based on plot yield tests. We demonstrated that GN1.1 interacted with and enhanced the stability of ADP‐ribosylation factor (Arf)‐GTPase‐activating protein (Gap), OsZAC. Loss of function of OsZAC results in increased grain number. Based on our data, we propose that GN1.1B facilitates the elevation of auxin content in young rice panicles by affecting polar auxin transport (PAT) through interaction with OsZAC. Our study unveils the pivotal role of the GN1.1 locus in rice panicle development and presents a novel, promising allele for enhancing rice grain yield through genetic improvement. [ABSTRACT FROM AUTHOR]

There has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, and potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, highlighting the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals who successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing a reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas. [ABSTRACT FROM AUTHOR]

Small-object detection has become a hot issue in complex traffic scenes. A global context multilevel fusion attention detection method for small-object detection is proposed in this paper. First, a global context feature fusion network model is designed with cross-stage partial DarkNet (CSPDarkNet) as the backbone to capture the global context semantic information and refine the local information. To further refine the local information, a hierarchical hybrid attention module is designed that uses global average pooling to obtain the H direction weight matrix, fuse it with the W direction weight matrix, fuse the results with the channel direction weight matrix, and finally obtain a feature map with multidimensional weights. Second, to increase the receptive field of the multidimensional weighted feature map, atrous convolution is added in the spatial pyramid pooling (SPP) module. To improve the small-object detection accuracy, a 160 × 160 small-object detection head is added. Finally, the Focal-EIOU (efficient intersection over union) loss function is adopted to better converge in the training process. Full experiments have been carried out in the open traffic datasets Cityscapes and KITTI, and this paper proposed model is the best-performing method. [ABSTRACT FROM AUTHOR]

The myosin heavy chain 9 (MYH9) gene, located on human chromosome 22, encodes non-muscle myosin heavy chain IIA (NM IIA). This protein is essential to various cellular events, such as generating intracellular chemomechanical force and facilitating the movement of the actin cytoskeleton. Mutations associated with thrombocytopenia in autosomal dominant diseases first highlighted the significance of the MYH9 gene. In recent years, numerous studies have demonstrated the pivotal roles of MYH9 in various cancers. However, its effects on cancer are intricate and not fully comprehended. Furthermore, the elevated expression of MYH9 in certain malignancies suggests its potential as a target for tumor therapy. Nonetheless, there is a paucity of literature summarizing MYH9's role in tumors and the therapeutic strategies centered on it, necessitating a systematic analysis. This paper comprehensively reviews and analyzes the pertinent literature in this domain, elucidating the fundamental structural characteristics, biological functions, and the nexus between MYH9 and tumors. The mechanisms through which MYH9 contributes to tumor development and its multifaceted roles in the tumorigenic process are also explored. Additionally, we discuss the relationship between MYH9-related diseases (MYH9-RD) and tumors and also summarize tumor therapeutic approaches targeting MYH9. The potential clinical applications of studying the MYH9 gene include improving early diagnosis, clinical staging, and prognosis of tumors. This paper is anticipated to provide novel insights for tumor therapy. [ABSTRACT FROM AUTHOR]

Background: The widespread use of smartphones has significantly increased smartphone addiction among college students, especially during the COVID-19 pandemic. Since the COVID-19 outbreak, university campuses in mainland China have strictly followed the Chinese government's strict quarantine policy, including closed campus management, prohibitions against gatherings, and social distancing, increasing student loneliness and anxiety and thus increasing the risk of smartphone addiction. Extant Studies have revealed that social isolation is a prominent predictor of smartphone addiction but have failed to systematically explore the complex relationship between social isolation and smartphone addiction in the context of COVID-19; therefore, the underlying mechanisms of these factors in the post-pandemic era are unclear. Objective: This study is the first attempt to consider loneliness, COVID-19 anxiety and social isolation as a whole and to clarify the underlying mechanisms of social isolation and smartphone addiction by constructing a multiple mediating model. Method: This study included students enrolled at eight higher education institutions in Conghua District (Guangzhou city). Quota proportional sampling was adopted, 900 self-report questionnaires were distributed through the WeChat groups of these universities from December 10 to December 15, 2022, and 868 valid questionnaires (620 females, 248 males) were ultimately obtained. Results: The direct effect of social isolation on smartphone addiction was significant, and loneliness and COVID-19 anxiety mediated the association between social isolation and smartphone addiction in both parallel and sequential ways. Moreover, a reverse mediation model with COVID-19 anxiety as the first mediator and loneliness as the second mediator was found. Conclusion: College students who experience social isolation are at greater risk for smartphone addiction, and the core factor leading to their smartphone addiction is the subjective psychological state triggered by campus isolation and social distancing, such as loneliness and anxiety. These risky behaviors of people should receive extra attention, and psychological factors such as loneliness and COVID-19 anxiety should be considered in future therapies aimed at reducing addiction. [ABSTRACT FROM AUTHOR]

Light pollution imposes significant and far-reaching adverse effects on human society, necessitating its stringent regulation. However, intervention policies could be customized to suit the unique characteristics of each region, taking into account local conditions. To address this challenge, we have developed a comprehensive light pollution risk assessment model using a combination of objective and subjective weighting methods, including analytic hierarchy process (AHP), independent weighting method (IWM), entropy weight method (EWM), coefficient of variation (CV), criteria importance through intercriteria correlation (CRITIC), and principal component analysis (PCA). This model facilitates a systematic evaluation of light pollution risk levels across diverse regions in China. Subsequently, we have proposed intervention policies targeting light pollution risk reduction and assessed their efficacy using the synthetic control method. Our findings reveal elevated light pollution risk levels in coastal and mountainous regions with heightened concentrations closer to urban centers. Strategies focused on enhancing lighting hardware, optimizing lighting schedules, and upgrading light sources demonstrated the impact on reducing light pollution risk levels (LPRL). This study not only lays a solid theoretical foundation for assessing urban light pollution risks but furnishes empirical evidence to aid relevant authorities in formulating effective light pollution control strategies. [ABSTRACT FROM AUTHOR]

Introduction: The carbon storage service of ecosystems in ecologically fragile areas is highly sensitive to regional land use/land cover (LULC) changes. Predicting changes in regional carbon storage under different LULC scenarios is crucial for land use management decisions and exploring carbon sink potential. This study focuses on the Luan River Basin, a typical ecologically fragile area, to analyze the impact of LULC changes on carbon storage. Methods: The PLUS-InVEST model was employed to simulate LULC patterns for the year 2030 under three scenarios: natural development, cropland protection and urban development, and ecological protection. The model projected the future carbon sink potential of the basin under these scenarios. Results: From 2000 to 2020, carbon storage showed a trend of decrease followed by an increase. By 2030, compared to 2020, carbon storage is projected to increase by 16.97% under the ecological protection scenario and decrease by 22.14% under the cropland protection and urban development scenario. The increase in carbon storage was primarily due to the conversion of cropland and grassland to forestland, while the decrease was mainly associated with the conversion of forestland to grassland and cropland, and the transformation of grassland to cropland and construction land. In the potential LULC scenarios of 2030, certain regions within the basin exhibited unstable carbon sink potential, strongly influenced by LULC changes. These areas were predominantly characterized by artificially cultivated forests, shrubs, and agricultural land. Implementing appropriate forest management measures and optimizing agricultural land management practices are essential to enhance carbon sink potential in these regions. Population density, annual average temperature, and DEM (Digital Elevation Model) were the dominant factors driving the spatial variation of carbon sink potential in the Luan River Basin. Discussion: The research results provide a theoretical basis for rational planning of land use and the enhancement of carbon sink potential in ecologically fragile regions. [ABSTRACT FROM AUTHOR]

This study examines the evolution of immersive journalism and its significant impact on news formats and user experiences through technological mediation. It investigates key technological shifts within the industry, notably the transition from traditional virtual reality to the development of virtual scenes and the increased adoption of multi-source data collection. These advancements have facilitated a transformation of news presentation from two-dimensional to three-dimensional formats, shifting interfaces from tactile to technical, thereby deepening audience engagement and understanding of news content. The methodology employed involves an in-depth analysis of these technological transitions and their implications for journalistic practice. The research assesses the influence of these changes on journalistic objectivity and ethical norms. Findings highlight the dual challenges and opportunities presented by immersive journalism, stressing the necessity for a balanced approach that aligns economic interests with societal responsibilities. The result of this research emphasizes the crucial role of maintaining journalistic integrity amidst the adoption of technological innovations that enhance news reporting. This study contributes to the broader understanding of how immersive technologies can be ethically integrated into journalism to benefit society and enrich public discourse, setting a foundation for future explorations into responsible media practice. [ABSTRACT FROM AUTHOR]

[Objectives] To explore the current situation and effects of online learning from the perspective of students, as well as the learning dynamics, and to explore the online teaching methods. It is possible to put forward relevant suggestions for the problems presented by online teaching, find effective teaching methods, and explore appropriate online teaching methods. [Methods] The nursing students of the 2020, 2021, and 2022 grades of Chengde Nursing Vocational College were selected as the research subjects. A self-made questionnaire survey method was adopted. The questionnaire had 5 items and 44 questions; 3 questions on personal information, 9 questions on the teacher level, 12 questions on the student level, 7 questions on the technical level, and 13 questions on online learning satisfaction. [Results] In the process of online teaching, the cooperation between family and school can be carried out to give full play to the important role of family supervision in online learning and other education, which is conducive to maintaining the discipline of online courses on the Internet, increasing the online learning effect of students, and avoiding the temptation of the Internet to the greatest extent. In the process, we should increase students' self-control in online learning, help students shape realistic goals, and thus improve the effect of online learning. Technical level; increase information-based teaching, enrich teaching content, and introduce virtual simulation software to simulate clinical operations, so as to increase students' interest and enthusiasm in learning. [Conclusions] This study is expected to provide a certain reference for the smooth and efficient development of online teaching and online learning skills. [ABSTRACT FROM AUTHOR]

Introduction: In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles. Methods: Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators. Results: Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA. Conclusion: The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis. [ABSTRACT FROM AUTHOR]

Purpose: Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is a serious complication severely affecting patients' prognoses. We aimed to compare the clinicopathological features and prognosis of synchronous and metachronous BM from NSCLC. Methods: Clinical data of 461 patients with brain metastases from NSCLC who visited the Cancer Hospital of China Medical University from 2005 to 2017 were retrospectively collected. We analyzed the pathophysiological characteristics of synchronous and metachronous BM from NSCLC and survival rates of the patients. Propensity score matching analysis was used to reduce bias between groups. In addition, we used the Kaplan-Meier method for survival analysis, log-rank test to compare survival rates, and Cox proportional hazards regression model for multivariate prognosis analysis. Results: Among 461 patients with BM, the number of people who met the inclusion criteria was 400 cases, and after 1:2 propensity score matching,130 had synchronous BM and 260 had metachronous BM. The survival time was longer for metachronous BM in driver mutation-negative patients with squamous cell carcinoma than synchronous BM. Conversely, metachronous and synchronous BM with gene mutations and adenocarcinoma showed no differences in survival time. Multivariate analysis showed that metachronous BM was an independent prognostic factor for overall survival. Furthermore, the pathological type squamous cell carcinoma and Karnofsky Performance Status score <80 were independent risk factors affecting overall survival. Conclusion: BM status is an independent factor influencing patient outcome. Moreover, synchronous and metachronous BM from NSCLC differ in gene mutation profile, pathological type, and disease progression and hence require different treatments. [ABSTRACT FROM AUTHOR]

With the outbreak of the COVID pandemic, preservice teachers have experienced an unprecedented situation and faced various kinds of issues due to uncertain learning and teaching environments. As a result, they felt insecure and disappointed about their teaching performance during student teaching. Self-efficacy to teach and pedagogical beliefs are crucial elements that influence preservice teachers' teaching performance during student teaching and their professional development in the early stage. This study adopted a quantitative research method to examine the changes in the self-efficacy and pedagogical beliefs of preservice teachers after student teaching during the initial teacher education stage in the Japanese context and how preservice teachers' self-efficacy and pedagogical beliefs changed during the COVID-19 pandemic. A sample of 133 preservice primary teachers in a university in Western Japan was recruited in this study. Two structured surveys were used to collect the data, and factor analyses and paired t-tests were fitted. This study verified the validity and internal consistency of two surveys in the Japanese context. The results showed that the Japanese preservice teachers' self-efficacy made a steeper change after student teaching. Their pedagogical beliefs increased significantly, however, yielded a small effect. The results suggested that student teaching is an essential source of influence on preservice teachers' self-efficacy and pedagogical beliefs. This study contributes to the meaningful application of theories developed in the West to Japan by highlighting the Japanese educational context. This study provides implications for effectively reinforcing preservice teachers' self-efficacy and pedagogical beliefs through developing deeper reflection skills, thus supporting them to overcome various challenges in their future teaching careers. [ABSTRACT FROM AUTHOR]

Amid the discourse on foreign influence investigations in research, this study examines the impact of NIH-initiated investigations starting in 2018 on U.S. scientists' productivity, focusing on those collaborating with Chinese peers. Using publication data from 2010 to 2021, we analyze over 113,000 scientists and find that investigations coincide with reduced productivity for those with China collaborations compared to those with other international collaborators, especially when accounting for publication impact. The decline is particularly pronounced in fields that received greater preinvestigation NIH funding and engaged more in U.S.-China collaborations. Indications of scientist migration and broader scientific progress implications also emerge. We also offer insights into the underlying mechanisms via qualitative interviews. [ABSTRACT FROM AUTHOR]

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Objective: Major pathological response (MPR) helps evaluate the prognosis of patients with lung squamous cell carcinoma (LUSC). However, the clinical factors that affect the achievement of MPR after neoadjuvant chemoimmunotherapy (NCIO) in patients with LUSC remain unclear. This study aimed to explore the clinical factors affecting the MPR after NCIO in patients with potentially resectable LUSC. Methods: This retrospective study included patients with stage IIB-IIIC LUSC who underwent surgical resection after receiving NCIO at a center between March 2020 and November 2022. In addition to the postoperative pathological remission rate, sex, age, body mass index (BMI), smoking history, TNM stage, hematological and imaging test results, and other indicators were examined before NCIO. According to the pathological response rate of the surgically removed tumor tissue, the patients were split into MPR and non-MPR groups. Results: In total, 91 LUSC patients who met the study's eligibility criteria were enrolled: 32 (35%) patients in the non-MPR group and 59 (65%) in the MPR group, which included 43 cases of pathological complete remission (pCR). Pretreatment lymphocyte level (LY) (odds ratio [OR] =5.997), tumor burden (OR=0.958), N classification (OR=15.915), radiographic response (OR=11.590), pulmonary atelectasis (OR=5.413), and PD-L1 expression (OR=1.028) were independently associated with MPR (all P < 0.05). Based on these six independent predictors, we developed a nomogram model of prediction having an area under the curve (AUC) of 0.914 that is simple to apply clinically to predict the MPR. The MPR group showed greater disease-free survival (DFS) than the non-MPR group, according to the survival analysis (P < 0.001). Conclusion: The MPR rate of NCIO for potentially resectable LUSC was 65%. LY, tumor burden, N classification, radiographic response, pulmonary atelectasis, and PD-L1 expression in patients with LUSC before NCIO were the independent and ideal predictors of MPR. The developed nomogram demonstrated a good degree of accuracy and resilience in predicting the MPR following NCIO, indicating that it is a useful tool for assuring customized therapy for patients with possibly resectable LUSC. [ABSTRACT FROM AUTHOR]

Background: Sect. Chrysantha Chang, belonging to the Camellia genus, is one of the rare and precious ornamental plants distinguished by a distinctive array of yellow-toned petals. However, the variation mechanisms of petal color in Sect. Chrysantha Chang remains largely unclear. Methods: We conducted an integrated analysis of metabolome and transcriptome to reveal petal coloration mechanism in three species, which have different yellow tones petals, including C. chuongtsoensis (CZ, golden yellow), C. achrysantha (ZD, light yellow), and C. parvipetala (XB, milk white). Results: A total of 356 flavonoid metabolites were detected, and 295 differential metabolites were screened. The contents of 74 differential metabolites showed an upward trend and 19 metabolites showed a downward trend, among which 11 metabolites were annotated to the KEGG pathway database. We speculated that 10 metabolites were closely related to the deepening of the yellowness. Transcriptome analysis indicated that there were 2,948, 14,018 and 13,366 differentially expressed genes (DEGs) between CZ vs. ZD, CZ vs. XB and ZD vs. XB, respectively. Six key structural genes (CcCHI, CcFLS, CcDFR1, CcDFR2, CcDFR3, and CcCYP75B1) and five candidate transcription factors (MYB22, MYB28, MYB17, EREBP9, and EREBP13) were involved in the regulation of flavonoid metabolites. The findings indicate that flavonoid compounds influence the color intensity of yellow-toned petals in Sect. Chrysantha Chang. Our results provide a new perspective on the molecular mechanisms underlying flower color variation and present potential candidate genes for Camellia breeding. [ABSTRACT FROM AUTHOR]

Bearings, as widely employed supporting components, frequently work in challenging working conditions, leading to diverse fault types. Traditional methods for diagnosing bearing faults primarily center on time–frequency analysis, but this often requires expert experience for accurate fault identification. Conversely, intelligent fault recognition and classification methods frequently lack interpretability. To address this challenge, this paper introduces a convolutional neural network with an attention mechanism method, denoted as CBAM-CNN, for bearing fault diagnosis. This approach incorporates an attention mechanism, creating a Convolutional Block Attention Module (CBAM), to enhance the fault feature extraction capability of the network in the time–frequency domain. In addition, the proposed method integrates a weight visualization module known as the Gradient-Weighted Class Activation Map (Grad-CAM), enhancing the interpretability of the convolutional neural network by generating visual heatmaps on fault time–frequency graphs. The experimental results demonstrate that utilizing the dataset employed in this study, the CBAM-CNN achieves an accuracy of 99.81%, outperforming the Base-CNN with enhanced convergence speed. Furthermore, the analysis of attention weights reveals that this method exhibits distinct focus of attention under various fault types and degrees. The interpretability experiments indicate that the CBAM module balances the weight allocation, emphasizing signal frequency distribution rather than amplitude distribution. Consequently, this mitigates the impact of the signal amplitude on the diagnostic model to some extent. [ABSTRACT FROM AUTHOR]

High electric fields affect the diffusion dynamics of atoms on a metal surface, causing biased surface diffusion that possibly leads to the growth of intensively field emitting protrusions and consequent vacuum breakdown (VBD). The scientific understanding of this process, as well as other fundamental VBD initiation mechanisms, is far from complete. Here we investigate the exact atomic behaviour of metal surfaces exposed to extremely high electric fields using density functional theory (DFT). Previous theories describe the field-surface dynamics in terms of the effective dipole moments and polarizability of surface atoms, disregarding higher-order (hyperpolarizability) terms. The validity of this approximation has been evaluated only for electric fields up to 3 GV/m, due to computational limitations of the plane-wave DFT basis used in previous works. In this work, we test the validity of this approximation for a much wider field range, relevant for VBD and field emission (FE), using Cu nanoparticles as our test structures. We find that although such high fields can change the entire structure of Cu nanoparticles, their energetics are described very precisely by the permanent dipole moment and polarizability terms. Thus, we show that neglecting the hyperpolarizability terms is valid even for field values that exceeds the range that is relevant for intense FE and VBD. This work lays a solid foundation for further developing atomic-level simulation models for electric field-induced surface diffusion on metal surfaces and its effects on protrusion growth and VBD initiation. [ABSTRACT FROM AUTHOR]

Non-specific endonucleases can be used for the digestion of nucleic acids because they hydrolyze DNA/RNA into 3–5 base pairs (bp) length oligonucleotide fragments without strict selectivity. In this work, a novel non-specific endonuclease from Pseudomonas fluorescens (PfNuc) with high activities for both DNA and RNA was successfully cloned and expressed in Escherichia coli. The production of PfNuc in flask scale could be achieved to 1.73 × 106 U/L and 4.82 × 106 U/L for DNA and RNA by investigation of the culture and induction conditions. The characterization of PfNuc indicated that it was Mg2+-dependent and the catalytic activity was enhanced by 3.74 folds for DNA and 1.06 folds for RNA in the presence of 5 mM Mg2+. The specific activity of PfNuc for DNA was 1.44 × 105 U/mg at pH 8.0 and 40 °C, and 3.93 × 105 U/mg for RNA at pH 8.5 and 45 °C. The Km of the enzyme for both DNA and RNA was close to 43 µM. The Vmax was 6.40 × 105 U/mg and 1.11 × 106 U/mg for DNA and RNA, respectively. There was no observed activity loss when PfNuc was stored at 4 °C and − 20 °C after 28 days or 10 repeated freeze–thaw cycles at − 80 °C. Molecular docking revealed that PfNuc formed 17 and 19 hydrogen bonds with single-stranded RNA and double-stranded DNA, respectively. These results could explain the high activity and stability of PfNuc, suggesting its great potential applications in the industry and clinic. [ABSTRACT FROM AUTHOR]

Maire yew (Taxus mairei), an evergreen conifer, has high ornamental and medicinal value. The arils of this species has three different colors. However, the variation mechanisms of arils color formation remains unclear. Here, the gene expression and metabolite concentration were profiled for red (RTM), yellow (YTM), and purple (PTM) arils in different developmental stages. A total of 266 flavonoids and 35 carotenoids were identified. The predominant pigments identified in YTM were epiafzelechin, lutein, and β-Cryptoxanthin, while malvidin-3,5-di-O-glucoside and apigenin played crucial roles in PTM. And significant differential expression was observed among the HCT, DFR, LAR, ANS, crtB, NCED, and CCoAOMT genes across different color arils. During the maturation of yellow arils, the upregulation of HCT was strongly correlated with the accumulation of epiafzelechin. The diminished expression of DFR, LAR, and ANS seemed to inhibit the production of delphinidin-3-O-rutinoside. The decrease in crtB expression and concurrent increase in NCED expression potentially regulate the heightened accumulation of lutein. Meanwhile, the accumulation of β-cryptoxanthin appeared seemed to be positively influenced by NCED. As aril turning purple, the decreased expression of CCoAOMT seemed to facilitate the synthesis of apigenin. The substantial upregulation of DFR promoted the production of malvidin-3,5-di-O-glucoside. Additionally, the overexpression of MYBs may plays the important role in regulating the formation of different colored arils. In total, 14 genes were selected for qRT-PCR validation, the results indicated the reliability of the transcriptome sequences data. Our findings could provide valuable insight into the molecular breeding, development, and application of Maire yew resources. [ABSTRACT FROM AUTHOR]

As a unique and native conifer in China, Platycladus orientalis is widely used in soil erosion control, garden landscapes, timber, and traditional Chinese medicine. However, due to the lack of reference genome and transcriptome, it is limited to the further molecular mechanism research and gene function mining. To develop a full-length reference transcriptome, tissues from five different parts of P. orientalis and four cone developmental stages were sequenced and analyzed by single-molecule real-time (SMRT) sequencing through the PacBio platform in this study. Overall, 37,111 isoforms were detected by PacBio with an N50 length of 2,317 nt, an average length of 1,999 bp, and the GC content of 41.81%. Meanwhile, 36,120 coding sequences, 5,645 simple sequence repeats (SSRs), 1,201 noncoding RNAs (lncRNAs), and 182 alternative splicing (AS) events with five types were identified using the results obtained from the PacBio transcript isoforms. Furthermore, 1,659 transcription factors (TFs) were detected and belonged to 51 TF families. A total of 35,689 transcripts (96.17%) were annotated through the NCBI nr, KOG, Swiss-Prot and KEGG databases, and 385 transcript isoforms related to 8 types of hormones were identified incorporated into plant hormone signal transduction pathways. The assembly and revelation of the full-length transcriptome of P. orientalis offer a pioneering insight for future investigations into gene function and genetic breeding within Platycladus species. [ABSTRACT FROM AUTHOR]

Oxidative stress is one of the main causes of testicular spermatogenesis disorders. Resveratrol (RES) can inhibit oxidative stress levels, reduce germ cell damage, and promote spermatogenesis. To investigate the molecular mechanism by which RES promotes spermatogenesis, the effects of hydrogen peroxide (H2O2) on the pathological damage of mouse testis tissue were assessed. The expression of key genes associated with pyroptosis, apoptosis, and autophagy, and the effects of RES on this process were determined. Experimental mice were divided into three groups with intraperitoneally injection of H2O2 (3 mmol/kg/d), RES (100 mg/kg/d) + H2O2 (3 mmol/kg/d), and normal saline, respectively. The testicular tissues were collected, and the pathological changes were observed by hematoxylin and eosin staining. The ultrastructure was observed using transmission electron microscopy (TEM). The transcriptional levels of pyroptosis, apoptosis, and autophagy-related genes were measured and analyzed by fluorescence quantitative polymerase chain reaction. The results showed that, in the H2O2 group, the basal membrane of spermatogenic tubules was damaged, atrophic, and thin. Interstitial cells were fragmented, and the gap of spermatogenic tubules increased. Compared with the H2O2 group, the pathological damage of testicular tissue structure in the H2O2 + RES group was significantly ameliorated. TEM results showed no evident damage to the cell structure in the control group, while apoptosis, autophagy, and pyroptosis were observed in the testicular tissue of H2O2 and H2O2 + RES groups, where cell damage was less, but apoptotic bodies, autophagosomes, and pyroptosomes were observed. The transcription levels of key pyroptosis genes increased in the H2O2 group but decreased significantly after RES treatment. The results indicated that H2O2 could induce pyroptosis, while RES inhibited pyroptosis and led to the release of inflammatory factors by regulating the expression of genes in signaling pathways. After H2O2 injection, the transcript levels of key apoptosis genes in testicular tissue were lower than those in the control group, while RES promoted the occurrence of H2O2-induced apoptosis, to achieve the purpose of protecting itself from oxidative damage. H2O2 could promote autophagy in mouse testicular tissue. RES enhanced the level of H2O2-induced autophagy, removed the damaged cells in the testicular tissue, and protected the development of the body. This study provided the experimental basis for the study of RES in oxidative damage, pyroptosis, apoptosis, and autophagy, and theoretical guidance and new ideas for drug development and treatment of male reproductive diseases in clinical practice. [ABSTRACT FROM AUTHOR]

Tobacco smoke is the leading risk factor for lung cancer, accounting for over 80% of lung cancer deaths. Reducing the damage of cigarette smoke to the lungs through dietary therapy is currently a research hotspot. It has been reported that cigarette smoke extract induced inflammation and contributed to pyroptosis through the ROS/NLRP3/caspase-1 pathway in human bronchial epithelial cells. To investigate the effect of ginger and snow pear beverage on smoke-induced pyroptosis, ginger, snow pear, loquat, honey, and skimmed milk powder were used to prepare a lung moistening drink with excellent palatability. Male rats were divided into the drink group and control group and exposed to cigarette smoke for 60 days. Blood biochemical indices and organ coefficients were measured, and lung and small intestine tissues were excised for HE staining. The mRNA expression of pyroptosis in the lung tissue was evaluated by fluorescence quantitative polymerase chain reaction (qPCR). The results showed that globulin and urea nitrogen levels were significantly higher in control (C) group than that in beverage (B) group, while the opposite effect was observed for the albumin/globulin ratio and cholesterol level. The changes in the weight of the lung tissue were obvious and significantly higher in group B than that in group C. The histological structure of the lung tissue in group C was abnormal with evidence of significant pathological changes in the alveolar wall and capillary bronchial tube wall along with a few inflammatory cells. The pathological changes in group B showed significantly improved. The small intestinal villus length, intestinal crypt depth, goblet cell number, and V/C value were significantly higher in group B. In addition, the drink significantly reduced the mRNA expression of NLRP3, caspase1, GSDMD, IL-18, and IL-1β genes in the lung tissue. The results indicated that the tested drink exerted protective effects on the lungs and small intestine, which inhibited the release of inflammatory factors from the cellular pyroptosis signaling pathway, alleviated the occurrence of pyroptosis, protected the lung tissue, and reduced the cigarette smoke-induced damage and lesions. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Genetics titled "Application of multi-omics technologies to explore novel biological process and molecular function in immunology and oncology." The editorial discusses the use of multiomics profiling in biomedical studies, which integrates various levels of gene regulation data to gain insights into molecular mechanisms in cancer and immunology. The editorial highlights specific studies that apply multiomics analyses to lung cancer, oral squamous cell carcinoma, and diffuse large B-cell lymphoma, providing new insights into these diseases. The authors emphasize the potential of multiomics technologies for personalized therapy and improved understanding of complex diseases. [Extracted from the article]

Microorganisms are important sources of lipolytic enzymes with characteristics for wide promising usages in the specific industrial biotechnology. The cellulolytic myxobacterium Sorangium cellulosum is rich of lipolytic enzymes in the genome, but little has been investigated. Here, we discerned 406 potential lipolytic enzymes in 13 sequenced S. cellulosum genomes. These lipolytic enzymes belonged to 12 families, and most are novel with low identities (14-37%) to those reported. We characterized a new carboxylesterase, LipB, from the alkaline-adaptive So0157-2. This enzyme, belonging to family VIII, hydrolyzed glyceryl tributyrate and p-nitrophenyl esters with short chain fatty acids (=C12), and exhibited the highest activity against p-nitrophenyl butyrate. It retained over 50% of the activities in a broad temperature range (from 20°C to 60°C), alkaline conditions (pH 8.0-9.5), and the enzymatic activity was stable with methanol, ethanol and isopropanol, and stimulated significantly in the presence of 5 mM Ni2+. LipB also exhibited ß-lactamase activity on nitrocefin, but not ampicillin, cefotaxime and imipenem. The bioinformatic analysis and specific enzymatic characteristics indicate that S. cellulosum is a promising resource to explore lipolytic enzymes for industrial adaptations. [ABSTRACT FROM AUTHOR]

Improved chondrogenic differentiation of mesenchymal stem cells (MSCs) by genetic regulation is a potential method for regenerating articular cartilage. LncRNA MIR22HG has been proven to accelerate osteogenic differentiation, but the regulation mechanism of chondrogenic differentiation is still unclear. Human adipose-derived stem cells (hADSCs) have been widely utilised for bone tissue engineering applications. The present study aimed to examine the effect of MIR22HG on the chondrogenic differentiation of hADSCs. The results confirmed that MIR22HG was downregulated in the process of chondrogenic differentiation. Subsequently, gain- and loss-of-function of MIR22HG experiments showed that the overexpression of MIR22HG suppressed the deposition of cartilage matrix proteoglycans and decreased the expression of cartilage-related markers (e.g. Sox9, ACAN and Col2A1), whereas the knockdown of MIR22HG had the opposite effect. MIR22HG could bind to CTCF (CCCTC-binding factor), and CTCF could bind to the CRLF1 (cytokine receptor-like factor 1) promoter and upregulate CRLF1 gene expression. Besides, inhibition of CRLF1 can reverse the effect of MIR22HG on cell chondrogenic differentiation of hADSCs. Taken together, our outcomes reveal that MIR22HG suppressed chondrogenic differentiation by interaction with CTCF to stabilise CRLF1. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is recognized as a pathogen associated with several gastrointestinal diseases. The current treatments exhibit numerous drawbacks, including antibiotic resistance. H. pylori can adhere to and colonize the gastric mucosa through H. pylori adhesin A (HpaA), and antibodies against HpaA may be an effective therapeutic approach. The variable domain of immunoglobulin new antigen receptor (VNAR) is a novel type of single-domain antibody with a small size, good stability, and easy manufacturability. This study isolated VNARs against HpaA from an immune shark VNAR phage display library. The VNARs can bind both recombinant and native HpaA proteins. The VNARs, 2A2 and 3D6, showed high binding affinities to HpaA with different epitopes. Furthermore, homodimeric bivalent VNARs, biNb-2A2 and biNb-3D6, were constructed to enhance the binding affinity. The biNb-2A2 and biNb-3D6 had excellent stability at gastrointestinal pH conditions. Finally, a sandwich ELISA assay was developed to quantify the HpaA protein using BiNb-2A2 as the capture antibody and BiNb-3D6 as the detection antibody. This study provides a potential foundation for novel alternative approaches to treatment or diagnostics applications of H. pylori infection. [ABSTRACT FROM AUTHOR]