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Abstract Background Cuscutae Semen (CS) has been prescribed in traditional Chinese medicine (TCM) for millennia as an aging inhibitor, an anti-inflammatory agent, a pain reliever, and an aphrodisiac. Its three main forms include crude Cuscutae Semen (CCS), wine-processed CS (WCS), and stir-frying-processed CS (SFCS). Premature ovarian insufficiency (POI) is a globally occurring medical condition. The present work sought a highly efficacious multi-target therapeutic approach against POI with minimal side effects. Finally, it analyzed the relative differences among CCS, WCS and SFCS in terms of their therapeutic efficacy and modes of action against H2O2-challenged KGN human granulosa cell line. Methods In this study, ultrahigh-performance liquid chromatography (UPLC)-Q-ExactiveTM Orbitrap-mass spectrometry (MS), oxidative stress indices, reactive oxygen species (ROS), Mitochondrial membrane potential (MMP), real-time PCR, Western blotting, and molecular docking were used to investigate the protective effect of CCS, WCS and SFCS on KGN cells oxidative stress and apoptosis mechanisms. Results The results confirmed that pretreatment with CCS, WCS and SFCS reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the KGN cells. CCS, WCS and SFCS upregulated the expression of antioxidative levels (GSH, GSH/GSSG ratio, SOD, T-AOC),mitochondrial membrane potential (MMP) and the relative mRNA(Nrf2, Keap1, NQO-1, HO-1, SOD-1, CAT). They inhibited apoptosis by upregulating Bcl-2, downregulating Bax, cleaved caspase-9, and cleaved caspase-3, and lowering the Bax/Bcl-2 ratio. They also exerted antioxidant efficacy by partially activating the PI3K/Akt and Keap1-Nrf2/HO-1 signaling pathways. Conclusions The results of the present work demonstrated the inhibitory efficacy of CCS, WCS and SFCS against H2O2-induced oxidative stress and apoptosis in KGN cells and showed that the associated mechanisms included Keap1-Nrf2/HO-1 activation, P-PI3K upregulation, and P-Akt-mediated PI3K-Akt pathway induction.

Abstract Aquifer confinement represents a pivotal property that significantly influences the vulnerability and contamination risk of groundwater resources. Several methods have been proposed for determining aquifer confinement by analyzing the response of well water level to Earth tides and atmospheric tides. In this study, we evaluated the performance of the existing single methods and put forward an optimized comprehensive approach. We compared the determination results of the three single methods with those of a comprehensive method using water-level data from 39 earthquake precursor monitoring wells in North China. The results demonstrate that the comprehensive method effectively determined aquifer confinement, significantly reducing the uncertainty associated with the three single methods. The application of the comprehensive method in North China reveals that aquifer confinement may undergo temporal variations during long-term continuous observation, especially in areas where the confining properties of aquifers may vary due to human activities and earthquakes. In such areas, the comprehensive method facilitates accurate assessment of groundwater vulnerability, as well as the potential dispersion of underground pollutants.

Abstract It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.

Abstract Background A subset of Graves’ disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. Methods A prospective cohort study (2018–2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. Results Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves’ ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium–low cumulative dosage group (average

Abstract Although global navigation satellite systems (GNSS) have been routinely applied to determine attitudes, there exists no literature on determining angular velocity and/or angular acceleration from GNSS. Motivated by the invention of computerized accelerometers of the correspondence author and following the success of accurately recovering translational velocity and acceleration waveforms from very high-rate GNSS precise positioning by Xu and his collaborators in 2021, we propose the concept of GNSS gyroscopes and reconstruct angular velocity and acceleration from very high-rate GNSS attitudes by applying regularization under the criterion of minimum mean squared errors. The major results from the experiments can be summarized in the following: (i) angular velocity and acceleration waveforms computed by applying the difference methods to high-rate GNSS attitudes are too noisy and can be physically not meaningful and numerically incorrect. The same can be said about inertial measurement unit (IMU) attitudes, if IMU gyros are not of very high accuracy; (ii) regularization is successfully applied to reconstruct the high-rate angular velocity and acceleration waveforms from 50 Hz GNSS attitudes and significantly outperforms the difference methods, validating the proposed concept of GNSS gyroscopes. By comparing the angular velocity and acceleration results by using the difference methods and regularization, we find that the peak values of angular velocity and acceleration by regularization are much smaller by a maximum factor of 1.57 in the angular velocity to a maximum factor of 8662.53 times in the angular acceleration in the case of high-rate GNSS, and by a maximum factor of 1.26 in the angular velocity to a maximum factor of 2819.85 times in the angular acceleration in the case of IMU, respectively; and (iii) the IMU attitudes apparently lead to better regularized angular velocity and acceleration waveforms than the high-rate GNSS attitudes, which can well be explained by the fact that the former is of better accuracy than the latter. As a result, to suppress the significant amplification of noise in GNSS attitudes, larger regularization parameters have to be chosen for the high-rate GNSS attitudes, resulting in smaller peak angular accelerations by a maximum factor of 37.55 percent in the angular velocity to a maximum factor of 6.20 times in the angular acceleration in comparison of the corresponding IMU results. Nevertheless, the regularized angular acceleration waveforms for both GNSS and IMU look more or less similar in pattern or waveform shape.

Enterprise innovation remains a cornerstone of economic development, with the direct influence of financialization on enterprise innovation standing as a critical factor. In contrast with the existing research, this study constructs an evolutionary game model by utilizing the Cournot model to analyze the innovation behavior of enterprises, and analyzes the influence of financialization on enterprise innovation by incorporating investment returns, market competition, and demand scale into the research framework. In addition, this study selects the sample of the Chinese non-financial listed enterprises and using panel data for the period 2009 to 2021. Based on the findings from the empirical analysis, this study reveals that excessive financialization hinders innovation in Chinese enterprises. Additionally, an intermediary pathway involving 'financialization - investment returns - enterprise innovation' is identified as a transmission mechanism. The demand scale generated by innovation inversely correlates with the inhibitory effects of financialization on enterprise innovation behavior. Meanwhile, heightened market competition amplifies the inhibitory influence of financialization on innovation. This study provided valuable empirical evidence, facilitating the enhancement of enterprise innovation efficiency.

BackgroundEmerging evidence indicates that individuals with type 2 diabetes (T2D) are more prone to mental health issues than the general population; however, there is a significant lack of data concerning the mental health burden in Chinese Americans with T2D. ObjectiveThe aim of this study was to explore the comorbid mental health status, health-seeking behaviors, and mental service utilization among Chinese Americans with T2D. MethodsA cross-sectional telephone survey was performed among 74 Chinese Americans with T2D in New York City. We used standardized questionnaires to assess mental health status and to gather data on mental health–seeking behaviors and service utilization. Descriptive statistics were applied for data analysis. ResultsA total of 74 Chinese Americans with T2D completed the survey. Most participants (mean age 56, SD 10 years) identified as female (42/74, 57%), were born outside the United States (73/74, 99%), and had limited English proficiency (71/74, 96%). Despite nearly half of the participants (34/74, 46%) reporting at least one mental health concern (elevated stress, depressive symptoms, and/or anxiety), only 3% (2/74) were currently using mental health services. Common reasons for not seeking care included no perceived need, lack of information about Chinese-speaking providers, cost, and time constraints. The cultural and language competence of the provider was ranked as the top factor related to seeking mental health care. ConclusionsChinese Americans with T2D experience relatively high comorbid mental health concerns yet have low service utilization. Clinicians may consider team-based care to incorporate mental health screening and identify strategies to provide culturally and linguistically concordant mental health services to engage Chinese Americans with T2D.

Aiming to address the issue of mapping failure resulting from unsmooth motion during SLAM (Simultaneous Localization and Mapping) performed by a quadruped robot, a tightly coupled SLAM algorithm that integrates LIDAR and IMU sensors is proposed in this paper. Firstly, the IMU information, after undergoing deviation correction, is utilized to remove point cloud distortion and serve as the initial value for point cloud registration. Subsequently, a registration algorithm based on Normal Distribution Transform (NDT) and sliding window is presented to ensure real-time positioning and accuracy. Then, an error function combining IMU and LIDAR is formulated using a factor graph, which iteratively optimizes position, attitude, and IMU deviation. Finally, loop closure detection based on Scan Context is introduced, and loop closure factors are incorporated into the factor graph to achieve effective mapping. An experimental platform is established to conduct accuracy and robustness comparison experiments. Results showed that the proposed algorithm significantly outperforms the LOAM algorithm, the NDT-based SLAM algorithm and the LeGO-LOAM algorithm in terms of positioning accuracy, with a reduction of 65.08%, 22.81%, and 37.14% in root mean square error, respectively. Moreover, the proposed algorithm exhibits superior robustness compared to LOAM, NDT-based SLAM and LeGO-LOAM.

ABSTRACT Drug efflux systems have recently been recognized as a significant mechanism responsible for multidrug resistance in bacteria. In this study, we described the identification and characterization of a new chromosomally encoded efflux pump (SA00565) in Staphylococcus aureus. SA00565, which belongs to the drug/metabolite transporter (DMT) superfamily, was predicted to be a 10-transmembrane segment transporter. To evaluate the role of sa00565 in resistance, we generated sa00565 gene deletion mutant (Δsa00565) and assessed its susceptibility to 35 different antibiotic treatments. Our results demonstrated that the Δsa00565 mutant exhibited reduced resistance to tetracycline and doxycycline, with 64-fold and 12-fold decreased MICs, respectively. The mechanism of SA00565-mediated tetracycline resistance was demonstrated that SA00565 possesses the capability to efficiently extrud intracellular tetracycline into the environment. The efflux activity of SA00565 was further validated using EtBr accumulation and efflux assays. In summary, our study uncovered a previously unknown function of a DMT family transporter, which serves as a tetracycline efflux pump, thereby contributing to tetracycline resistance in S. aureus.IMPORTANCEIn this study, we addressed the significance of drug efflux systems in multidrug resistance of Staphylococcus aureus, focusing on the unexplored efflux pump SA00565 in the drug/metabolite transporter (DMT) superfamily. Through phylogenetic analysis, gene knockout, and overexpression experiments, we identified the role of SA00565 in antibiotic resistance. The Δsa00565 mutant showed increased susceptibility to tetracycline and doxycycline in disk diffusion assays, with significantly lower MICs compared to the WT. Remarkably, intracellular tetracycline concentration in the mutant was two- to threefold higher, indicating SA00565 actively eliminates intracellular tetracycline. Our findings emphasize the pivotal contribution of SA00565 to tetracycline antibiotic resistance in S. aureus, shedding light on its functional attributes within the DMT superfamily and providing valuable insights for combating multidrug resistance.

Abstract Background The utilization of fructose as a carbon source and energy provider plays a crucial role in bacterial metabolism. Additionally, fructose metabolism directly impacts the pathogenicity and virulence of certain pathogenic microorganisms. Results In this study, we report the discovery of a fructose phosphotransferase system (PTS) in S. aureus. This system comprises three genes, namely fruR, fruK, and fruT, which are co-located in an operon that is indispensable for fructose utilization in S. aureus. Our findings confirm that these three genes are transcribed from a single promoter located upstream of the fruRKT operon. The fruR gene encodes a DeoR-type transcriptional regulator, designated as FruR, which represses the expression of the fruRKT operon by direct binding to its promoter region. Significantly, our experimental data demonstrate that the fruRKT operon can be induced by fructose, suggesting a potential regulatory mechanism involving intracellular fructose-1-phosphate as a direct inducer. Furthermore, we conducted RNA-seq analysis to investigate the specificity of FruR regulation in S. aureus, revealing that the fruRKT operon is predominantly regulated by FruR. Conclusions In summary, this study has uncovered a fructose phosphotransferase system (PTS) in S. aureus, highlighting the essential role of the fruR, fruK, and fruT genes in fructose utilization. We confirmed their co-location within an operon and established FruR as a key regulator by binding to the operon’s promoter. Importantly, we demonstrated that fructose can induce this operon, possibly through intracellular fructose-1-phosphate. Our identification of this PTS system represents the initial characterization of a fructose metabolism system in S. aureus.

Geological assurance system is an important foundation to realize intelligent mining and guarantee coal mine safety. With the development of intelligent mining technology in coal mines, precise mining becomes a new requirement for coal mining. In order to achieve safe planning and efficient mining in coal mines, a mining control method based on geological support technology is proposed. The method builds a geological model based on roadway exposure exploration technology, borehole detection technology and channel wave seismic exploration technology, and uses the geological assurance system to collect relevant data in the process of mining adaptive mining and cooperative mining to correct the intelligent decision-making platform and improve the decision-making level. The relevant equipment and module systems are optimized to realize automatic control of the working face and cooperative deployment of modules to achieve safe planning and efficient mining of the working face. The practical application of the system in Huangling No.2 mine has realized the function of reducing losses and increasing efficiency.

ObjectiveThere has been a significant increase in international student exchange in recent years, with medical students comprising a large proportion of international students. This study aimed to develop and validate a questionnaire, the Medical Student Overseas Exchange Willingness and Demand Survey Questionnaire (MS-OEWDSQ), to assess medical students’ intentions to study abroad and explore the potential influencing factors.MethodsThis study was conducted in three stages: item generation and scale development; pilot study; and examination of scale reliability and validity. The item pool for the questionnaire was compiled from a literature review, an assessment of other relevant questionnaires, and interviews with medical students. Descriptive statistics were generated, and correlation analysis was performed to analyze the questionnaire data. The reliability of the measure was examined according to its internal consistency and split-half reliability. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to determine the factor structure and test the construct validity.ResultsThe final version of the MS-OEWDSQ comprised three factors with a total of 14 items. The total Cronbach’s α coefficient of the questionnaire was 0.844, and the total split-half reliability coefficient was 0.639. This study also identified several factors that may affect medical students’ willingness to go abroad for exchange. Specifically, education (p

Exposure to cadmium (Cd), a toxic heavy metal classified as an environmental endocrine disruptor, can exert significant toxicity in both animals and humans. However, the potential effects of Cd exposure on socioemotional behaviors are still poorly understood, as are the underlying mechanisms. In the present study, employing a series of behavioral tests as well as 16 S rRNA sequencing analysis, we investigated the long-term effects of Cd exposure on socioemotional behaviors and their associated mechanisms in mice based on the brain–gut interaction theory. The results showed that postweaning exposure to Cd reduced the ability to resist depression, decreased social interaction, subtly altered sexual preference, and changed the composition of the gut microbiota in male mice during adolescence. These findings provided direct evidence for the deleterious effects of exposure to Cd in the postweaning period on socioemotional behaviors later in adolescence, and suggested that these effects of Cd exposure may be linked to changes in the gut microbiota.

Abstract Purpose The overexpression of TRIP13 has been observed in many types of cancer and has been identified as an oncogene. However, its role in hepatocellular carcinoma (HCC) has not been extensively studied. This study aimed to investigate the expression of TRIP13 in HCC and its impact on immune cell infiltration and prognosis. Methods We analyzed TCGA and GSE62232 datasets to assess TRIP13 expression in HCC. Kaplan–Meier and subgroup analysis were performed to examine the correlation between TRIP13 expression and HCC. Univariate and Cox regression analysis were conducted to determine the predictive value of TRIP13 in assessing patient outcomes. A nomogram was developed using TRIP13 mRNA expression to predict HCC prognosis. TRIP13 expression was validated using immunohistochemistry in our patient cohort. Survival and subgroup analyses were conducted to investigate the role of TRIP13 in HCC prognosis. Results The results indicated that TRIP13 upregulation in HCC was a strong independent predictor of poor outcome, as determined by Kaplan–Meier and Cox regression analyses. A high AUC value of 0.982 from ROC curves suggested that TRIP13 upregulation could serve as a reliable diagnostic indicator for HCC. The immunohistochemical validation of TRIP13 expression in the patient cohort confirmed its prognostic significance, and high TRIP13 expression was found to be associated with increased infiltration of Th2 cells and decreased infiltration of neutrophils, Th17 cells, and dendritic cells. Conclusion These findings suggest that TRIP13 could be a potential prognostic biomarker for HCC.

ObjectivesTo test the feasibility, acceptability, and potential efficacy of a mHealth intervention tailored for Chinese immigrant families with type 2 diabetes (T2D).MethodsWe conducted a pilot randomized controlled trial (RCT) with baseline, 3-, and 6-month measurements. Participating dyads, T2D patients and families/friends from NYC, were randomized into the intervention group (n = 11) or the wait-list control group (n = 12). Intervention includes 24 videos covering T2D self-management, behavioral techniques, and family-oriented sessions. Feasibility and acceptability were measured respectively by the retention rate and video watch rate, and a satisfaction survey. Patients' HbA1c, weight, and self-management were also assessed to test potential efficacy.ResultsMost T2D patients (n = 23; mean age 56.2±9.4 years; 52.2% male) and families/friends (n = 23, mean age 54.6±11.2 years; 52.2% female) had high school education or less (69.6% and 69.6%), annual household income < $25,000 (65.2% and 52.2%), and limited English proficiency (95.7% and 95.7%). The retention rates were not significantly different between the intervention and the control groups for both the patients (90.91% vs 83.3%, p = 0.589); and their families/friends (3-month: 90.9% vs 75%, p = 0.313; 6-month: 90.9% vs 83.3%, p = 0.589). The mean video watch rate was 76.8% (7%). T2D patients and families/friends rated satisfaction as 9.4 and 10 out of 10, respectively. Despite no between-group differences, the intervention group had significantly lower HbA1c (p = 0.014) and better self-management (p = 0.009), and lost 12 lbs. on average at 6 months (p = 0.079), compared to their baseline levels.ConclusionsA culturally-tailored, family-based mHealth intervention is feasible and acceptable among low-income, limited English-proficient Chinese families with T2D in NYC. Significant changes in HbA1c and self-management within the intervention group indicate this intervention may have potential efficacy. Given the small sample size of this study, a future RCT with adequate power is needed to test efficacy.

The processing of traditional Chinese medicine (TCM) is a unique traditional pharmaceutical technology in China, which is the most important feature that distinguishes Chinese medicine from natural medicine and plant medicine. Since the record in Huangdi Neijing (Inner Canon of the Yellow Emperor), till now, the processing of TCM has experienced more than 2000 years of inheritance, innovation, and development, which is a combination of TCM theory and clinical practice, and plays an extremely important position in the field of TCM. In recent years, as a clinical prescription of TCM, Chinese herbal pieces have played a significant role in the prevention and control of the COVID-19 and exhibited their unique value, and therefore they have become the highlight of China's clinical treatment protocol and provided Chinese experience and wisdom for the international community in the prevention and control of the COVID-19 epidemic. This paper outlines the research progress in the processing of representative TCM in recent years, reviews the mechanism of the related effects of TCM materials after processing, such as changing the drug efficacy and reducing the toxicity, puts forward the integration and application of a variety of new technologies and methods, so as to reveal the modern scientific mystery of the processing technology of TCM.

IntroductionWith continuously increasing labor costs, an urgent need for automated apple- Qpicking equipment has emerged in the agricultural sector. Prior to apple harvesting, it is imperative that the equipment not only accurately locates the apples, but also discerns the graspability of the fruit. While numerous studies on apple detection have been conducted, the challenges related to determining apple graspability remain unresolved.MethodsThis study introduces a method for detecting multi-occluded apples based on an enhanced YOLOv5s model, with the aim of identifying the type of apple occlusion in complex orchard environments and determining apple graspability. Using bootstrap your own atent(BYOL) and knowledge transfer(KT) strategies, we effectively enhance the classification accuracy for multi-occluded apples while reducing data production costs. A selective kernel (SK) module is also incorporated, enabling the network model to more precisely identify various apple occlusion types. To evaluate the performance of our network model, we define three key metrics: APGA, APTUGA, and APUGA, representing the average detection accuracy for graspable, temporarily ungraspable, and ungraspable apples, respectively.ResultsExperimental results indicate that the improved YOLOv5s model performs exceptionally well, achieving detection accuracies of 94.78%, 93.86%, and 94.98% for APGA, APTUGA, and APUGA, respectively.DiscussionCompared to current lightweight network models such as YOLOX-s and YOLOv7s, our proposed method demonstrates significant advantages across multiple evaluation metrics. In future research, we intend to integrate fruit posture and occlusion detection to f]urther enhance the visual perception capabilities of apple-picking equipment.

Automatic surface water body mapping using remote sensing technology is greatly meaningful for studying inland water dynamics at regional to global scales. Convolutional neural networks (CNN) have become an efficient semantic segmentation technique for the interpretation of remote sensing images. However, the receptive field value of a CNN is restricted by the convolutional kernel size because the network only focuses on local features. The Swin Transformer has recently demonstrated its outstanding performance in computer vision tasks, and it could be useful for processing multispectral remote sensing images. In this article, a Water Index and Swin Transformer Ensemble (WISTE) method for automatic water body extraction is proposed. First, a dual-branch encoder architecture is designed for the Swin Transformer, aggregating the global semantic information and pixel neighbor relationships captured by fully convolutional networks (FCN) and multihead self-attention. Second, to prevent the Swin Transformer from ignoring multispectral information, we construct a prediction map ensemble module. The predictions of the Swin Transformer and the Normalized Difference Water Index (NDWI) are combined by a Bayesian averaging strategy. Finally, the experimental results obtained on two distinct datasets demonstrate that the WISTE has advantages over other segmentation methods and achieves the best results. The method proposed in this study can be used for improving regional to continental surface water mapping and related hydrological studies.

ABSTRACTBackground With increasing knowledge about the gut – bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of Lactobacillus rhamnosus GG (LGG) on ovariectomized (OVX) model rats and the immunological and microecological mechanisms involved.Results We found a protective effect of LGG treatment in OVX rats through changes in bone microarchitecture, bone biomechanics, and CTX-I, PINP, Ca, and RANKL expression levels. LGG was more advantageous in promoting osteogenesis, which may be responsible for the alleviation of osteoporosis. Th17 cells were imbalanced with Treg cells in mediastinal lymph nodes and bone marrow, with RORγt and FOXP3 expression following a similar trend. TNF-α and IL-17 expression in colon and bone marrow increased, while TGF-β and IL-10 expression decreased; however, LGG treatment modulated these changes and improved the Th17/Treg balance significantly. Regarding the intestinal barrier, we found that LGG treatment ameliorated estrogen deficiency-induced inflammation and mucosal damage and increased the expression of GLP-2 R and tight junction proteins. Importantly, 16S rRNA sequencing showed a significant increase in the Firmicutes/Bacteroidetes ratio during estrogen deficiency. Dominant intestinal flora showed significant differences in composition; LGG treatment regulated the various genera that were imbalanced in OVX, along with modifying those that did not change significantly in other groups with respect to the intestinal barrier, inflammation development, and bile acid metabolism.Conclusions Overall, LGG ameliorated estrogen deficiency-induced osteoporosis by regulating the gut microbiome and intestinal barrier and stimulating Th17/Treg balance in gut and bone.

Abstract Background Long noncoding RNAs (lncRNAs) have been identified as important regulatory factors implicated in a wide array of diseases, including various forms of cancer. However, the roles of most lncRNAs in the progression of gastric cancer (GC) remain largely unexplored. This study investigates the biological function and underlying mechanism of a novel lncRNA, XLOC_004787 in GC. Methods The location of XLOC_004787 in GES-1 cells and HGC-27 cells were detected by fluorescence in situ hybridization (FISH) assay. The expression levels of XLOC_004787 were assessed using quantitative real-time fluorescence PCR (qRT-PCR) in various cell lines, including GES-1, MGC-803, MKN-45, BGC-823, SGC-7901, and HGC-27 cells. Functional assays such as Transwell migration, cell counting kit-8 (CCK-8), and colony formation experiments were employed to analyze the effects of XLOC_004787 and miR-203a-3p on cell migration and proliferation. Protein levels associated with GC in these cell lines were examined by Western blotting. The intracellular localization of β-catenin and P-Smad2/3 was assessed using immunofluorescence (IF) assay. Additionally, the interaction between XLOC_004787 and miR-203a-3p was investigated using a dual luciferase assay. Results XLOC_004787 was localized at both the cytoplasm and nucleus of GES-1 cells and HGC-27 cells. Compared to normal tissues and GES-1 cells, XLOC_004787 expression was significantly upregulated in GC tissues and cells, with the highest and lowest expression observed in SGC-7901 and HGC-27 cells, respectively. Furthermore, a reduced expression of XLOC_004787 was seen to inhibit migration and proliferation in SGC-7901 cells. Western blotting analysis revealed that a decrease in XLOC_004787 expression correspondingly decreased the expression of N-cadherin, mmp2, mmp9, Snail, Vimentin, β-catenin, C-myc, Cyclin D1, and TGF-β, while concurrently increasing E-cadherin expression. This was also associated with diminished expression of P-Smad2/3 in relation to Smad2/3, and reduced P-Gsk3β expression in comparison to Gsk3β. Additionally, the nuclear entry of P-Smad2/3 and β-catenin was reduced by lower XLOC_004787 expression. Amplifying XLOC_004787 expression via pcDNA_XLOC_004787 suggested a potential for cancer promotion. Notably, XLOC_004787 was found to negatively regulate mir-203a-3p expression, with potential binding sites identified between the two. Higher mir-203a-3p expression was observed to decrease migration and proliferation, and enhance E-cadherin expression. Conversely, suppression of mir-203a-3p expression suggested a potential promotion of proliferation and migration in GC cells. Conclusions These results suggest that XLOC_004787, found to be upregulated in GC tissues, potentially promotes proliferation and migration in GC cells. This occurs through the activation of TGF-β and Wnt/β-catenin signaling pathways and the expression of EMT-related proteins. Additionally, XLOC_004787 may influence cell migration and proliferation by modulating the signaling pathway via the adsorption and inhibition of mir-203a-3p.

Parkinson’s disease (PD) is characterized not only by motor symptoms but also by non-motor dysfunctions, such as olfactory impairment; the cause is not fully understood. Our study suggests that neuronal loss and inflammation in brain regions along the olfactory pathway, such as the olfactory bulb (OB) and the piriform cortex (PC), may contribute to olfactory dysfunction in PD mice, which might be related to the downregulation of the trace amine-associated receptor 1 (TAAR1) in these areas. In the striatum, although only a decrease in mRNA level, but not in protein level, of TAAR1 was detected, bioinformatic analyses substantiated its correlation with PD. Moreover, we discovered that neuronal death and inflammation in the OB and the PC in PD mice might be regulated by TAAR through the Bcl-2/caspase3 pathway. This manifested as a decrease of anti-apoptotic protein Bcl-2 and an increase of the pro-apoptotic protein cleaved caspase3, or through regulating astrocytes activity, manifested as the increase of TAAR1 in astrocytes, which might lead to the decreased clearance of glutamate and consequent neurotoxicity. In summary, we have identified a possible mechanism to elucidate the olfactory dysfunction in PD, positing neuronal damage and inflammation due to apoptosis and astrocyte activity along the olfactory pathway in conjunction with the downregulation of TAAR1.

Epigenetic mechanisms are processes that affect gene expression and cellular functions without involving changes in the DNA sequence. This abnormal or unstable expression of genes regulated by epigenetics can trigger cancer and other various diseases. The immune cells involved in anti-tumor responses and the immunogenicity of tumors may also be affected by epigenomic changes. This holds significant implications for the development and application of cancer immunotherapy, epigenetic therapy, and their combined treatments in the fight against cancer. We provide an overview of recent research literature focusing on how epigenomic changes in immune cells influence immune cell behavior and function, as well as the immunogenicity of cancer cells. And the combined utilization of epigenetic medications with immune checkpoint inhibitors that focus on immune checkpoint molecules [e.g., Programmed Death 1 (PD-1), Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4), T cell Immunoglobulin and Mucin Domain (TIM-3), Lymphocyte Activation Gene-3 (LAG-3)] present in immune cells and stromal cells associated with tumors. We highlight the potential of small-molecule inhibitors targeting epigenetic regulators to amplify anti-tumor immune responses. Moreover, we discuss how to leverage the intricate relationship between cancer epigenetics and cancer immunology to create treatment regimens that integrate epigenetic therapies with immunotherapies.

Rising labor costs and a workforce shortage have impeded the development and economic benefits of the global grape industry. Research and development of intelligent grape harvesting technologies is desperately needed. Therefore, rapid and accurate identification of grapes is crucial for intelligent grape harvesting. However, object detection algorithms encounter multiple challenges in unstructured vineyards, such as similar background colors, light obstruction from greenhouses and leaves, and fruit occlusion. All of these factors contribute to the difficulty of correctly identifying grapes. The GrapeDetectNet (GDN), based on the YOLO (You Only Look Once) v5s, is proposed to improve grape detection accuracy and recall in unstructured vineyards. dual-channel feature extraction attention (DCFE) is a new attention structure introduced in GDN. We also use dynamic snake convolution (DS-Conv) in the backbone network. We collected an independent dataset of 1280 images after a strict selection process to evaluate GDN’s performance. The dataset encompasses examples of Shine Muscat and unripe Kyoho grapes, covering a range of complex outdoor situations. The results of the experiment demonstrate that GDN performed outstandingly on this dataset. Compared to YOLOv5s, this model increased metrics such as 2.02% of mAP0.5:0.95, 2.5% of mAP0.5, 1.4% of precision, 1.6% of recall, and 1.5% of F1 score. Finally, we test the method on a grape-picking robot, and the results show that our algorithm works remarkably well in harvesting experiments. The results indicate that the GDN grape detection model in this study exhibits high detection accuracy. It is proficient in identifying grapes and demonstrates good robustness in unstructured vineyards, providing a valuable empirical reference for the practical application of intelligent grape harvesting technology.

ObjectiveImmune checkpoint inhibitors(ICIs) have improved survival and are increasingly used for cancer. However, ICIs use may be limited by immune-related adverse events (irAEs), such as ICI-induced diabetes mellitus(ICI-DM). The objective of the present study was to characterize ICI-DM patients and real-world adherence to guidelines.Research design and methodsThe present study was a retrospective review of electronic records of ICI-DM patients at the First Affiliated Hospital of Nanjing Medical University between July 2018 and October 2022.Results34.8% (8/23)patients monitored blood glucose in every treatment cycle. The proportion of patients with severe diabetic ketoacidosis(DKA) was lower in the tight glycemic monitoring group than the non-tight glycemic monitoring group (16.7% vs. 55.6%, p = 0.049). 78.3%(18/23) patients with hyperglycemia visited a non-endocrinologist first, but 95.7% of patients were then referred to an endocrinologist. Twenty patients were tested for distinguishing the etiology of hyperglycemia and 20% patients with positive glutamic acid decarboxylase antibody(GADA), 55% with C-peptide

Introduction Mesenteric lymph nodes (MLNs) are central in immune anatomy. MLNs are associated with the composition of gut microbiota, affecting the central system and immune system. Gut microbiota was found to differ among individuals of different social hierarchies. Nowadays, excision of MLNs is more frequently involved in gastrointestinal surgery; however, the potential side effects of excision of MLNs on social dominance are still unknown. Methods MLNs were removed from male mice (7–8 weeks old). Four weeks after MLN removal, social dominance test was performed to investigate social dominance; hippocampal and serum interleukin (IL)‐1β, IL‐10, and tumor necrosis factor‐alpha (TNF‐α) were investigated; and histopathology was used to evaluate local inflammation of the ileum. The composition of the gut microbiota was then examined to understand the possible mechanism, and finally intraperitoneal injection of IL‐10 was used to validate the effect of IL‐10 on social dominance. Results There was a decrease in social dominance in the operation group compared to the control group, as well as a decrease in serum and hippocampal IL‐10 levels, but no difference in serum and hippocampal IL‐1β and TNF‐α levels, and no local inflammation of the ileum after MLN removal. 16S rRNA sequencing analysis showed that the relative abundance of the class Clostridia was decreased in the operation group. This decrease was positively associated with serum IL‐10 levels. Furthermore, intraperitoneal injection of IL‐10 in a subset of mice increased social dominance. Conclusions Our findings suggested that MLNs contributed to maintaining social dominance, which might be associated with reduced IL‐10 and the imbalance of specific flora in gut microbiota.

As a highly disruptive digital technology, blockchain provides new solutions for reshaping corporate governance mechanisms and improving resource allocation. We empirically examine the relationship between blockchain and corporate investment inefficiency. We find that blockchain can help improve corporate investment efficiency, and this result is valid after a series of robustness tests. Blockchain can not only significantly restrain overinvestment but also alleviate underinvestment. Reducing financing costs and alleviating agency conflicts are the two channels through which blockchain is associated with corporate investment efficiency, and financial reporting quality is the condition on which the channels depend. When the CEO holds few shares or the trade credit environment in the region where the company is located is poor, the effect of blockchain is more prominent than it is otherwise. Investment efficiency cannot be improved by blockchain for companies providing blockchain products or services to customers, only for those promoting their own operations and management with blockchain. Ultimately, blockchain can enhance companies’ value by alleviating inefficient investment. We reveal the role of blockchain in corporate investment efficiency, furnish microeconomic evidence for the integration of digital technology and the real economy and provide implications for China to promote digital technology to drive high-quality company development.

Staphylococcus aureus secrete numerous effectors to evade or inhibit the host immune response, yet the mechanism underlying the effectors ability to manipulate the signalling pathways of macrophages remain unclear. Authors utilise in vitro and in vivo models to explore the role of extracellular fibrinogen-binding protein (Efb) in immune response modulation and pathogenicity.

Abstract Ovarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress (OS) is considered to be a key factor. This review focuses on the fact that OS status accelerates the ovarian aging process by promoting apoptosis, inflammation, mitochondrial damage, telomere shortening and biomacromolecular damage. Current evidence suggests that aging, smoking, high-sugar diets, pressure, superovulation, chemotherapeutic agents and industrial pollutants can be factors that accelerate ovarian aging by exacerbating OS status. In addition, we review the role of nuclear factor E2-related factor 2 (Nrf2), Sirtuin (Sirt), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), Forkhead box O (FoxO) and Klotho signaling pathways during the process of ovarian aging. We also explore the role of antioxidant therapies such as melatonin, vitamins, stem cell therapies, antioxidant monomers and Traditional Chinese Medicine (TCM), and investigate the roles of these supplements with respect to the reduction of OS and the improvement of ovarian function. This review provides a rationale for antioxidant therapy to improve ovarian aging.

Abstract Background Anovulation is one of the main causes of female infertility. This study will evaluate the effectiveness and safety of Bushen Culuan Decoction for anovulatory infertility caused by six diseases, including anovulatory abnormal uterine bleeding, polycystic ovarian syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, corpus luteum insufficiency, and premature ovarian insufficiency. Methods This is a randomized, double-blinded, double-dummy, parallel, positively controlled, adaptive, multicenter clinical trial. All participants will be randomly allocated by a central randomization system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo a 14-day treatment with Bushen Culuan Decoction 13 g three times a day and a 5-day treatment with clomiphene citrate placebo tablets 50 mg once a day starting on day 5 of every menstrual period. The control group will undergo a 14-day treatment with Bushen Culuan Decoction placebo 13 g three times a day and a 5-day treatment with clomiphene citrate tablets 50 mg once a day from day 5 in every menstrual period. The whole treatment will last through 3 menstrual periods or 6 menstrual periods, depending on whether ovulation is regained in the first 3 menstrual periods. All statistical analyses will be performed in SPSS 21.0 (SPSS, Chicago, Illinois, USA), and a p value

Abstract Background The efficacy and validity of excimer laser ablation (ELA) in the in-stent restenosis (ISR) has been confirmed. However, its application in de novo atherosclerotic lesions of lower extremity artery disease (LEAD) has not been clearly defined and its procedure has not been standardized. Methods ELABORATE is a prospective, multicenter, real-world study designed to evaluate the efficacy and safety between ELA combined with drug-coated balloon (DCB) and DCB alone in de novo atherosclerotic lesions of LEAD. Discussion ELABORATE is a prospective, multicenter, real-world study designed to assess the efficacy and safety between ELA combined with drug-coated balloon (DCB) and DCB alone in patients with de novo atherosclerotic lesions of LEAD. According to the real-world situation, eligible patients will be allocated to ELA + DCB group (group E) and DCB group (group C). Baseline and follow-up information (at 3, 6, and 12 months) will be collected. The primary efficacy point is primary patency at 12-months, and the secondary efficacy points include clinically driven target lesion reintervention (CD-TLR), change of Rutherford class, ankle-brachial index and ulcer healing rate. These indexes will be assessed and recorded at 3, 6, and 12-month follow-up. Also, safety evaluation, including major adverse event, all-cause mortality through 30-day follow-up, unplanned major amputation, bailout stent and distal embolization, will also be evaluated by an independent core laboratory. All the data will be collected and recorded by the electric data capture system. This study will be finished in 3 years and the 12-month results will be available in 2023. All the patients will be followed for 5 years. Trial registration number Chinese Clinical Trial Registry (ChiCTR2100051263). Registered 17 September 2019. http://www.chictr.org.cn/listbycreater.aspx .

BackgroundThe pathogenesis of depression is closely related to changes in hippocampal synaptic plasticity; however, the underlying mechanism is still unclear. Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2), a postsynaptic scaffold protein in excitatory synapses important for synaptic plasticity, is highly expressed in the hippocampus and has been implicated in several psychiatric disorders. However, the role of BAIAP2 in depression remains poorly understood.MethodsIn the present study, a mouse model of depression was established via exposure to chronic mild stress (CMS). An adeno-associated virus (AAV) vector expressing BAIAP2 was injected into the hippocampal brain region of mice and a BAIAP2 overexpression plasmid was transfected into HT22 cells to upregulate BAIAP2 expression. Depression- and anxiety-like behaviors and dendritic spine density were examined in mice using behavioral tests and Golgi staining, respectively. In vitro, hippocampal HT22 cells were treated with corticosterone (CORT) to simulate the stress state, and the effect of BAIAP2 on CORT-induced cell injury was explored. Reverse transcription-quantitative PCR and western blotting were employed to determine the expression levels of BAIAP2 and those of the synaptic plasticity-related proteins glutamate receptor ionotropic, AMPA 1 (GluA1), and synapsin 1 (SYN1).ResultsMice exposed to CMS exhibited depression- and anxiety-like behaviors accompanied by decreased levels of BAIAP2 in the hippocampus. In vitro, the overexpression of BAIAP2 increased the survival rate of CORT-treated HT22 cells and upregulated the expression of GluA1 and SYN1. Consistent with the in vitro data, the AAV-mediated overexpression of BAIAP2 in the hippocampus of mice significantly inhibited CMS-induced depression-like behavior, concomitant with increases in dendritic spine density and the expression of GluA1 and SYN1 in hippocampal regions.ConclusionOur findings indicate that hippocampal BAIAP2 can prevent stress-induced depression-like behavior and may be a promising target for the treatment of depression or other stress-related diseases.

Summary: Huddling behavior, a typical social interaction among animals, has the benefits of obtaining social support and adapting environment. Huddling behavior is determined by social (social hierarchy), environmental factors (stress events), and the neuroendocrine system. Nevertheless, the huddling behavior of different social hierarchies and the underlying mechanisms have not been fully elucidated. In the present study, acute 2-methyl-2-thiazoline (2 MT) can induce huddling behavior and significantly increase serum levels of testosterone (T) in mice; and the increased T level was positively correlated with huddling behavior. Further, the T treatment significantly increased the huddling behavior in mice under 2 MT exposure condition. More interestingly, T can quickly promote dominant individuals to occupy safe positions when huddling together under predator odor. Collectively, T can rapidly regulate the individual’s adaptive response to threats in a social rank-dependent manner, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms of huddling behavior.

Abstract Background Previous studies reported that patients with asthma showed higher levels of interleukin (IL)‐33 in peripheral blood, compared to healthy control (HCs). However, we also noticed that there were no significant differences of IL‐33 levels between controls and asthma patients in a recent study. We aim to conduct this meta‐analysis and evaluate the feasibility of IL‐33 in peripheral blood that may act as a promising biomarker in asthma. Methods Articles published before December 2022 were searched in these databases (PubMed, Web of Science, EMBASE, and Google Scholar). We used STATA 12.0 software to compute the results. Results The study showed that asthmatics showed higher IL‐33 level in serum and plasma, compared to HCs (serum: standard mean difference [SMD] 2.06, 95% confidence interval [CI] 1.12−3.00, I2 = 98.4%, p

AimsGrowth differentiation factor-15 (GDF-15) and adiponectin are adipokines that regulate metabolism. This study aimed to evaluate the roles of GDF-15, adiponectin, and GDF-15/adiponectin ratio (G/A ratio) as biomarkers for detecting metabolic syndrome (MS).Materials and methodsThis cross-sectional study included 676 participants aged 20–70 years in Jurong, China. The participants were divided into four groups based on sex and age (

Purpose: To analyze the effect of the physiological deformation of the vessel wall on the hemodynamics in the abdominal aortic aneurysm (AAA), this paper compared the hemodynamics in AAA based on the moving boundary (MB) simulation and the rigid wall (RW) simulation.Method: Patient-specific models were reconstructed to generate mesh based on four-dimensional computed tomography angiography (4D CT) data. The dynamic mesh technique was used to achieve deformation of the vessel wall, surface mesh and volume mesh of the fluid domain were successively remeshed at each time step. Besides, another rigid wall simulation was performed. Hemodynamics obtained from these two simulations were compared.Results: Flow field and wall shear stress (WSS) distribution are similar. When using the moving boundary method (MBM), mean time-averaged wall shear stress (TAWSS) is lower, mean oscillatory shear index (OSI) and mean relative residence time (RRT) are higher. When using the 10th and 20th percentile values for TAWSS and 80th and 90th percentile values for RRT, the ratios of areas with low TAWSS, high OSI and high RRT to the entire vessel wall are higher than those assuming the vessel as rigid. In addition, one overlapping region of low TAWSS, high OSI and high RRT by using the MBM is consistent with the location of thrombus obtained from the follow-up imaging data.Conclusion: The hemodynamics results by using the MBM reflect a higher blood retention effect. This paper presents a potential tool to assess the risk of intraluminal thrombus (ILT) formation based on the MBM.

Respiratory infections are a major public health concern caused by pathogens that colonize and invade the respiratory mucosal surface. Nasal vaccines have the advantage of providing protection at the primary site of pathogen infection, as they induce higher levels of mucosal secretory IgA antibodies and antigen-specific T and B cell responses. Adjuvants are crucial components of vaccine formulation that enhance the immunogenicity of the antigen to confer long-term and effective protection. Saponins, natural glycosides derived from plants, shown potential as vaccine adjuvants, as they can activate the mammalian immune system. Several licensed human vaccines containing saponins-based adjuvants administrated through intramuscular injection have demonstrated good efficacy and safety. Increasing evidence suggests that saponins can also be used as adjuvants for nasal vaccines, owing to their safety profile and potential to augment immune response. In this review, we will discuss the structure-activity-relationship of saponins, their important role in nasal vaccines, and future prospects for improving their efficacy and application in nasal vaccine for respiratory infection.

This research introduces a method to enhance the biocompatibility of bioinert Al2O3-based ceramics by incorporating calcium phosphates (hydroxyapatite (HAp) and tricalcium phosphate (TCP)) into alumina via spark plasma sintering-reactive sintering (SPS-RS). TGA/DTG/DTA and XRD revealed phase formation of HAp and TCP and determined the main temperature points of solid-phase reactions occurring in situ during the sintering of the CaO-CaHPO4 mixture within the volume of Al2O3 under SPS-RS conditions in the range of 900–1200 °C. SEM, EDX, low temperature, and nitrogen physisorption were used to monitor changes in the morphology, structure, and elemental composition of bioceramics. Structural meso- and macroporosity, with a mean mesopore size of 10 nm, were revealed in the ceramic volume, while sintering temperature was shown to play a destructive role towards the porous inorganic framework. The physico-chemical characterization demonstrated increased relative density (up to 95.1%), compressive strength (640 MPa and above), and Vickers microhardness (up to 700 HV) depending on the HAp and TCP content and sintering temperature. Four bioceramic samples with different contents of HAP (20 and 50 wt.%) were bio-tested in in vivo models. The samples were implanted into the soft tissues under the superficial fascia of the thorax of a laboratory animal (a New Zealand White rabbit, female) in the area of the trapezius muscle and the broadest muscle of the back. Based on the results of the assessment of the surrounding tissue reaction, the absence of specific inflammation, necrosis, and tumor formation in the tissues during the implantation period of 90 days was proven. Microbial tests and dynamics of Pseudomonas aeruginosa bacterial film formation on bioceramic surfaces were studied with respect to HAp content (20 and 50 wt.%) and holding time (18, 24, and 48 h) in the feed medium.

Cytokines play vital roles in the pathogenesis of inflammatory bowel disease. IL17B is protective in the development of colitis. However, how IL17B regulates intestinal inflammation and what cells are regulated by IL17B is still unknown. Here, we aimed to illustrate the IL17B dependent cellular and molecular changes in colon tissue in a mouse colitis model. The results showed that IL17B expression in colon tissues was elevated in inflamed tissues than non-inflamed tissues of IBD patients. Wild type (WT) and Il17b deficient (Il17b-/-) mice were given 2.5% dextran sodium sulfate (DSS) water, and in some case, Il17b-/- mice were treated with recombinant mouse IL17B. IL17B deficiency resulted in severe DSS-induced colitis with exaggerated weight loss, shorter colon length, and elevated proinflammatory cytokines in colon. Reconstitution of Il17b-/- mice with recombinant IL17B alleviated the severity of DSS-induced colitis. Single cell transcriptional analyses of CD45+ immune cells in colonic lamina propria revealed that loss of IL17B resulted in an increased neutrophil infiltration and enhanced inflammatory cytokines in intestinal macrophages in colitis, which were confirmed by real-time PCR and flow cytometry. IL17B treatment also inhibited lipopolysaccharide-induced inflammation in bone marrow-derived macrophages and mice. IL17B inhibits colitis by regulating colonic myeloid cell response. It might represent a novel potential therapeutic approach to treat the colitis.

Organic–inorganic composite scintillators, demonstrating advantages of easy large-area preparation and a high detection efficiency, have shown enormous potential application prospects in radiation detection and imaging. In this study, bulk polystyrene (PS) composite scintillators were successfully prepared by embedding inorganic BaF2 particles with a loading amount of up to 80 wt% during the polymerization process of the plastic scintillator. The inorganic BaF2 particles were uniformly dispersed in the organic matrix. With the increase of the loading amounts of BaF2 particles, the X-ray-excited luminescence intensity of the PS-BaF2 composite scintillators was about eight times higher than that of the commercial pure plastic scintillator. The scintillation counts under the gamma ray (59.5 KeV) irradiation also showed that the detection efficiency was obviously enhanced by BaF2 particle loading. More importantly, their scintillation pulse retains the decay kinetics of the organic matrix without loading the slow-decay component of BaF2. This work provides a promising solution for the application of the PS-BaF2 composite scintillator in high-efficiency radiation detection and large-area imaging.

In this report, we establish a straightforward method for estimating the equilibrium constant for the creatine kinase reaction (CK Keq″) over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq″ is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we were able to obtain improved estimates of ΔGATP, necessitating the reinvestigation of previously reported ADP- and ΔGATP-dependent processes. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies and pH is not altered, the maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis around the role of submicromolar ADP in force generation.

This paper reports a method for the fabrication of mineral-like SrMoO4 ceramics with a powellite structure, which is promising for the immobilization of the high-energy 90Sr radioisotope. The reported method is based on the solid-phase “in situ” interaction between SrO and MoO3 oxides initiated under spark plasma sintering (SPS) conditions. Dilatometry, XRD, SEM, and EDX methods were used to investigate the consolidation dynamics, phase formation, and structural changes in the reactive powder blend and sintered ceramics. The temperature conditions for SrMoO4 formation under SPS were determined, yielding ceramics with a relative density of 84.0–96.3%, Vickers microhardness of 157–295 HV, and compressive strength of 54–331 MPa. Ceramic samples demonstrate a low Sr leaching rate of 10−6 g/cm2·day, indicating a rather high hydrolytic stability and meeting the requirements of GOST R 50926-96 imposed on solid radioactive wastes. The results presented here show a wide range of prospects for the application of ceramic matrixes with the mineral-like composition studied here to radioactive waste processing and radioisotope manufacturing.

Abstract Background Cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), but few studies have been conducted to identify CVD risk in COPD patients. This study was to develop a predictive model of CVD in COPD patients based on the National Health and Nutrition Examination Survey (NHANES) database. Methods A total of 3,226 COPD patients were retrieved from NHANES 2007–2012, dividing into the training (n = 2351) and testing (n = 895) sets. The prediction models were conducted using the multivariable logistic regression and random forest analyses, respectively. Receiver operating characteristic (ROC) curves, area under the curves (AUC) and internal validation were used to assess the predictive performance of models. Results The logistic regression model for predicting the risk of CVD was developed regarding age, gender, body mass index (BMI), high-density lipoprotein (HDL), glycosylated hemoglobin (HbA1c), family history of heart disease, and stayed overnight in the hospital due to illness last year, which the AUC of the internal validation was 0.741. According to the random forest analysis, the important variables-associated with CVD risk were screened including smoking (NNAL and cotinine), HbA1c, HDL, age, gender, diastolic blood pressure, poverty income ratio, BMI, systolic blood pressure, and sedentary activity per day. The AUC of the internal validation was 0.984, indicating the random forest model for predicting the CVD risk in COPD cases was superior to the logistic regression model. Conclusion The random forest model performed better predictive effectiveness for the cardiovascular risk among COPD patients, which may be useful for clinicians to guide the clinical practice.

BackgroundType 2 diabetes (T2D) in Chinese Americans is a rising public health concern for the US health care system. The majority of Chinese Americans with T2D are foreign-born older immigrants and report limited English proficiency and health literacy. Multiple social determinants of health limit access to evidence-based diabetes interventions for underserved Chinese immigrants. A social media–based diabetes intervention may be feasible to reach this community. ObjectiveThe purpose of the Chinese American Research and Education (CARE) study was to examine the potential efficacy of a social media–based intervention on glycemic control in Chinese Americans with T2D. Additionally, the study aimed to explore the potential effects of the intervention on psychosocial and behavioral factors involved in successful T2D management. In this report, we describe the design and protocol of the CARE trial. MethodsCARE was a pilot randomized controlled trial (RCT; n=60) of a 3-month intervention. Participants were randomized to one of two arms (n=30 each): wait-list control or CARE intervention. Each week, CARE intervention participants received two culturally and linguistically tailored diabetes self-management videos for a total of 12 weeks. Video links were delivered to participants via WeChat, a free and popular social media app among Chinese immigrants. In addition, CARE intervention participants received biweekly phone calls from the study’s community health workers to set goals related to T2D self-management and work on addressing goal-achievement barriers. Hemoglobin A1c (HbA1c), self-efficacy, diabetes self-management behaviors, dietary intake, and physical activity were measured at baseline, 3 months, and 6 months. Piecewise linear mixed-effects modeling will be performed to examine intergroup differences in HbA1c and psychosocial and behavioral outcomes. ResultsThis pilot RCT study was approved by the Institutional Review Board at NYU Grossman School of Medicine in March 2021. The first participant was enrolled in March 2021, and the recruitment goal (n=60) was met in March 2022. All data collection is expected to conclude by November 2022, with data analysis and study results ready for reporting by December 2023. Findings from this pilot RCT will further guide the team in planning a future large-scale study. ConclusionsThis study will serve as an important first step in exploring scalable interventions to increase access to evidence-based diabetes interventions among underserved, low-income, immigrant populations. This has significant implications for chronic care in other high-risk immigrant groups, such as low-income Hispanic immigrants, who also bear a high T2D burden, face similar barriers to accessing diabetes programs, and report frequent social media use (eg, WhatsApp). Trial RegistrationClinicalTrials.gov NCT03557697; https://clinicaltrials.gov/ct2/show/NCT03557697 International Registered Report Identifier (IRRID)DERR1-10.2196/42554

Objectives: To assess whether the extension of the flushing interval will increase risks of complications associated with totally implantable venous access port (TIVAP) in the off-treatment period. Methods: A retrospective single-center observational study was performed. Patients with a TIVAP in the off-treatment period that underwent regular flushing in our clinic were included. Data concerning patients and their TIVAPs were recorded. Patient baseline characteristics and TIVAP-related complications were analyzed. Continuous variables were analyzed by ANOVA or the Kruskal-Wallis H test. To compare the occurrence of TIVAP-related complications, the chi-square test was used; if needed, Fisher’s exact test was used. Results: Totally 607 patients were reviewed, and 563 patients were finally included. Thirteen complications were recorded, including 11 cases of catheter occlusion (1.95%), one case of port cannula rotation (0.18%), and one case of catheter tip malposition (0.18%). No device-related infection or venous thrombosis was recorded. Among these patients, the average flushing interval was 35.27 ± 13.09 days. Patients were divided into three groups according to the flushing interval: every 28 days or less (Group 1, n = 133); every 29–44 days (Group 2, n = 350); and every 45 days or more (Group 3, n = 80). No significant difference in catheter-related complications was found among the three groups (P > 0.05). Conclusions: In the TIVAP off-treatment period, patients without any history of TIVAP-related complications during approximately one year can attempt to prolong the flushing interval to more than 4 weeks; we further suggest that 5–6 weeks may be an appropriate option for these patients.

Introduction There is an enormous imbalance between the rapid development of day surgery and the current conventional medical services. Hence, an effective day surgery management mode should be developed that can be used to constantly follow up on patients both preoperatively and postoperatively. In this study, WeChat was chosen as the platform. This study aimed to investigate the feasibility and effectiveness of a new day surgery management mode.Methods and analysis This randomised controlled study investigated the efficacy of a new day surgery management mode based on WeChat. The target number of participants was 1000 per group. The application (app) will send personalised information based on the medical history of the patient and the type of surgery at different time points preoperatively and postoperatively. The healthcare worker can follow up the patient and acquire clinical data by simply signing into the app. The patient and the healthcare worker can also engage in video or voice chats using the app when necessary. Multiple departments, including anaesthesiology, internal medicine, surgery, nursing and psychology, will participate in this new mode.Ethics and dissemination Ethical approval was obtained from the West China Hospital of Sichuan University Biomedical Research Ethics Committee. Results of this study will be published in peer-reviewed journals and presented at international conferences.Trial registration number ChiCTR2100050793.

Breast cancer (BC) is now the most frequent and lethal cancer among women. Cuproptosis is a newly identified programmed cell death process that has been connected to tumor therapeutic sensitivity, patient outcomes, and the genesis of cancer. Cuproptosis-related genes (CRGs) are involved in breast cancer, although their roles and potential mechanisms are still unclear. First, we examined the effect of gene mutations and copy number changes on overall survival in 1168 breast cancer samples. Breast cancer patients were split into two molecular categories as determined by the variation in CRG based on clinicopathological traits, overall survival, and cell-infiltrating traits in tumor microenvironments. In addition, we created and validated a CRG score to calculate breast cancer patients' OS. Finally, we created a comprehensive nomogram for the clinical use of the CRG score. Patients whose CRG scores were low showed increased odds of developing OS, a larger mutation load, and immunological activation than those with high CRG scores. The CRG score, the cancer stem cell index, and the responsiveness to chemotherapy or targeted therapies were also shown to be statistically significantly correlated. Our thorough examination of CRGs in breast cancer patients demonstrated that they may be useful predictors of prognosis, clinical characteristics, and tumor microenvironment. These findings provide fresh insight into CRGs in breast cancer and might inspire brand-new approaches to both diagnosing and treating patients there.

ObjectiveConvolutional Neural Network(CNN) is increasingly being applied in the diagnosis of gastric cancer. However, the impact of proportion of internal data in the training set on test results has not been sufficiently studied. Here, we constructed an artificial intelligence (AI) system called EGC-YOLOV4 using the YOLO-v4 algorithm to explore the optimal ratio of training set with the power to diagnose early gastric cancer.DesignA total of 22,0918 gastroscopic images from Yixing People’s Hospital were collected. 7 training set models were established to identify 4 test sets. Respective sensitivity, specificity, Youden index, accuracy, and corresponding thresholds were tested, and ROC curves were plotted.Results1. The EGC-YOLOV4 system completes all tests at an average reading speed of about 15 ms/sheet; 2. The AUC values in training set 1 model were 0.8325, 0.8307, 0.8706, and 0.8279, in training set 2 model were 0.8674, 0.8635, 0.9056, and 0.9249, in training set 3 model were 0.8544, 0.8881, 0.9072, and 0.9237, in training set 4 model were 0.8271, 0.9020, 0.9102, and 0.9316, in training set 5 model were 0.8249, 0.8484, 0.8796, and 0.8931, in training set 6 model were 0.8235, 0.8539, 0.9002, and 0.9051, in training set 7 model were 0.7581, 0.8082, 0.8803, and 0.8763.ConclusionEGC-YOLOV4 can quickly and accurately identify the early gastric cancer lesions in gastroscopic images, and has good generalization.The proportion of positive and negative samples in the training set will affect the overall diagnostic performance of AI.In this study, the optimal ratio of positive samples to negative samples in the training set is 1:1~ 1:2.

Glioblastoma multiforme (GBM) is the most common, malignant, and deadly primary brain tumor in adults. Brain-expressed X-link (BEX) protein family is involved in tumorigenesis. Here, we have explored the biological function and the prognostic value of the BEX family in GBM. Differentially expressed BEX genes between GBM and normal tissue were screened by using The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses identified the prognosis‐related genes BEX1, BEX2, and BEX4, which were involved in the regulation of immune response. The results of correlation analysis and protein–protein interaction network (PPI network) showed that there was a significant correlation between the BEX family and TCEAL family in GBM. Furthermore, the expression of transcription elongation factor A (SII)-like (TCEAL) family is generally decreased in GBM and related to poor prognosis. With the use of the least absolute shrinkage and selection operator (LASSO) Cox regression, a prognostic model including the BEX family and TCEAL family was built to accurately predict the likelihood of overall survival (OS) in GBM patients. Therefore, we demonstrated that the BEX family and TCEAL family possessed great potential as therapeutic targets and prognostic biomarkers in GBM. Further investigations in large‐scale, multicenter, and prospective clinical cohorts are needed to confirm the prognostic model developed in our study.

Objective: Globally, cerebral ischemia has been shown to be the second leading cause of death. Our previous studies have shown that Taohong Siwu Decoction (THSWD) exhibits obvious neuroprotective effects on cerebral ischemia/reperfusion (I/R) injury (CIRI). In this study, we further explored the modulatory effect of THSWD on mitochondrial autophagy in CIRI and the relationship between modulatory effect and NLRP3 inflammatory vesicle activation, so as to further explain the mechanism of neuroprotective effect of THSWD.Methods: Middle cerebral artery occlusion reperfusion (MCAO/R) model in rats was built to simulate I/R. Adult male SD rats (220–270 g) were randomly divided into the following four groups: the sham group, the MCAO/R group, the MCAO/R + THSWD group, and the MCAO/R + THSWD + Mitochondrial division inhibitor 1 (Mdivi-1) group. Neurological defect scores were used to evaluate neurological function. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was conducted to measure cerebral infarct volume. Nissl staining, H&E staining and TUNEL staining were executed to detect ischemic cortical neuronal cell viability and apoptosis. Electron microscopy was used to observe the ultrastructural changes of mitochondria. Total Reactive Oxygen Species (ROS) in tissue were measured by fluorescence spectrophotometry, and the activation status of microglia was evaluated by Iba-1/CD16 immunofluorescence staining. The levels of mitophagy-related proteins (LC3, Parkin, PINK1), NLRP3 inflammasome-related proteins (NLRP3, ASC, Pro-caspase-1, Cleaved-caspase-1), and inflammatory cytokines (Pro-IL-18, Pro-IL-1β, IL-18, IL-1β) were evaluated by western blotting.Results: The studies showed that THSWD treatment alleviated cerebral infarction and neurological deficiencies. THSWD upregulated the expressions of autophagy markers (LC3-II/LC3-I and Beclin1) mitochondrial autophagy markers (Parkin and PINK1) after CIRI. Furthermore, THSWD treatment attenuated microglia activation and damage to mitochondrial structures, thereby reducing ROS production and NLRP3 inflammasome activation. In contrast, the mitochondrial autophagy inhibitor Mdivi-1 inhibited the above beneficial effects of THSWD.Conclusions: THSWD exhibits neuroprotective effects against MCAO/R in rats by enhancing mitochondrial autophagy and reducing NLRP3 inflammasome activation.