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Abstract Realizing an efficient turnover frequency in the acidic oxygen evolution reaction by modifying the reaction configuration is crucial in designing high-performance single-atom catalysts. Here, we report a “single atom–double site” concept, which involves an activatable inert manganese atom redox chemistry in a single-atom Ru-Mn dual-site platform with tunnel Ni ions as the trigger. In contrast to conventional single-atom catalysts, the proposed configuration allows direct intramolecular oxygen coupling driven by the Ni ions intercalation effect, bypassing the secondary deprotonation step instead of the kinetically sluggish adsorbate evolution mechanism. The strong bonding of Ni ions activates the inert manganese terminal groups and inhibits the cross-site disproportionation process inherent in the Mn scaffolding, which is crucial to ensure the dual-site platform. As a result, the single-atom Ru-Ni-Mn octahedral molecular sieves catalyst delivers a low overpotential, adequate mass activity and good stability.

Abstract The apparent optimum air temperature for vegetation photosynthesis (Topt) is a key temperature parameter in terrestrial ecosystem models estimating daily photosynthesis or gross primary production (GPP, g C/m2/day). To date, most models use biome-specific Topt (Topt-biome) parameter values. Given vegetation acclimation and adaptation to local climate, site-specific Topt (Topt-site) is needed to reduce uncertainties in estimating daily GPP across the scales from site to region and the globe. Previous studies have demonstrated using the Enhanced Vegetation Index (EVI) derived from Moderate Resolution Imaging Spectroradiometer (MODIS) images and daytime air temperature data to estimate the Topt-site at the eddy covariance tower sites. This study used MODIS-derived EVI and ERA5 climate data to estimate and generate global Topt-site data products from 2000 to 2019. The Topt-site of individual pixels within a biome has large variation, which clearly cannot be represented accurately by the widely used Topt-biome. Therefore, using this global dataset of Topt-site estimates might significantly affect GPP simulation in current ecosystem models.

To effectively replace diseased and damaged thoracic vertebrae, a series of three-dimensional (3D) printed titanium (Ti) alloy (Ti6Al4V) thoracic fusion cages with varying volume ratio of reinforced scaffolds are designed, and their structure-function relationships are investigated systematically. It is demonstrated that the mechanical strength of fusion cage is gradually enhanced as the scaffold volume increases, which may be attributed to its textural transformation from α phase to β phase. The compressive, shear, and fatigue of fusion cages successfully attain the International Organization for Standardization (ISO 23089), when the scaffold volume ratio exceeds 15%. Furthermore, the biomechanical analyses, including stress distributions and subsidence in flexion, extension, axial rotation, and lateral bending sections of fusion cages, further shed light on their potential clinical applications. This work deeply deciphers the intrinsic connection between biomechanical property and material texture of the thoracic fusion cages, offering valuable insights into their strengthening mechanism, which providing a guidance for the precise design and quick synthesis of other 3D-printed Ti6Al4V implants.

Abstract Background Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers. Methods This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored. Results Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy. Conclusions Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.

Abstract In order to obtain amphiphilic polysaccharide self-assembly micelles, the hydrophobic modification by grafting stearic acid (SA) onto the backbone of burdock root polysaccharide (BRP) was carried out and its main physicochemical properties were characterized. The results showed that the optimal esterification conditions were as follows: reaction time of 2 h, reaction temperature of 55 ℃, system pH of 8.0 and the SA addition of 4 mmol, a maximum substitution degree (DS) of the esterification products was obtained as 0.1012. The FTIR analysis verified that the modified polysaccharide successfully introduced the ester carbonyl group. 1H NMR spectra further confirmed that the esterification reaction occurred. The SA-modified BRP micelles were roughly spherical with uniform dispersion and the particle size was in the range of 259–352 nm, which showed a negative correlation with the DS. The solubility of the esterification products also decreased. The smaller critical micelle concentration (CMC) led to easier formation of self-aggregating micelles and stronger solubilization effect. The above results indicated that SA-modified BRP as a novel carrier material possessed potential to deliver hydrophobic active substances. Graphical Abstract

BackgroundVaccination services are increasingly in demand by the public, and mobile apps are an effective tool to meet that demand. However, the characteristics and quality of these apps are unknown. ObjectiveCommonly used vaccination service apps on the market were surveyed with regard to quality, service content, and user experience to evaluate and guide users. MethodsThe Qimai Data mobile app data analytics platform was used to search for common vaccination service apps by keyword, and the WeChat and Alipay platforms were searched for apps. The apps included in the study were independently evaluated by two reviewers using the Mobile Application Rating Scale, and the service content and user experience of the apps were analyzed. The intragroup correlation coefficient between raters was used to measure interrater reliability. ResultsIn the app stores of the four major Android platforms and the iOS app store, 1092 and 207 apps were found, respectively; 189 WeChat applets and 30 Alipay applets were also found. A total of 29 apps was ultimately included in this study according to the inclusion criteria, including 21 independent apps, 4 WeChat applets, and 4 Alipay applets. Significant differences were found between independent apps and applets in terms of the quality score (t449.57=–5.301; P

Summary: Background: Oesophagogastroduodenoscopy (OGD) quality and identification of the early upper gastrointestinal (UGI) neoplasm play an important role in detecting the UGI neoplasm. However, the optimal method for quality control in daily OGD procedures is currently lacking. We aimed to evaluate the efficacy of a real-time intelligent quality-control system (IQCS), which combines OGD quality control with lesion detection of early UGI neoplasms. Methods: We performed a multicentre, single-blinded, randomised controlled trial at 6 hospitals in China. Patients aged 40–80 years old who underwent painless OGD were screened for enrolment in this study. Patients with a history of advanced UGI cancer, stenosis, or obstruction in UGI tract were excluded. Eligible subjects were randomly assigned (1:1) to either the routine or IQCS group to undergo standard OGD examination and OGD examination aided by IQCS, respectively. Patients were masked to the randomisation status. The primary outcome was the detection of early UGI neoplasms. All analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, NCT04720924. Findings: Between January 16, 2021 and December 23, 2022, 1840 patients were randomised (IQCS group: 919, routine group: 921). The full analysis set consisted of 914 in the IQCS group and 915 in the routine group. The early UGI neoplasms detection rate in the IQCS group (6.1%, 56/914) was significantly higher than in the routine group (2.3%, 21/915; P = 0.0001). The IQCS group had fewer blind spots (2.3 vs. 6.2, P

BackgroundmicroRNAs (miRNAs) were recognized as a promising source of diagnostic biomarker. Herein, we aim to evaluate the performance of an ultrasensitive method for detecting serum miRNAs using single molecule arrays (Simoa).MethodsIn this study, candidate miRNAs were trained and tested by RT-qPCR in a cohort of PTB patients. Besides that, ultrasensitive serum miRNA detection were developed using the Single Molecule Array (Simoa) platform. In this ultra-sensitive sandwich assay, two target-specific LNA-modified oligonucleotide probes can be simply designed to be complementary to the half-sequence of the target miRNA respectively. We characterized its analytical performance and measured miRNAs in the serum of patients with pulmonary tuberculosis and healthy individuals.ResultsWe identified a five signature including three upregulated (miR-101, miR-196b, miR-29a) and two downregulated (miR-320b, miR-99b) miRNAs for distinguishing PTB patients from HCs, and validated in our 104 PTB patients. On the basis of Simoa technology, we developed a novel, fully automated digital analyser, which can be used to directly detect miRNAs in serum samples without pre-amplification. We successfully detected miRNAs at femtomolar concentrations (with limits of detection [LODs] ranging from 0.449 to 1.889 fM). Simoa-determined serum miR-29a and miR-99b concentrations in patients with PTB ((median 6.06 fM [range 0.00–75.22]), (median 2.53 fM [range 0.00–24.95]), respectively) were significantly higher than those in HCs ((median 2.42 fM [range 0.00–28.64]) (P < 0.05), (median 0.54 fM [range 0.00–9.12] (P < 0.0001), respectively). Serum levels of miR-320b were significantly reduced in patients with PTB (median 2.11 fM [range 0.00–39.30]) compared with those in the HCs (median 4.76 fM [range 0.00–25.10]) (P < 0.001). A combination of three miRNAs (miR-29a, miR-99b, and miR-320b) exhibited a good capacity to distinguish PTB from HCs, with an area under the curve (AUC) of 0.818 (sensitivity: 83.9%; specificity: 79.7%).ConclusionsThis study benchmarks the role of Simoa as a promising tool for monitoring miRNAs in serum and offers considerable potential as a non-invasive platform for the early diagnosis of PTB.

Modern medical understanding suggests that hyperproliferative skin diseases (HSDs) are complex syndromes characterized by localized hypertrophy or hyperplasia and infiltration of inflammatory cells. Various treatments, including systemic and topical pharmacotherapy, laser interventions, photodynamic therapy, and surgery, have been proposed for managing HSDs. However, challenges such as wound healing and recurrence after laser treatment have hindered the effectiveness of laser therapy. To overcome these challenges, we conducted a study combining laser therapy with cold atmospheric plasma (CAP) for the treatment of HSDs. Seven patients with different forms of HSDs, who had not responded well to conventional treatments, were enrolled in the study. These HSDs included cases of erythroplasia of Queyrat, pyoderma gangrenosum, keloids and hypertrophic scars, cellulitis, cutaneous lichen planus, and verruca vulgaris. Laser therapy was performed to remove the hyperplastic skin lesions, followed immediately by daily CAP treatment. The results were promising, with all patients successfully treated and no recurrence observed during the follow-up periods. The combined application of CAP and laser therapy proved to be an effective and complementary strategy for managing HSDs. This innovative approach provide evidence for addressing the limitation of laser therapy by utilizing CAP to promote wound healing and mitigate inflammatory responses.Chinese Clinical Trial Registry (ChiCTR2300069993).

Abstract Background The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. Methods Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. Results After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P

Kidney renal papillary cell carcinoma (KIRP) is a highly heterogeneous type of kidney cancer, resulting in limited effective prognostic targets for KIRP patients. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the regulation of ferroptosis and iron metabolism, making them potential targets for the treatment and prognosis of KIRP. In this study, we constructed a ferroptosis-related lncRNA risk score model (FRM) based on the TCGA-KIRP dataset, which represents a novel subtype of KIRP not previously reported. The model demonstrated promising diagnostic accuracy and holds potential for clinical translation. We observed significant differences in metabolic activities, immune microenvironment, mutation landscape, ferroptosis sensitivity, and drug sensitivity between different risk groups. The high-risk groups exhibit significantly higher fractions of cancer-associated fibroblasts (CAFs), hematopoietic stem cells (HSC), and pericytes. Drugs (IC50) analysis provided a range of medication options based on different FRM typing. Additionally, we employed single-cell transcriptomics to further analyze the impact of immune invasion on the occurrence and development of KIRP. Overall, we have developed an accurate prognostic model based on the expression patterns of ferroptosis-related lncRNAs for KIRP. This model has the potential to contribute to the evaluation of patient prognosis, molecular characteristics, and treatment modalities, and can be further translated into clinical applications.

Abstract Objective Evaluation of the accuracy and effectiveness of 3D printed guides to assist femoral tunnel preparation in individualised reconstruction of the anterior cruciate ligament. Methods Sixty patients who attended the Affiliated Hospital of Binzhou Medical College for autologous hamstring single bundle reconstruction of the anterior cruciate ligament from October 2018 to October 2020 were selected and randomly divided into two groups, including 31 cases in the 3D printing group (14 males and 17 females, mean age 41.94 ± 10.15 years) and 29 cases in the control group (13 males and 16 females, mean age 37.76 ± 10.34 years). Patients in both groups were assessed for intraoperative femoral tunnel accuracy, the number of intraoperative positioning and the time taken to prepare the femoral tunnel, the length of the anteromedial approach incision, the pre-planned bone tunnel length and intraoperative bone tunnel length in the 3D printed group, IKDC score and Lysholm score preoperatively and at 3, 6 and 12 months postoperatively, the Lachman、pivot-shift test preoperatively and at 6 months postoperatively, gait analysis to assess internal and external rotation in flexion of the knee at 12 months postoperatively and postoperative complications in both groups. Results There was no statistical difference in functional knee scores and anteromedial approach incision length between the 3D printed and control groups (p > 0.05), while there was a statistical difference in the accuracy of tunnel positioning, the time taken to prepare the femoral bone tunnel and the degree of external rotation of the knee in flexion between the two groups (p 0.05). Complications: One case in the 3D printing group developed intermuscular vein thrombosis in the affected lower limb after surgery, which disappeared after treatment, while three cases in the control group developed intermuscular vein thrombosis in the affected lower limb. No complications such as bone tunnel rupture, deep vein thrombosis in the lower limb and infection occurred in either group. Conclusion 3D printed guides assisted with individualized ACL reconstruction may improve the accuracy of femoral tunnel positioning, which is safe and effective, while reducing the operative time and the number of intraoperative positioning, without increasing the length of incision, and may obtain higher functional scores and rotational stability of the knee joint, which is in line with the concept of individualized ACL reconstruction.

How to reduce the quality loss of aquatic products during storage is a topic worth exploring. This study proposed a method combining orthogonal dual-frequency ultrasound-assisted treatment (20 kHz vertically, 40 kHz horizontally, 400 W) with bioactive coating (Melissa officinalis L. essential oil-carboxymethyl chitosan-locust bean gum) and discussed the effects of this combined treatment on the quality, lipid, and protein of large yellow croaker during cold storage (4 °C). The results showed that both ultrasound-assisted treatment (US) and bioactive coating (CMCS) significantly inhibited microbial growth and quality deterioration in the fish, with the combined treatment group (US+CMCS) showing the best effect. The shelf life of large yellow croaker in the control group (CK) was 6 d, while the shelf life for US, CMCS, and US+CMCS treatments was 12 d, 12 d, and 18 d, respectively. Additionally, the combined treatment inhibited lipid oxidation and effectively delayed the oxidative degradation of protein in the large yellow croaker during cold storage. Therefore, the method of orthogonal dual-frequency ultrasound-assisted treatment (20 kHz vertically, 40 kHz horizontally, 400 W) combined with bioactive coating (Melissa officinalis L. essential oil-carboxymethyl chitosan-locust bean gum) proposed in this study was a promising approach for the preservation of aquatic products during storage.

Influence mechanism of various ion chelators on the mechanical, transport, and microstructure properties of cement-based materials was explored. The ion chelators included pentasodium diethylenetriamine pentaacetate, tetrasodium ethylenediaminetetraacetate, sodium hexametaphosphate and tetrasodium glutamate diacetate, with a dosage of 1 % of the cement mass. The effect of ion chelators on the mechanical, transport, and pore structure properties was evaluated by compressive, sorptivity, and mercury intrusion porosimetry (MIP) tests. The composition and microstructure of hydration products were studied by scanning electron microscope (SEM) and X-ray diffractometer (XRD). Test results indicated that four ion chelators reduced the mechanical and transport properties, and increased the porosity of specimens at 3 d and 7 d. And four ion chelators improved the mechanical and transport properties, and reduced porosity at 28 d and 56 d. The fundamental reason for the differences in the basic properties of cement-based materials caused by the types of ion chelators is that different ion chelators possess various calcium chelating capacities and stability of calcium complexes, which leads to different impact on the complexation substitution reaction process. Moreover, compared to the stability of calcium complexes, the influence of calcium chelating ability on the basic properties of specimens is more significant in the early curing ages.

The southern Great Plains (SGP) grassland of the United States has been largely encroached by evergreen forest in recent decades. The response of the grassland water and carbon cycles to the encroachment is not clear yet. Given so, this study quantified the changes in gross primary production (GPP), evapotranspiration (ET), and ecosystem water use efficiency (EWUE) between grassland pixels with evergreen forest encroachment and neighboring pure grassland pixels (500 m). We also assessed the spatial variation of the changes in relation to precipitation (mm), air temperature (°C), and evergreen forest coverage (%). These analyses were repeated, respectively for the years of 2004, 2008, 2016, and 2019 as robustness check. Results suggest that across the 4 years, 62–72% of encroached grassland pixels exhibit higher annual GPP, 67–74% exhibit higher annual ET, whereas 65–71% exhibit lower annual EWUE. The change ratio of ET is positively correlated with that of GPP but negatively correlated with that of EWUE. Additionally, the spatial variation in the change ratios of annual GPP and ET can be explained to a certain degree by the encroachment amount. These results further clarify the response of water and carbon cycles to evergreen forest encroachment in the SGP grassland.

BackgroundEnhancing speech-language therapy remains the most effective strategy for improving post-stroke aphasia, However, conventional face-to-face interventions often lack the necessary therapeutic intensity. In recent years, mobile application-based speech-language therapy has emerged progressively, offering new opportunities for independent rehabilitation among aphasic patients. This review aims to evaluate the impact of mobile application-based interventions on post-stroke aphasic.MethodsBy conducting a systematic search across five databases (PubMed, Web of Science, EMBASE, CINAHL, and Scopus), we identified and included studies that investigated the utilization of mobile application-based technologies (such as computers, iPads, etc.) for treating post-stroke aphasia.ResultsThis study included 15 research investigations, including 10 randomized controlled trials (RCTs), four self-controlled studies and one cross-over experimental design study. Among these, eight studies demonstrated the efficacy of mobile application-based therapy in enhancing overall language functionality for post-stroke aphasia patients, three studies highlighted its potential for improving communication skills, three studies observed its positive impact on spontaneous speech expression. Moreover, four studies indicated its effectiveness in enhancing naming abilities, two studies underscored the positive influence of mobile application-based interventions on the quality of life for individuals with aphasia. Six studies noted that speech improvement effects were maintained during the follow-up period.ConclusionThe results of this review demonstrate the potential of mobile application-based interventions for improving speech-language function in individuals with aphasia. However, further high-quality research is needed to establish their effects across different domains and to delve into the comparative advantages of various treatment approaches.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=405248

Background The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood.Methods From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC.Results Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6–8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria (Actinomyces_sp_ICM47, and Senegalimassilia_anaerobia) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI.Conclusions In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers.

A neurogenic dysphagia is dysphagia caused by problems with the central and peripheral nervous systems, is particularly prevalent in conditions such as Parkinson’s disease and stroke. It significantly impacts the quality of life for affected individuals and causes additional burdens, such as malnutrition, aspiration pneumonia, asphyxia, or even death from choking due to improper eating. Physical therapy offers a non-invasive treatment with high efficacy and low cost. Evidence supporting the use of physical therapy in dysphagia treatment is increasing, including techniques such as neuromuscular electrical stimulation, sensory stimulation, transcranial direct current stimulation, and repetitive transcranial magnetic stimulation. While initial studies have shown promising results, the effectiveness of specific treatment regimens still requires further validation. At present, there is a lack of scientific evidence to guide patient selection, develop appropriate treatment regimens, and accurately evaluate treatment outcomes. Therefore, the primary objectives of this review are to review the results of existing research, summarize the application of physical therapy in dysphagia management, we also discussed the mechanisms and treatments of physical therapy for neurogenic dysphagia.

In this paper, a back-incidence 3D Composite Electrode Silicon Detector (3DCESD) is proposed and simulated. The electrode structure comprises 70% trench-like and 30% column-like features, achieved through a single etching step utilizing the RIE-lag phenomenon of the Bosch process. The performance of the 3DCESD device is influenced by the structural parameter ${S}$ . Comparative simulations were conducted using TCAD. The overall electric field and weighting potential of 3DCESD are significantly optimized. MIP and continuous pulse laser were performed separately under bias voltages of –50V and –5V. The 3DCESD exhibits notable advantages, including rapid response speed, high charge collection efficiency, minimal inhomogeneity, and low power consumption.

From September 20 to 23, 2023, the 17th National Postgraduates Symposium on Environmental and Occupational Medicine was successfully held in Baotou, Inner Mongolia. This symposium was co-sponsored by the Editorial Board of Journal of Environmental and Occupational Medicine and School of Public Health, Baotou Medical College, Inner Mongolia University of Science and Technology. Themed "Research and practice: Healing the schism", the symposium aimed to activate academic thinking, expand research perspectives, encourage innovation awareness, enhance school-to-school exchanges, and cultivate young talents, especially to promote the close integration of academic research and public health practice. Participants from more than 30 universities and research institutions submitted a total of 82 articles. The symposium also gathered about 200 authors and postgraduates from all over the country to discuss the latest progress and future development in the field of environment and occupational medicine and strive to apply the research results to public health practice.

Abstract Background Cell transplantation has been demonstrated as a promising approach in tissue regeneration. However, the reactive oxygen species (ROS) accumulation and inflammation condition establish a harsh microenvironment in degenerated tissue, which makes the transplanted cells difficult to survive. Methods In this study, we constructed a keep-charging hydrogel microsphere system to enable cells actively proliferate and function in the degenerated intervertebral disc. Specifically, we combined Mg2+ to histidine-functionalized hyaluronic acid (HA-His-Mg2+) through coordination reaction, which was further intercrossed with GelMA to construct a double-network hydrogel microsphere (GelMA/HA-His-Mg2+, GHHM) with microfluidic methods. In vitro, the GHHM loaded with nucleus pulposus cells (GHHM@NPCs) was further tested for its ability to promote NPCs proliferation and anti-inflammatory properties. In vivo, the ability of GHHM@NPCs to promote regeneration of NP tissue and rescue intervertebral disc degeneration (IVDD) was evaluated by the rat intervertebral disc acupuncture model. Results The GHHM significantly enhanced NPCs adhesion and proliferation, providing an ideal platform for the NPCs to grow on. The loaded NPCs were kept active in the degenerative intervertebral disc microenvironment as charged by the Mg2+ in GHHM microspheres to effectively support the loaded NPCs to reply against the ROS-induced inflammation and senescence. Moreover, we observed that GHHM@NPCs effectively alleviated nucleus pulposus degeneration and promoted its regeneration in the rat IVDD model. Conclusion In conclusion, we constructed a keep charging system with a double-network hydrogel microsphere as a framework and Mg2+ as a cell activity enhancer, which effectively maintains NPCs active to fight against the harsh microenvironment in the degenerative intervertebral disc. The GHHM@NPCs system provides a promising approach for IVDD management. Graphical Abstract

With the passage of time, the constant changes in relevant factors, and the daily maintenance of tailings ponds, the difficulty of tailings pond safety management is increasing day by day. In order to systematically improve the early warning ability for tailings pond dam break risk, the relationship between and influence of various related dam break risk factors of tailings ponds are utilised and the combination with dual attention is innovatively proposed. The risk prediction model for tailings ponds, EEMD-DA-LSTM, is improved. First, Pearson correlation coefficients are used to analyse the correlation between risk factors of tailings ponds. Then, the EEMD method is used to decompose the nonlinear displacement sequence, and the weights of input features are dynamically adjusted by double attention (DA). Finally, the LSTM network model is constructed to predict the displacement change. Taking valley-type tailings pond WKB-1 and mountainside tailings pond WKB-2 as examples, the dam break risk prediction models for tailings ponds are constructed based on three different models, the prediction results of different models are compared and analysed, and the prediction accuracy of the models is evaluated by three different evaluation criteria. The research results show that the integration of the EEMD-LSTM model with the DA model, that is, the EEMD-DA-LSTM model, has a better prediction effect for the dam break risk of tailings ponds WKB-1 and WKB-2 than other models through experimental verification. Therefore, the EEMD-DA-LSTM model is of great significance for preventing and resolving the safety risks of tailings ponds. It is valuable for practitioners in the mining industry and environmentally sustainable development.

The increasing utilization of upper limb rehabilitation robots in rehabilitation therapy has brought to light significant safety concerns regarding their mechanical structures and control systems. This study focuses on a six degrees of freedom (DOF) upper limb rehabilitation robot, which has been designed with an emphasis on safety through careful consideration of its mechanical structure and trajectory planning. Various parameter schemes for the shoulder joint angles were proposed, and the robotic arm’s structure was developed by analyzing the spatial motion trajectories of the shoulder joint motor. This design successfully achieves the objective of minimizing the installation space while maximizing the range of motion. Additionally, an enhanced artificial field method is introduced to facilitate the planning of self-collision avoidance trajectories for dual-arm movements. This approach effectively mitigates the risk of collisions between the robotic arm and the human body, as well as between the two robotic arms, during movement. The efficacy of this method has been validated through experimental testing.

Pathogenic microorganisms have been detected in fermented food. Combining the enormous class of the pathogens and their continuously appearing mutants or novel species, it is important to select suitable and safe antibacterial agents for fermented food safety. Lactic acid bacteria (LAB) which produce diverse imperative antimicrobial metabolites have an immense number of applications in the food industry. Here, the human-derived strain YT was isolated due to its cell-free supernatant (CFS-YT) and cells (Cs-YT), respectively performed obvious inhibitory ring to Gram-positive and -negative spoilage bacteria. Strain YT was identified as Lacticaseibacillus rhamnosus by the 16s rDNA sequence and morphology. The antibacterial activity of CFS-YT was demonstrated to be growth-dependent, pHs-sensitive, broadly thermostable and enzyme-insensitive. Cs-YT displayed a broad antibacterial spectrum with the action mode of bacteriostasis. The antibacterial activity of Cs-YT was due to substances located at the cell surface which were sensitive to heat, stable at broad pH gradients and sensitive to specific enzymes. These data suggested that L. rhamnosus YT could be used as an alternative antimicrobial agent in fermented food biopreservation.

As astronauts stay in the China Space Station for a long time during the operation phase, how to ensure the long-term safety of the scientific experimental rack (SER) in the field of space application is a problem that needs to be solved urgently. Each SER in the field of space station applications is a complex system that faces risks from different hazards. At present, there is no generalized monitoring and diagnosis system for the common risks faced by the SER. In this paper, a generalized safety fault diagnosis system is proposed to ensure the long-term safe and stable work of SERs in orbit, considering the actual risks faced by the SER. With the design of a generalized main control board, a measurement and control board, and an SSPC (solid-state power controller) board, the software and hardware cooperate to realize the acquisition of various physical quantities, data processing, power supply and distribution management, and other functions. Combined with relevant fault detection algorithms, the real-time detection and diagnosis of the relevant risks, abnormality warnings, and fault disposal operations are realized, which can effectively ensure the safety of the payloads in the field of space application, astronauts, and the space-station system.

The MYB gene family exerts significant influence over various biological processes and stress responses in plants. Despite this, a comprehensive analysis of this gene family in pumpkin remains absent. In this study, the MYB genes of Cucurbita moschata were identified and clustered into 33 groups (C1-33), with members of each group being highly conserved in terms of their motif composition. Furthermore, the distribution of 175 CmoMYB genes across all 20 chromosomes was found to be non-uniform. Examination of the promoter regions of these genes revealed the presence of cis-acting elements associated with phytohormone responses and abiotic/biotic stress. Utilizing quantitative real-time polymerase chain reaction (qRT-PCR), the expression patterns of 13 selected CmoMYB genes were validated, particularly in response to exogenous phytohormone exposure and various abiotic stressors, including ABA, SA, MeJA, and drought treatments. Expression analysis in different tissues showed that CmoMYB genes are expressed at different levels in different tissues, suggesting that they are functionally divergent in regulating growth and abiotic stresses. These results provide a basis for future studies to characterize the function of the MYB gene family under abiotic stresses in pumpkins.

BackgroundObstruction is a common complication of advanced colorectal cancer. This study was aimed at investigating the safety, efficacy, and feasibility of transcatheter arterial perfusion chemotherapy combined with lipiodol chemoembolization for treating advanced colorectal cancer complicated by obstruction.Patients and methodsThis retrospective analysis was conducted using clinical data of patients with advanced colorectal cancer who received arterial infusion chemotherapy combined with lipiodol chemoembolization treatment at our center. Treatment efficacy was evaluated in terms of obstruction-free survival and overall survival, and treatment complications were monitored.ResultsFifty-four patients with colorectal cancer complicated by obstruction were included. All patients successfully underwent transcatheter arterial infusion combined with lipiodol chemoembolization treatment. The average lipiodol dose administered was 2.62 ± 1.45 ml (0.5–5.5 ml). No serious complications such as perforation or tumor dissemination occurred. The clinical success rate was 83.3% (45/54). One month after treatment, the objective response rate (ORR) and disease control rate (DCR) were 66.67% and 88.9%, respectively. The median obstruction-free survival was 5.0 months. No serious adverse events occurred. As of the last follow-up, 6 patients survived, 44 died, and 4 were lost to follow-up.ConclusionOur findings revealed that transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization is safe and effective for treating advanced colorectal cancer complicated by obstruction. It may serve as a new treatment strategy for patients with advanced colorectal cancer complicated by obstruction.

Objectives In view of the serious ageing of China’s population and the low desire of elderly people to purchase institutionalised elderly care services, we explored the willingness of Chinese elderly people to purchase institutionalised elderly care services and its influencing factors.Design This was a cross-sectional study. Three multivariate logistic regression analysis models of the willingness of elderly people to purchase institutionalised elderly care services were established (model 1: ‘reluctance – willingness’; model 2: ‘reluctance – hesitation’; and model 3: ‘hesitation – willingness’) to explore the factors that influence elderly people’s willingness to purchase institutionalised elderly care services.Setting This study was based on the 2022 Psychology and Behaviour Investigation of Chinese Residents database.Participants Research data from 4123 older adults who met the requirements of this study were screened from the database.Results Of the 4123 respondents, roughly equal numbers had negative and positive attitudes towards purchasing institutionalised senior care services (1125, 27.3% vs 1079, 26.2%, respectively), and 1919 (46.5%) had hesitant attitudes. The analysis of model 1 showed that medical insurance participation, the number of children and siblings, chronic diseases and per capita monthly household income had an influential effect on the willingness of elderly people to purchase institutional care. In model 2, we found that factors such as per capita monthly household income and anxiety led to hesitancy among older adults to purchase institutionalised senior care services. In model 3, we further found that social support and health literacy led to a shift from hesitation to willingness to purchase institutionalised elderly care services.Conclusion The number of children, number of siblings, per capita monthly income of the family, medical insurance participation, health status, health literacy and social support were found to be the main factors influencing the purchase of institutionalised care by elderly individuals.

In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined presence has raised widespread concern regarding potential risks to organisms. However, the combined toxicity and mechanisms of NPs and TCS remain unclear. In this study, we investigated the toxic effects of polystyrene NPs and TCS and their mechanisms on KGN cells, a human ovarian granulosa cell line. We exposed KGN cells to NPs (150 μg/mL) and TCS (15 μM) alone or together for 24 hours. Co-exposure significantly reduced cell viability. Compared with exposure to NPs or TCS alone, co-exposure increased reactive oxygen species (ROS) production. Interestingly, co-exposure to NPs and TCS produced synergistic effects. We examined the activity of superoxide dismutase (SOD) and catalase (CAT), two antioxidant enzymes; it was significantly decreased after co-exposure. We also noted an increase in the lipid oxidation product malondialdehyde (MDA) after co-exposure. Furthermore, co-exposure to NPs and TCS had a more detrimental effect on mitochondrial function than the individual treatments. Co-exposure activated the NRF2–KEAP1–HO-1 antioxidant stress pathway. Surprisingly, the expression of SESTRIN2, an antioxidant protein, was inhibited by co-exposure treatments. Co-exposure to NPs and TCS significantly increased the autophagy-related proteins LC3B-II and LC3B-Ⅰ and decreased P62. Moreover, co-exposure enhanced CASPASE-3 expression and inhibited the BCL-2/BAX ratio. In summary, our study revealed the synergistic toxic effects of NPs and TCS in vitro exposure. Our findings provide insight into the toxic mechanisms associated with co-exposure to NPs and TCS to KGN cells by inducing oxidative stress, activations of the NRF2-KEAP1-HO-1 pathway, autophagy, and apoptosis.

IntroductionInternet addiction disorder (IAD) has grown into public health concern of global proportions. Previous studies have indicated that individuals with IAD may exhibit altered levels of serotonin and dopamine, which are known to play crucial roles in depression, anxiety, impulsivity, and addiction. Therefore, polymorphisms in the receptors that mediate the effects of serotonin and dopamine and affect their functional states as well as their activities are suspect. In this study, we aimed to investigate the association between IAD and rs6313 (T102C) polymorphism in the serotonin 2A receptor (5-HT2A) gene, (HTR2A).MethodsTwenty patients with IAD and twenty healthy controls (HCs) were included in this study. Young’s Internet Addiction Test (IAT), Self-Rating Anxiety Scale, Self-Rating Depression Scale, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Barratt Impulse Scale, Pittsburgh Sleep Quality Index (PSQI), and Social Support Rating Scale (SSRS) were used to assess the severity of internet addiction, mental status, impulsive traits, sleep quality, and social support. Genotyping was performed to identify rs6313 polymorphisms in the HTR2A gene of all participants.ResultsThe frequencies of the C and T alleles of HTR2A T102C were 28% and 72% in the IAD group and 53% and 47% in the HCs group, respectively, indicating that the differences between these two groups were significant. No significant difference was observed in the distribution of the CC, CT, and TT genotypes of HTR2A gene T102C between the IAD and the HCs groups. Additionally, there was no difference in the distribution of the frequencies of the HTR2A gene T102C CC and CT+TT genotypes between the two groups. However, the distribution between the TT and CC+CT genotypes showed an apparent statistical difference in the HTR2A gene T102C between the two groups. Correlation analysis indicated that the IAT score was positively correlated with the Y-BOCS and BIS scores for the CC+CT genotype in patients with IAD. Moreover, the IAT score was positively correlated with the PSQI score in patients with IAD carrying the TT genotype.ConclusionThe present study demonstrates that rs6313 in HTR2A is associated with IAD, and that the T allele of rs6313 in HTR2A may be a risk factor for IAD.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, prone positioning has been widely applied for non-intubated, spontaneously breathing patients. However, the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear. We aimed to systematically analyze the outcomes associated with awake prone positioning (APP). Methods: We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science from January 1, 2020, to June 3, 2022. This study included adult patients with acute respiratory failure caused by COVID-19. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed using the Cochrane risk-of-bias tool. The primary outcome was the reported cumulative intubation risk across randomized controlled trials (RCTs), and the effect estimates were calculated as risk ratios (RRs; 95% confidence interval [CI]). Results: A total of 495 studies were identified, of which 10 fulfilled the selection criteria, and 2294 patients were included. In comparison to supine positioning, APP significantly reduced the need for intubation in the overall population (RR=0.84, 95% CI: 0.74–0.95). The two groups showed no significant differences in the incidence of adverse events (RR=1.16, 95% CI: 0.48–2.76). The meta-analysis revealed no difference in mortality between the groups (RR=0.93, 95% CI: 0.77–1.11). Conclusions: APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19. However, it did not significantly reduce mortality in comparison to usual care without prone positioning.

Abstract Background Accumulating studies have suggested metabolic syndrome (MetS) contributed to colorectal cancer (CRC) development. However, advanced CRC might decrease the detection proportion of MetS due to chronic malnutrition, we included patients with early-stage CRC to examine the associations among MetS, onset age, and different tumorigenesis pathways of CRC. Methods We conducted a retrospective study that included 638 patients with early-stage CRC from January 2014 to December 2018. Patient information was collected from the medical record system and further refined during the follow-up. Stratified analyses of the associations between MetS and different stratification factors were determined by the Cochran‒Mantel‒Haenszel test. Results There were 16 (13.3%) and 111 (21.4%) cases suffering from MetS in the early-onset and late-onset CRC groups, respectively. MetS coexisted in early-stage CRC patients ≥ 50 years of age more frequently than patients

Abstract Background Oro-gastrointestinal stress in the digestive tract is the main stress to which orally administered probiotics are exposed. The regulation of oro-gastrointestinal transit (OGT) stress on the adhesion and survival of probiotics under continuous exposure to simulated salivary-gastric juice-intestinal juice was researched in this study. Results Lactobacillus plantarum S7 had a higher survival rate after exposure to simulated OGT1 (containing 0.15% bile salt) stress and OGT2 (containing 0.30% bile salt) stress. The adhesion ability of L. plantarum S7 was significantly increased by OGT1 stress (P 0.05), and this trend was also observed in terms of the thickness of the surface material of L. plantarum S7 cells. The expression of surface proteins of L. plantarum S7, such as the 30 S ribosomal proteins, mucus-binding protein and S-layer protein, was significantly downregulated by OGT stress (P

Abstract Large river deltas are usually ecologically important wetland habitats, but also fertile agricultural exploitation areas, creating a conflict of long‐running substantial interest between agricultural expansion and wetland conservation. Over the past several years, large‐scale cultivation of water‐consuming rice has been growing rapidly in the semi‐arid climate of the Yellow River Delta (YRD). Timely monitoring of rice cultivation dynamics is of great significance for sustainable ecological conservation of the delta, which has insufficient freshwater resources. This study proposed a stratified metrics‐based method that integrates statistical spectral indices and phenological metrics at different growing stages to improve the accuracy of rice paddy classification in areas where rice and wetlands coexist. We applied the method to time‐series Sentinel‐1/2 images to produce annual rice paddy maps of the YRD from 2016 to 2021. Together with rice paddy data from 2011 to 2015 from Statistical Yearbooks of Dongying Bureau of Statistics, we investigated the expansion dynamics over the past decade and in this paper discuss the advantages and disadvantages of rice cultivation expansion over wetland ecosystem conservation. Rapid expansion of rice cultivation intensifies water conflicts, and adversely affects wetland restoration in the YRD. Considering the important ecological services of rice paddies as alternative habitats, we argue for maintaining a reasonable scale of rice paddies and optimizing their distribution as a potential solution to achieving the overall sustainable conservation of the YRD in the context of water scarcity.

Abstract Unsafe sex has become a public safety problem that endangers society, and research on deaths and disability-adjusted life years (DALYs) related to unsafe sex is valuable for global policy-making. We aimed to estimate the deaths and DALYs attributable to unsafe sex by country, gender, age group, and sociodemographic status from 1990 to 2019. We extracted data on disease burden from the Global Disease Burden 2019 (GBD 2019) database for unsafe sex, including deaths, DALYs and age-standardized rates (ASRs). Comparative analyses were performed on data about deaths, DALYs and the responding ASRs attributable to unsafe sex in different countries and regions using the Social Demographic Index (SDI). The global age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) attributable to unsafe sex were 11.98 (95% uncertainty intervals (UI): 10.97–13.52) per 100,000 people and 570.78 (95% UI: 510.24–658.10) per 100,000 people, respectively. Both the ASMRs and ASDRs were the highest in southern sub-Saharan Africa and lowest in Australasia and decreased with increasing SDI levels. About unsafe-sex-related disease, HIV/AIDS has the highest ASMR [8.48 (95% UI: 7.62–9.95)/100,000 people] and ASDR [447.44 (95% UI: 394.82–533.10)/100,000 people], followed by Cervical cancer [ASMR: 3.40 (95% UI: 2.90–3.81)/100,000 people and ASDR: 107.2 (95% UI: 90.52–119.43)/100,000 people] and sexually transmitted infections excluding HIV [ASMR: 0.10 (95% UI: 0.08–0.11)/100,000 people and ASDR: 16.14 (95% UI: 10.51–25.83)/100,000 people]. The death and DALY burden caused by these three diseases were more serious in the over 75 years old age group. The 40–44 age group for men and the 35–39 age group for women had the highest population of unsafe sex-related deaths and DALYs, respectively. In addition, the burden of unsafe sex in women was more serious than those in men. Unsafe sex is an important risk factor for global disease burden and a leading cause of substantial health loss. We found that the risk of ASMRs and ASDRs attributable to unsafe sex had negative correlation with SDI levels. These results demonstrate that the need for revised policies that focus on efforts to reduce overall unsafe sex worldwide.

Abstract Background Esophagojejunal anastomotic leakage is a serious complication after total gastrectomy. This study evaluated the safety and efficacy of transnasal placement of drainage catheter, jejunal decompression tube, and jejunal nutrition tube under fluoroscopy for treatment of esophagojejunal anastomotic fistula after gastrectomy in gastric cancer patients. Methods This is retrospective review of patients with esophagojejunal anastomotic fistula treated with transnasal placement of abscess drainage catheter, decompression tube, and jejunal nutrition tube under fluoroscopy. Fistula healing time, patient survival, and Eastern Cooperative Oncology Group (ECOG) performance status before and after treatment were evaluated. Results Sixty-four patients were included in the study. Insertion of the transnasal abscess drainage catheter, decompression tube, and jejunal nutrition tube was successful on the first attempt in all patients, while 35 patients received transnasal abscess drainage, 13 received percutaneous abscess drainage, and 16 received transnasal drainage plus percutaneous abscess drainage. Immediately after placement of the tube, the mean volume of drainage was 180 mL (range, 10–850 mL); the amount steadily decreased from then on. The clinical success rate was 84.3% (54/64). Median time to fistula healing was 58 days (range, 7–357 days). Conclusions Transnasal insertion of transnasal abscess drainage catheter, jejunal decompression tube, and jejunal nutrition tube under fluoroscopy appears to be a simple, minimally invasive, effective, and safe method for treating esophagojejunal anastomotic fistula after gastrectomy.

This paper presents an integrated framework for aircraft engines, which consists of three phases: modeling, control, and experimental testing. The engine is formulated as an uncertain T–S fuzzy model. By a hierarchical dynamical parameter clustering, the number and premise variables of fuzzy rules are optimized, which keeps the engine’s prime and representative dynamics. For each fuzzy rule, a global stability-guaranteed method is developed for the identification of the consequent uncertain dynamic model. The resulting stable T–S fuzzy model accurately approximates the actual engine dynamics in the operation space. Based on this fuzzy model, a new robust control is constructed with hierarchical compensators. The control parameters take advantage of the fuzzy blend of engine prime dynamics and uncertainty thresholds. Extensive hardware-in-loop (HIL) experimental tests in the flight envelope and a flight task cycle demonstrate the effectiveness and real-time performance of the proposed control. The settling times and overshoots of engine response are suppressed to be under 2.5 s and 10%, respectively.

Novel self-assembled aggregates of stearic acid (SA)-modified burdock polysaccharide (BP) for loading lutein were constructed, and the release and absorption properties of lutein in the aggregates in simulated gastrointestinal fluid were investigated. Three different degrees of substitution (DS) of SA-BPs were used to embed lutein, resulting in the encapsulation efficiency exceeding 90%. The aggregates were uniformly spherical, with a particle size range of 227–341 nm. XRD analysis revealed that lutein was present in a non-crystalline state within the aggregates. FT-IR and FS analysis demonstrated that lutein was located in the hydrophobic domains of SA-BP. The highest bioavailability of lutein in these aggregates reached 4.36 times that in the unmodified samples. These aggregates were able to remain stable in gastric juice and enhance the release rate of lutein in intestinal fluid. The transport of lutein-loaded SA-BP aggregates in Caco-2 cells competed with P-glycoprotein inhibitors, mainly promoting the transmembrane absorption of lutein through caveolae (or lipid raft)-related and clathrin-dependent endocytosis pathways. The above results suggest that SA-BP aggregates have the potential to be promising carriers for the efficient delivery of hydrophobic lutein.

With an advancement in global climate change, the frequency of extreme climatic events, such as high temperature, drought, and flooding, has increased. Meanwhile, outbreaks of crop fungal diseases are becoming more frequent and serious, and crop growth and food production are seriously threatened. This article focuses on the climate change-related aggravation of crop fungal diseases; summarizes the progress in research on the impact of climate change on soil-borne fungal diseases, air-borne fungal diseases, and seed-borne fungal diseases; and discusses the conventional methods for diagnosing crop fungal diseases. On the basis of comparative analysis, the concept of ecological control is proposed; ecological control can maintain the dynamic balance of crop–biology–soil, provide a good environment for the healthy growth of crops, and provide a new fungal disease control method in the context of climate change.

Photo plethysmo graphy (PPG) is widely used to detect heart rate and pulse activity due to its simple design, low cost, and signal cycle that can effectively reflect the heart rhythm.Owing to the partial overlap between the emission and the detection spectra of GaN multiple quantum well (MQW) diode, the MQW receiver can respond to the light emitted from the transmitter sharing identical MQW structures.Thus, the fabricate and characterize monolithic integration of GaN transmitter and receiver was proposed as a single unit onto a conventional GaN-on-sapphire platform.This not only can effectively reduce the size and cost of the device, but also fully improves the sensitivity of the system.The experimental results show that the gallium nitride integrated optoelectronic chip can effectively receive the reflected light modulated by the heart pulse.Combined with circuit processing, the tester’s heart rate and pulse beat frequency can be calculated according to the restored PPG signal, so as to play the role of detection and warning.

In this paper, the extraction process of burdock root polysaccharide was optimized using dynamic high pressure microfluidization (DHPM) combined with water extraction, and its infrared spectral structure and monosaccharide composition were analyzed to evaluate its scavenging activities against DPPH·, ·OH and ABTS＋· radicals. The results showed that the factors affecting the yield of burdock root polysaccharide were DHPM pressure>extraction temperature>liquid to solid ratio>extraction time> number of treatments in descending order. The optimal extraction conditions were determined by response surface methodology: DHPM pressure of 148.0 MPa, liquid-solid ratio of 25:1 mL/g, two times of treatment, extraction temperature of 63 ℃ and extraction time of 1 h. Under these conditions, the predicted yield of burdock root polysaccharide reached 29.6%, and the relative error between the actual yield of 29.7% and predicted values was only 0.3%. The polysaccharides were mainly composed of fructose, glucose, arabinose, galactose and glucosamine hydrochloride, with molar ratios of 0.844:0.122:0.024:0.008:0.002. The polysaccharides of burdock root had different effects on DPPH·, ABTS+· and ·OH radicals. The IC50 values were 0.30, 0.36 and 3.93 mg/mL, respectively. The study would provide a reference for the green and efficient extraction of burdock root polysaccharide.

Abstract Purpose The Asia-Pacific Colorectal Screening (APCS) score and its derivatives have been used to predict advanced colorectal neoplasia (ACN). However, it remains unknown whether they apply to the current Chinese population in general clinical practice. Therefore, we aimed to update the APCS score system by applying data from two independent asymptomatic populations to predict the risk of ACN in China. Methods We developed an adjusted APCS (A-APCS) score by using the data of asymptomatic Chinese patients undergoing colonoscopies from January 2014 to December 2018. Furthermore, we validated this system in another cohort of 812 patients who underwent screening colonoscopy between January and December 2021. The discriminative calibration ability of the A-APCS and APCS scores was comparatively evaluated. Results Univariate and multivariate logistic regression were applied to assess the risk factors for ACN, and an adjusted scoring system of 0 to 6.5 points was schemed according to the results. Utilizing the developed score, 20.2%, 41.2%, and 38.6% of patients in the validation cohort were classified as average, moderate, and high risk, respectively. The corresponding ACN incidence rates were 1.2%, 6.0%, and 11.1%, respectively. In addition, the A-APCS score (c-statistics: 0.68 for the derivation and 0.80 for the validation cohort) showed better discriminative power than using predictors of APCS alone. Conclusions The A-APCS score may be simple and useful in clinical applications for predicting ACN risk in China.

PurposeThis study aimed to assess the efficacy and safety of berberine(BBR) plus 5-aminosalicylic acid (5-ASA) for treating ulcerative colitis (UC).MethodsA comprehensive search was conducted in electronic databases, including Medline/PubMed, Sinomed, Embase, CNKI, Wanfang, and VIP, through January 2024 to identify all randomized controlled trials (RCTs) that administered BBR conjunction in standard therapy(5-ASA) for to support the treatment of UC. The data were synthesized using a meta-analysis approach with RevMan 5.4.1. The primary endpoint was the clinical efficacy rate. In contrast, the secondary endpoints included the Baron score, disease activity index (DAI) score, symptom relief latency, inflammatory markers, immunological indicators, and adverse events.ResultsIn this analysis, 10 RCTs comprising 952 patients with UC were examined. BBR considerably improved the clinical efficacy rate (RR = 1.22, 95% CI [1.15, 1.30], P < 0.00001), attenuated the Baron score (SMD = -1.72, 95% CI [-2.30, -1.13], P < 0.00001) and reduced the DAI score (SMD = -2.93, 95% CI [-4.42, -1.43], P < 0.00001). Additionally, it ameliorated clinical symptoms (SMD = -2.74, 95% CI [-3.45, 2.02], P < 0.00001), diminished inflammatory responses (SMD = -1.59, 95% CI [-2.14, 1.04], P < 0.00001), and modulated immune reactions (SMD = 1.06,95% CI [0.24,1.87], P 0.05).ConclusionBBR demonstrates substantial efficacy in treating UC without causing severe adverse reactions and may serve as a viable complementary therapy. However, its clinical application warrants confirmation by additional high-quality, low-bias RCTs.

Streptomycin-resistant (SM-resistant) Mycobacterium tuberculosis (M. tuberculosis) is a major concern in tuberculosis (TB) treatment. However, the mechanisms underlying streptomycin resistance remain unclear. This study primarily aimed to perform preliminary screening of genes associated with streptomycin resistance through conjoint analysis of multiple genomics. Genome-wide methylation, transcriptome, and proteome analyses were used to elucidate the associations between specific genes and streptomycin resistance in M. tuberculosis H37Rv. Methylation analysis revealed that 188 genes were differentially methylated between the SM-resistant and normal groups, with 89 and 99 genes being hypermethylated and hypomethylated, respectively. Furthermore, functional analysis revealed that these 188 differentially methylated genes were enriched in 74 pathways, with most of them being enriched in metabolic pathways. Transcriptome analysis revealed that 516 genes were differentially expressed between the drug-resistant and normal groups, with 263 and 253 genes being significantly upregulated and downregulated, respectively. KEGG analysis indicated that these 516 genes were enriched in 79 pathways, with most of them being enriched in histidine metabolism. The methylation level was negatively related to mRNA abundance. Proteome analysis revealed 56 differentially expressed proteins, including 14 upregulated and 42 downregulated proteins. Moreover, three hub genes (coaE, fadE5, and mprA) were obtained using synthetic analysis. The findings of this study suggest that an integrated DNA methylation, transcriptome, and proteome analysis can provide important resources for epigenetic studies in SM-resistant M. tuberculosis H37Rv.

The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. Expression of the MCR-1 protein affects bacterial fitness and this cost correlates with lipid A perturbation. However, the exact molecular mechanism remains unclear. Here, we identified the MCR-1 M6 variant carrying two-point mutations that conferred co-resistance to β-lactam antibiotics. Compared to wild-type (WT) MCR-1, this variant caused severe disturbance in lipid A, resulting in up-regulation of L, D-transpeptidases (LDTs) pathway, which explains co-resistance to β-lactams. Moreover, we show that a lipid A loading pocket is localized at the linker domain of MCR-1 where these 2 mutations are located. This pocket governs colistin resistance and bacterial membrane permeability, and the mutated pocket in M6 enhances the binding affinity towards lipid A. Based on this new information, we also designed synthetic peptides derived from M6 that exhibit broad-spectrum antimicrobial activity, exposing a potential vulnerability that could be exploited for future antimicrobial drug design.

ABSTRACTBackground We aimed to explore saliva microbiome alterations in dental fluorosis population.Methods The prevalence of dental fluorosis was examined in 957 college students. Dean’s fluorosis index was used to evaluate the dental fluorosis status. Changes in the composition of the salivary microbiome were assessed in a subset of these patients (100 healthy controls, 100 dental fluorosis patients).Results Dental fluorosis affected 47% of the student sample, and incidence was unrelated to gender. Compared with healthy controls, the microbiota of patients with dental fluorosis exhibited increased diversity, with increased abundance of Treponema lecithinolyticum, Vibrio metschnikovii, Cupriavidus pauculus, Pseudomonas, Pseudomonadaceae, Pseudomonadales, and decreased abundance of Streptococcus mutans, Streptococcus sanguinis, Gemella, and Staphylococcales. Function analyses showed increases in arginine biosynthesis in patients affected by dental fluorosis, together with reductions in amino sugar and nucleotide sugar metabolism, fructose and mannose metabolism, and starch and sucrose metabolism.Conclusions These results suggest that there are striking differences in salivary microbiome between healthy controls and dental fluorosis patients. Dental fluorosis may contribute to periodontitis and systemic lung diseases. There is a need for cohort studies to determine whether altering the salivary microbiota in dental fluorosis patients can alter the development of oral or systemic diseases.

Abstract Background Internet addiction (IA), recognized as a behavioral addiction, is emerging as a global public health problem. Acupuncture has been demonstrated to be effective in alleviating IA; however, the mechanism is not yet clear. To fill this knowledge gap, our study aimed to investigate the modulatory effects of acupuncture on the functional interactions among the addiction‐related networks in adolescents with IA. Methods Thirty individuals with IA and thirty age‐ and sex‐matched healthy control subjects (HCs) were recruited. Subjects with IA were given a 40‐day acupuncture treatment, and resting‐state functional magnetic resonance imaging (fMRI) data were collected before and after acupuncture sessions. HCs received no treatment and underwent one fMRI scan after enrollment. The intergroup differences in functional connectivity (FC) among the subcortical nucleus (SN) and fronto‐parietal network (FPN) were compared between HCs and subjects with IA at baseline. Then, the intragroup FC differences between the pre‐ and post‐treatment were analyzed in the IA group. A multiple linear regression model was further employed to fit the FC changes to symptom relief in the IA group. Results In comparison to HCs, subjects with IA exhibited significantly heightened FC within and between the SN and FPN at baseline. After 40 days of acupuncture treatment, the FC within the FPN and between the SN and FPN were significantly decreased in individuals with IA. Symptom improvement in subjects with IA was well fitted by the decrease in FC between the left midbrain and ventral prefrontal cortex and between the left thalamus and ventral anterior prefrontal cortex. Conclusion These findings confirmed the modulatory effects of acupuncture on the aberrant functional interactions among the SN and FPN, which may partly reflect the neurophysiological mechanism of acupuncture for IA.

Abstract Diabetic foot ulcers (DFUs) are associated with complex pathogenic factors and are considered a serious complication of diabetes. The potential mechanisms underlying DFUs have been increasingly investigated. Previous studies have focused on the three aspects of diabetic peripheral vascular disease, neuropathy, and wound infections. With advances in technology, researchers have been gradually conducting studies using immune cells, endothelial cells, keratinocytes, and fibroblasts, as they are involved in wound healing. It has been reported that the upregulation or downregulation of molecular signaling pathways is essential for the healing of DFUs. With a recent increase in the awareness of epigenetics, its regulatory role in wound healing has become a much sought‐after trend in the treatment of DFUs. This review focuses on four aspects involved in the pathogenesis of DFUs: physiological and pathological mechanisms, cellular mechanisms, molecular signaling pathway mechanisms, and epigenetics. Given the challenge in the treatment of DFUs, we are hopeful that our review will provide new ideas for peers.

ABSTRACT: A growing stream of research suggests that probiotic fermented milk has a good effect on nonalcoholic fatty liver disease. This work aimed to study the beneficial effects of Lactobacillus rhamnosus hsryfm 1301 fermented milk (fermented milk) on rats with nonalcoholic fatty liver disease induced by a high-fat diet. The results showed that the body weight and the serum levels of total cholesterol, total glyceride, low-density lipoprotein, alanine transaminase, aspartate aminotransferase, free fatty acid, and reactive oxygen species were significantly increased in rats fed a high-fat diet (M) for 8 wk, whereas high-density lipoprotein cholesterol and superoxide dismutase were significantly decreased. However, the body weight and the serum levels of total cholesterol, total glyceride, alanine transaminase, aspartate aminotransferase, free fatty acid, reactive oxygen species, interleukin-8, tumor necrosis factor-α, and interleukin-6 were significantly decreased with fermented milk (T) for 8 wk, and the number of fat vacuoles in hepatocytes was lower than that in the M group. There were significant differences in 19 metabolites in serum between the M group and the C group (administration of nonfermented milk) and in 17 metabolites between the T group and the M group. The contents of 7 different metabolites, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, thioetheramide-PC, d-aspartic acid, oleic acid, and l-glutamate, were significantly increased in the M group rat serum, and l-palmitoyl carnitine, N6-methyl-l-lysine, thymine, and 2-oxadipic acid were significantly decreased. In the T group rat serum, the contents of 8 different metabolites—1-O-(cis-9-octadecenyl)-2-O-acetyl-sn-glycero-3-phosphocholine, acetylcarnitine, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, d-aspartic acid, oleic acid, and l-glutamate were significantly decreased, whereas creatinine and thymine were significantly increased. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that 50 metabolic pathways were enriched in the M/C group and T/M group rat serum, of which 12 metabolic pathways were significantly different, mainly distributed in lipid metabolism, amino acid, and endocrine system metabolic pathways. Fermented milk ameliorated inflammation, oxygenation, and hepatocyte injury by regulating lipid metabolism, amino acid metabolic pathways, and related metabolites in the serum of rats with nonalcoholic fatty liver disease.

Emotion is one of the most important higher cognitive functions of the human brain and plays an important role in transaction processing and decisions. In traditional emotion recognition studies, the frequency band features in EEG signals have been shown to have a high correlation with emotion production. However, traditional emotion recognition methods cannot satisfactorily solve the problem of individual differences in subjects and data heterogeneity in EEG, and subject-independent emotion recognition based on EEG signals has attracted extensive attention from researchers. In this paper, we propose a subject-independent emotion recognition model based on adaptive extraction of layer structure based on frequency bands (BFE-Net), which is adaptive in extracting EEG map features through the multi-graphic layer construction module to obtain a frequency band-based multi-graphic layer emotion representation. To evaluate the performance of the model in subject-independent emotion recognition studies, extensive experiments are conducted on two public datasets including SEED and SEED-IV. The experimental results show that in most experimental settings, our model has a more advanced performance than the existing studies of the same type. In addition, the visualization of brain connectivity patterns reveals that some of the findings are consistent with previous neuroscientific validations, further validating the model in subject-independent emotion recognition studies.