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Objective: This study aimed to evaluate the biomechanical effectiveness of 3D-printed integrated acetabular prosthesis (IAP) and modular acetabular prosthesis (MAP) in reconstructing the acetabulum for patients with Crowe III developmental dysplasia of the hip (DDH). The results of this study can provide a theoretical foundation for the treatment of Crowe III DDH in total hip arthroplasty (THA).Methods: Finite element (FE) analysis models were created to reconstruct Crowe III DDH acetabular defects using IAP and MAP. The contact stress and relative micromotion between the acetabular prosthesis and the host bone were analyzed by gradually loading in three increments (210 N, 2100 N, and 4200 N). In addition, five patients with Crowe III DDH who underwent IAP acetabular reconstruction were observed.Results: At the same load, the peak values of IAP contact stress and relative micromotion were lower than those of MAP acetabular reconstruction. Under jogging load, the MAP metal augment’s peak stress exceeded porous tantalum yield strength, and the risk of prosthesis fracture was higher. The peak stress in the bone interface in contact with the MAP during walking and jogging was higher than that in the cancellous bone, while that of IAP was higher than that of the cancellous bone only under jogging load, so the risk of MAP cancellous bone failure was greater. Under jogging load, the relative micromotion of the MAP reconstruction acetabular implant was 45.2 μm, which was not conducive to bone growth, while under three different loads, the relative micromotion of the IAP acetabular implant was 1.5–11.2 μm, all

BackgroundHypertension is the most prevalent chronic condition and a significant risk factor for cardiovascular and kidney diseases. The efficacy of health behavioral interventions in blood pressure (BP) control has been demonstrated by a large and expanding body of literature, with “adherence” playing a crucial role. WeChat is the most common social communication mobile app in China, and it has been shown to be an acceptable delivery platform for delivering health interventions. The WeChat-based health behavioral digital intervention program (WHBDIP) showed high feasibility and efficacy. However, the results regarding BP improvement between the WHBDIP and control groups were inconsistent. ObjectiveThe objective of this study is to develop a WHBDIP and assess its efficacy in controlling BP and improving adherence among patients with hypertension. MethodsA 2-arm, parallel-group, and randomized trial design was used. Patients older than 60 years and with hypertension were randomly assigned to either the control group or the experimental group, which received a 12-week intervention. The program, primarily developed based on the Behavior Change Wheel (BCW) theory, offers health education on exercise, diet, BP monitoring, and medicine adherence (MA). It also includes other behavior interventions guided by an intervention manual, incorporating behavior change techniques (BCTs). The primary outcomes encompass BP and adherence indicators, while the secondary outcomes encompass cardiovascular function indicators, body composition indicators, learning performance, satisfaction, and acceptability. The exercise and blood pressure monitoring adherence (BPMA) indicators for the WHBDIP group were assessed weekly via WeChat during the initial 3 months, while other outcome data for both groups will be collected at the baseline assessment phase, 3 months after the intervention, and 1 year after the program. ResultsThe trial will assess the efficacy of WHBDIP for patients with hypertension (N=68). The WHBDIP seeks to enhance participants' knowledge of healthy behaviors and assist patients in developing positive health behaviors to improve their health outcomes. Patient recruitment for individuals with hypertension commenced on September 5, 2022, and concluded on September 19, 2022. The 3-month intervention and phased data collection were finalized in January 2023. Data analysis will commence in August 2023, and the final 1-year health outcome results will be collected in September 2023. ConclusionsA successful WHBDIP will establish the management mode as a feasible approach for hypertension management in the community. Additionally, it will pave the way for the development of related mobile health programs. Trial RegistrationChinese Clinical Trial Registry ChiCTR2200062643; https://tinyurl.com/mwyv67wk International Registered Report Identifier (IRRID)PRR1-10.2196/46883

BackgroundUniversity life typically occurs during a period of life transition, where the incidence of mental health and substance use problems and disorders peaks. However, relatively few students obtain effective treatment and support. e-Interventions have proven effective in improving the psychological outcomes of university students and have the potential to provide scalable services that can easily integrate into existing models of care. Minder is a mobile app codeveloped with university students that offers users a collection of evidence-based interventions tailored to help university students maintain their mental health and well-being and manage their substance use. ObjectiveThis paper describes the protocol for a randomized controlled trial (RCT) that aims to assess the effectiveness of the Minder app in improving the mental health and substance use outcomes of university students. MethodsThis study is a 2-arm, parallel assignment, single-blinded, 30-day RCT with 1 intervention group and 1 waitlist control group. Overall, 1496 (748 per trial arm) university students from the University of British Columbia Vancouver Campus (N=54,000) who are aged ≥17 years, have a smartphone with Wi-Fi or cellular data, and speak English will be recruited via a variety of web-based and offline strategies. Participants will be randomized into the intervention or control group after completing a baseline survey. Those randomized into the intervention group will gain immediate access to the Minder app and will be assessed at 2 weeks and 30 days. Those randomized into the control group will be given access to the app content after their follow-up assessment at 30 days. The primary outcomes are measured from baseline to follow-up at 30 days and include changes in general anxiety symptomology, depressive symptomology, and alcohol consumption risk measured by the General Anxiety Disorder 7-Item scale, Patient Health Questionnaire 9-Item scale, and US Alcohol Use Disorders Identification Test-Consumption Scale, respectively. Secondary outcomes include measures related to changes in the frequency of substance use, mental well-being, self-efficacy in managing mental health and substance use, readiness to change, and self-reported use of mental health services and supports (including referral) from baseline to follow-up at 30 days. ResultsTrial recruitment and data collection began in September 2022, and the completion of data collection for the trial is anticipated by June 2023. As of May 10, 2023, a total of 1425 participants have been enrolled. ConclusionsThe RCT described in this protocol paper will assess whether the Minder app is effective in improving the mental health and substance use outcomes of a general population of Canadian university students. Additional secondary outcome research aims to explore additional outcomes of interest for further research and better understand how to support students’ general mental well-being. Trial RegistrationClinicalTrials.gov NCT05606601; https://clinicaltrials.gov/ct2/show/NCT05606601 International Registered Report Identifier (IRRID)DERR1-10.2196/49364

Cisplatin-based chemotherapy has been associated with durable disease control in a small subset of patients with metastatic urothelial cancer. However, the mechanistic basis for this phenomenon has remained elusive. Antitumor immunity may underlie these exceptional responders. In a phase II trial evaluating a phased schedule of gemcitabine and cisplatin followed by gemcitabine and cisplatin with ipilimumab for metastatic urothelial cancer, 4 of 36 patients achieved durable disease-free treatment-free survival (DDFTFS) and remain in remission over 5 years after enrolment on the study. We sought to identify the genomic and immunological mechanisms associated with functional cures of such patients. Whole exome sequencing was performed on pretreatment archival tumor tissue. Neoantigen prediction and ranking were performed using a novel pipeline. For a subset of patients with available biospecimens, selected peptides were tested for neoantigen-specific T cell reactivity in peripheral blood CD4+ and CD8+ T cells cultured with autologous antigen-presenting cells at baseline, postchemotherapy, and postchemotherapy and ipilimumab timepoints. Multiplex assays of serum protein analytes were also assessed at each time point. Serum proteomic analysis revealed that pretreatment, patients achieving DDFTFS demonstrated an immune activated phenotype with elevations in TH1 adaptive immunity, costimulatory molecules, and immune checkpoint markers. After combination cisplatin-based chemotherapy and ipilimumab treatment, DDFTFS patients again displayed enrichment for markers of adaptive immunity, as well as T cell cytotoxicity. CD27 was uniquely enriched in DDFTFS patients at all timepoints. Neoantigen reactivity was not detected in any patient at baseline or post two cycles of chemotherapy. Both CD4+ and CD8+ neoantigen-specific T cell reactivity was detected in two of two DDFTFS patients in comparison to zero of five non-DDFTFS patients after combination cisplatin-based chemotherapy and ipilimumab treatment. Antitumor immunity may underlie functional cures achieved in patients with metastatic urothelial cancer treated with cisplatin-based chemotherapy and immune checkpoint blockade. Probing the mechanistic basis for DDFTFS may facilitate the identification of biomarkers, therapeutic components, and optimal treatment sequences necessary to extend this ultimate goal to a larger subset of patients.

In this study, we accurately calculated the propagation characteristics of extremely low-frequency (ELF) electromagnetic waves (EMWs) excited by horizontal electric dipoles (HEDs) in the uniformly infinite polar “sea-sea ice” half-space. This was achieved by combining the program platform written by the message passing interface (MPI) with the three-dimensional total field scattered field source finite difference time domain (TSS-FDTD) method to develop an improved calculation method of parallel TSS-FDTD electromagnetic field. Using equivalent principle and boundary grid field value transformation technology, the calculation space of electromagnetic field (EMF) in seawater and sea ice is divided into several regional grids to establish the calculation model of TSS-FDTD in the polar “sea-sea ice” half-space. The maximum radiation direction and average minimum attenuation of ELF EMF in the uniformly infinite polar “sea-sea ice” half-space (near the interface between seawater and sea ice) are obtained. The simulation results show that, at depth ${d}$ = 10 m and propagation distance $\rho $ = 125 m from the interface between seawater and sea ice, the maximum radiation directions of EMF intensity are vertical electric field direction $E_{z}$ and horizontal magnetic field direction $H_{x}$ , respectively; moreover, their average minimum attenuation values in the sea water medium are 30 dB and 20 dB, respectively, and their corresponding values in sea ice medium are 20 dB and 10 dB, respectively. Therefore, compared with the directions of other electric and magnetic field components, these directions more suitable for receiving underwater signals. Finally, we selected different thickness values of the sea ice medium for simulation, and compared the results with the Sommerfeld numerical integration method (SNIM) proposed by Pan. The results show that the calculation results of the two methods are consistent, and that the average error is less than 5%, which verifies the effectiveness and accuracy of the proposed method.

Abstract Background Lung adenocarcinoma (LUAD) is characterized by high morbidity and mortality rates and poor prognosis. N7-methylguanosine play an increasingly vital role in lung adenocarcinoma. However, the prognostic value of N7-methylguanosine related-miRNAs in lung adenocarcinoma remains unclear. Methods In the study, the mRNA and miRNA expression profiles and corresponding clinical informations were downloaded from the public database. The prognostic signature was built using least absolute shrinkage and selection operator Cox analysis. The Kaplan–Meier method was used to compare survival outcomes between the high- and low-risk groups. Signatures for the development of lung adenocarcinoma were tested using univariate and multivariate Cox regression models. Single-sample gene set enrichment analysis was used to determine the immune cell infiltration score. First, we predicted METTL1 and WDR4 chemosensitivities based on a public pharmacogenomics database. The area under the receiver operating characteristic curve showed that the performance of signature in 1-,3-, and 5-year survival predictions were 0.68, 0.65, and 0.683, respectively. Results We established a novel prognostic signature consisting of 9 N7-Methylguanosine related miRNAs using least absolute shrinkage and selection operator Cox analysis. Patients in the high-risk group had shorter survival times than those in the low-risk group did. The calibration curves at 1, 3, and 5-year also illustrate the high predictive power of the structure. Signature was corrected using the Toumor stage. The expression levels of METTL1 and WDR4 significantly correlated with the sensitivity of cancer cells to antitumor drugs. Conclusions A novel signature constructed using 9 N7-methylguanosine related-miRNAs can be used for prognostic prediction.

Abstract Background Image-guided system (IGS) has been gradually applied in the field of rhinology, making functional endoscopic sinus surgery (FESS) a truly minimally invasive and precise surgery. This study was based on real-world data from China hospitals and aimed to evaluate the clinical and economic benefits of the IGS navigation system in FESS. Methods This was a two-center retrospective chart review of patients with chronic rhinosinusitis who underwent FESS, including open frontal sinus between July 1, 2018 and December 31, 2019 in China. The intervention group consisted of 100 patients who underwent FESS with the IGS navigation system (IGS group), and the control group consisted of 100 patients who underwent conventional FESS (Non-IGS group). Data were collected from surgical notes and hospital medical records. The primary endpoints for clinical effectiveness and safety were avoid rehospitalization due to bleeding, avoid reoperation due to bleeding, and avoid reoperation due to recurrence. Results There were no cases of rehospitalization due to bleeding, reoperation due to bleeding, and reoperation due to recurrence in the IGS group, with an avoidance rate of 100%. In the non-IGS group, there were four cases of rehospitalization and reoperation due to bleeding, with an avoidance rate 96.00% (P = 0.121). No cases of reoperation due to recurrence were in the non-IGS group. The total hospitalization cost was 17,391.51 CNY in the IGS group and 17,742.41 CNY in the non-IGS group per patient, with no statistical difference between the two groups (P = 0.715). Compared with the non-IGS group, the IGS group had an overall cost saving of 350.90 CNY per patient. Although the procedure-related medical costs of IGS group were increased by 1,286.12 CNY compared with the non-IGS group, this was more than offset by other costs. Conclusion The results of the study indicated that the IGS may avoid occurrence of rehospitalization and reoperation due to postoperative bleeding. Although the use of navigation technology increased the cost of surgery, its clinical effectiveness brought other medical cost savings, resulting in no significant difference in the overall cost of navigation surgery compared to conventional surgery. The IGS should be considered cost-effectiveness in the treatment of FESS.

Abstract Objective To determine whether there were improvements in rheumatology care for rheumatoid arthritis (RA) between 2002 and 2019 in Ontario, Canada, and to evaluate the impact of rheumatologist regional supply on access. Methods We conducted a population-based retrospective study of all individuals diagnosed with RA between January 1, 2002 and December 31, 2019. Performance measures evaluated were: (i) percentage of RA patients seen by a rheumatologist within one year of diagnosis; and (ii) percentage of individuals with RA aged 66 years and older (whose prescription drugs are publicly funded) dispensed a disease modifying anti-rheumatic drug (DMARD) within 30 days after initial rheumatologist visit. Logistic regression was used to assess whether performance improved over time and whether the improvements differed by rheumatology supply, dichotomized as

Abstract Background Emerging evidence suggests that gut microbiota plays a predominant role in Crohn’s disease (CD). However, the microbiome alterations in the early stage of CD patients still remain unclear. The present study aimed to identify dysbacteriosis in patients with early CD and explore specific gut bacteria related to the progression of CD. Methods This study was nested within a longitudinal prospective Chinese CD cohort, and it included 18 early CD patients, 22 advanced CD patients and 30 healthy controls. The microbiota communities were investigated using high-throughput Illumina HiSeq sequencing targeting the V3–V4 region of 16S ribosomal DNA (rDNA) gene. The relationship between the gut microbiota and clinical characteristics of CD was analyzed. Results Differential microbiota compositions were observed in CD samples (including early and advanced CD samples) and healthy controls samples. Notably, Lachnospiracea_incertae_sedis and Parabacteroides were enriched in the early CD patients, Escherichia/Shigella, Enterococcus and Proteus were enriched in the advanced CD patients, and Roseburia, Gemmiger, Coprococcus, Ruminococcus 2, Butyricicoccus, Dorea, Fusicatenibacter, Anaerostipes, Clostridium IV were enriched in the healthy controls [LDA score (log10) > 2]. Furthermore, Kruskal–Wallis Rank sum test results showed that Blautia, Clostridium IV, Coprococcus, Dorea, Fusicatenibacter continued to significantly decrease in early and advanced CD patients, and Escherichia/Shigella and Proteus continued to significantly increase compared with healthy controls (P 2]. Some genera were significantly correlated with various clinical parameters, such as fecal calprotectin, erythrocyte sedimentation rate, C-reactive protein, gland reduce, goblet cells decreased, clinical symptoms (P

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the effectiveness of currently approved mRNA vaccines. To achieve wider coverage of VOCs, we first constructed a cohort of mRNAs harboring a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). The mutation abolished the cleavage between the S1 and S2 subunits. Systematic evaluation in vaccinated mice discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. In particular, the neutralizing antibodies (nAb) produced by immunization with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs. However, neither mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original Omicron variant and some sublineages. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we engineered an mRNA-based chimeric immunogen by introducing the receptor-binding domain of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA induced potent and broadly nAbs against Omicron and Delta, which paves the way to developing new vaccine candidates to target emerging variants in the future.

The objective of this paper is to explore the characteristics of Mycoplasma pneumoniae (MP) epidemics in Beijing, China. Patients with acute respiratory tract infection (ARTI) were enrolled from 35 sentinel hospitals in Beijing, 2015–2020. Their medical records were reviewed and respiratory specimens were collected for assay for nucleic acids of 24 respiratory pathogens, including MP. The genotypes of MP were analysed using a real-time PCR method. The domain V of 23s rRNA gene was sequenced to identify macrolide-resistant mutations. A total of 41,677 specimens of ARTI patients were included, with an MP positive rate of 6.16%. MP prevalence mainly occurred between August and January, and peaked in October. The increase in the MP detection rate was coincident with the elevation of the reported number of patients with pneumonia in the 35 sentinel hospitals. One or more respiratory pathogens were co-detected in 27.1% of the MP-positive patients. Type 1 MP remained predominant, and the macrolide-resistant rate of MP had exceeded over 90%. A2063G mutation accounted for 99.0% of macrolide-resistant MP infections. MP epidemic in Beijing mainly occurred between August and January with a remarkable high macrolide-resistant rate. MP is one of the important contributors to the pneumonia epidemic in autumn and winter in Beijing.

Context The traditional Chinese medicine Qing’e Pills (QEP) has been used to treat postmenopausal osteoporosis (PMO).Objective We evaluated the regulatory effects of QEP on gut microbiota in osteoporosis.Materials and methods Eighteen female SD rats were divided into three groups: sham surgery (SHAM), ovariectomized (OVX) and ovariectomized treated with QEP (OVX + QEP). Six weeks after ovariectomy, QEP was administered to OVX + QEP rats for eight weeks (4.5 g/kg/day, i.g.). After 14 weeks, the bone microstructure was evaluated. Differences in gut microbiota were analysed via 16S rRNA gene sequencing. Changes in endogenous metabolites were studied using UHPLC-Q-TOF/MS technology. GC–MS was used to detect short-chain fatty acids. Furthermore, we measured serum inflammatory factors, such as IL-6, TNF-α and IFN-γ, which may be related to gut microbiota.Results OVX + QEP exhibited increased bone mineral density (0.11 ± 0.03 vs. 0.21 ± 0.02, p

Abstract With the increasing traffic congestion in cities, the priority of public transit has become a consensus for the development and management of urban transportation. The traffic pre-signal mechanism, which gives priority in time and space to buses by optimizing road right-of-way allocation, has gained wide attention and application. In order to broaden the action exploration range of the agent and avoid the pre-signal decision from falling into suboptimal strategy or local optimal strategy. For the exploration strategy of the DDQN algorithm, this paper reduces the probability of directly selecting the local optimal action and increases the probability of selecting non-greedy actions based on the principle that “the action with a larger value function is more likely to be selected.” This paper addresses the problem that the existing urban traffic pre-signal mechanism cannot adaptively adjust the advance time, and proposes a traffic pre-signal adaptive timing mechanism based on a Hybrid Exploration Strategy Double Deep Q Network (HES-DDQN) by combining the $$\epsilon $$ ϵ -greedy strategy and Boltzmann strategy. We have used the traffic simulation software VISSIM to conduct simulation experiments on an intersection. The experimental results show that, compared with the method of setting no pre-signal and the formula method of setting pre-signal, the HES-DDQN pre-signal mechanism can significantly reduce the average delay of buses, the waiting queue length, and the number of stops of social vehicles.

Abstract Background Recently, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) have been applied in total hip arthroplasty (THA). However, doubts in clinicians’ minds about which medicine is more efficient and economical in THA need to be clarified. Therefore, this study compared the efficacy and cost of the intraoperative administration of TXA and EACA per surgery in decreasing perioperative blood transfusion rates in THA. Methods This study enrolled patients who underwent THA between January 2019 to December 2020. A total of 295 patients were retrospectively divided to receive topical combined with intravenous TXA (n = 94), EACA (n = 97) or control (n = 104). The primary endpoints included transfusions, estimated perioperative blood loss, cost per patient and the drop in the haemoglobin and haematocrit levels. Results Patients who received EACA had greater total blood loss, blood transfusion rates, changes in HGB levels and mean cost of blood transfusion per patient (P

Abstract Objective This paper intends to propose a method of using TransResSEUnet2.5D network for accurate automatic segmentation of the Gross Target Volume (GTV) in Radiotherapy for lung cancer. Methods A total of 11,370 computed tomograms (CT), deriving from 137 cases, of lung cancer patients under radiotherapy developed by radiotherapists were used as the training set; 1642 CT images in 20 cases were used as the validation set, and 1685 CT images in 20 cases were used as the test set. The proposed network was tuned and trained to obtain the best segmentation model and its performance was measured by the Dice Similarity Coefficient (DSC) and with 95% Hausdorff distance (HD95). Lastly, as to demonstrate the accuracy of the automatic segmentation of the network proposed in this study, all possible mirrors of the input images were put into Unet2D, Unet2.5D, Unet3D, ResSEUnet3D, ResSEUnet2.5D, and TransResUnet2.5D, and their respective segmentation performances were compared and assessed. Results The segmentation results of the test set showed that TransResSEUnet2.5D performed the best in the DSC (84.08 ± 0.04) %, HD95 (8.11 ± 3.43) mm and time (6.50 ± 1.31) s metrics compared to the other three networks. Conclusions The TransResSEUnet 2.5D proposed in this study can automatically segment the GTV of radiotherapy for lung cancer patients with more accuracy.

Abstract Objective To analyze the characteristics of global β-lactamase-producing Enterobacter cloacae including the distribution of β-lactamase, sequence types (STs) as well as plasmid replicons. Methods All the genomes of the E. cloacae were downloaded from GenBank. The distribution of β-lactamase encoding genes were investigated by genome annotation after the genome quality was checked. The STs of these strains were analyzed by multi-locus sequence typing (MLST). The distribution of plasmid replicons was further explored by submitting these genomes to the genome epidemiology center. The isolation information of these strains was extracted by Per program from GenBank. Results A total of 272 out of 276 strains were found to carry β-lactamase encoding genes. Among them, 23 varieties of β-lactamase were identified, bla CMH (n = 130, 47.8%) and bla ACT (n = 126, 46.3%) were the most predominant ones, 9 genotypes of carbapenem-hydrolyzing β-lactamase (CHβLs) were identified with bla VIM (n = 29, 10.7%) and bla KPC (n = 24, 8.9%) being the most dominant ones. In addition, 115 distinct STs for the 272 ß-lactamase-carrying E. cloacae and 48 different STs for 106 CHβLs-producing E. cloacae were detected. ST873 (n = 27, 9.9%) was the most common ST. Furthermore, 25 different plasmid replicons were identified, IncHI2 (n = 65, 23.9%), IncHI2A (n = 64, 23.5%) and IncFII (n = 62, 22.8%) were the most common ones. Notably, the distribution of plasmid replicons IncHI2 and IncHI2A among CHβLs-producing strains were significantly higher than theat among non-CHβLs-producing strains (p

The herbicide paraquat is an agonist of Stromal Interaction Molecule 1 (STIM1), leading to extracellular calcium entry observed in epithelial-mesenchymal transition in alveolar cells during pulmonary fibrosis.

Abstract Purpose To improve early detection and risk prediction of prostate cancer, we incorporated the urine urothelial carcinoembryonic antigen 1 (UCA1) gene expression levels and the serum PSA level. Patients and Methods In 897 patients the urine UCA1 gene expression was normalized and the performance of UCA1 score was evaluated by receiver operating characteristic (ROC) curve analysis, the Mann–Whitney U test, or decision curve analysis (DCA). Results In the Shengli training cohort (n = 517), the area under ROC curve (AUC) was 0.880, 0.728, and 0.705 for detecting prostate cancer, D'Amico, and cancer of the prostate risk assessment (CAPRA), respectively. The UCA1 scores of benign patients were significantly lower than those of nonhigh‐risk prostate cancer patients (−2.63 vs. 0.16, p

Abstract Recently, the interest in extracellular vesicles released by bacteria has rapidly increased. Bacterial extracellular vesicles (BEVs) have been involved in bacteria‐bacteria and bacteria‐host interactions, which strengthen health or bring about various pathologies. However, BEV separation, characterization, and functional studies require the establishment of guidelines and further optimization in order to stimulate the development of science in BEV research and a following successful transformation into clinical applications. This position paper is authored by the Microbial Vesicles Task Force of the Chinese Society for Extracellular Vesicles (CSEV) composed of experienced medical laboratory specialists, microbiologists, virologists, biologists and material biologists who are actively engaged in BEV research. Herein, we present a concise description of BEV research and discover challenges and critical gaps in current BEV‐based analyses for clinical applications. Finally, we also offer suggestions and considerations to improve experimental reproducibility and interoperability in BEV research to promote progress in the field.

Modern linguistic theories and network science propose that language and speech processing are organized into hierarchical, segregated large-scale subnetworks, with a core of dorsal (phonological) stream and ventral (semantic) stream. The two streams are asymmetrically recruited in receptive and expressive language or speech tasks, which showed flexible functional segregation and integration. We hypothesized that the functional segregation of the two streams was supported by the underlying network segregation. A dynamic conditional correlation approach was employed to construct framewise time-varying language networks and k-means clustering was employed to investigate the temporal-reoccurring patterns. We found that the framewise language network dynamics in resting state were robustly clustered into four states, which dynamically reconfigured following a domain-separation manner. Spatially, the hub distributions of the first three states highly resembled the neurobiology of speech perception and lexical-phonological processing, speech production, and semantic processing, respectively. The fourth state was characterized by the weakest functional connectivity and was regarded as a baseline state. Temporally, the first three states appeared exclusively in limited time bins (∼15%), and most of the time (> 55%), state 4 was dominant. Machine learning-based dFC-linguistics prediction analyses showed that dFCs of the four states significantly predicted individual linguistic performance. These findings suggest a domain-separation manner of language network dynamics in resting state, which forms a dynamic “meta-network” framework to support flexible functional segregation and integration during language and speech processing.

IntroductionXiaoai Jiedu recipe (XJR), a classical prescription of traditional Chinese medicine (TCM), has been clinically proven to be effective in ameliorating colorectal cancer (CRC). However, its exact mechanism of action is still elusive, limiting its clinical application and promotion to a certain extent. This study aims to evaluate the effect of XJR on CRC and further illustrate mechanism underlying its action.MethodsWe investigated the anti-tumor efficacy of XJR in vitro and vivo experiments. An integrated 16S rRNA gene sequencing and UPLC-MS based metabolomics approach were performed to explore possible mechanism of XJR anti-CRC on the gut microbiota and serum metabolic profiles. The correlation between altered gut microbiota and disturbed serum metabolites was investigated using Pearson’s correlation analysis.ResultsXJR effectively displayed anti-CRC effect both in vitro and in vivo. The abundance of aggressive bacteria such as Bacteroidetes, Bacteroides, and Prevotellaceae decreased, while the levels of beneficial bacteria increased (Firmicutes, Roseburia, and Actinobacteria). Metabolomics analysis identified 12 potential metabolic pathways and 50 serum metabolites with different abundances possibly affected by XJR. Correlation analysis showed that the relative abundance of aggressive bacteria was positively correlated with the levels of Arachidonic acid, Adrenic acid, 15(S)−HpETE, DL−Arginine, and Lysopc 18:2, which was different from the beneficial bacteria.DiscussionThe regulation of gut microbiota and related metabolites may be potential breakthrough point to elucidate the mechanism of XJR in the treatment of the CRC. The strategy employed would provide theoretical basis for clinical application of TCM.

ObjectiveTo use genomic analysis to identify Acinetobacter spp. and to explore the distribution characteristics of ß-lactamase oxallicinases (blaOXA) among Acinetobacter species globally.MethodsGenomes of global Acinetobacter spp. were downloaded from GenBank using Aspera batch. After quality check using CheckM and QUAST software, the genomes were annotated using Prokka software to investigate the distribution of blaOXAs across Acinetobacter spp.; a phylogenetic tree was constructed to explore the evolutionary relationship among the blaOXA genes in Acinetobacter spp. Average-nucleotide identification (ANI) was performed to re-type the Acinetobacter spp. BLASTN comparison analysis was implemented to determine the sequence type (ST) of Acinetobacter baumannii strain.ResultsA total of 7,853 genomes were downloaded, of which only 6,639 were left for further analysis after quality check. Among them, 282 blaOXA variants were identified from the genomes of 5,893 Acinetobacter spp.; blaOXA-23 (n = 3,168, 53.8%) and blaOXA-66 (2,630, 44.6%) were the most frequent blaOXAs, accounting for 52.6% (3,489/6639), and the co-carriage of blaOXA-23 and blaOXA-66 was seen in 2223 (37.7%) strains. The 282 blaOXA variants were divided into 27 clusters according to the phylogenetic tree. The biggest clade was blaOXA-51-family carbapenem-hydrolyzing enzymes composed of 108 blaOXA variants. Overall, 4,923 A. baumannii were identified out of the 6,639 Acinetobacter spp. strains and 291 distinct STs were identified among the 4,904 blaOXA-carrying A. baumannii. The most prevalent ST was ST2 (n = 3,023, 61.6%) followed by ST1 (n = 228, 4.6%).ConclusionOXA-like carbapenemases were the main blaOXA-type β-lactamase spread widely across Acinetobacter spp. Both blaOXA-23 and blaOXA-66 were the predominant blaOXAs, among all A. baumannii strains, with ST2 (belonging to CC2) being the main clone disseminated globally.

In this paper, the defect formation energies, the nature of chemical bonding, and electronic structures of Mn- and Mg-doped SnTe alloys were determined by first-principles calculations. The effects of substitutional atoms on thermoelectric parameters are analyzed by solving the Boltzmann equation. The solution solubility of Mg in SnTe alloy is higher than that of Mn, and the lattice distortion caused by Mn substituting Sn sites is more severe. In addition, the resonant level of Sn1-xMnxTe alloys possesses a flat trend of the valance band maximum, which improves the effective carrier mass and Seebeck coefficient. The Mg-doped alloys exhibit higher carrier mobility and electrical conductivity. The maximum value of the power factor is 5.78 mWm−1K−2 for the Sn0.97Mn0.03Te alloy. Corresponding directionally-solidified samples with the same composition were also prepared. The Sn0.97Mn0.03Te sample also achieves the highest ZT value of 1.28. These results provide theoretical reference for optimizing the thermoelectric performance of SnTe alloys by substituting atoms.

The aim of this study was to investigate whether selenomethionine (SeMet) could attenuate intestinal injury in rabbits induced by ochratoxin A (OTA). Sixty 35-day-old IRA rabbits with similar weights were randomly assigned to the control group, OTA group (0.2 mg OTA/kg b.w), OTA+ 0.2 mg/kg Se (0.2 mg OTA/kg b.w + 0.2 mg SeMet/kg feed), OTA+ 0.4 mg/kg Se (0.2 mg OTA/kg b.w + 0.4 mg SeMet/kg feed) and OTA+ 0.6 mg/kg Se (0.2 mg OTA/kg b.w + 0.6 mg SeMet/kg feed). The rabbits were examined after oral administration of different doses of SeMet for 21 days and were intragastrically administered OTA for 7 consecutive days. The results showed that pretreatment with different doses of SeMet protected against the changes in serum biochemical indicators and the decline in production performance caused by OTA exposure. In addition, the activities of SOD, GSH-PX and T-AOC were significantly increased, and the levels of MDA and ROS were decreased after SeMet pretreatment; thus, oxidative damage in rabbit jejunum tissue due to OTA exposure was inhibited. SeMet stimulates Nrf2 and inhibits the NF-κB signalling pathway; the anti-inflammatory response and antioxidative stress in rabbits were improved, and the intestinal barrier damage caused by OTA exposure was improved. In summary, SeMet alleviates OTA-induced intestinal toxicity in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation. Moreover, 0.4 mg/kg SeMet induced the most significant improvement.

Purpose: To investigate the baseline levels of serotype-specific IgG antibodies to Streptococcus pneumoniae (S. pneumoniae) and assess their impact on the assessment of vaccine immunogenicity. Methods: We used a subset of serum samples from a randomized controlled trial. The blood of 584 healthy participants was collected on day 0 before and day 28 after the 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination. Serotype-specific IgG against PPSV23-covered serotypes were measured by the World Health Organization (WHO) reference enzyme-linked immunosorbent assay (ELISA). Vaccine immunogenicity was compared using conversion rates (proportion of participants with IgG levels following immunization that are 2-fold greater than the baseline) and geometric mean fold rises (GMFRs) between the two groups, which were grouped according to pre-vaccination (baseline) IgG antibody levels. Results: Our data showed that over half of individuals have baseline IgG levels for 15 out of 23 serotypes above 1.3 µg/mL, and geometric mean concentrations (GMCs) were generally higher in the elderly group and the female group; significant differences were found in 15 serotypes for vaccine immunogenicity based on the seroconversion rate or GMFRs between individuals with baseline IgG ≥ 1.3 µg/mL and individuals with baseline IgG < 1.3 µg/mL. The seroconversion rate decreased with the increase of baseline IgG levels according to a linear regression model. Conclusions: The assessment of vaccine immunogenicity could be impacted by the fact that many adults had high baseline antibody levels. This study is registered in the Chinese Clinical Trial Registry, number NCT05298800.

Objective The study objective was to assess adherence to system‐level performance measures measuring retention in rheumatology care and disease modifying anti‐rheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). Methods We used a validated health administrative data case definition to identify individuals with RA in Ontario, Canada, between 2002 and 2014 who had at least 5 years of potential follow‐up prior to 2019. During the first 5 years following diagnosis, we assessed whether patients were seen by a rheumatologist yearly and the proportion dispensed a DMARD yearly (in those aged ≥66 for whom medication data were available). Multivariable logistic regression analyses were used to estimate the odds of remaining under rheumatologist care. Results The cohort included 50,883 patients with RA (26.1% aged 66 years and older). Over half (57.7%) saw a rheumatologist yearly in all 5 years of follow‐up. Sharp declines in the percentage of patients with an annual visit were observed in each subsequent year after diagnosis, although a linear trend to improved retention in rheumatology care was seen over the study period (P

【Objective】The study was carried out to improve the accuracy of the deep learning model through adjusting the distribution of training dataset of lab-condition and field-condition images, to reduce the dependence of plant diseases recognition models on field-condition data.【Method】The plant diseases recognition model was optimized through adjusting the distribution of images of lab-conditions and field-conditions in training datasets. Deep learning models of plant diseases trained by three artificial neural networks of ResNeSt-50, VGG-16 and ResNet-50 were tested and compared.【Result】In a training dataset composed of a certain number of plant disease images, it had an impact on the model accuracy through adjusting the distribution of images of different conditions. When the proportion of images of the fieldconditions reached 30%, the accuracy of the model was improved by more than 18%. Through adding field-conditions images at a number ratio of 30% into a training dataset composed of 100% lab-condition images, the accuracy of the model was improved by more than 17%. Through adding lab-conditions images into a training dataset composed of 100% field-condition images, the accuracy of the model was improved with the increasing number of images, and the improved ranges were between 2% and 4%.【Conclusion】This method is suitable for the rapid establishment of high-accuracy plant diseases recognition models in the complex agricultural environment. It could reduce the dependence of plant recognition models on field-condition images, shorten the field data collection cycle at the beginning of model establishment and reduce the cost of field-condition images collection. It promotes a more effective application of artificial intelligence in unmanned farms and smart agriculture.

Abstract Background Achalasia is a rare primary esophageal motility disorder disease. It is reported that the long-term effect of fully coated anti-reflux metal stent (FCARMS) implantation is satisfactory. Operated by a skilled and experienced endoscopist, the effect of per-oral endoscopic myotomy (POEM) treatment is equivalent to that of surgical myotomy. So far, there is still few evidence to prove FCARMS implantation or POEM which is better for achalasia. The choice of treatment for achalasia is still controversial. The aim of this study is to find a more suitable therapy for achalasia by comparing the efficacy of FCARMS implantation and POEM. Methods A propensity score (PS) matching (1:2) was used in this retrospective cohort study. Data collected from consecutive patients of Achalasia, receiving FCARMS implantation or POEM therapy at the department of gastroenterology, the Seventh Medical Center of the Chinese People’s Liberation Army General Hospital from May 2007 to May 2018. According to their previous treatment, they are divided into two groups, FCARMS group and POEM group. Clinical efficacy and complications were compared between the two groups. Results A total of 166 cases were collected, including 113 cases of FCARMS and 53 cases of POEM. By PS matching, 150 patients were enrolled (100 cases of FCARMS and 50 cases of POEM). By comparison, the FCARMS group has shorter operation time, shorter fasting time and lower hospitalization costs than the POEM group (p

ObjectivesWe investigated the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of mitral valve prolapse (MVP). MethodsFor RNA extraction, we obtained peripheral blood mononuclear cells (PBMCs) from five patients with MVP, with or without chordae tendineae rupture, and five healthy individuals. High-throughput sequencing was used for RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) analysis, alternative splicing (AS) analysis, functional enrichment analysis, co-expression of RBPs, and alternative splicing events (ASEs) analysis were conducted.ResultsThe MVP patients exhibited 306 up-regulated genes and 198 down-regulated genes. All down- and up-regulated genes were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, MVP was closely associated with the top 10 enriched terms and pathways. In MVP patients, 2,288 RASEs were found to be significantly different, and four suitable RASEs (CARD11 A3ss, RBM5 ES, NCF1 A5SS, and DAXX A3ss) were tested. We identified 13 RNA-binding proteins (RBPs) from the DEGs and screened out four RBPs (ZFP36, HSPA1A, TRIM21, and P2RX7). We selected four RASEs based on the co-expression analyses of RBPs and RASEs, including exon skipping (ES) of DEDD2, alternative 3′ splice site (A3SS) of ETV6, mutually exclusive 3′UTRs (3pMXE) of TNFAIP8L2, and A3SS of HLA-B. Furthermore, the selected four RBPs and four RASEs were validated by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and showed high consistency with RNA sequencing (RNA-seq).ConclusionDysregulated RBPs and their associated RASEs may play regulatory roles in MVP development and may therefore be used as therapeutic targets in the future.

Porous tantalum (Ta) implants have been developed and clinically applied as high-quality implant biomaterials in the orthopedics field because of their excellent corrosion resistance, biocompatibility, osteointegration, and bone conductivity. Porous Ta allows fine bone ingrowth and new bone formation through the inner space because of its high porosity and interconnected pore structure. It contributes to rapid bone integration and long-term stability of osseointegrated implants. Porous Ta has excellent wetting properties and high surface energy, which facilitate the adhesion, proliferation, and mineralization of osteoblasts. Moreover, porous Ta is superior to classical metallic materials in avoiding the stress shielding effect, minimizing the loss of marginal bone, and improving primary stability because of its low elastic modulus and high friction coefficient. Accordingly, the excellent biological and mechanical properties of porous Ta are primarily responsible for its rising clinical translation trend. Over the past 2 decades, advanced fabrication strategies such as emerging manufacturing technologies, surface modification techniques, and patient-oriented designs have remarkably influenced the microstructural characteristic, bioactive performance, and clinical indications of porous Ta scaffolds. The present review offers an overview of the fabrication methods, modification techniques, and orthopedic applications of porous Ta implants.

BackgroundRenal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes.MethodThe specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson’s correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections.ResultsThe expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable.ConclusionWe clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI.

Pseudomonas aeruginosa is an opportunistic human pathogen notorious for its remarkable capacity of multi-drug resistance, and has become one of the most important model bacteria in clinical bacteriology research. Quantitative real-time PCR is a reliable method widely used in gene expression analysis, for which the selection of a set of appropriate housekeeping genes is a key prerequisite for the accuracy of the results. However, it is easy to overlook that the expression level of housekeeping gene may vary in different conditions, especially in the condition of molecular microbiology assays, where tested strains are generally cultured under the pre-set antibiotic selection pressures, and how this affects the stability of commonly used housekeeping genes remains unclear. In this study, the expression stability of ten classic housekeeping genes (algD, gyrA, anr, nadB, recA, fabD, proC, ampC, rpoS, and rpsL) under the pressure of eight laboratory commonly used antibiotics (kanamycin, gentamycin, tetracycline, chloramphenicol, hygromycin B, apramycin, tellurite, and zeocin) were tested. Results showed that the stability of housekeeping gene expression was indeed affected by the types of antibiotics added, and of course the best reference gene set varied for different antibiotics. This study provides a comprehensive summary of the effects of laboratory antibiotics on the stability of housekeeping genes in P. aeruginosa, highlighting the necessity to select housekeeping genes according to the type of antibiotics used in the initial stage of experiment.

It is necessary to assess the appropriate dietary protein level of the forest musk deer (FMD), as nutritional needs are unclear. The microbiome in gastrointestinal tracts plays an important role in regulating nutrient utilization, absorption and host growth or development. Thus, we aimed to evaluate growth performance, nutrient digestibility and fecal microbiome of growing FMD supplied with different protein levels of diets. Eighteen 6-month-old male FMD with an initial weight 5.0 ± 0.2 kg were used in a 62-day trial. The animals were randomly distributed to three groups, the dietary crude protein (CP) level was 11.51% (L), 13.37% (M), and 15.48% (H). The results showed that the CP digestibility decreased as dietary CP level increased (p

Introduction: Developing a culture system that can effectively maintain chondrocyte phenotype and functionalization is a promising strategy for cartilage repair.Methods: An alginate/collagen (ALG/COL) hybrid hydrogel using different guluronate/mannuronate acid ratio (G/M ratio) of alginates (a G/M ratio of 64/36 and a G/M ratio of 34/66) with collagen was developed. The effects of G/M ratios on the properties of hydrogels and their effects on the chondrocytes behaviors were evaluated.Results: The results showed that the mechanical stiffness of the hydrogel was significantly affected by the G/M ratios of alginate. Chondrocytes cultured on Mid-G/M hydrogels exhibited better viability and phenotype preservation. Moreover, RT-qPCR analysis showed that the expression of cartilage-specific genes, including SOX9, COL2, and aggrecan was increased while the expression of RAC and ROCK1 was decreased in chondrocytes cultured on Mid-G/M hydrogels.Conclusion: These findings demonstrated that Mid-G/M hydrogels provided suitable matrix conditions for cultivating chondrocytes and may be useful in cartilage tissue engineering. More importantly, the results indicated the importance of taking alginate G/M ratios into account when designing alginate-based composite materials for cartilage tissue engineering.

Fe–Al–Cr coatings with different content of Cr additive were prepared on 1045 carbon steel substrates by a laser cladding process. The incorporation of Cr atoms can effectively enhance the corrosion resistance of the coatings. In particular, the Fe–28Al–5Cr laser cladding coating exhibits the best film quality without phase segregation. In addition, the interfacial adhesion between the Fe–28Al–5Cr coating and the 1045 carbon steel substrate is improved. As a result, the Fe–28Al–5Cr laser cladding coating exhibits the best corrosion resistance in a 3.5 wt% NaCl solution under both immersion and electrochemical conditions. However, excessive Cr additive lead to the formation of Al8Cr5 in the grain boundaries, resulting in inferior corrosion resistance. Therefore, the new findings demonstrated in this work may inspire the design of high-quality coatings with excellent corrosion resistance.

ObjectiveTo analyze the molecular epidemiology of carbapenem-resistant Enterobacter cloacae complex (CREC) by whole-genome sequencing and to explore its clinical characteristics.MethodsEnterobacter cloacae complex isolates collected in a tertiary hospital during 2013–2021 were subjected to whole-genome sequencing to determine the distribution of antimicrobial resistance genes (ARGs), sequence types (STs), and plasmid replicons. A phylogenetic tree of the CREC strains was constructed based on the whole-genome sequences to analyze their relationships. Clinical patient information was collected for risk factor analysis.ResultsAmong the 51 CREC strains collected, blaNDM-1 (n = 42, 82.4%) was the main carbapenem-hydrolyzing β-lactamase (CHβL), followed by blaIMP-4 (n = 11, 21.6%). Several other extended-spectrum β-lactamase-encoding genes were also identified, with blaSHV-12 (n = 30, 58.8%) and blaTEM-1B (n = 24, 47.1%) being the predominant ones. Multi-locus sequence typing revealed 25 distinct STs, and ST418 (n = 12, 23.5%) was the predominant clone. Plasmid analysis identified 15 types of plasmid replicons, among which IncHI2 (n = 33, 64.7%) and IncHI2A (n = 33, 64.7%) were the main ones. Risk factor analysis showed that intensive care unit (ICU) admission, autoimmune disease, pulmonary infection, and previous corticosteroid use within 1 month were major risk factors for acquiring CREC. Logistic regression analysis showed that ICU admission was an independent risk factor for CREC acquisition and was closely related with acquiring infection by CREC with ST418.ConclusionBlaNDM-1 and blaIMP-4 were the predominant carbapenem resistance genes. ST418 carrying BlaNDM-1 not only was the main clone, but also circulated in the ICU of our hospital during 2019–2021, which highlights the necessity for surveillance of this strain in the ICU. Furthermore, patients with risk factors for CREC acquisition, including ICU admission, autoimmune disease, pulmonary infection, and previous corticosteroid use within 1 month, need to be closely monitored for CREC infection.

BackgroundDespite tremendous advances in cancer research, breast cancer (BC) remains a major health concern and is the most common cancer affecting women worldwide. Breast cancer is a highly heterogeneous cancer with potentially aggressive and complex biology, and precision treatment for specific subtypes may improve survival in breast cancer patients. Sphingolipids are important components of lipids that play a key role in the growth and death of tumor cells and are increasingly the subject of new anti-cancer therapies. Key enzymes and intermediates of sphingolipid metabolism (SM) play an important role in regulating tumor cells and further influencing clinical prognosis.MethodsWe downloaded BC data from the TCGA database and GEO database, on which we performed in depth single-cell sequencing analysis (scRNA-seq), weighted co-expression network analysis, and transcriptome differential expression analysis. Then seven sphingolipid-related genes (SRGs) were identified using Cox regression, least absolute shrinkage, and selection operator (Lasso) regression analysis to construct a prognostic model for BC patients. Finally, the expression and function of the key gene PGK1 in the model were verified by in vitro experiments.ResultsThis prognostic model allows for the classification of BC patients into high-risk and low-risk groups, with a statistically significant difference in survival time between the two groups. The model is also able to show high prediction accuracy in both internal and external validation sets. After further analysis of the immune microenvironment and immunotherapy, it was found that this risk grouping could be used as a guide for the immunotherapy of BC. The proliferation, migration, and invasive ability of MDA-MB-231 and MCF-7 cell lines were dramatically reduced after knocking down the key gene PGK1 in the model through cellular experiments.ConclusionThis study suggests that prognostic features based on genes related to SM are associated with clinical outcomes, tumor progression, and immune alterations in BC patients. Our findings may provide insights for the development of new strategies for early intervention and prognostic prediction in BC.

BackgroundAlthough breast cancer (BC) treatment has entered the era of precision therapy, the prognosis is good in the case of comprehensive multimodal treatment such as neoadjuvant, endocrine, and targeted therapy. However, due to its high heterogeneity, some patients still cannot benefit from conventional treatment and have poor survival prognoses. Amino acids and their metabolites affect tumor development, alter the tumor microenvironment, play an increasingly obvious role in immune response and regulation of immune cell function, and are involved in acquired and innate immune regulation; therefore, amino acid metabolism is receiving increasing attention.MethodsBased on public datasets, we carried out a comprehensive transcriptome and single-cell sequencing investigation. Then we used 2.5 Weighted Co-Expression Network Analysis (WGCNA) and Cox to evaluate glutamine metabolism-related genes (GRGs) in BC and constructed a prognostic model for BC patients. Finally, the expression and function of the signature key gene SNX3 were examined by in vitro experiments.ResultsIn this study, we constituted a risk signature to predict overall survival (OS) in BC patients by glutamine-related genes. According to our risk signature, BC patients can obtain a Prognostic Risk Signature (PRS), and the response to immunotherapy can be further stratified according to PRS. Compared with traditional clinicopathological features, PRS demonstrated robust prognostic power and accurate survival prediction. In addition, altered pathways and mutational patterns were analyzed in PRS subgroups. Our study sheds some light on the immune status of BC. In in vitro experiments, the knockdown of SNX3, an essential gene in the signature, resulted in a dramatic reduction in proliferation, invasion, and migration of MDA-MB-231 and MCF-7 cell lines.ConclusionWe established a brand-new PRS consisting of genes associated with glutamine metabolism. It expands unique ideas for the diagnosis, treatment, and prognosis of BC.

Abstract Background The use of tramadol among osteoarthritis (OA) patients has been increasing rapidly around the world, but population-based studies on its safety profile among OA patients are scarce. We sought to determine if tramadol use in OA patients is associated with increased risks of all-cause mortality, cardiovascular diseases (CVD), venous thromboembolism (VTE), and hip fractures compared with commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) or codeine. Methods Using administrative health datasets from British Columbia, Canada, we conducted a sequential propensity score-matched cohort study among all OA patients between 2005 and 2013. The tramadol cohort (i.e., tramadol initiation) was matched with four comparator cohorts (i.e., initiation of naproxen, diclofenac, cyclooxygenase-2 [Cox-2] inhibitors, or codeine). Outcomes are all-cause mortality, first-ever CVD, VTE, and hip fractures within the year after the treatment initiation. Patients were followed until they either experienced an event, left the province, or the 1-year follow-up period ended, whichever occurred first. Cox proportional hazard models were used to estimate hazard ratios after adjusting for competing risk of death. Results Overall, 100,358 OA patients were included (mean age: 68 years, 63% females). All-cause mortality was higher for tramadol compared to NSAIDs with rate differences (RDs/1000 person-years, 95% CI) ranging from 3.3 (0.0–6.7) to 8.1 (4.9–11.4) and hazard ratios (HRs, 95% CI) ranging from 1.2 (1.0–1.4) to 1.5 (1.3–1.8). For CVD, no differences were observed between tramadol and NSAIDs. Tramadol had a higher risk of VTE compared to diclofenac, with RD/1000 person-years (95% CI) of 2.2 (0.7–3.7) and HR (95% CI) of 1.7 (1.3–2.2). Tramadol also had a higher risk of hip fractures compared to diclofenac and Cox-2 inhibitors with RDs/1000 person-years (95% CI) of 1.9 (0.4–3.4) and 1.7 (0.2–3.3), respectively, and HRs (95% CI) of 1.6 (1.2–2.0) and 1.4 (1.1–1.9), respectively. No differences were observed between tramadol and NSAIDs for all events. Conclusions OA patients initiating tramadol have an increased risk of mortality, VTE, and hip fractures within 1 year compared with commonly prescribed NSAIDs, but not with codeine.

Metal plates have always been the gold standard in the clinic for internal fracture fixation due to their high strength advantages. However, high elastic modulus can cause stress shielding and lead to bone embrittlement. This study used an electron beam melting method to prepare personalized porous Ti6Al4V (pTi) bone plates. Then, chemical vapor deposition (CVD) technology coats tantalum (Ta) metal on the pTi bone plates. The prepared porous Ta-coated bone plate has an elastic modulus similar to cortical bone, and no stress shielding occurred. In vitro experiments showed that compared with pTi plates, Ta coating significantly enhances the attachment and proliferation of cells on the surface of the scaffold. To better evaluate the function of the Ta-coated bone plate, animal experiments were conducted using a coat tibia fracture model. Our results showed that the Ta-coated bone plate could effectively fix the fracture. Both imaging and histological analysis showed that the Ta-coated bone plate had prominent indirect binding of callus formation. Histological results showed that new bone grew at the interface and formed good osseointegration with the host bone. Therefore, this study provides an alternative to bio-functional Ta-coated bone plates with improved osseointegration and osteogenic functions for orthopaedic applications.

Objectives: To determine the status of immune responses after primary and booster immunization for SARS-CoV-2 variants and evaluate the differences in disease resistance based upon titers of neutralizing antibodies (NAbs) against the variants. Methods: Participants aged 18–59 years received 2 doses of inactivated COVID-19 vaccine, 14 days apart, and a booster dose after 12 months. Blood samples were collected before vaccination (baseline), 1 and 6 months after primary immunization, and at multiple instances within 21 days of the booster dose. NAbs against the spike protein of Wuhan-Hu-1 and 3 variants were measured using pseudovirus neutralization assays. Results: Of 400 enrolled participants, 387 completed visits scheduled within 6 months of the second dose and 346 participants received the booster dose in the follow-up research. After 1 month of primary immunization, geometric mean titers (GMTs) of NAbs peaked for Wuhan-Hu-1, whereas GMTs of other variants were

This study uncovers the role of extracellular vesicles from bone matrix as a messenger in the development of osteoporosis and vascular calcification (calcification paradox) during skeletal aging and menopause by transferring miR-483-5p and miR-2861.

Cu matrix composites reinforced by ex-situ added CrB2 ceramic particles were prepared by powder metallurgy and hot extrusion, and then the effect of CrB2 content on microstructure and mechanical properties was studied. Results show that the strength of Cu matrix composites depends mainly on the dispersion degree of CrB2 particles, which is closely corresponded to the content of CrB2 particles. When the content is below 3vol.%, CrB2 particles disperses uniformly in the Cu matrix, and the strength of Cu matrix composites increases continuously with the content of CrB2. However, when the content is above 3vol.%, the strength of Cu matrix composites decreases significantly with the increase of CrB2 content, which is ascribed to the serious agglomeration phenomenon. Although both the electrical conductivity and plasticity decrease with the increase of CrB2 content, they remain quite a high level. The excellent combination properties are obtained when the content of CrB2 is 3vol.%, viz. The tensile strength is 304 MPa, the elongation is 22% and the electrical conductivity is 90 %IACS, better than most of the reported Cu matrix composites especially electrical conductivity prepared by in-situ method. Furthermore, dislocation strengthening caused by thermal mismatch and Orowan strengthen of CrB2 is demonstrated as the main strengthening mechanism of Cu/CrB2 composites, based on the theoretical and experimental investigations.

Abstract Background Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a common pathogen that usually causes bacteraemia, osteomyelitis, as well as skin and soft tissue infections. However, deep venous thrombosis (DVT) and necrotising pneumonia are rare in infants. Case presentation We report the case of a one-month-five-day-old girl who was hospitalised for DVT and necrotising pneumonia due to septicaemia associated with Staphylococcus aureus. She recovered after treatment with intravenous antibiotics and multiple anticoagulant therapy, but DVT persisted at the three-year follow-up. Collateral circulation around the DVT was well-formed. Post thrombotic syndrome was not observed. Conclusions Staphylococcus aureus complicated by DVT and necrotising pneumonia is rare and can be successfully treated.

Near-surface PM2.5 concentrations have been greatly exacerbated by urban land expansion and dense urban traffic. This study aims to clarify the effects of multiple factors on near-surface PM2.5 concentrations from three perspectives of background climatic variables, urban morphology variables, and traffic-related emission intensity. First, two case areas covering multiple local blocks were selected to conduct mobile measurements under different climatic conditions. The observed meteorological parameters and PM2.5 concentration were obtained through GIS-based imaging. These interpolation results of air temperature and relative humidity reveal highly spatiotemporal diversity, which is greatly influenced by artificial heat emissions and spatial morphology characteristics in local areas. The PM2.5 concentration on measurement days also varies considerably from the lowest value of 44~56 μg/m3 in October to about 500 μg/m3 in December in Harbin winter and ranges between about 5 μg/m3 and 50 μg/m3 in Guangzhou summer. The correlation analysis reveals that both the climatic conditions and urban morphology characteristics are significantly correlated with local PM2.5 concentration. Especially for Guangzhou summer, the PM2.5 concentration was positively correlated with the street traffic emission source intensity with correlation coefficient reaching about 0.79. Multivariate nonlinear formulas were applied to fit the association between these factors and PM2.5 concentration with higher determined coefficients. And optimization strategies are thus suggested to improve the urban air quality in local-scale areas. This attribution analysis contributes to environmentally friendly urban construction.

The number of resident space objects (RSOs) has been steadily increasing over time, posing significant risks to the safe operation of on-orbit assets. The accurate prediction of potential collision events and implementation of effective and nonredundant avoidance maneuvers require the precise estimation of the orbit positions of objects of interest and propagation of their associated uncertainties. Previous research mainly focuses on striking a balance between accurate propagation and efficient computation. A recently proposed approach that integrates uncertainty propagation with different coordinate representations has the potential to achieve such a balance. This paper proposes combining the generalized equinoctial orbital elements (GEqOE) representation with an adaptive Gaussian mixture model (GMM) for uncertainty propagation. Specifically, we implement a reformulation for the orbital dynamics so that the underlying state and the moment feature of the GMM are propagated under the GEqOE coordinates. Starting from an initial Gaussian probability distribution function (PDF), the algorithm iteratively propagates the uncertainty distribution using a detection-splitting module. A differential entropy-based nonlinear detector and a splitting library are utilized to adjust the number of GMM components dynamically. Component splitting is triggered when a predefined threshold of differential entropy is violated, generating several GMM components. The final probability density function (PDF) is obtained by a weighted summation of the component distributions at the target time. Benefiting from the nonlinearity reduction caused by the GEqOE representation, the number of triggered events largely decreases, causing the necessary number of components to maintain uncertainty realism also to decrease, which enables the proposed approach to achieve good performance with much more efficiency. As demonstrated by the results of propagation in three scenarios with different degrees of complexity, compared with the Cartesian-based approach, the proposed approach achieves comparable accuracy to the Monte Carlo method while largely reducing the number of components generated during propagation. Our results confirm that a judicious choice of coordinate representation can significantly improve the performance of uncertainty propagation methods in terms of accuracy and computational efficiency.