Search

Abstract Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.

Abstract Since the first report on single-layer MoS2 based transistor, rapid progress has been achieved in two-dimensional (2D) material-based atomically thin electronics, providing an alternative approach to solve the bottleneck in silicon device miniaturization. In this scenario, reliable contact between the metal electrodes and the subnanometer-thick 2D materials becomes crucial in determining the device performance. Here, utilizing the quasi-van der Waals (vdW) epitaxy of metals on fluorophlogopite mica, we demonstrate an all-stacking method for the fabrication of 2D devices with high-quality vdW contacts by mechanically transferring pre-deposited metal electrodes. This technique is applicable for complex device integration with sizes up to the wafer scale and is also capable of tuning the electric characteristics of the interfacial junctions by transferring selective metals. Our results provide an efficient, scalable, and low-cost technique for 2D electronics, allowing high-density device integration as well as a handy tool for fundamental research in vdW materials.

Abstract The universal flexoelectric effect in solids provides a mechanical pathway for controlling electric polarization in ultrathin ferroelectrics, eliminating potential material breakdown from a giant electric field at the nanoscale. One challenge of this approach is arbitrary implementation, which is strongly hindered by one-way switching capability. Here, utilizing the innate flexibility of van der Waals materials, we demonstrate that ferroelectric polarization and domain structures can be mechanically, reversibly, and arbitrarily switched in two-dimensional CuInP2S6 via the nano-tip imprinting technique. The bidirectional flexoelectric control is attributed to the extended tip-induced deformation in two-dimensional systems with innate flexibility at the atomic scale. By employing an elastic substrate, artificial ferroelectric nanodomains with lateral sizes as small as ~80 nm are noninvasively generated in an area of 1 μm2, equal to a density of 31.4 Gbit/in2. Our results highlight the potential applications of van der Waals ferroelectrics in data storage and flexoelectronics.

Rhododendron simsii plays important roles in maintaining ecological system stability in the north temperate zone. However, its natural growth is greatly affected by soil microorganisms, particularly rhizosphere microbes. In this study, a comparative analysis was conducted of the bacterial community structure in the rhizosphere of R. simsii at the old, adult, juvenile, and seedlings stages. The results showed that Proteobacteria (38.53%‒47.63%), Actinobacteria (23.45%‒34.03%), and Acidobacteria (10.33%‒17.79%) were the dominant phyla in the R. simsii rhizosphere. In particular, 3, 5, 42, and 33 OTUs were unique to the soil samples of ‘old trees’, ‘adult trees’, ‘juvenile trees’, and ‘seedlings’, respectively. Across four sets of R. simsii rhizosphere microbes sampled from seedlings to old trees, the OTUs first increased, then decreased, and finally increased. Overall, alpha diversity (Chao, ACE, and Sobs) revealed similar trends with the highest value i‒n recorded for the rhizosphere sample of ‘adult trees’ and the lowest for the ‘seedlings’ sample. The bacterial genera in the rhizosphere samples from ‘old trees’ and ‘adult trees’ exhibited close clustering. Notably, the R. simsii population of ‘juvenile trees’, demonstrating the highest genetic diversity, were rich in Bradyrhizobium and Streptomycetes. This research serves to benefit the domestication of wild R. simsii and other Rhododendron resources.

Background Musculoskeletal (MSK) disorders, affecting billions of people worldwide, pose significant challenges to the healthcare system and require effective management models. The rapid development of digital healthcare technologies (DHTs) has revolutionized the healthcare industry. DHT-based interventions have shown promising clinical benefits in managing MSK disorders, alleviating pain, and improving functional impairment. There is, however, no bibliometric analysis of the overall trends on this topic. Methods We extracted all relevant publications from the Web of Science Core Collection (WoSCC) database until April 30, 2023. We performed bibliometric analysis and visualization using CiteSpace, VOSviewer, and R software. Annual trends of publications, countries/regions distributions, funding agencies, institutions, co-cited journals, author contributions, references, core journals, and keywords and research hotspots were analyzed. Results A total of 6810 papers were enrolled in this study. Publications have increased drastically from 16 in 1995 to 1198 in 2022, with 4067 articles published in the last five years. In all, 53 countries contributed with publications to this research area. The United States, the United Kingdom, and China were the most productive countries. Harvard University was the most contributing institution. Regarding keywords, research focuses include artificial intelligence, deep learning, machine learning, telemedicine, rehabilitation, and robotics. Conclusion The COVID-19 pandemic has further accelerated the adoption of DHTs, highlighting the need for remote care options. The analysis reveals the positive impact of DHTs on improving physician productivity, enhancing patient care and quality of life, reducing healthcare expenditures, and predicting outcomes. DHTs are a hot topic of research not only in the clinical field but also in the multidisciplinary intersection of rehabilitation, nursing, education, social and economic fields. The analysis identifies four promising hotspots in the integration of DHTs in MSK pain management, biomechanics assessment, MSK diagnosis and prediction, and robotics and tele-rehabilitation in arthroplasty care.

Abstract Background Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. Methods Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p

Abstract Background The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients. Methods Patients who underwent curative − intent resection of ICC between 2011 and 2019 were identified from a large multi − institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence − free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage. Results A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 − year survival (both p

Abstract Background Periprosthetic joint infection (PJI) is a serious complication after total joint arthroplasty (TJA). Although some risk factors of PJI were well studied, the association between trauma and PJI remains unknown in revision patients. Materials and methods Between 2015 and 2018, a total of 71 patients with trauma history before revisions (trauma cohort) were propensity score matched (PSM) at a ratio of 1 to 5 with a control cohort of revision patients without a history of trauma. Then, the cumulative incidence rate of PJI within 3 years after operation between the two groups was compared. The secondary endpoints were aseptic revisions within 3 postoperative years, complications up to 30 postoperative days, and readmission up to 90 days. During a minimal 3-year follow-up, the survival was comparatively analyzed between the trauma cohort and the control cohort. Results The cumulative incidence of PJI was 40.85% in patients with trauma history against 27.04% in the controls (P = 0.02). Correspondingly, the cumulative incidence of aseptic re-revisions was 12.68% in patients with trauma history compared with 5.07% in the control cohort (P = 0.028). Cox regression revealed that trauma history was a risk factor of PJI (HR, 1.533 [95%CI, (1.019,2.306)]; P = 0.04) and aseptic re-revisions (HR, 3.285 [95%CI, (1.790,6.028)]; P

This study designs an energy management strategy for fuel cell hybrid vehicles aimed to alleviating the performance degradation of Proton Exchange Membrane Fuel Cells (PEMFC), fuel consumption, and battery State of Charge (SOC) fluctuations during vehicle operation. The research focuses on the decrease in Electrochemical Surface Area (ECSA) due to Platinum (Pt) catalyst degradation, which is a key factor influencing PEMFC durability. An ECSA model based on the Pt dissolution mechanism is established, and a dynamic condition accelerated stress test (DC-AST) is designed to specifically investigate the impacts of key parameters, such as cycle period, amplitude, and duty cycle on the degradation of ECSA. This reveals the association between ECSA degradation and irregular potential fluctuations. A hierarchical power allocation strategy is then proposed, combining the global search capabilities of optimization algorithms with heuristic strategies in light of these features. The upper level employs Pontryagin’s Minimum Principle (PMP) strategy for global power allocation optimization, while the lower level uses a satisfaction-based heuristic strategy that is tailored to the ECSA degradation characteristics, to dynamically adjust power output. Simulation results demonstrate that, compared to traditional rule-based strategies and classical PMP-based strategies, the proposed energy management strategy more effectively mitigates ECSA degradation of PEMFC under typical vehicle conditions.

AIM: To explore the factors influencing individuals' willingness to participate in ophthalmic clinical trials. METHODS: A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center, Sun Yat-sen University, in Guangzhou, China. The survey gathered data on respondents' willingness, demographic and socioeconomic profiles, as well as their reasons and concerns regarding engagement in clinical trials. RESULTS: Of the 1078 residents surveyed (mean age 31.2±13.1y; 65.8% females) in Guangzhou, 749 (69.5%) expressed a willingness to participate in future ophthalmic clinical trials. Specific characteristics associated with greater willingness included a younger age, lower annual income, higher education, prior participation experience, previous ophthalmic treatment, and a better understanding of clinical trials. With the exception of age, these characteristics were significantly linked to a higher willingness. The primary barrier to participation, expressed by 64.8% of those willing and 54.4% of those unwilling, was “Uncertain efficacy”. In terms of motivations, the willing group ranked “Better therapeutic benefits” (35.0%), “Professional monitoring” (34.3%), and “Trust in healthcare professionals” (33.1%) as their top three reasons, whereas the unwilling participants indicated “Full comprehension of the protocol” (46.2%) as the key facilitator. CONCLUSION: This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors. Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies. Importantly, the need for and trust in healthcare professionals stand out as powerful motivations, underscoring the importance of enhancing physician-patient relationships, adopting patient-centered communication approaches, and addressing individualized needs to improve accrual rates.

AbstractAgricultural modernization urgently requires precise control of pear tree leaf diseases, with accurate identification and segmentation of disease spots becoming crucial aspects for ensuring crop health. Addressing potential issues such as missed segmentation, missegmentation, and low segmentation accuracy in the traditional DeepLabv3+ model for this task, this study proposes an innovative approach based on an improved DeepLabv3+ network model. To enhance computational efficiency, MobileNetV2 is introduced as the backbone network. This reduces the model’s computational load and significantly improves segmentation speed, making it more suitable for real-time applications. Secondly, after the ASPP (Atrous Spatial Pyramid Pooling) convolution, the Squeeze-and-Excitation (SE) attention mechanism is introduced, integrating the features of pear tree leaf diseases to make the network focus more on the critical components of disease spots, thereby enhancing segmentation accuracy. Finally, the loss function is optimized by employing a linear combination of the cross-entropy loss function and Dice loss, encompassing comprehensive overall image loss and accurate loss calculation for the target area. Experimental validation demonstrates a significant improvement in the enhanced DeepLabv3+ across metrics such as MIoU, mPA, mPr, and mRecall, reaching 86.32%, 88.97%, 91.10%, and 88.97%, respectively. The improved model excels in pear tree leaf disease segmentation compared to traditional methods like DeepLabv3+, SegNet, FCN, and PSPNet. This confirms the enhanced model’s outstanding performance and generalization ability in segmenting pear tree leaf lesions, highlighting its potential value in practical applications.

BackgroundThe utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated.MethodsFrom a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns.ResultsPreoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers.ConclusionsAFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

Abstract Digital PCR (dPCR) holds immense potential for precisely detecting nucleic acid markers essential for personalized medicine. However, its broader application is hindered by high consumable costs, complex procedures, and restricted multiplexing capabilities. To address these challenges, an all‐in‐one dPCR system is introduced that eliminates the need for microfabricated chips, offering fully automated operations and enhanced multiplexing capabilities. Using this innovative oscillation‐induced droplet generation technique, OsciDrop, this system supports a comprehensive dPCR workflow, including precise liquid handling, pipette‐based droplet printing, in situ thermocycling, multicolor fluorescence imaging, and machine learning‐driven analysis. The system's reliability is demonstrated by quantifying reference materials and evaluating HER2 copy number variation in breast cancer. Its multiplexing capability is showcased with a quadruplex dPCR assay that detects key EGFR mutations, including 19Del, L858R, and T790M in lung cancer. Moreover, the digital stepwise melting analysis (dSMA) technique is introduced, enabling high‐multiplex profiling of seven major EGFR variants spanning 35 subtypes. This innovative dPCR system presents a cost‐effective and versatile alternative, overcoming existing limitations and paving the way for transformative advances in precision diagnostics.

BackgroundCervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity.MethodsUsing advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively.Results55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined.ConclusionOur findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies.

Abstract Background Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP). Methods Data from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP’s prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging. Results Preoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P

Objectives: During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage. Methods: This study was a follow-up trial of the “Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial.” Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines. Results: The geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period. Conclusion: Co-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.

Abstract Objectives The purpose of this study was to develop and validate a radiomics nomogram for predicting thymidylate synthase (TYMS) status in hepatocellular carcinoma (HCC) by using Gd-DTPA contrast enhanced MRI. Methods We retrospectively enrolled 147 consecutive patients with surgically confirmed HCC and randomly allocated to training and validation set (7:3). The TYMS status was immunohistochemical determined and classified into low TYMS (positive cells ≤ 25%) and high TYMS (positive cells > 25%) groups. Radiomics features were extracted from the arterial phases and portal venous phase of Gd-DTPA contrast enhanced MRI. Least absolute shrinkage and selection operator (LASSO) were applied for generating the Rad score. Clinical data and MRI findings were assessed to build a clinical model. Rad score combined with clinical features was used to construct radiomics nomogram. Results A total of 2260 features were extracted and reduced to 7 features as the most important discriminators to build the Rad score. InAFP was identified as the only independent clinical factors for TYMS status. The radiomics nomogram showed good discrimination in training (AUC, 0.759; 95% CI 0.665–0.838) and validation set (AUC, 0.739; 95% CI 0.585–0.860), and showed better discrimination capability (P

Rhododendron simsii Planchon is an important ornamental species in the northern hemisphere. Flower color is an important objective of Rhododendron breeding programs. However, information on anthocyanin synthesis in R. simsii is limited. In this research, the regulatory mechanism of anthocyanin biosynthesis in R. simsii was performed through the integrated analysis of metabolome and RNA-seq. A total of 805 and 513 metabolites were screened by positive and negative ionization modes, respectively, In total, 79 flavonoids contained seven anthocyanidins, 42 flavanones, 10 flavans, 13 flavones, and seven flavonols. Methylated and glycosylated derivatives took up the most. Differentially accumulated metabolites were mainly involved in “flavone and flavonol biosynthesis”, “cyanoamino acid metabolism”, “pyrimidine metabolism”, and “phenylalanine metabolism” pathways. For flavonoid biosynthesis, different expression of shikimate O-hydroxycinnamoyltransferase, caffeoyl-CoA O-methyltransferase, flavonoid 3′-monooxygenase, flavonol synthase, dihydroflavonol 4-reductase/flavanone 4-reductase, F3′5′H, chalcone synthase, leucoanthocyanidin reductase, and 5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase genes ultimately led to different accumulations of quercetin, myricetin, cyanidin, and eriodictyol. In flavone and flavonol biosynthesis pathway, differential expression of F3′5′H, flavonoid 3′-monooxygenase and flavonol-3-O-glucoside/galactoside glucosyltransferase genes led to the differential accumulation of quercetin, isovitexin, and laricitrin. This research will provide a biochemical basis for further modification of flower color and genetic breeding in R. simsii and related Rhododendron species.

Accurate time synchronisation is critical in modern communication, navigation, and scientific research. In this context, the eLoran receiver, which is an advanced timing device, has attracted increasing scholarly attention. This study aims to comprehensively analyse the performance and potential applications of eLoran systems for timing monitoring and to specifically explore the relevant indices of two eLoran receivers. To this end, we evaluated the performance of these receivers in receiving time signals through both simulated and empirical data and conducted a regularity analysis to uncover their potential value in practical applications. The findings demonstrate that the eLoran receiver excels at timing monitoring and provides highly accurate time information. An analysis of the timing performance of the eLoran system improved its accuracy and integrity.

This paper explores linear waves’ instability in nonuniform complex plasmas with dust size distribution and non-adiabatic dust charge fluctuation. For this purpose, the dispersion relation is obtained with the aid of linearizing the hydrodynamic equations governing the properties of linear waves. The contribution of physical parameters such as inhomogeneity, nonadiabatic dust charge fluctuation, and dust size distribution to the features of dust acoustic waves is examined at great length. The numerical results show that the present research results are very important in the phenomenon of space astrophysical and experimental plasmas.

Background: Rising evidence indicates the development of pyroptosis in the initiation and pathogenesis of spinal cord injury (SCI). However, the associated effects of pyroptosis-related genes (PRGs) in SCI are unclear. Methods: We obtained the gene expression profiles of SCI and normal samples in the GEO. Database: The R package limma screened for differentially expressed (DE) PRGs and performed functional enrichment analysis. Mechanical learning and PPI analysis helped filter essential PRGs to diagnose SCI. Peripheral blood was collected for validation from ten SCI patients and eight healthy individuals. The association of essential PRGs with immune infiltration was evaluated, and pyroptosis subtypes were recognized in SCI patients by unsupervised cluster analysis. Besides, a SCI model was built for in vivo validation of essential PRGs. Result: We identified 25 DE-PRGs between SCI and normal controls. Functional enrichment analysis revealed the principal involvement of DE-PRGs in pyroptosis, inflammasome complex, interleukin-1 beta production, etc. Subsequently, three essential PRGs were identified and validated, showing excellent diagnostic efficacy and significant correlation with immune cell infiltration. Additionally, we developed diagnostic nomograms to predict the occurrence of SCI. Two pyroptosis subtypes exhibited distinct biological functions and immune landscapes among SCI patients. Finally, the expression of these essential PRGswas verified in vivo. Conclusion: The current study described the vital effects of pyroptosis-related genes in SCI, providing a novel direction for effective assessment and management of SCI.

Background: The immune response associated with periprosthetic joint infection (PJI) is an emerging but relatively unexplored topic. The aim of this study was to investigate immune cell infiltration in periprosthetic tissues and identify potential immune-related biomarkers. Methods: The GSE7103 dataset from the GEO database was selected as the data source. Differentially expressed genes (DEGs) and significant modular genes in weighted correlation network analysis (WGCNA) were identified. Functional enrichment analysis and transcription factor prediction were performed on the overlapping genes. Next, immune-related genes from the ImmPort database were matched. The protein-protein interaction (PPI) analysis was performed to identify hub genes. CIBERSORTx was used to evaluate the immune cell infiltration pattern. Spearman correlation analysis was used to evaluate the relationship between hub genes and immune cells. Results: A total of 667 DEGs were identified between PJI and control samples, and 1847 PJI-related module genes were obtained in WGCNA. Enrichment analysis revealed that the common genes were mainly enriched in immune and host defense-related terms. TFEC, SPI1, and TWIST2 were the top three transcription factors. Three hub genes, SDC1, MMP9, and IGF1, were identified in the immune-related PPI network. Higher levels of plasma cells, CD4+ memory resting T cells, follicular helper T cells, resting mast cells, and neutrophils were found in the PJI group, while levels of M0 macrophages were lower. Notably, the expression of all three hub genes correlated with the infiltration levels of seven types of immune cells. Conclusion: The present study revealed immune infiltration signatures in the periprosthetic tissues of PJI patients. SDC1, MMP9, and IGF1 were potential immune-related biomarkers for PJI.

In order to broaden the muffler frequency band in the low-frequency range of the exhaust muffler and to achieve the purpose of broadband noise reduction, in this paper, a model of an annular connecting pipe muffler is proposed using the finite element method (FEM) to simulate the nonreflection boundary condition and to solve the transmission loss (TL). In addition, the experimental value is obtained by the spatial five-point measurement method and compared with the simulated value, and the validity and reliability of the solution model are verified. Compared with a simple expansion muffler, the average TL of the annular connecting pipe muffler is increased by 11.86 dB, and the maximum TL is increased by 18.31 dB, effectively widening the muffler frequency area, and the overall performance is effectively improved. Finally, the influence of structural factors is analyzed, including the width (W) of the annular connecting pipe, the length (L) of the annular connecting pipe, and the length ratio (m) of the front and rear chambers on the TL and on the width of the anechoic frequency band. The results reveal that the width and length of the annular connecting pipe and front-to-back cavity length ratio are the most significant factors to influence the TL, muffler frequency band, and elimination or reduction of the passing frequency, respectively.

Abstract Background Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier’s gangrene (FG). Methods Data of patients surgically treated for FG were retrospectively analyzed. Results Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28–74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. Conclusion VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.

Abstract Aims Periprosthetic joint infection (PJI) is one of the most serious complications after total joint arthroplasty (TJA) but the characterization of the periprosthetic environment microbiome after TJA remains unknown. Here, we performed a prospective study based on metagenomic next-generation sequencing to explore the periprosthetic microbiota in patients with suspected PJI. Methods We recruited 28 patients with culture-positive PJI, 14 patients with culture-negative PJI, and 35 patients without PJI, which was followed by joint aspiration, untargeted metagenomic next-generation sequencing (mNGS), and bioinformatics analysis. Our results showed that the periprosthetic environment microbiome was significantly different between the PJI group and the non-PJI group. Then, we built a “typing system” for the periprosthetic microbiota based on the RandomForest Model. After that, the ‘typing system’ was verified externally. Results We found the periprosthetic microbiota can be classified into four types generally: “Staphylococcus type,” “Pseudomonas type,” “Escherichia type,” and “Cutibacterium type.” Importantly, these four types of microbiotas had different clinical signatures, and the patients with the former two microbiota types showed obvious inflammatory responses compared to the latter ones. Based on the 2014 Musculoskeletal Infection Society (MSIS) criteria, clinical PJI was more likely to be confirmed when the former two types were encountered. In addition, the Staphylococcus spp. with compositional changes were correlated with C-reactive protein levels, the erythrocyte sedimentation rate, and the synovial fluid white blood cell count and granulocyte percentage. Conclusions Our study shed light on the characterization of the periprosthetic environment microbiome in patients after TJA. Based on the RandomForest model, we established a basic “typing system” for the microbiota in the periprosthetic environment. This work can provide a reference for future studies about the characterization of periprosthetic microbiota in periprosthetic joint infection patients.

Abstract Background N6-methyladenosine (m6A) is associated with mammalian mRNA biogenesis, decay, translation and metabolism, and also contributes greatly to gastrointestinal tumor formation and development. Therefore, the specific mechanisms and signaling pathways mediated by methyltransferase-like 3 (METTL3), which catalyzes the formation of m6A chemical labeling in stomach adenocarcinoma (STAD), are still worth exploring. Methods Quantitative real-time PCR (qRT-PCR) was constructed to detect the expression of METTL3 in gastric cancer cell lines and patient tissues. The biological function of METTL3 was investigated in vitro/in vivo by Cell Counting Kit-8, colony formation assay, Transwell assay and nude mouse tumorigenesis assay. Based on the LinkedOmics database, the genes co-expressed with METTL3 in the TCGA STAD cohort were analyzed to clarify the downstream targets of METTL3. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA stability analysis were employed to explore the mechanism of METTL3 in gastric cancer progression. Results We analyzed TCGA data and found that METTL3 was frequently elevated in STAD, and demonstrated that METTL3 was present at high levels in clinical STAD tissues and cells. High METTL3 expression was more likely to have advanced TNM tumors and distant metastasis. On the other hand, METTL3 silencing effectively impeded the higher oncogenic capacity of AGS and HGC27 cells in vivo and in vitro, as reflected by slowed cell growth and diminished migration and invasion capacities. Continued mining of the TCGA dataset identified the co-expression of angiopoietin-like 3 (ANGPTL3) and METTL3 in STAD. Lower level of ANGPTL3 was related to increased level of METTL3 in STAD samples and shorter survival times in STAD patients. ANGPTL3 enrichment limited the growth and metastasis of STAD cells. Besides, ANGPTL3 mRNA levels could be decreased by METTL3-dominated m6A modifications, a result derived from a combination of MeRIP-qPCR and RNA half-life experiments. Importantly, the inhibitory effect of METTL3 silencing on cancer could be reversed to some extent by ANGPTL3 inhibition. Conclusions Overall, our findings suggested that METTL3 functioned an oncogenic role in STAD by reducing ANGPTL3 expression in an m6A-dependent manner. The discovery of the METTL3-ANGPTL3 axis and its effect on STAD tumor growth will contribute to further studies on the mechanisms of gastric adenocarcinoma development.

Abstract Background Periprosthetic joint infection is a serious complication after total joint arthroplasty. Despite that alpha-defensin was used as diagnostic test in the 2018 ICM (international consensus meeting) criteria, its position in the PJI diagnostic pipeline was controversial. Therefore, we performed a retrospective pilot study to identify whether synovial fluid alpha-defensin test was necessary when corresponding synovial fluid analysis (WBC count, PMN% and LE tests) was performed. Methods Between May 2015 and October 2018, a total of 90 suspected PJI patients who underwent revisions after TJA were included in this study. Based on the 2018 ICM criteria, the interobserver agreements between preoperative diagnostic results and postoperative diagnostic results and the interobserver reliability between preoperative diagnostic results and postoperative diagnostic results with or without synovial fluid alpha-defensin tests were calculated. After that, the ROC analysis, and the direct cost-effectiveness of adding alpha-defensin was performed. Results There were 48,16 and 26 patients in the PJI group, inconclusive group and non-PJI group, respectively. Adding the alpha-defensin tests into 2018 ICM criteria can’t change the preoperative diagnostic results, postoperative diagnostic results, and the concordance between preoperative and postoperative diagnostic results. Moreover, the Risk–benefit Ratio is over 90 per changed decision and the direct cost-effectiveness of alpha-defensin was more than $8370($93*90) per case. Conclusions Alpha-defensin assay exhibit high sensitivity and specificity for PJI detection as a standalone test based on the 2018 ICM criteria. However, the additional order of Alpha-defensin can’t offer additional evidence for PJI diagnosis when corresponding synovial fluid analysis was performed (synovial fluid WBC count, PMN% and LE strip tests). Evidence level Level II, Diagnostic study.

Objective Periprosthetic joint infection (PJI) caused by non‐tubercular mycobacteria (NTM) is uncommon but catastrophic. However, conclusive clinical data on PJI caused by NTM are lacking. In this case series and systematic review, the clinical manifestations, diagnosis, and management of NTM PJI are summarized and analyzed. Methods From 2012 to 2020, we retrospectively analyzed consecutive PJI cases caused by NTM in our institution. A literature review was also conducted from January 2000 to December 2021, utilizing the PubMed, MEDLINE, Cochrane Library, and EMBASE databases to identify all reported NTM‐induced PJI cases. The clinical characteristics, demographics, pathogen identification, treatment protocols, and prognosis of NTM PJI were summarized and analyzed. Results In this retrospective analysis, seven patients infected with NTM following total joint arthroplasty at our institution were included, including six cases of PJI caused by NTM and one case of septic arthritis (SA) caused by NTM. There were six men and one woman, and their average age was 62.3 years. The average interval between TJA and PJI onset was 4 months. The preoperative serological markers, including the mean ESR (51 mm/h), CRP (4.0 mg/dL), fibrinogen (5.7 g/L), and D‐dimer (1.1 g/L), were increased. Six patients underwent staged revision surgery, and one patient with SA received antibiotic‐loaded bone cement beads to treat the infection. After an average of 33 months of observation following surgical intervention, none of the patients showed any symptoms of infection recurrence. From 2000 to 2021, 68 patients with NTM PJI were found in 39 studies in the published literature. Reinfections occurred within 1 year after arthroplasty in more than half (53.2%) of the patients. M. fortuitum and M. abscesses were the most prevalent rapidly growing mycobacteria (RGM) in all PJI patients, whereas Mycobacterium avium intracellulare (MAC) was the most prevalent slowly growing mycobacterium (SGM). The corresponding antibiotics were amikacin and ethambutol. The rate of culture‐negative without specific clinical symptoms was as high as 36.4% (12/33), while 45% (18/40) utilized additional diagnostic techniques such as NGS. A final clinical follow‐up record was available for 59 patients (86.7%; mean follow‐up period, 29 months), and 10.1% of patients failed to respond to treatment. Conclusion Orthopaedic surgeons should consider NTM in patients with negative routine cultures who are at risk for Mycobacterium infection. Treatment options rely on the accurate result of microbiologic identification and drug sensitivity testing, and to achieve this, it may be necessary to send multiple culture specimens, extend the culture time, and change the culture medium. Every effort should be made to identify NTM and its various subtypes through modern diagnostic tools if necessary.

Abstract Background To develop and assess the performance of machine learning (ML) models based on magnetic resonance imaging (MRI) radiomics analysis for knee osteoarthritis (KOA) diagnosis. Methods This retrospective study analysed 148 consecutive patients (72 with KOA and 76 without) with available MRI image data, where radiomics features in cartilage portions were extracted and then filtered. Intraclass correlation coefficient (ICC) was calculated to quantify the reproducibility of features, and a threshold of 0.8 was set. The training and validation cohorts consisted of 117 and 31 cases, respectively. Least absolute shrinkage and selection operator (LASSO) regression method was employed for feature selection. The ML classifiers were logistic regression (LR), K-nearest neighbour (KNN) and support vector machine (SVM). In each algorithm, ten models derived from all available planes of three joint compartments and their various combinations were, respectively, constructed for comparative analysis. The performance of classifiers was mainly evaluated and compared by receiver operating characteristic (ROC) analysis. Results All models achieved satisfying performances, especially the Final model, where accuracy and area under ROC curve (AUC) of LR classifier were 0.968, 0.983 (0.957–1.000, 95% CI) in the validation cohort, and 0.940, 0.984 (0.969–0.995, 95% CI) in the training cohort, respectively. Conclusion The MRI radiomics analysis represented promising performance in noninvasive and preoperative KOA diagnosis, especially when considering all available planes of all three compartments of knee joints.

Abstract Background Biological nitrogen fixation converting atmospheric dinitrogen to ammonia is an important way to provide nitrogen for plants. Pseudomonas stutzeri DSM4166 is a diazotrophic Gram-negative bacterium isolated from the rhizosphere of cereal Sorghum nutans. Endogenous constitutive promoters are important for engineering of the nitrogen fixation pathway, however, they have not been systematically characterized in DSM4166. Results Twenty-six candidate promoters were identified from DSM4166 by RNA-seq analysis. These 26 promoters were cloned and characterized using the firefly luciferase gene. The strengths of nineteen promoters varied from 100 to 959% of the strength of the gentamicin resistance gene promoter. The strongest P12445 promoter was used to overexpress the biological nitrogen fixation pathway-specific positive regulator gene nifA. The transcription level of nitrogen fixation genes in DSM4166 were significantly increased and the nitrogenase activity was enhanced by 4.1 folds determined by the acetylene reduction method. The nifA overexpressed strain produced 359.1 µM of extracellular ammonium which was 25.6 times higher than that produced by the wild-type strain. Conclusions The endogenous strong constitutive promoters identified in this study will facilitate development of DSM4166 as a microbial cell factory for nitrogen fixation and production of other useful compounds.

Abstract Background Soil salinization is a major abiotic environmental stress factor threatening crop production throughout the world. Salt stress drastically affects the growth, development, and grain yield of rice (Oryza sativa L.), and the improvement of rice tolerance to salt stress is a desirable approach for meeting increasing food demand. Receptor-like cytoplasmic kinases (RLCKs) play essential roles in plant growth, development and responses to environmental stresses. However, little is known about their functions in salt stress. Previous reports have demonstrated that overexpression of an RLCK gene SALT TOLERANCE KINASE (STK) enhances salt tolerance in rice, and that STK may regulate the expression of GST (Glutathione S-transferase) genes. Results The expression of STK was rapidly induced by ABA. STK was highest expressed in the stem at the heading stage. STK was localized at the plasma membrane. Overexpression of STK in rice increased tolerance to salt stress and oxidative stress by increasing ROS scavenging ability and ABA sensitivity. In contrast, CRISPR/Cas9-mediated knockout of STK increased the sensitivity of rice to salt stress and oxidative stress. Transcriptome sequencing analysis suggested that STK increased the expression of GST genes (LOC_Os03g17480, LOC_Os10g38140 and LOC_Os10g38710) under salt stress. Reverse transcription quantitative PCR (RT-qPCR) suggested that four stress-related genes may be regulated by STK including OsABAR1, Os3BGlu6, OSBZ8 and OsSIK1. Conclusions These findings suggest that STK plays a positive regulatory role in salt stress tolerance by inducing antioxidant defense and associated with the ABA signaling pathway in rice.

Background: The Panbio™ COVID-19 IgG Rapid Test Device (“Panbio™”) detects IgG antibodies against the SARS-CoV-2 spike protein from viral infection or vaccination. Objectives: To determine the diagnostic sensitivity and specificity of the Panbio™ professional use test, using fingerstick whole blood and venous plasma. Study design: Fingerstick whole blood and venous plasma from each participant were tested with Panbio™ and compared against the SARS-CoV-2 IgG II assay on the Abbott Architect™ platform (Europe) or the equivalent AdviseDx SARS-CoV-2 IgG II Abbott Alinity i™ platform (US). 447 evaluable participants were enrolled across 6 US and 9 European clinical centers. Results: For unvaccinated participants with PCR-confirmed infection ≥21 days post-symptom onset, the Panbio™ sensitivity with fingerstick whole blood was 92.6 % (95 % CI: 85.9, 96.7), and the specificity was 97.0 % (95 % CI: 93.1, 99.0). For venous plasma, the sensitivity was 90.0 % (95 % CI: 79.5, 96.2) for participants with PCR-confirmed infection and symptom onset 22–180 days ago; the specificity was 96.3 % (92.2, 98.6). For vaccinated participants, the sensitivity was 98.4 % (95 % CI: 91.2, 100.0) for fingerstick whole blood and 96.7 % (95 % CI: 88.7, 99.6) for venous plasma. Conclusion: The Panbio™ test had high sensitivity and specificity for detecting IgG against the SARS-CoV-2 spike protein.

Solar-driven interfacial evaporation has emerged as an efficient and sustainable way to generate freshwater from seawater to address the crisis of drinkable water. Though rational designs of photothermal materials and structures are essential to the interfacial solar evaporation process, the salt accumulation remains a challenge to the long-term operation of seawater desalination. Here, we report a high-yield and low-cost natural sphagnum as solar steam generator with ultra-fast water transportation, unique microstructure to prevent salting out, and high evaporation rates. The carbonized sphagnum based photothermal evaporator exhibits a strong broad-band light absorption (>97.0 %). During the solar steam generation, a high evaporation rate of 3.53 kg m−2 h−1 was achieved under 1.0 sun illumination. More significantly, the 3D sphagnum evaporator shows excellent selective filtration of salt ions and cycling stability in actual sea water even high salinity solution (10 wt.% NaCl) for 7 days. This work provides an environmentally friendly and cost-effective photothermal material for large-scale seawater desalination, and treatment of waste water with high ions concentration.

Silicon carbide (SiC) nanowhiskers have many application prospects owing to their excellent mechanical properties, thermal conductivity, and good chemical stability. Herein, we examined the effect of enhancing the mechanical properties and impermeability of cement mortar (CM) by improving the microstructural compactness and reducing the porosity after mixing CM using SiC nanowhiskers. Macroscopic and microscopic tests and analyses of CM blended with different amounts of SiC nanowhiskers were performed using an electro-hydraulic flexural and compressive testing machine, cement mortar penetration tester, field-emission scanning electron microscopy, energy-dispersive spectrometry, X-ray diffraction, and three-dimensional X-ray microscopy. Results demonstrated that the incorporation of SiC nanowhiskers can lead to the following: (1) enhance the mechanical properties of CM, especially in the early stage; (2) fulfill the role of crystal nucleation and promote the hydration reaction; (3) fill the pores, play the role of micro-aggregate filling, improve the compactness, and reduce the porosity and relative permeability coefficient; and (4) play a bridging role and connect internal structures. Our results provide a valuable reference for developing nanowhisker-blended CM.

Abstract Background Inflammation is implicated in tumorigenesis and has been reported as an important prognostic factor in cancers. In this study, we aimed to develop and validate a novel inflammation score (IFS) system based on 12 inflammatory markers and explore its impact on intrahepatic cholangiocarcinoma (ICC) survival after hepatectomy. Methods Clinical data of 446 ICC patients undergoing surgical treatment were collected from the Primary Liver Cancer Big Data, and then served as a training cohort to establish the IFS. Furthermore, an internal validation cohort including 175 patients was used as internal validation cohort of the IFS. A survival tree analysis was used to divide ICC patients into three groups (low-, median-, and high- IFS-score groups) according to different IFS values. Kaplan-Meier (KM) curves were used to compare the overall survival (OS) and recurrence-free survival (RFS) rates among three different groups. Cox regression analyses were applied to explore the independent risk factors influencing OS and RFS. Results In the training cohort, 149 patients were in the low-IFS-score group, 187 in the median-IFS-score group, and 110 in the high-IFS-score group. KM curves showed that the high-IFS-score group had worse OS and RFS rates than those of the low- and median-IFS-score groups (P

Abstract Background Spinosad is a macrolide insecticide with the tetracyclic lactone backbone to which forosamine and tri-o-methylrhamnose are attached. Both the sugar moieties are essential for its insecticidal activity. In biosynthesis of spinosad, the amino group of forosamine is dimethylated by SpnS and then transferred onto the lactone backbone by SpnP. Because the spinosad native producer is difficult to genetically manipulate, we previously changed promoters, ribosome binding sites and start codons of 23 spinosad biosynthetic genes to construct an artificial gene cluster which resulted in a 328-fold yield improvement in the heterologous host Streptomyces albus J1074 compared with the native gene cluster. However, in fermentation of J1074 with the artificial gene cluster, the N-monodesmethyl spinosad with lower insecticidal activity was always produced with the same titer as spinosad. Results By tuning expression of SpnS with an inducible promotor, we found that the undesired less active byproduct N-monodesmethyl spinosad was produced when SpnS was expressed at low level. Although N-monodesmethyl spinosad can be almost fully eliminated with high SpnS expression level, the titer of desired product spinosad was only increased by less than 38%. When the forosaminyl transferase SpnP was further overexpressed together with SpnS, the titer of spinosad was improved by 5.3 folds and the content of N-desmethyl derivatives was decreased by ~ 90%. Conclusion N-monodesmethyl spinosad was produced due to unbalanced expression of spnS and upstream biosynthetic genes in the refactored artificial gene cluster. The accumulated N-desmethyl forosamine was transferred onto the lactone backbone by SpnP. This study suggested that balanced expression of biosynthetic genes should be considered in the refactoring strategy to avoid accumulation of undesired intermediates or analogues which may affect optimal production of desired compounds.

Introduction: The herpesviridae are DNA viruses with large and complicated genomes. The herpesvirus bacterial artificial chromosomes (BACs) have been useful for generating recombinant viruses to study the biology and pathogenesis. However, the conventional method using homologous recombination is not only time consuming but also prone to accumulate attenuating mutations during serial passage of the virus in cells. Elimination of the BAC vector from the recombinant viral genome requires additional step for phenotypically consistence with the original strain. Objectives: To generate a streamlined approach for generating infectious BAC clones of herpesvirus. Methods: The 142-kb pseudorabies virus genome was directly cloned into a bacterial artificial chromosome (BAC) in Escherichia coli by Exonuclease Combined with RecET recombination (ExoCET). Placement of the BAC vector at the terminus of the linear virus genome enabled excision of the BAC backbone from the viral genome by restriction endonuclease for delivery into mammalian cells, with the subsequent rapid rescue of virus that was genetically identical to the original strain. Results: This new approach for molecular cloning of the genome from a large DNA virus and isolation of pure virus lacking the BAC vector from transfected mammalian cells bypass the tedious and time-consuming method of multiple rounds of plaque purification. The viral BAC was stable in E. coli, allowing further mutagenesis mediated by the Red system or various site-specific recombination methods. Conclusion: An efficient method for construction of infectious clones of herpesvirus was established. It is expected to be potentially useful for other viruses with large double-stranded DNA genomes.

Estimation of vivo muscle forces during human motion is important for understanding human motion control mechanisms and joint mechanics. This paper combined the advantages of the convolutional neural network (CNN) and long-short-term memory (LSTM) and proposed a novel muscle force estimation method based on CNN–LSTM. A wearable sensor system was also developed to collect the angles and angular velocities of the hip, knee, and ankle joints in the sagittal plane during walking, and the collected kinematic data were used as the input for the neural network model. In this paper, the muscle forces calculated using OpenSim based on the Static Optimization (SO) method were used as the standard value to train the neural network model. Four lower limb muscles of the left leg, including gluteus maximus (GM), rectus femoris (RF), gastrocnemius (GAST), and soleus (SOL), were selected as the studying objects in this paper. The experiment results showed that compared to the standard CNN and the standard LSTM, the CNN–LSTM performed better in muscle forces estimation under slow (1.2 m/s), medium (1.5 m/s), and fast walking speeds (1.8 m/s). The average correlation coefficients between true and estimated values of four muscle forces under slow, medium, and fast walking speeds were 0.9801, 0.9829, and 0.9809, respectively. The average correlation coefficients had smaller fluctuations under different walking speeds, which indicated that the model had good robustness. The external testing experiment showed that the CNN–LSTM also had good generalization. The model performed well when the estimated object was not included in the training sample. This article proposed a convenient method for estimating muscle forces, which could provide theoretical assistance for the quantitative analysis of human motion and muscle injury. The method has established the relationship between joint kinematic signals and muscle forces during walking based on a neural network model; compared to the SO method to calculate muscle forces in OpenSim, it is more convenient and efficient in clinical analysis or engineering applications.

Current research on the interference of GNSS (Global Navigation Satellite System) array antennas focuses on the single interference effect and the improvement of interference hardware capability, while the multi-degree-of-freedom (DOF) interference model and mechanism remain to be fully studied. Aiming at this problem, this paper analyzes the preconditions for the definition of anti-jamming degrees of freedom and the characteristics of super-DOF interference through formula derivation and simulation. First, by analyzing the influence of the number of interfering signals on the angular resolution, the prerequisite of the definition of anti-interference degrees of freedom in the airspace is proposed. Second, the definition of anti-interference degrees of freedom is used to calculate the change rule of the critical power of the interference under different numbers of interfering signals. Finally, the influence of super-DOF interference on the array antenna is analyzed. The results show that the prerequisite for the anti-interference freedom of the array antenna is that the distribution interval of the interfering signal is greater than 15°, taking a four-array element uniform circular array antenna as an example. The critical interference power of the array antenna decreases by about 15 dB when the number of interfering signals exceeds the degrees of freedom of the array antenna’s interference immunity, provided that the interference resolution is satisfied. The conclusions of this paper give the critical power change rule of multi-DOF interference and the effect of super-DOF interference, as well as the prerequisites for the setting of interference signals, which can be used, for example, in the deployment of distributed interference sources and the development of anti-jamming algorithms.

ABSTRACT: Recombineering is a valuable technique for generating recombinant DNA in vivo, primarily in bacterial cells, and is based on homologous recombination using phage-encoded homologous recombinases, such as Redαβγ from the lambda phage and RecET from the Rac prophage. The recombineering technique can efficiently mediate homologous recombination using short homologous arms (∼50 bp) and is unlimited by the size of the DNA molecules or positions of restriction sites. In this review, we summarize characteristics of recombinases, mechanism of recombineering, and advances in recombineering for DNA manipulation in Escherichia coli and other bacteria. Furthermore, the broad applications of recombineering for mining new bioactive microbial natural products, and for viral mutagenesis, phage genome engineering, and understanding bacterial metabolism are also reviewed.

BackgroundTwo-stage exchange with placement of antibiotic cement spacer (ACS) is the gold standard for the treatment of chronic periprosthetic joint infection (PJI), but it could cause a high prevalence of acute kidney injury (AKI). However, the results of the current evidence on this topic are too mixed to effectively guide clinical practice.MethodsWe retrospectively identified 340 chronic PJI patients who underwent the first-stage exchange with placement of ACS. The Kidney Disease Improving Global Outcomes guideline was used to define postoperative AKI. Multivariate logistic analysis was performed to determine the potential factors associated with AKI. Furthermore, a systematic review and meta-analysis on this topic were conducted to summarize the knowledge in the current literature further.ResultsIn our cohort, the incidence of AKI following first-stage exchange was 12.1%. Older age (per 10 years, OR= 1.509) and preoperative hypoalbuminemia (OR= 3.593) were independent predictors for postoperative AKI. Eight AKI patients progressed to chronic kidney disease after 90 days. A meta-analysis including a total of 2525 PJI patients showed the incidence of AKI was 16.6%, and AKI requiring acute dialysis was 1.4%. Besides, host characteristics, poor baseline liver function, factors contributing to acute renal blood flow injury, and the use of nephrotoxic drugs may be associated with the development of AKI. However, only a few studies supported an association between antibiotic dose and AKI.ConclusionAKI occurs in approximately one out of every six PJI patients undergoing first-stage exchange. The pathogenesis of AKI is multifactorial, with hypoalbuminemia could be an overlooked associated factor. Although the need for acute dialysis is uncommon, the fact that some AKI patients will develop CKD still needs to be taken into consideration.

Bacillus subtilis plays an important role in fundamental and applied research, and it has been widely used as a cell factory for the production of enzymes, antimicrobial materials, and chemicals for agriculture, medicine, and industry. However, genetic manipulation tools for B. subtilis have low efficiency. In this work, our goal was to develop a simple recombineering system for B. subtilis. We showed that genome editing can be achieved in B. subtiliis 1A751 through co-expression of YqaJ/YqaK, a native phage recombinase pair found in B. subtilis 168, and the competence master regulator ComK using a double-stranded DNA substrate with short homology arms (100 bp) and a phosphorothioate modification at the 5′-end. Efficient gene knockouts and large DNA insertions were achieved using this new recombineering system in B. subtilis 1A751. As far as we know, this is the first recombineering system using the native phage recombinase pair YqaJ/YqaK in B. subtilis. In conclusion, this new recombineering system provides a simple and fast tool for genetic manipulation of B. subtilis, and it will promote studies of genome function, construction of production strains, and genome mining in B. subtilis.

BackgroundThe coronavirus disease (COVID-19) pandemic is a serious threat to public health worldwide. Growing evidence reveals that there are certain links between COVID-19 and autoimmune diseases; in particular, COVID-19 and idiopathic inflammatory myopathies (IIM) have been observed to be clinically comorbid. Hence, this study aimed to elucidate the molecular mechanisms of COVID-19 and IIM from a genomic perspective.MethodsWe obtained transcriptome data of patients with COVID-19 and IIM separately from the GEO database and identified common differentially expressed genes (DEGs) by intersection. We then performed functional enrichment, PPI, machine learning, gene expression regulatory network, and immune infiltration analyses of co-expressed genes.ResultsA total of 91 common genes were identified between COVID-19 and IIM. Functional enrichment analysis revealed that these genes were mainly involved in immune dysregulation, response to external stimuli, and MAPK signaling pathways. The MCODE algorithm recognized two densely linked clusters in the common genes, which were related to inflammatory factors and interferon signaling. Subsequently, three key genes (CDKN1A, IFI27, and STAB1) were screened using machine learning to predict the occurrence of COVID-19 related IIM. These key genes exhibited excellent diagnostic performance in both training and validation cohorts. Moreover, we created TF-gene and miRNA-gene networks to reveal the regulation of key genes. Finally, we estimated the relationship between key genes and immune cell infiltration, of which IFI27 was positively associated with M1 macrophages.ConclusionOur work revealed common molecular mechanisms, core genes, potential targets, and therapeutic approaches for COVID-19 and IIM from a genomic perspective. This provides new ideas for the diagnosis and treatment of COVID-19 related IIM in the future.

Abstract Objective Minimal invasive approach has been increasingly used in total knee arthroplasty (TKA) and more is expected of early rehabilitation in terms of pain release and recovery of knee function. The approach type is one of the major factors that determines the early rehabilitation after TKA. The purpose of this study is to determine whether mini‐subvastus approach (MSVA) is superior to the traditional medial parapatellar approach (MPA) in TKA. Methods From 2018 to 2019, a randomized double‐blinded prospective study was conducted on 58 patients who underwent simultaneous bilateral TKA. The subjects included eight men and 50 women, with an average age of 65 years. One side was randomized using MSVA and the other side using MPA. Visual analog scale (VAS), operative duration, recovery time to straight leg raising (SLR), range of motion (ROM), HSS score, release rate of lateral retinaculum, satisfaction rate were recorded and compared. Paired‐samples T test were used for quantitative data and chi‐square test for qualitative data. Results There was no statistical difference in the ratio of left and right sides, preoperative ROM, VAS, HSS score, muscular strength of lower limbs, KL grade, operative order, and operative duration between the two groups. The average ROM (118.91 ± 8.21 vs. 107.60 ± 7.99, t = 14.320, p = 0.0000) and HSS score (72.03 ± 4.55 vs. 61.22 ± 4.36, t = 13.095, p = 0.0000) on POD 3, VAS in rest and motion on POD 1 and 3, the recovery time to SLR (1.17 ± 0.38 vs. 3.09 ± 0.76, t = 19.902, p = 0.0000), and the satisfaction rate on POD 1 (96.55% vs. 74.14%, χ2 = 9.9251, p = 0.0016) were superior in the MSVA group over MPA group. ROM in rest and motion and HSS score on POD 30 had no difference. The release rate of lateral retinaculum was less in the MSVA group than in the MPA group. The mean value of HKA, FFC, and FTC and the proportion of outliers did not differ significantly between the two groups. Conclusions Compared with MPA, MSVA can make ROM of knee and SLR recover earlier, reduce postoperative pain after TKA, improve the early postoperative satisfaction and reduce the lateral release rate. MSVA can be used as a favorable measure in the concept of enhanced recovery after surgery (ERAS).

Objective Robot‐assisted surgery has been promoted worldwide in recent years. The development of a domestic orthopaedic robot and its clinical application are therefore of great significance. This study aimed to compare the early clinical and radiographic outcomes of domestic robot‐assisted total knee arthroplasty (RA‐TKA) with conventional manual total knee arthroplasty (CM‐TKA). Methods A total of 77 patients who underwent primary single‐sided TKA from June to December 2020 were prospectively enrolled; resulting in the inclusion of 72 patients. The patients were randomly divided into the RA‐TKA group (37 cases, with TKA being assisted by the Yuanhua Orthopaedic Robotic System) and the CM‐TKA group (35 cases, with TKA being performed using conventional tools). Knee function was evaluated by the knee range of motion (ROM), the American Knee Society Score (KSS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Postoperative radiographic results were evaluated by full‐length weight‐bearing X‐rays of the lower limb and anteroposterior and lateral X‐rays of the knee were obtained preoperatively and at 90 days postoperative. The operative duration, blood loss, postoperative knee function, radiographic outcomes, and incidence of complications were compared by Student's t‐test, Mann–Whitney U test, or chi‐square test. Serum levels of inflammatory markers before the operation and 1, 3, and 30 days after the operation were recorded and compared between the two groups. Results The operation was significantly longer in the RA‐TKA group than in the CM‐TKA group (154.3 vs 115.2 min, p 0.05). The incidence of postoperative deep vein thrombosis was not statistically different between the two groups. In the radiographic findings at 90 days postoperatively we found the frequency of lateral tibial component (LTC) angle outliers was significantly lower in the RA‐TKA group (3.0% vs 29.4%, p = 0.003). The neutrophil‐to‐lymphocyte ratio (NLR) was significantly lower in the RA‐TKA group than in the CM‐TKA group on day 1 after surgery (9.9 vs 12.7, p = 0.024). Conclusions RA‐TKA requires more time than CM‐TKA, which may be related to the learning curve and intraoperative registration. The short‐term postoperative knee functional outcomes had no differences between the two groups, and RA‐TKA improved the accuracy of tibial component alignment. Further follow‐up studies are required to investigate the long‐term outcomes.

Abstract Little is known on the relationship between the expression of pyroptosis related genes (PRGs) and prognosis of hepatocellular carcinoma (HCC). In this study, a specific PRGs prognostic model was developed with an aim to improve therapeutic efficiency among HCC patients. In total, 42 PRGs that were differentially expressed between HCC tissues and adjacent tissues and we exhibited the mutation frequency, classification, the location of copy number variation (CNV) alteration and the CNV variation frequency of PRGs. Two clusters were distinguished by the consensus clustering analysis based on the 42 differentially expressed genes (DEGs). There were significant differences in clinical features including T stage, grade, gender, and stage among different clusters. Kaplan–Meier curve analysis showed that cluster 1 had a better prognosis than cluster 2. The prognostic value of PRGs for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. Based on the univariate analysis and multivariate analysis, a 10-gene signature was built and all HCC patients in the TCGA cohort were divided into low-risk group and high-risk group. HCC patients in the high-risk group showed significantly lower survival possibilities than those in the low-risk group (P

Background Artificial intelligence (AI) has promising applications in arthroplasty. In response to the knowledge explosion resulting from the rapid growth of publications, we applied bibliometric analysis to explore the research profile and topical trends in this field. Methods The articles and reviews related to AI in arthroplasty were retrieved from 2000 to 2021. The Java-based Citespace, VOSviewer, R software-based Bibiometrix, and an online platform systematically evaluated publications by countries, institutions, authors, journals, references, and keywords. Results A total of 867 publications were included. Over the past 22 years, the number of AI-related publications in the field of arthroplasty has grown exponentially. The United States was the most productive and academically influential country. The Cleveland Clinic was the most prolific institution. Most publications were published in high academic impact journals. However, collaborative networks revealed a lack and imbalance of inter-regional, inter-institutional, and inter-author cooperation. Two emerging research areas represented the development trends: major AI subfields such as machine learning and deep learning, and the other is research related to clinical outcomes. Conclusion AI in arthroplasty is evolving rapidly. Collaboration between different regions and institutions should be strengthened to deepen our understanding further and exert critical implications for decision-making. Predicting clinical outcomes of arthroplasty using novel AI strategies may be a promising application in this field.

With complex coupling of multiple degrees of freedom, transition metal oxides (TMOs) provide a promising platform to tune the magnetic property in heterostructures via the magnetic proximity effect. Recent realization of freestanding TMO thin films allows further extension of this technique to novel two-dimensional heterostructures by mechanically stacking with van der Waals materials. Here, we demonstrate the presence of significant magnetic exchange interactions in a heterostructure of 8 nm freestanding LaMnO3 and monolayer WS2. The high magnetization in freestanding LaMnO3 leads to valley degeneracy breaking in WS2, resulting in unbalanced valley polarization in the photoluminescence (PL). Further temperature-dependent PL measurements reveal the same transition behavior as the magnetization in the freestanding LaMnO3 film. Our results unlock new approaches for tuning the magnetism and the valley degree of freedom in ultrathin two-dimensional heterostructures.

Abstract Background and Aim Diet is a major contributor to irritable bowel syndrome (IBS) and is also a powerful tool for treatment of IBS. This study compared two diets and explored the effectiveness of the diets when combined with a probiotic for treatment of IBS‐D patients. Methods Phase I, patients were randomized into groups; control, cold/spicy/fried restricted diet (CSF res diet), IgG positive restricted diet (IgG res diet), and a combination both diets (CSF + IgG res diet). Phase II, patients were randomized into IgG res diet + placebo and IgG res diet + probiotic. Both interventions were 12 weeks in duration. Symptom Severity Scale (IBS‐D‐SSS) and IgG titer were assessed at the beginning and the end of the study. Results Totals of 214 and 167 patients completed the two parts of the study, respectively. After intervention, IBS‐D‐SSS and TIgG grade were significantly improved compared to baseline, with results similar to the control group. In general, there were decreases in IBS‐D‐SSS and TIgG grade that were significantly different among the groups. There were exceptions; no differences were observed for IBS‐D‐SSS between the IgG res diet and CSF + IgG res diet, or TIgG grade between the CSF res diet, IgG res diet, and CSF + IgG res diet. However, the CSF res diet and IgG res diet had a synergistic effect that decreased IBS‐D‐SSS and TIgG titer, with a greater contribution by the IgG res diet. Therefore, we evaluated the IgG res diet with either placebo or probiotic and found that IBS‐D‐SSS and TIgG grade decreased from baseline. There was a significant decrease in IBS‐D‐SSS with the probiotic but TIgG grade was not significantly different between the IgG diet + placebo and IgG diet + probiotic diet. Conclusions Both the CSF res diet and IgG res diet improved IBS symptoms and demonstrated synergy, although the IgG res diet had a greater contribution. Further, when intolerant foods cannot be eliminated from a diet, avoiding uncooked, cold, spicy, fried, and alcoholic foods is a superior choice. The IgG res diet combined with Bifidobacteria was the best dietary choice and may function though a non‐IgG pathway.