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Abstract Background Sarcopenia and osteoarthritis are prevalent age-related diseases that mutually exacerbate each other, creating a vicious cycle that worsens both conditions. Exercise is key to breaking this detrimental cycle. Facing increasing demand for rehabilitation services within this patient demographic, ChatGPT-4 and wearable device may increase the availability, efficiency and personalization of such health care. Aim To evaluate the clinical efficacy and cost-effectiveness of a rehabilitation system implemented on mobile platforms, utilizing the integration of ChatGPT-4 and wearable devices. Methods The study design is a prospective randomized open blinded end-point (PROBE) non-inferiority trial. 278 patients diagnosed with osteoarthritis and sarcopenia will be recruited and randomly assigned to the intervention group and the control group. In the intervention group patients receive mobile phone-based rehabilitation service where ChatGPT-4 generates personalized exercise therapy, and wearable device guides and monitor the patient to implement the exercise therapy. Traditional clinic based face-to-face exercise therapy will be prescribed and implemented in the control group. All patients will receive three-months exercise therapies following the frequency, intensity, type, time, volume and progression (FITT-VP) principle. The patients will be assessed at baseline, one month, three months, and six months after initiation. Outcome measures will include ROM, gait patterns, Visual Analogue Scale (VAS) for pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) for functional assessment, Short-Form Health Survey 12 (SF-12) for quality of life, Minimal Clinically Important Difference (MCID), Patient Acceptable Symptom State (PASS), and Substantial Clinical Benefit (SCB) for clinically significant measures. Discussion A rehabilitation system combining the capabilities of ChatGPT-4 and wearable devices potentially enhance the availability and efficiency of professional rehabilitation services, thus enhancing the therapeutic outcomes for a substantial population concurrently afflicted with sarcopenia and osteoarthritis.

Abstract Objective A hybrid manufacturing technique that combines selective laser melting (SLM) and computer numerical control (CNC) has been developed for the fabrication of implant-platform/framework interfaces (PFIs) for mandibular and maxillary full-arch implant-supported titanium frameworks. The aim of this study was to compare the discrepancies in specimens fabricated using the hybrid technique (termed SLM/m hereafter) with those in specimens fabricated by conventional CNC milling. Materials and methods Based on a mandibular four-PFI CAD model and a maxillary six-PFI CAD model, four groups of titanium frameworks (eight per group, totaling 32) were fabricated according to the fabrication technique (SLM/m or milling) and number of PFIs (four or six). The frameworks were scanned by a structured light scanner and aligned with the CAD model in Geomagic Control X. Discrepancy was defined as the difference between the PFIs of the scanned framework and those of the CAD model. Discrepancies were measured and evaluated by multilevel analysis using a mixed-effects model (α = 0.05), followed by independent samples t-tests (α = 0.0125). Furthermore, the manufacturing times and raw-material costs were recorded and compared. Results The maximum discrepancy values for the four-PFI and six-PFI hybrid frameworks were 52.2 and 64.3 μm, respectively. Multilevel analysis revealed that the fabrication technique and the number of PFIs had no significant effect on the discrepancy value. However, a significant interaction between the two factors was observed (P = 0.020). The discrepancies for the four-PFI hybrid frameworks were significantly lower than those for the four-PFI milled frameworks (P = 0.001). No significant difference in discrepancies between the six-PFI hybrid frameworks and six-PFI milled frameworks was observed (P = 0.697). Furthermore, the hybrid frameworks required only 11% of the raw materials and 25% of the milling time required for the conventionally milled frameworks. Conclusion SLM/m hybrid frameworks are viable, accurate alternatives to CNC-milled frameworks, with the added benefit of substantial cost reduction.

Abstract [Objective] The study aims to explore the effects of compound fungi inoculant application on the growth, root morphology, and photosynthetic characteristics of Chinese flowering cabbage seedlings, and provide a theoretical basis for the application of compound fungi inoculant to alleviate the obstacle of continuous cropping of Chinese flowering cabbage. [Methods] The Chinese flowering cabbage variety ‘Jianye- 70’, with which microbial agents and soil had been continuously cropped for 9 years, were used in pot experiments. Four treatments were set up: No compound microbial agents (control), foliar spraying, soil spraying, and foliar spraying plus soil spraying. The plant growth indicators, root system configuration, and leaf photosynthetic characteristics were observed after sowing for 30 days. [Results] Every application method could increase growth indicators, root system conformation, leaf photosynthetic characteristics net photosynthetic rate (Pn), actual photochemical efficiency (ΦPSⅡ ), and photochemical quenching coefficient (qp) etc., as well as decrease transpiration rate (Tr), intercellular carbon dioxide concentration (Ci), and non photochemical quenching coefficient (NPQ) etc. Among the application methods, foliar spraying had the best effect. Its above-ground and underground dry weight and root length were significantly increased by 128.57%, 85.71%, and 91.81%. Pn, qp, and ΦPSⅡ were significantly increased by 24.55%, 22.68%, and 23.93%, while Tr, Ci, and NPQ were significantly decreased by 72.73%, 20.01%, and 39.78%, respectively. [Conclusion] Foliar spraying of compound fungi can effectively promote the growth of continuous cropping cabbage seedlings, improve root configuration, enhance plant photosynthetic efficiency, which is the best way of compound fungi application

Abstract Background Neurocognitive disorders frequently occur in patients with cyanotic congenital heart disease (CCHD) because of the hemodynamic abnormalities induced by preoperative cardiac structural changes. We aimed to evaluate subcortical nuclei volume changes and cognition in postoperative tetralogy of Fallot (TOF) children, and analyze their relationship with preoperative cardiac structural changes. Methods This case-control study involved thirty-six children with repaired TOF and twenty-nine healthy controls (HCs). We utilized three-dimensional (3D) T1-weighted high-resolution structural images alongside the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) to evaluate the cognitive differences between the TOF and HC group. Results We observed notable differences in subcortical nuclei volume between the TOF and HC group, specifically in the left amygdala nucleus (LAM, TOF: 1292.60 ± 155.57; HC: 1436.27 ± 140.62, p

Abstract The synthesis of facial sketch-photo has important applications in practical life, such as crime investigation. Many convolutional neural networks (CNNs) based methods have been proposed to address this issue. However, due to the substantial modal differences between sketch and photo, the CNN’s insensitivity to global information, and insufficient utilization of hierarchical features, synthesized photos struggle to balance both identity preservation and image quality. Recently, State Space Sequence Models (SSMs) have achieved exciting results in computer vision (CV) tasks. Inspired by SSMs, we design a hybrid CNN–SSM model called FaceMamba for the Face Sketch-Photo Synthesis (FSPS) task. It includes an original Face Vision Mamba Attention for modeling in latent space using SSM. Additionally, it incorporates a general auxiliary method called Attention Feature Injection that combines encoding features, decoding features, and external auxiliary features using attention mechanisms. FaceMamba combines Mamba’s modeling ability for long-range dependencies with CNN’s powerful local feature extraction ability, and utilizes hierarchical features at the appropriate position. Adequate experimental and evaluation results reveal that FaceMamba has strong competitiveness in FSPS task, achieving the best balance between identity preservation and image quality.

Abstract Background Acute myeloid leukaemia (AML) comprises a group of heterogeneous and aggressive haematological malignancies with unsatisfactory prognoses and limited treatment options. Treatments targeting B-cell lymphoma-2 (BCL-2) with venetoclax have been approved for patients with AML, and venetoclax-based drug combinations are becoming the standard of care for older patients unfit for intensive chemotherapy. However, the therapeutic duration of either single or combination strategies is limited, and the development of resistance seems inevitable. Therefore, more effective combination regimens are urgently needed. Methods The efficacy of combination therapy with NL101, a SAHA-bendamustine hybrid, and venetoclax was evaluated in preclinical models of AML including established cell lines, primary blasts from patients, and animal models. RNA-sequencing and immunoblotting were used to explore the underlying mechanism. Results NL101 significantly potentiated the activity of venetoclax in AML cell lines, as evidenced by the enhanced decrease in viability and induction of apoptosis. Mechanistically, the addition of NL101 to venetoclax decreased the stability of the antiapoptotic protein myeloid cell leukaemia-1 (MCL-1) by inhibiting ERK, thereby facilitating the release of BIM and triggering mitochondrial apoptosis. Moreover, the strong synergy between NL101 and venetoclax also relied on the downregulation of c-Myc via PI3K/Akt/GSK3β signalling. The combination of NL101 and venetoclax synergistically eliminated primary blasts from 10 AML patients and reduced the leukaemia burden in an MV4-11 cell-derived xenograft model. Conclusions Our results encourage the pursuit of clinical trials of combined treatment with NL101 and venetoclax and provide a novel venetoclax-incorporating therapeutic strategy for AML.

Abstract Background Amelogenesis imperfecta (AI) is a group of genetic disorders characterized by tooth discoloration and enamel defects. Patients with AI always exhibit generalized attrition and defective tooth structure, leading to the loss of occlusal vertical dimension (OVD). Appropriate rehabilitation is challenging and essential to improve patients’ aesthetics and function. Case presentation This case report presents a comprehensive management of a 30-year-old woman with hypoplastic AI. A 52-month follow-up revealed satisfactory full-mouth rehabilitation performances of lithium disilicate ceramic crowns after clinical crown lengthening, with increased vertical dimension. Conclusions Patients with severe hypoplastic AI require proper full-mouth rehabilitation. Using full-crown lithium disilicate restorations to increase the OVD by 2‒4 mm is a safe and predictable recommendation for such cases. In addition, patients with AI require complex and comprehensive management. The long-term effects of full-mouth rehabilitation with lithium disilicate ceramic crowns still necessitate further follow-ups.

Abstract Neurodevelopmental disorders are currently one of the major complications faced by patients with congenital heart disease (CHD). Chronic hypoxia in the prenatal and postnatal preoperative brain may be associated with neurological damage and impaired long-term cognitive function, but the exact mechanisms are unknown. In this study, we find that delayed neuronal migration and impaired synaptic development are attributed to altered Atoh1 under chronic hypoxia. This is due to the fact that excessive Atoh1 facilitates expression of Kif21b, which causes excess in free-state α-tubulin, leading to disrupted microtubule dynamic stability. Furthermore, the delay in neonatal brain maturation induces cognitive disabilities in adult mice. Then, by down-regulating Atoh1 we alleviate the impairment of cell migration and synaptic development, improving the cognitive behavior of mice to some extent. Taken together, our work unveil that Atoh1 may be one of the targets to ameliorate hypoxia-induced neurodevelopmental disabilities and cognitive impairment in CHD.

Abstract The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA. Graphical abstract

Esophageal cancer (EC) is among the most aggressive malignancies, ranking as the seventh most prevalent malignant tumor worldwide. Lymph node metastasis (LNM) indicates localized spread of cancer and often correlates with a poorer prognosis, emphasizing the necessity for neoadjuvant systemic therapy before surgery. However, accurate identification of LNM in EC presents challenges due to the lack of satisfactory diagnostic techniques. Imaging techniques, including ultrasound and computerized tomography scans, have low sensitivity and accuracy in assessing LNM. Additionally, the existing serological detection lacks precise biomarkers. The intricate and not fully understood molecular processes involved in LNM of EC contribute to current detective limitations. Recent research has shown potential in using various molecules, circulating tumor cells (CTCs), and changes in the microbiota to identify LNM in individuals with EC. Through summarizing potential biomarkers associated with LNM in EC and organizing the underlying mechanisms involved, this review aims to provide insights that facilitate biomarker development, enhance our understanding of the underlying mechanisms, and ultimately address the diagnostic challenges of LNM in clinical practice.

Abstract BackgroundPhysical therapy has demonstrated efficacy in managing nonspecific low back pain (NLBP) among patients. Nevertheless, the prevalence of NLBP poses a challenge, as the existing medical infrastructure may be insufficient to care for the large patient population, particularly in geographically remote regions. Telerehabilitation emerges as a promising method to address this concern by offering a method to deliver superior medical care to a greater number of patients with NLBP. ObjectiveThe purpose of this study is to demonstrate the physical and psychological effectiveness of a user-centered telerehabilitation program, consisting of a smartphone app and integrated sensors, for patients with NLBP. MethodsThis was a single-center, prospective, randomized controlled trial for individuals with NLBP for a duration exceeding 3 months. All participants were assigned randomly to either the telerehabilitation-based exercise group (TBEG) or the outpatient-based exercise group (OBEG). All participants completed a 30-minute regimen of strength and stretching exercises 3 times per week, for a total of 8 weeks, and were required to complete assessment questionnaires at 0, 2, 4, and 8 weeks. The TBEG completed home-based exercises and questionnaires using a telerehabilitation program, while the OBEG completed them in outpatient rehabilitation. The Oswestry Disability Index (ODI) served as the primary outcome measure, assessing physical disability. Secondary outcomes included the Numeric Pain Rating Scale, Fear-Avoidance Beliefs Questionnaire, and 36-item Short-Form Health Survey. ResultsIn total, 54 of 129 eligible patients were enrolled and randomly assigned to the study. The completion of all the interventions and assessments in the TBEG and OBEG was 89% (24/27) and 81% (22/27). The findings indicate that no statistical significance was found in the difference of ODI scores between the TBEG and the OBEG at 2 weeks (mean difference −0.91; odds ratio [OR] 0.78, 95% CI −5.96 to 4.14; PPPPP ConclusionsTelerehabilitation interventions demonstrate comparable therapeutic efficacy for individuals with NLBP when compared to conventional outpatient-based physical therapy, yielding comparable outcomes in pain reduction and improvement in functional limitations.

IntroductionMicrobial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection.MethodsDPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed.ResultsDPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-κB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were up-regulated in DPSC.7 cells when stimulated with C.a.ConclusionsOur study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-κB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections.

Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease that primarily affects the synovium of diarthrodial joints. Inflammatory macrophages and fibroblast-like synoviocytes (FLS) in the synovial microenvironment produce pathogenic mediators such as cytokines and proteases that perpetuate immune-mediated inflammation and contribute to the destruction of cartilage and bone. Polydatin (PD), a natural active compound, has demonstrated potential anti-inflammatory and anti-arthritic effects. However, drug development and delivery of PD is still a great challenge owing to its low solubility, short half-life, and high dose requirement. In order to overcome these drawbacks, we developed a novel nanodrug system named HA-M@PB@Ag@PD NPs. This system is composed of hybrid membrane (M), hyaluronic acid (HA), Prussian blue nanoparticles (PB NPs), PD, and chitosan-silver (Chi-Ag). In vitro experiments demonstrated that HA-M@PB@Ag@PD NPs effectively cleared ROS, promoted the repolarization of inflammatory macrophages, and induced apoptosis of RA-FLS. Using a rat model of RA, HA-M@PB@Ag@PD NPs markedly suppressed joint inflammation, inhibited synovial hyperplasia, and protected joints against destruction of cartilage and bone. Moreover, HA-M@PB@Ag@PD NPs significantly improved the synovial microenvironment of arthritic rats by reducing the number of RA-FLS and inflammatory macrophages, and facilitating the repolarization of inflammatory macrophages.

The incidence of cancer is increasing worldwide and is the most common cause of death. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Cyclin-dependent kinase subunit 2 (CKS2) is involved in cell cycle and proliferation processes, and based on these processes, CKS2 was identified as a cancer gene. CKS2 is expressed in a variety of tissues in the human body, but its abnormal expression is associated with cancer in a variety of systems. CKS2 is generally elevated in cancer, plays a role in almost all aspects of cancer biology (such as cell proliferation, invasion, metastasis, and drug resistance) through multiple mechanisms regulating certain important genes, and is associated with clinicopathological features of patients. In addition, CKS2 expression patterns are closely related to cancer type, stage and other clinical variables. Therefore, CKS2 is considered as a tool for cancer diagnosis and prognosis and may be a promising tumor biomarker and therapeutic target. This article reviews the biological function, mechanism of action and potential clinical significance of CKS2 in cancer, in order to provide a new theoretical basis for clinical molecular diagnosis, molecular targeted therapy and scientific research of cancer.

Objective(s): Luteolin is a flavone that provides defense against myocardial ischemia/reperfusion (I/R) injury. However, this compound is subjected to methylation mediated by catechol-O-methyltransferase (COMT), thus influencing its pharmacological effect. To synthesize a new flavone from luteolin that avoids COMT-catalyzed methylation and find out the protective mechanism of LUA in myocardial I/R injury.Materials and Methods: Luteolin and 2,2’-azobis (2-amidinopropane) dihydrochloride (AAPH) were used to synthesize the new flavone known as LUAAPH-1 (LUA). Then, the myocardial ischemia/reperfusion injury cell model was established using H9c2 cells to detect the effect in myocardial ischemia/reperfusion regulation and to identify the underlying mechanism. Results: Pretreatment with LUA (20 μmol/l) substantially increased cell viability while reducing cell apoptosis rate and caspase-3 expression induced by I/R, and the protective effect of LUA on cell viability was stronger than diosmetin, which is the major methylated metabolite of luteolin. In addition, intracellular reactive oxygen species (ROS) production and calcium accumulation were both inhibited by LUA. Furthermore, we identified that LUA markedly relieved the promotive effects of I/R stimulation upon JNK and p38 phosphorylation.Conclusion: LUT pretreatment conveys significant cardioprotective effects after myocardial I/R injury, and JNK and p38 MAPK signaling pathway may be involved.

Abstract Background Postoperative cone-beam computed tomography (CBCT) examination is considered a reliable method for clinicians to assess the positions of implants. Nevertheless, CBCT has drawbacks involving radiation exposure and high costs. Moreover, the image quality can be affected by artifacts. Recently, some literature has mentioned a digital registration method (DRM) as an alternative to CBCT for evaluating implant positions. The aim of this clinical study was to verify the accuracy of the DRM compared to CBCT scans in postoperative implant positioning. Materials and methods A total of 36 patients who received anterior maxillary implants were included in this clinical study, involving a total of 48 implants. The study included 24 patients in the single implant group and 12 patients in the dual implant group. The postoperative three-dimensional (3D) positions of implants were obtained using both CBCT and DRM. The DRM included three main steps. Firstly, the postoperative 3D data of the dentition and intraoral scan body (ISB) was obtained through the intraoral scan (IOS). Secondly, a virtual model named registration unit which comprised an implant replica and a matching ISB was created with the help of a lab scanner and reverse engineering software. Thirdly, by superimposing the registration unit and IOS data, the postoperative position of the implant was determined. The accuracy of DRM was evaluated by calculating the Root Mean Square (RMS) values after superimposing the implant positions obtained from DRM with those from postoperative CBCT. The accuracy of DRM was compared between the single implant group and the dual implant group using independent sample t-tests. The superimposition deviations of CBCT and IOS were also evaluated. Results The overall mean RMS was 0.29 ± 0.05 mm. The mean RMS was 0.30 ± 0.03 mm in the single implant group and 0.29 ± 0.06 mm in the dual implant group, with no significant difference (p = 0.27). The overall registration accuracy of the IOS and CBCT data ranged from 0.14 ± 0.05 mm to 0.21 ± 0.08 mm. Conclusion In comparison with the 3D implant positions obtained by CBCT, the implant positions located by the DRM showed clinically acceptable deviation ranges. This method can be used in single and dual implant treatments to assess the implant positions.

The advancement of computers and data explosion have ushered in the third wave of artificial intelligence(AI). AI is an interdisciplinary field that encompasses new ideas, new theories, and new technologies, etc. AI has brought convenience to ophthalmology application and promoted its intelligent, precise, and minimally invasive development. At present, AI has been widely applied in various fields of ophthalmology, especially in oculoplastic surgery. AI has made rapid progress in image detection, facial recognition, etc., and its performance and accuracy have even surpassed humans in some aspects. This article reviews the relevant research and applications of AI in oculoplastic surgery, including ptosis, single eyelid, pouch, eyelid mass, and exophthalmos, and discusses the challenges and opportunities faced by AI in oculoplastic surgery, and provides prospects for its future development, aiming to provide new ideas for the development of AI in oculoplastic surgery.

Abstract Background Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by chronic synovitis as well as cartilage and bone destruction. Halofuginone hydrobromide (HF), a bioactive compound derived from the Chinese herbal plant Dichroa febrifuga Lour., has demonstrated substantial anti-arthritic effects in RA. Nevertheless, the molecular mechanisms responsible for the anti-RA effects of HF remain unclear. Methods This study employed a combination of network pharmacology, molecular docking, and experimental validation to investigate potential targets of HF in RA. Results Network pharmacology analyses identified 109 differentially expressed genes (DEGs) resulting from HF treatment in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses unveiled a robust association between these DEGs and the IL-17 signaling pathway. Subsequently, a protein-protein interaction (PPI) network analysis revealed 10 core DEGs, that is, EGFR, MMP9, TLR4, ESR1, MMP2, PPARG, MAPK1, JAK2, STAT1, and MAPK8. Among them, MMP9 displayed the greatest binding energy for HF. In an in vitro assay, HF significantly inhibited the activity of inflammatory macrophages, and regulated the IL-17 signaling pathway by decreasing the levels of IL-17 C, p-NF-κB, and MMP9. Conclusion In summary, these findings suggest that HF has the potential to inhibit the activation of inflammatory macrophages through its regulation of the IL-17 signaling pathway, underscoring its potential in the suppression of immune-mediated inflammation in RA.

Immunometabolism has been an emerging hotspot in the fields of tumors, obesity, and atherosclerosis in recent decades, yet few studies have investigated its connection with rheumatoid arthritis (RA). In principle, intracellular metabolic pathways upstream regulated by nutrients and growth factors control the effector functions of immune cells. Dynamic communication and hypermetabolic lesions of immune cells within the inflammatory synovial microenvironment contributes to the development and progression of RA. Hence, targeting metabolic pathways within immune subpopulations and pathological cells may represent novel therapeutic strategies for RA. Natural products constitute a great potential treasury for the research and development of novel drugs targeting RA. Here, we aimed to delineate an atlas of glycolysis, lipid metabolism, amino acid biosynthesis, and nucleotide metabolism in the synovial microenvironment of RA that affect the pathological processes of synovial cells. Meanwhile, therapeutic potentials and pharmacological mechanisms of natural products that are demonstrated to inhibit related key enzymes in the metabolic pathways or reverse the metabolic microenvironment and communication signals were discussed and highlighted.

Abstract The regenerative treatment of infectious vertical bone defects remains difficult and challenging today. Current clinical treatments are limited in their ability to control bacteria and infection, which is unfavorable for new bone formation and calls for a new type of material with excellent osteogenic and antibacterial properties. Here a multifunctional scaffold is synthesized that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix (IMC/AgNWs), to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs. An appropriate concentration of 0.5 mg mL−1 AgNWs is selected to balance biocompatibility and antibacterial properties. The achieved IMC/AgNWs exhibit a broad spectrum of antimicrobial properties against Gram‐negative Porphyromonas gingivalis and Gram‐positive Streptococcus mutans. When the IMC/AgNWs are cocultured with periodontal ligament stem cells, it possesses excellent osteoinductive activities under both non‐inflammatory and inflammatory conditions. By constructing a rat mandibular infected periodontal defect model, the IMC/AgNWs achieve a near‐complete healing through the canonical BMP/Smad signaling. Moreover, the IMC/AgNWs enhance vertical bone height and osseointegration in peri‐implantitis in beagle dogs, indicating the clinical translational potential of IMC/AgNWs for infectious vertical bone augmentation.

The global repercussions of the COVID-19 pandemic on economies and public health worldwide have been profound. This study aims to examine the developmental trends of the COVID-19 pandemic, establish predictive models, and provide insights for effective control measures against potential future disease outbreaks. Considering the coexistence of both linear and nonlinear factors in COVID-19 data, conventional single-machine learning and traditional forecasting models encounter challenges in accurately predicting pandemic trends. To enhance the precision of COVID-19 pandemic predictions by integrating linear and nonlinear factors, this study proposes three combined forecasting models: CNN-LSTM-ARIMA, TCN-LSTM-ARIMA, and SSA-LSTM-ARIMA. These models leverage the strengths of deep learning in capturing nonlinear factors and the capabilities of the traditional ARIMA model in handling linear factors. Initially, LSTM and ARIMA models are used to model and predict the COVID-19 pandemic in Quebec, Canada. Subsequently, CNN models, TCN models, and the Sparrow Search Algorithm are employed to integrate predictions from the LSTM and ARIMA models. Comparative analyses of the three combined models, it was found that the CNN-LSTM-ARIMA model exhibits the highest predictive accuracy, with an MSE of 7048.26, RMSE of 83.95, MAE of 61.18, MAPE of 0.16, and $R^{2}$ of 0.95. To validate the applicability and stability of the CNN-LSTM-ARIMA model in predicting COVID-19 pandemics, Italian COVID-19 pandemic data was employed. The three combined forecasting models are established and evaluated using model evaluation metrics. The results affirm that the CNN-LSTM-ARIMA model remains the optimal choice, underscoring its high stability and suitability for COVID-19 pandemic forecasting endeavors.

Abstract Background The lack of access to physical therapists in developing countries and rural areas poses a significant challenge in supervising postsurgical rehabilitation, potentially impeding desirable outcomes following surgical interventions. For this reason, this study aims to evaluate the feasibility, safety, and effectiveness of utilizing a digital rehabilitation program based on computer vision and augmented reality in comparison with traditional care for patients who will undergo isolated meniscus repair, since to date, there is no literature on this topic. Methods This study intends to enroll two groups of participants, each to be provided with informed consent before undergoing randomization into either the experimental or control group. The experimental group will undergo a digital rehabilitation program utilizing computer vision and augmented reality (AR) technology following their surgical procedure, while the control group will receive conventional care, involving in-clinic physical therapy sessions weekly. Both groups will adhere to a standardized rehabilitation protocol over a six-month duration. Follow-up assessments will be conducted at various intervals, including preoperatively, and at 2 weeks, 6 weeks, 12 weeks, and 24 weeks postoperatively. Imaging assessments and return-to-play evaluations will be conducted during the final follow-up. Clinical functionality will be assessed based on improvements in International Knee Documentation Committee (IKDC) and Visual Analog Scale (VAS) scores. Registration number ChiCTR2300070582.

Abstract Due to the advantages of rapid deployment, flexible response and strong invulnerability, unmanned aerial vehicle (UAV) swarm has been widely applied in collaborative warfare and emergency communication. However, UAV swarm in complex environments is prone to chaotic collapse due to obstructions. A UAV swarm obstacle avoidance system model for multi-narrow type obstacles is established. Due to the fact that only one UAV is allowed to pass through each small hole at any given moment, addressing the issue of congestion caused by swarming effects becomes crucial in addition to managing the competitive allocation of multiple UAVs to multiple holes. Aiming at this problem, a dual-game real-time obstacle avoidance scheme is proposed for UAV swarm with multi-narrow type obstacle scenarios, which divides the flight process of the UAV swarm into two stages: maintaining the flight state of the UAV swarm unchanged when no obstacles are encountered, and implementing matching separation and motion state switching by means of dual-game strategy when facing multi-narrow type obstacles, ultimately achieving orderly passage after multiple rounds of games. For the proposed scheme, a dual-game based Flocking (DGF) obstacle avoidance algorithm is proposed. Specifically, the motion state of each UAV obtained from the game is parameterized and integrated with the Flocking algorithm to calculate the motion control input for each UAV. The solution is iteratively obtained until the UAV swarm completes the obstacle avoidance. Simulation results demonstrate that the proposed DGF algorithm not only enables smooth obstacle avoidance for the UAV swarm in multi-narrow type obstacle scenarios, but also effectively resolves the internal chaos problem in the UAV swarm, thereby preventing rigid collisions.

Dissipative particle dynamics (DPD) simulations is used to study the effect of Am/2BmAm/2 and H-shaped (Am/4)2Bm(Am/4)2 block copolymers on the interfacial properties of ternary blends. Our simulations show the following: (i) The capacity of block copolymers to diminish interfacial tension is closely linked to their compositions. With identical molecular weights and concentrations, H-shaped block copolymers outperform triblock copolymers in mitigating interfacial tension. (ii) The interfacial tension within the blends correlates positively with the escalation in H-shaped block copolymer molecular weight. This correlation suggests that H-shaped block copolymers featuring a low molecular weight demonstrate superior efficacy as compatibilizers when contrasted with those possessing a high molecular weight. (iii) Enhancing the concentration of H-shaped block copolymers fosters their accumulation at the interface, leading to a reduction in correlations between immiscible homopolymers and a consequent decrease in interfacial tension. (iv) As the length of the homopolymer chains increases, there is a concurrent elevation in interfacial tension, suggesting that H-shaped block copolymers perform more effectively as compatibilizers in blends characterized by shorter homopolymer chain lengths. These findings elucidate the associations between the efficacy of H-shaped block copolymer compatibilizers and their specific molecular characteristics.

Achyranthes japonica Nakai (AJN) is a medicinal plant known to be beneficial for the joints. Since it takes at least two years from sowing to harvesting in an open field, new AJN cultivation strategies are needed to shorten the production period and improve quality. In this study, high-quality AJN is produced as microgreens in a vertical farm using a commercial ginseng soil mix (Myeongpum-Insamsangto, Shinsung Mineral Co., Ltd., Goesan, Republic of Korea) and controlled environmental conditions. The cultivation conditions included a temperature of 23 ± 2 °C, relative humidity of 50 ± 10%, and a photosynthetic photon flux density of 170 ± 15 µmol·m−2·s−1. Pre-harvest intermittent UV-B exposure, with an intensity of 1.0 ± 0.3 W/m−2, was applied for one day before harvest to evaluate its effects, using controlled environmental conditions in the vertical farm. Ultraviolet-B (UV-B) irradiation increases secondary metabolite levels in plants; however, the effect of UV-B on 20-hydroxyecdysone (20E), an indicator of AJN, is unclear. Therefore, we aimed to investigate whether UV-B treatment of AJN microgreens affected growth and secondary metabolites. The treatment group was set to 12 h of continuous UV-B treatment during the day, two 6 h UV-B treatments, and four 3 h UV-B treatments to confirm the effectiveness of regular and intermittent treatment and recovery. Short-term UV-B treatment before harvesting increased phenols, flavonoids, antioxidant capacity, and 20E levels without affecting AJN biomass. The intermittent 6 h UV-B irradiation with a 6 h recovery time stimulated 20E content by approximately 1.4 times compared to the control. These study findings indicate that short-term UV-B treatment before harvesting, an appropriate recovery time, and intermittent UV-B exposure are more effective at increasing 20E content than continuous treatment. This approach provides a promising strategy for improving the nutritional and health benefits of AJN microgreens in vertical farming systems.

BackgroundLung cancer is the most common global cancer in terms of incidence and mortality. Its main driver is tobacco smoking. The identification of modifiable risk factors isa public health priority. Green tea consumption has been examined in epidemiological studies, with inconsistent findings. Thus, we aimed to apply Mendelian randomization to clarify any causal link between green tea consumption and the risk of lung cancer.MethodsWe utilized a two-sample Mendelian randomization (MR) approach. Genetic variants served as instrumental variables. The goal was to explore a causal link between green tea consumption and different lung cancer types. Green tea consumption data was sourced from the UK Biobank dataset, and the genetic association data for various types of lung cancer were sourced from multiple databases. Our analysis included primary inverse-variance weighted (IVW) analyses and various sensitivity test.ResultsNo significant associations were found between green tea intake and any lung cancer subtypes, including non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma) and small cell lung cancer. These findings were consistent when applying multiple Mendelian randomization methods.ConclusionGreen tea does not appear to offer protective benefits against lung cancer at a population level. However, lung cancer's complex etiology and green tea's potential health benefitssuggest more research is needed. Further studies should include diverse populations, improved exposure measurements and randomized controlled trials, are warranted.

Abstract Background Computer-aided design and computer-aided manufacturing (CAD-CAM) materials for prosthetic is gaining popularity in dentistry. However, limited information exists regarding the impact of thickness and roughening treatment on the optical properties of contemporary CAD-CAM restorative materials. This study aimed to quantitatively evaluate the translucency and opalescence of six dental CAD-CAM materials in response to different thicknesses and roughening treatments. Methods Six dental CAD-CAM materials, lithium disilicate glass–ceramic (IPS e.max CAD, LS), polymer-infiltrated ceramic (VITA Enamic, VE), resin-nano ceramic glass–ceramic (LAVA Ultimate, LU), polymethyl methacrylate (Telio CAD, TE), and two zirconia reinforced lithium silicate (VITA Suprinity, VS, and Celtra Duo, CD), in shade A2 were prepared as 12 × 12mm2 specimens of four thicknesses (0.5mm, 1.0mm, 1.5mm, and 2.0mm) (N = 240, n = 10). After three different treatments (polished, roughened by SiC P800-grit, and SiC P300-grit), the translucency parameter (TP00) and opalescence parameter (OP) were measured with a spectrophotometer (VITA Easyshade V). The surface roughness was analyzed with a shape measurement laser microscope. The data were analyzed using a MANOVA, post hoc Tukey–Kramer test, the t test, and regression analysis (α = .05). Results The TP00 and OP were significantly influenced by material type, thickness and roughening treatment (P

Osteoporosis is the most common metabolic bone disorder and is characterized by decreased bone density, which has a relationship with the quality of life among the aging population. Previous research has found that activation of the dopamine D1 receptor can improve bone mass formation. SKF38393 is an agonist of dopamine D1 receptors. However, as a small-molecule drug, SKF38393 is unstable and releases quickly. The aim of this study was to prototype polylactic-co-glycolic acid (PLGA)/SKF38393 microspheres and assess their potential osteogenic effects compared to those under the free administration of SKF38393. The cytocompatibility of PLGA/SKF38393 was determined via CCK-8 and live/dead cell staining; the osteogenic effects in vitro were determined with ALP and alizarin red staining, qRT-PCR, and Western blotting; and the in vivo effects were assessed using 25 Balb/c mice. We also used a PCR array to explore the possible signaling pathway changes after employing PLGA/SKF38393. Our experiments demonstrated that the osteogenic effect of D1Rs activated by the PLGA/SKF38393 microsphere was better than that under free administration, both in vitro and in vivo. According to the PCR array, this result might be associated with six signaling pathways (graphical abstract). Ultimately, in this study, we prototyped PLGA/SKF38393, demonstrated its effectiveness, and preliminarily analyzed its mechanism of action.

Objective Lumbar lateral interbody fusion (LLIF) allows placement of large interbody cages while preserving ligamentous structures important for stability. Multiple clinical and biomechanical studies have demonstrated the feasibility of stand-alone LLIF in single-level fusion. We sought to compare the stability of 4-level stand-alone LLIF utilizing wide (26 mm) cages with bilateral pedicle screw and rod fixation. Methods Eight human cadaveric specimens of L1–5 were included. Specimens were attached to a universal testing machine (MTS 30/G). Flexion, extension, and lateral bending were attained by applying a 200 N load at a rate of 2 mm/sec. Axial rotation of ±8° of the specimen was performed at 2°/sec. Three-dimensional specimen motion was recorded using an optical motion-tracking device. Specimens were tested in 4 conditions: (1) intact, (2) bilateral pedicle screws and rods, (3) 26-mm stand-alone LLIF, (4) 26-mm LLIF with bilateral pedicle screws and rods. Results Compared to the stand-alone LLIF, bilateral pedicle screws and rods had 47% less range of motion in flexion-extension (p < 0.001), 21% less in lateral bending (p < 0.05), and 20% less in axial rotation (p = 0.1). The addition of bilateral posterior instrumentation to the stand-alone LLIF resulted in decreases of all 3 planes of motion: 61% in flexion-extension (p < 0.001), 57% in lateral bending (p < 0.001), 22% in axial rotation (p = 0.002). Conclusion Despite the biomechanical advantages associated with the lateral approach and 26 mm wide cages, stand-alone LLIF for 4-level fusion is not equivalent to pedicle screws and rods.

Abstract Background Many studies demonstrated that surgical guides might reduce discrepancies compared with freehand implant placement. This randomized crossover study aimed to assess the effects of approaches, practitioners’ experience and learning sequences on the accuracy of single tooth implantation via digital registration method. No similar study was found. Methods This in vitro randomized crossover study enrolled 60 novice students (Group S) and 10 experienced instructors (Group I). Sixty students were randomly and evenly assigned to two groups (Group SA and SB). In Group SA, 30 students first performed single molar implant on a simulation model freehand (Group SAFH), and then with a CAD/CAM surgical guide (Group SASG). In Group SB, another 30 students first performed guided (Group SBSG) and then freehand (Group SBFH). Ten instructors were also divided into Group IAFH/IASG (n = 5) and IBSG/IBFH (n = 5) following the same rules. The accuracy of implant placement was assessed by the coronal and apical distance (mm) and angular (°) deviations using the digital registration method. T tests and nonparametric tests were used to compare the results among different groups of approaches, experience and sequences. Results For students, the coronal and apical distance and the angular deviations were significantly lower in surgical guide group than freehand group in total and in learning freehand first subgroup, but for learning surgical guide first subgroup the apical distance deviation showed no significant difference between two approaches. For students, the angular deviation of freehand group was significantly lower in learning surgical guide first group than learning freehand first group. For instructors, the coronal and apical distance and angular deviations showed no significant difference between two approaches and two sequences. For freehand approach, the coronal and apical distance and the angular deviations were significantly higher in student group than instructor group, while not significantly different between two groups for surgical guide approach. Conclusions For novices, using a surgical guide for the first implant placement may reduce the potential deviations compared with freehand surgery, and may reach a comparable accuracy with that of specialists. For simple single molar implantation, the surgical guide may not be significantly helpful for experienced specialists.

A quantitative investigation of poly(vinyl) chloride (PVC) de-chlorination using Fe2O3, together with the impact of SiO2 addition on the co-pyrolysis of PVC and Fe2O3, was conducted below 673 K in an Ar atmosphere aiming to cut the emission of gaseous Cl⁻ products. It was found that chlorine in PVC can be fixed in FeCl2 by the reaction between PVC and Fe2O3. The co-pyrolysis of PVC and Fe2O3 proceeds in two stages with a temperature boundary of around 543 K. Below 543 K, a direct reaction occurs between PVC and Fe2O3, resulting in a small mass loss ratio and some extent of chlorine fixing ratio in FeCl2. However, above 543 K, PVC starts to decompose to release gaseous H2, HCl, etc., which react with Fe2O3 through two possible pathways to form FeCl2. In Pathway 1, first Fe2O3 is reduced to Fe3O4 by H2, followed by the chlorination of Fe3O4 to FeCl2 by HCl. In Pathway 2, first Fe2O3 is chlorinated to FeCl3 by HCl, followed by the reduction of FeCl3 to FeCl2 by H2. The chlorine fixing ratio in FeCl2 and the volatile generation ratio increase with decreasing PVC content in the initial mixtures. The addition of SiO2 promotes the chlorine fixing ratio in FeCl2 and volatile generation, and the impact gets stronger with decreasing PVC content in the mixtures. The chlorine fixing ratio is increased from 70.8 to 82.6% by SiO2 addition for the mixtures containing 25% PVC, whereas the difference in the chlorine fixing ratio in FeCl2 caused by SiO2 addition is negligible for the mixtures containing 90% PVC. Fayalite (Fe2SiO4) was not detected in the solid residues after the experiments. After separating FeCl2 using water leaching, the filter residue, a composite of iron oxide and conjugated polyene, can be used as a raw material for iron-making.

The Tengchong Cenozoic volcano is located near the collision boundary between the Indian and Eurasian plates. The tectonic activity in this area is strong, and the volcano has a potential for eruption. Studying the origin of the Tengchong volcano is important for understanding plate subduction processes and the mechanism of volcano eruption. This review first summarizes the latest researches on the origin of the Tengchong volcano, including new advances in geophysics and geochemistry, and then discusses the magma source and deep dynamic mechanism. These studies have found that the genesis of Tengchong volcanism is mainly related to plate subduction. The subducted residual oceanic plate and the currently subducting Indian plate may both contribute to the source of metasomatic materials. The oceanic plate released melt and fluid to form metasomatized asthenospheric and lithospheric mantles, and Tengchong magma originated from the mixing of lithospheric and asthenosphere mantle melts. The metasomatized lithospheric mantle is characterized by low 3He/4He (< 7.0 Ra) and Nb/La (average of 0.36) ratios as well as high 87Sr/86Sr (average of 0.707928) and La/Yb (average of 22.0) ratios. In contrast, the enriched asthenospheric mantle is characterized by high 3He/4He (> 7.0 Ra) and Nb/La (average of 0.52) ratios with relatively low 87Sr/86Sr (average of 0.706708) and La/Yb (average of 17.0) ratios. The increasing trend of 3He/4He ratios and decreasing trend of 87Sr/86Sr ratios over time suggest that the contribution of the metasomatized lithospheric mantle decreased relative to that of the enriched asthenosphere after the late Pleistocene, reflecting the progressive lithospheric extension and thinning. Tengchong basalts do not show clear correlation between 87Sr/86Sr ratio and SiO2 content, whereas basaltic andesite, andesite, and dacite display positive correlation between 87Sr/86Sr ratio and SiO2 content. This phenomenon indicates that Tengchong basalt suffered limited crustal contamination, while basaltic andesite, andesite, and dacite underwent obvious crustal contamination. Moreover, seismic imaging along with magnetotelluric and geothermal studies revealed several magma chambers (low-speed anomalies) in the crust beneath the Tengchong volcano. However, the size and depth of the magma chambers vary between different studies. The low-velocity bodies in the crust extend downward to the upper mantle, which may indicate that the magma chambers in the crust are fed by hot materials from the upper mantle. However, a consensus on the origin of hot materials has yet to be reached. Seismic tomography studies suggest that hot materials could be generated from the dehydration of the stagnant slab in the mantle transition zone, tearing of the subducted plate, or slab rollback. Differences in seismic imaging results may be caused by the limited observation data, data imaging methods, and the multi-solution of geophysical inversion. The utilization of more data and advanced geophysical methods will help obtain high-resolution imaging results to further constrain the origin of the Tengchong volcano.

Wood surface broken defects seriously damage the structure of wooden products, these defects have to be detected and eliminated. However, current defect detection methods based on machine vision have difficulty distinguishing the interference, similar to the broken defects, such as stains and mineral lines, and can result in frequent false detections. To address this issue, a multi-source data fusion network based on U-Net is proposed for wood broken defect detection, combining image and depth data, to suppress the interference and achieve complete segmentation of the defects. To efficiently extract various semantic information of defects, an improved ResNet34 is designed to, respectively, generate multi-level features of the image and depth data, in which the depthwise separable convolution (DSC) and dilated convolution (DC) are introduced to decrease the computational expense and feature redundancy. To take full advantages of two types of data, an adaptive interacting fusion module (AIF) is designed to adaptively integrate them, thereby generating accurate feature representation of the broken defects. The experiments demonstrate that the multi-source data fusion network can effectively improve the detection accuracy of wood broken defects and reduce the false detections of interference, such as stains and mineral lines.

Phase-locked loop-based grid-forming converters （PLL-GFCs） can regulate frequency and voltage. However， the transient synchronization stability after their connection to the high-voltage AC power grid is unclear. Therefore， the transient synchronization stability mechanism of the PLL-GFC-based MMC-HVDC （modular multilevel converter-based HVDC） systems is studied. Firstly， the control strategy of the PLL-GFC-based MMC-HVDC systems is introduced， and the power response characteristics are analyzed. Secondly， the grid-connected MMC-HVDC systems' transient synchronization stability model is built. The instability mechanism of the converters after grid faults and the influence of the dynamic changes of the grid current on the transient synchronization stability are studied based on phrase diagram curves. It is concluded that the equilibrium point is crucial to the transient stability after the fault occurs on the inverter-connected power grid. Therefore， an enhancement measure to improve the transient synchronization stability by dynamically adjusting active current command values is proposed. Finally， an electromagnetic transient simulation model is built by PSCAD/EMTDC to verify the correctness of the instability mechanism analysis and the effectiveness of the enhancement measure.

The accurate quantification of transmission limit and grid strength of the multi-infeed LCC-HVDC （line-commutated converter technology-based high-voltage DC） and VSC-HVDC （voltage source converter technology-based high-voltage DC） systems has become one of the critical measures to ensure the stable operation of new power systems. Through the improvement of the grid strength quantification method of the traditional LCC-HVDC AC/DC systems， a short-circuit ratio （SCR） index for quantifying the grid strength of the hybrid DC infeed systems is proposed to analyze the transmission limit of the AC/DC systems. Firstly， a quasi-steady-state （QSS） model of the hybrid DC infeed systems is built under the flow equation. Secondly， the SCR index for evaluating the transmission limit of LCC-HVDC in the hybrid DC infeed systems is obtained by analysis of the relationship between the Jacobian matrix singularity and the power transmission limit of the DC infeed systems. The sensitivity relationship between the index threshold and the operation mode of the VSC-HVDC system is analyzed. Finally， the effectiveness of the SCR index is verified using PSCAD/EMTDC and MATLAB platform. The analysis results show that the VSC-HVDC system is superior in voltage support under the constant voltage control mode at the receiving end. The operation mode of the VSC-HVDC system that exerts less influence on the transmission limit of the LCC-HVDC system can be quantitatively analyzed by the proposed index.

Abstract Background The stiffness of titanium mesh is a double-blade sword to repair larger alveolar ridges defect with excellent space maintenance ability, while invade the surrounding soft tissue and lead to higher mesh exposure rates. Understanding the mechanical of oral mucosa/titanium mesh/bone interface is clinically meaningful. In this study, the above relationship was analyzed by finite elements and verified by setting different keratinized tissue width in oral mucosa. Methods Two three-dimensional finite element models were constructed with 5 mm keratinized tissue in labial mucosa (KM cases) and 0 mm keratinized tissue in labial mucosa (LM cases). Each model was composed of titanium mesh, titanium screws, graft materials, bone, teeth and oral mucosa. After that, a vertical (30 N) loadings were applied from both alveolar ridges direction and labial mucosa direction to stimulate the force from masticatory system. The displacements and von Mises stress of each element at the interfaces were analyzed. Results Little displacements were found for titanium mesh, titanium screws, graft materials, bone and teeth in both LM and KM cases under different loading conditions. The maximum von Mises stress was found around the lingual titanium screw insertion place for those elements in all cases. The keratinized tissue decreased the displacement of oral mucosa, decreased the maximum von Mises stress generated by an alveolar ridges direction load, while increased those stress from labial mucosa direction load. Only the von Mises stress of the KM cases was all lower than the tensile strength of the oral mucosa. Conclusion The mucosa was vulnerable under the increasing stress generated by the force from masticatory system. The adequate buccal keratinized mucosa width are critical factors in reducing the stress beyond the titanium mesh, which might reduce the titanium exposure rate.

Background:. Pancreaticoduodenectomy (PD) has been widely applied in general hospitals in China; however, there is still a lack of unified standards for each surgical technique and procedure. This survey is intended to investigate the current status of digestive tract reconstruction after PD in university hospitals in China. Method:. A cross-sectional survey was conducted among the members of the Young Elite Pancreatic Surgery Club of China by using the Questionnaire for Digestive Tract Reconstruction after Pancreaticoduodenectomy. The questionnaire was disseminated and collected by point-to-point communication via WeChat public platforms. Results:. A total of 73 valid questionnaires were returned from 65 university hospitals in 28 provincial divisions of mainland China. The respondents who performed PD surgery with an annual volume of over 100 cases accounted for 63%. Generally, laparoscopic PD was performed less often than open PD. Child and Whipple reconstructions accounted for 70% and 26%, respectively. The sequence of pancreatoenteric, biliary-enteric, and gastrointestinal reconstruction accounted for 84% of cases. In pancreatoenteric anastomosis, double-layer anastomosis is the most commonly employed type, accounting for approximately 67%, while single-layer anastomosis accounts for 30%. Of the double-layer anastomoses, duct-to-mucosa/dunking (94%/4%) pancreatojejunostomy was performed with duct-mucosa using the Blumgart method (39%) and Cattel-Warren (29%), with continuous/interrupted sutures in the inner layer (69%/31%) and continuous/interrupted sutures in the outer layer (53%/23%). In single-layer anastomosis, continuous/interrupted sutures accounted for 41%/45%. In hepatojejunostomy, single-layer/double-layer suture accounted for 79%/4%, and continuous/interrupted suture accounted for 75%/9%. Forty-six percent of the responding units had not applied double-layer biliary-intestinal anastomosis in the last 3 years, 75% of the responding surgeons chose the anastomosis method according to bile duct diameter, with absorbable/non-absorbable suture accounting for 86%/12%. PD/pylorus-preserving PD accounted for 79%/11% of gastrojejunostomy (GJ) cases, the distance between GJ and hepaticojejunostomy < 30, 30–50, and > 50 cm were 11%, 75%, and 14%, respectively. Antecolic/retrocolic GJ accounted for 71%/23% of cases. Twenty-two percent of GJ cases employed Braun anastomosis, while 55% and 19% of GJ cases used linear cutting staplers/tube-type staplers, respectively; 60%/14% were reinforced/not reinforced via manual suturing after stapler anastomosis. Manual anastomosis in GJ surgery employed absorbable/non-absorbable sutures (91%/9%). Significant differences in reconstruction techniques were detected between different volumes of PD procedures (100/year), regions with different economic development levels, and between north and south China. Conclusion:. Digestive tract reconstruction following PD exists heterogeneity in Chinese university hospitals. Corresponding prospective clinical studies are needed to determine the consensus on pancreatic surgery that meets the clinical reality in China.

The quick， accurate and instantaneous evaluation of power limit of transmission section is of great significance to safe， stable and economic operation of power grid. The paper proposes an adaptive method based on a hybrid supervised learning algorithm. Through numerous simulations and analysis of historic operation modes， characteristic extraction， training， and regular updating of AI model， the correct matching relationship between grid operation status and power limit is established for fast， accurate and instantaneous power limit evaluation of the transmission section. The proposed method employs multiple supervised learning forecast algorithms， including deep neural networks， support vector regression， gradient boosting decision tree， and random forest. The hybrid models for power limit forecasting can make best of the advantages of the algorithms. The effectiveness of the method is verified on a 500-bus transmission model with real operation characteristics.

Background: Rapid and reliable diagnostic methods for Aspergillus fumigatus infection are urgently needed. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 13a (Cas13a) has high sensitivity and specificity in the diagnosis of viral infection. However, its potential use in detecting A. fumigatus remains unexplored. A highly sensitive and specific method using the CRISPR/Cas13a system was developed for the reliable and rapid detection of A. fumigatus. Methods: The conserved internal transcribed spacer (ITS) region of A. fumigatus was used to design CRISPR-derived RNA (crRNA) and the corresponding recombinase polymerase amplification (RPA) primer sequence with the T7 promoter for the CRISPR assay. Twenty-five clinical isolates and 43 bronchoalveolar lavage fluid (BALF) remaining from routine examinations of patients with confirmed pulmonary aspergillosis were collected to further validate the CRISPR assay. Results: No amplification signal was observed when genomic DNA from closely clinically related Aspergillus species, such as Aspergillus flavus, Aspergillus niger, and Aspergillus terreus, as well as Monascus purpureus Went and Escherichia coli, was tested by this assay, and the detection limit for A. fumigatus was 3 copies in a single reaction system. Validation experiments using the 25 clinical isolates demonstrated 91.7% specificity for the A. fumigatus section, and the sensitivity was 100% when first-generation sequencing was used as the standard. There was no significant difference between the PCR and CRISPR methods (P = 1.0), and the diagnosis results of the two methods were consistent (Kappa = 0.459, P = 0.003). Conclusion: The study offers a new validated CRISPR/Cas13a technique for A. fumigatus detection, providing a simple, rapid and affordable test that is ready for application in the diagnosis of A. fumigatus infection.

Abstract Near‐infrared (NIR) fluorescence imaging poses significant superiority over traditional medical imaging for tumor resection, thus having attracted widely attention. However, for tiny tumor residues, it requires relative high sensitivity to determine. Here, based on persistent luminescence nanoparticles (PLNPs), an ultrasensitive nanoprobe with extraordinary tumor imaging result is developed to guide surgical removal. Persistent luminescence (PersL) is quenched in normal tissue by the outer layer of MnO2, and is recovered due to the degradation of MnO2 in tumor microenvironment, significantly improving the sensitivity of tumor imaging. Combined with the absence of background fluorescence in imaging of PLNPs, ultrahigh sensitivity is achieved. In orthotopic breast cancer model, the intraoperative tumor‐to‐normal tissue (T/NT) signal ratio of the nanoprobe is 58.8, about 9 times that of downconversion nanoparticles. The T/NT ratio of residual tumor (

Radical innovations can shift the global competitiveness of entire nations. While countries typically struggle to absorb knowledge about novel technologies quickly, in which knowledge tends to be spatially sticky, an important exception is the fast catch-up of the Korean Li-ion battery industry from Japan in the early 2000s. In this paper, we conduct an exploratory case study on this surprising success story. Focussing on patent co-inventions between Korea and Japan, we investigate their significance, as well as underlying types of co-inventions and types of transferred knowledge. To this end, we proceed in four steps: (1) a Poisson regression model; (2) social network analyses; (3) patent inventor tracking and (4) patent coding. Our results indicate that Korean–Japanese co-inventions hold significantly greater influence than other cross-country co-inventions, including with patents without cross-country collaboration. We find a pronounced knowledge-transfer intensity during the early 2000s and observe two types of co-inventions: organisation-level and inventor-level. Predominantly, we observe inventor-level co-inventions, i.e. Korean companies hiring experienced Japanese engineers, that proved important to transferring sticky knowledge. Moreover, while most patents target the design of core battery components, the share of manufacturing patents are—contrary to theoretical expectations—highest during the first half of the observation period. We also discuss our findings and draw implications for policy, industrial and academic players, including industry localisation policies, technology-inherent catch-up strategies and directions for future research.

Cepola schlegelii (Bleeker 1854) belongs to the genus Cepola in the family Cepolidae and order Priacanthiformes. The complete mitochondrial genome of C. schlegelii was sequenced and analyzed by a high-throughput sequencing approach. The full length of the genome is 17,020 bp, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a non-coding control region (D-loop). Phylogenetic analysis based on complete mitochondrial genomes revealed that C. schlegelii was most closely related to Acanthocepola krusensternii. The complete mitochondrial sequence of C. schlegelii will enrich the mitochondrial genome database and provide useful resources for population genetics and evolution analyses.

As the most commonly used antipyretic and analgesic drug, paracetamol (PA) coexists with neurotransmitter dopamine (DA) in real biological samples. Their simultaneous determination is extremely important for human health, but they also interfere with each other. In order to improve the conductivity, adsorption affinity, sensitivity, and selectivity of TiO2-based electrochemical sensor, N-doped carbon@TiO2 double-shelled hollow sphere (H–C/N@TiO2) is designed and synthesized by simple alcoholic and hydrothermal method, using polystyrene sphere (PS) as a template. Meanwhile, TiO2 hollow spheres (H–TiO2) or N-doped carbon hollow spheres (H–C/N) are also prepared by the same method. H–C/N@TiO2 has good conductivity, charge separation, and the highly enhanced and stable current responses for the detection of PA and DA. The detection limit and linear range are 50.0 nmol/L and 0.3–50 μmol/L for PA, 40.0 nmol/L and 0.3–50 μmol/L for DA, respectively, which are better than those of carbon-based sensors. Moreover, this electrochemical sensor, with high selectivity, strong anti-interference, high reliability, and long time durability, can be used for the simultaneous detection of PA and DA in human blood serum and saliva. The high electrochemical performance of H–C/N@TiO2 is attributed to the multi-functional combination of different layers, because of good conductivity, absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO2.

As the planning and dispatching of new types of power systems become increasingly complicated， dynamic and dubious， it is very challenging to lay down operating mode for power grid that satisfies both security and economic constraints. This process typically requires intensive manual tuning and simulation calculations to search for feasible solutions in a high-dimensional action space that fulfills the requirements on safety and economy of the grid in ground state and fault conditions. Therefore， an approach based on multi-DRL-agent architecture is proposed to describe the problem as a Markov decision process （MDP）. The approach automatically adjusts different types of controllable grid resources by training centralized and distributed multi-DRL-agent to control the power of transmission lines， thus complying with various safety indicators of grid operation. The method is proved to be effective in a power grid model.

Large-scale photovoltaic power connected to the distribution network will raise the voltage at the system nodes， and， in serious cases， the voltage overlimit. Therefore， a voltage regulation strategy based on shunt and series reactors as well as genetic algorithm is proposed. Firstly， the causes of voltage rise in the distribution network and the roles of shunt and series reactors in voltage regulation are analyzed. Then， a reactive power optimization model with the objective of economic optimization is established， and the genetic algorithm is used to solve the optimal reactor configuration scheme. Finally， the effectiveness of the method is verified by simulating the IEEE 33-node system incorporated into a high-power PV plant based on the MATLAB simulation platform.

The incidence of cancer is increasing globally, and it is the most common cause of death. The identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. SHCSH2 domain-binding protein 1 (SHCBP1) is a protein that specifically binds to the SH2 domain of Src homology–collagen. It participates in the regulation of a variety of signal transduction pathways and can activate a variety of signaling molecules to perform a series of physiological functions. SHCBP1 is expressed in a variety of human tissues, but its abnormal expression in various systems is associated with cancer. SHCBP1 is abnormally expressed in a variety of tumors, and plays roles in almost all aspects of cancer biology (such as cell proliferation, apoptosis prevention, invasion, and metastasis) through various possible mechanisms. Its expression level is related to the clinicopathological characteristics of patients. In addition, the SHCBP1 expression pattern is closely related to cancer type, stage, and other clinical variables. Therefore, SHCBP1 is a promising tumor biomarker for cancer diagnosis and prognosis and a potential therapeutic target. This article reviews the expression, biological functions, mechanisms, and potential clinical significance of SHCBP1 in various human tumors to provide a new theoretical basis for clinical molecular diagnosis, molecular targeted therapy, and scientific research on cancer.

BackgroundAccumulating evidence has revealed that CD8+ T cell exhaustion (Tex) results in worse immunotherapy outcomes. However, the molecular functions and mechanisms of action of Tex in chemoresistance needed to be elucidated.MethodsThe populations of tumor-infiltrating CD8+ T cells (TILCD8Ts) in chemoresistant and chemosensitive groups of the GSE25066 dataset were calculated using CIBERSORT. Differentially expressed genes (DEGs) between TILCD8Ts and other immune cells were explored by integrating 16 immune cell datasets downloaded from the gene expression omnibus (GEO) database. Gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression of TILCD8T-specific upregulated genes were used to construct a chemoresistant TILCD8T signature (cr-TILCD8TSig). Clinical prognostic data, genomic alterations, chemotherapy response, and immunotherapy response were compared between the different cr-TILCD8TSig subgroups in the GSE25066 and the cancer genome atlas breast cancer (TCGA-BRCA) cohorts.ResultsA cr-TILCD8TSig with exhausted features was identified, consisting of seven genes (TCF7, RARRES3, ARL4C, ITK, CDH3, GZMB, and KLRD1), which were identified from 104 TILCD8Ts-specific DEGs. Our results showed that compared to the cr-TILCD8TSig-low subgroup, the -high subgroup had a poorer distant relapse-free survival (DRFS) in the GSE25066 cohort and worse progression-free survival (PFS) in the TCGA-BRCA cohort. Univariate and multivariate Cox regression analyses also demonstrated that cr-TILCD8TSig was an independent prognostic factor in the two independent cohorts. Furthermore, cr-TILCD8TSig-low patients benefited more from chemotherapy and immunotherapy than cr-TILCD8TSig-high patients. Besides, we found cell transmembrane signal transduction and the ECM may provide the molecular basis for resistance to antitumor agents in the cr-TILCD8Sig-high subgroup. For genomic alterations, we revealed that mutations in PIK3CA, DMD, and APOB were more common in the cr-TILCD8Sig-high subgroup than in the cr-TILCD8Sig-low subgroup. A nomogram was finally constructed with good discrimination and calibration.Conclusionscr-TILCD8TSig is a useful tool to independently predict prognosis, chemotherapy response, and immunotherapy outcomes in patients with breast cancer.

Background: We presented the performance of a Chinese-made cryptococcal glucuronoxylomannan (GXM) antigen test using serum and bronchoalveolar lavage fluid (BALF) samples in the HIV-negative Chinese population. Methods: Between February 2017 and January 2019, HIV-negative patients with pulmonary cryptococcosis were recruited and followed-up every three months, including completion of a chest CT examination and collection of serum and BALF samples. Results: Here, thirty-seven confirmed and ten clinically diagnosed patients were recruited. Furthermore, samples from 174 noncryptococcosis patients that may cause false positives were also collected. The sensitivity of a lateral flow assay (LFA) for detecting cryptococcal GXM antigen in serum and BALF samples from confirmed cases was 97% and 95%, respectively, and the specificity was 98.2% and 93%, respectively, and the differences in these values between the BALF and serum samples were not significant. The serum cryptococcal GXM antigen value showed a positive correlation (r: 0.581, p