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Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal original tumor in gastrointestinal (GI) tract and is considered to have varying malignant potential. With the advancement of computer science, radiomics technology and deep learning had been applied in medical researches. It’s vital to construct a more accurate and reliable multimodal predictive model for recurrence-free survival (RFS) aiding for clinical decision-making. A total of 254 patients underwent surgery and pathologically diagnosed with GIST in The First Hospital of China Medical University from 2019 to 2022 were included in the study. Preoperative contrast enhanced computerized tomography (CE-CT) and hematoxylin/eosin (H&E) stained whole slide images (WSI) were acquired for analysis. In the present study, we constructed a sum of 11 models while the multimodal model (average C-index of 0.917 on validation set in 10-fold cross validation) performed the best on external validation cohort with an average C-index of 0.864. The multimodal model also reached statistical significance when validated in the external validation cohort (n = 42) with a p-value of 0.0088 which pertained to the recurrence-free survival (RFS) comparison between the high and low groups using the optimal threshold on the predictive score. We also explored the biological significance of radiomics and pathomics features by visualization and quantitative analysis. In the present study, we constructed a multimodal model predicting RFS of GIST which was prior over unimodal models. We also proposed hypothesis on the correlation between morphology of tumor cell and prognosis.

Abstract Postexercise blood pressure (BP) may be a better predictor of cardiovascular risk than office BP, but there is a lack of data supporting this claim. We hypothesized that postexercise BP may be an important prognostic marker. Our aim was to evaluate the association of postexercise BP with major adverse cardiovascular events (MACE) and all‐cause mortality. A total of 2581 participants (median age, 46 years; 55.9% women) from the Coronary Artery Risk Development in Young Adults study at year 20 (2005–2006) who underwent a graded exercise treadmill test using a modified Balke graded protocol were included. Postexercise BP was measured at baseline. Cox models were used to estimate the associations of postexercise BP with MACE and all‐cause mortality. Participants were followed up until December 31, 2021. In the entire population, postexercise systolic BP showed no significant association with MACE or all‐cause mortality, while postexercise diastolic BP was associated with MACE (hazard ratios [HR], 1.27 [95% CI, 1.06–1.52], per 10 mmHg increase) and all‐cause mortality (HR, 1.26 [95% CI, 1.05–1.51], per 10 mmHg increase). In the normal BP group, postexercise systolic BP was not significantly associated with MACE or all‐cause mortality, and postexercise diastolic BP was strongly associated with MACE (HR, 1.57 [95% CI, 1.18–2.09], per 10 mmHg increase). In this population‐based cohort study, postexercise diastolic BP was significantly associated with the risk of MACE and all‐cause mortality. Among individuals with normal BP, postexercise diastolic BP could identify those at a higher risk of cardiovascular events.

Abstract Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p

Abstract Background Deep sternal wound infection (DSWI) constitutes a serious complication after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the dose-response relationship between glycated hemoglobin (HbA1c) level and the risk of DSWI after CABG. Methods PubMed, Scopus, and Cochrane Library databases were searched to identify potentially relevant articles. According to rigorous inclusion and exclusion criteria, fourteen studies including 15,570 patients were enrolled in our meta-analysis. Odds ratio (OR) with 95% confidence intervals (CIs) was used as the summary statistic. The robust-error meta-regression model was used to synthesize the dose-response relationship. Results Our meta-analysis shows that among patients undergoing CABG, preoperative elevated HbA1c was associated with the risk of developing DSWI (OR = 2.67, 95% CI 2.00–3.58) but with low prognostic accuracy (diagnostic OR = 2.70, 95% CI 1.96–3.73; area under the curve = 0.66, 95% CI 0.62–0.70) for predicting postoperative DSWI. Subgroup analyses showed the relationship became nonsignificant in patients without diabetes and studies adopting lower HbA1c thresholds. Dose-response analysis showed a significant nonlinear (p = 0.03) relationship between HbA1c and DSWI, with a significantly increased risk of DSWI when HbA1c was > 5.7%. Conclusions An elevated HbA1c level of > 5.7% was related to a higher risk of developing DSWI after CABG, and the risk increased as the HbA1c level grew. The association between HbA1c and DSWI was nonsignificant among nondiabetic patients while significant among diabetic patients.

This study presents an innovative approach for estimating the azimuth cutoff wavelength ($\lambda _{c}$) using a multipolarization combination technique to enhance the retrieval of significant wave height (SWH) and wind speed (WS) from Gaofen-3 (GF-3) SAR wave mode data. The study identifies distinct advantages of copolarization for low to moderate sea states and cross-polarization for high sea states in the $\lambda _{c}$ estimation. Consequently, a suite of dual and quad-polarization combination methods is proposed, with the VV+VH combination demonstrating superior cost-efficiency, reducing the root mean square error (RMSE) of $\lambda _{c}$ estimation by around 20% compared with VV polarization. Correlation analysis between $\lambda _{c}$ at various polarizations, particularly VV+VH, and factors such as SWH, WS, wind direction, wave direction, and incidence angle, indicates a strong positive relationship with SWH and WS, and a moderate relationship with incidence angle. This insight informs the development of three $\lambda _{c}$-based SWH and WS retrieval models: single linear regression, multiple linear regression (MLR), and Gaussian process regression (GPR). The MLR and GPR models integrate normalized radar cross section (NRCS) and incidence angle to improve retrieval accuracy. The GPR model achieves more accurate estimation of SWH and WS compared with existing $\lambda _{c}$-based algorithms, with an RMSE of 0.485 m for SWH retrieval and 1.390 m/s for WS retrieval. Despite the performance gap with state-of-the-art algorithms, the GPR model offers exceptional cost-effectiveness and surpasses NRCS-based models for WS retrieval without requiring wind direction input.

Different interacting contexts influence the decision-making process, as revealed by the computational modeling. Through four studies, we investigated how smartphone addiction and anxiety influenced impulsive behaviors, along with the underlying psychological mechanisms and dynamic decision-making processes. In the first and second studies, we found no significant correlation between smartphone addiction and impulsive behavior. However, in the third study, we found that smartphone separation increased impulsive decision-making and purchases, and state anxiety, but not trait anxiety, mediated this effect. We explored the dynamic decision-making process using a multi-attribute drift diffusion model (DDM). The results showed that anxiety triggered by smartphone separation changed the trade-offs between decision weights for the fundamental components of the dynamic choice process. In the fourth study, we investigated why smartphone addiction led to increased anxiety and found that extended-self was a mediating factor. Our findings show that smartphone addiction was not correlated with impulsive behaviors, but was correlated with state anxiety in the context of smartphone separation. Further, this study shows how emotional states triggered by different interacting contexts affect the dynamic decision-making process and consumer behaviors.

Summary: Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88–0.92 in the internal verification and 0.83–0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

Abstract Backgrounds Salivary biomarkers hold huge potential for the non-invasive diagnosis of oral squamous cell carcinoma. Angiogenic factors and matrix-metalloproteinases (MMPs) are highly expressed in OSCC tissue, but their expression patterns in the saliva are unknown. This study aimed to analyze the levels of angiogenic factors and MMPs in tumor tissue and saliva of OSCC patients. Methods OSCC-tissue, adjacent normal tissue (ANT), saliva from OSCC patients, and healthy controls were obtained. The expression patterns of angiogenic factors and MMPs were analyzed by immunohistochemistry, protein chip array, and RT-qPCR. Results Results showed higher expression of ANG, ANG-2, HGF, PIGF, VEGF, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in OSCC-tissues compared to the ANT. Among the overexpressed markers in OSCC-tissues, HGF, VEGF, PIGF, PDGF-BB, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were significantly upregulated in the saliva of OSCC patients compared to healthy controls. Conclusions The levels of HGF, VEGF, PIGF, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were upregulated both in OSCC tissue and saliva of OSCC patients. Bioinformatic analysis revealed the correlation of these factors with patient survival and cancer functional states in head and neck cancer, indicating these factors as possible saliva-based non-invasive diagnostic/prognostic markers and therapeutic targets of OSCC.

Abstract. Background:. The complete mesogastrium excision (CME) based on D2 radical gastrectomy is believed to significantly reduce the local-regional recurrence compared with D2 radical gastrectomy in advanced gastric cancer, and it is widely used in China. This study aimed to explore whether D2 + CME is superior to D2 on surgical outcomes during gastrectomy from Chinese data. Methods:. Feasible studies comparing the D2 + CME (D2 + CME group) and D2 (D2 group) published up to March 2020 are searched from electronic databases. The data showing surgical and complication outcomes are extracted to be pooled and analyzed. Results:. Fourteen records including 1352 patients were included. The D2 + CME group had a shorter mean operative time (weighted mean difference [WMD] = —16.72 min, 95% confidence interval [CI]: −26.56 to −6.87 min, P

An efficient catalyst is key to achieving the synthesis of electrochemical ammonia and improving safety. In this work, using biomass walnut shell as a carbon source and sodium thiosulfate as a sulfur source, sulfur-modified walnut shell-derived carbon material was synthesized via a simple low-temperature impregnation method at room temperature and atmospheric pressure as an effective electrochemical ammonia synthesis catalyst with high thermal stability. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), nitrogen adsorption–desorption apparatus, thermogravimetry (TG), and other characterization methods were applied to analyze the micro-morphology and physicochemical structure of the electrocatalyst. The synthesized ammonia performance of the catalyst was measured using an ultraviolet (UV) spectrophotometer and electrochemical workstation. The catalyst design used the doping of sulfur atoms to create rich catalytic active sites, while the presence of elemental sulfur on the catalyst surface provided hydrophobicity, which was conducive to inhibiting competitive hydrogen evolution reaction (HER) and enhancing the electrocatalytic ammonia synthesis performance of the catalyst. Under normal temperature and pressure conditions, when a voltage of −0.45 V was applied, the ammonia yield in 0.05 M H2SO4 electrolyte was 10.39 μgNH3 mgcat.−1 h−1. The results showed that the introduction of sulfur effectively improved the electrocatalytic and thermal safety performance of bio-derived carbon materials, and the test presented that the performance of the catalyst was stable and reusable.

The shear behavior of shear connectors in steel-concrete composite structures mainly depends on its load-slip relationship. The load-slip relationship not only reflects the shear capacity and slip capacity of the shear connectors, but also the degradation of shear stiffness during loading. In this study, fifteen push-out tests were carried out to investigate the load-slip relationship of the novel bearing-shear (B-S) connectors, which consist of pressuring-bearing plates and shear plates. Based on push-out tests, the influence of the shape and height of the pressure-bearing plate, and the shear plate shape on the load-slip relationship of the B-S connectors was analyzed. Then, an effective finite element model, validated by push-out tests, was used to study the influence of the concrete strength, and the thickness and tensile strength of the shear plate on the load-slip relationship of B-S connectors. Finally, based on the push-out tests, numerical analysis and theoretical analysis, an analytical model expressing the load-slip relationship of the B-S connectors was proposed.

MicroRNA-155 (miR155) is overexpressed in various inflammatory diseases and cancer, in which bone resorption and osteolysis are frequently observed. However, the role of miR155 on osteogenesis and bone mass phenotype is still unknown. Here, we report a low bone mass phenotype in the long bone of Mir155-Tg mice compared with wild-type mice. In contrast, Mir155-KO mice showed a high bone mass phenotype and protective effect against inflammation-induced bone loss. Mir155-KO mice showed robust bone regeneration in the ectopic and orthotopic model, but Mir155-Tg mice showed compromised bone regeneration compared with the wild-type mice. Similarly, the osteogenic differentiation potential of bone marrow stromal stem cells (BMSCs) from Mir155-KO mice was robust and Mir155-Tg was compromised compared with that of wild-type mice. Moreover, Mir155 knockdown in BMSCs from wild-type mice showed higher osteogenic differentiation potential, supporting the results from Mir155-KO mice. TargetScan analysis predicted sphingosine 1-phosphate receptor-1 (S1pr1) as a target gene of Mir155, which was further confirmed by luciferase assay and Mir155 knockdown. S1pr1 overexpression in BMSCs robustly promoted osteogenic differentiation without affecting cell viability and proliferation. Furthermore, osteoclastogenic differentiation of Mir155-Tg bone marrow-derived macrophages was inhibited compared with that of wild-type mice. Thus, Mir155 showed a catabolic effect on osteogenesis and bone mass phenotype via interaction with the S1pr1 gene, suggesting inhibition of Mir155 as a potential strategy for bone regeneration and bone defect healing.

Background and aims Endoscopic submucosal dissection (ESD) remains an investigational issue for early gastric cancer (EGC) with expanded indications owing to the risk of lymph node metastasis. In this study, we aimed to evaluate the clinical outcomes and safety of ESD versus surgical resection (SR) for EGC with expanded indications.Methods The systematic review selected studies from PubMed, Embase, Cochrane and Web of Science databases from 2010 to 2020, and compared survival and clinical safety data of ESD with those of surgical resection for EGC with expanded indications. The fixed-effects or random-effects model was used to calculate the differences between the two groups. To assess the validity of the eligible studies, risk of bias was measured using the Newcastle–Ottawa Quality Assessment Scale.Results Nine retrospective studies were used to calculate the differences in survival and clinical safety data between the two groups for EGC with expanded indications. Differences were not significant between the groups in terms of age, sex, tumour size, tumour histology or lesion morphology. Regarding tumour site, tumours located in the L area (the lower third of the stomach) were more likely to be found in the ESD group. With regard to metachronous and synchronous carcinomas, there was a significant difference favouring SR treatment (metachronous: OR=0.12, 95% CI=0.05 to 0.25, p

The bearing-shear connector (B-SC) is a newly developed connector that exhibits excellent shear behaviour and is easy to process. However, research on the application of B-SCs as substitutes for grouped studs in prefabricated steel–concrete composite beams is rare, and systematically studying their shear behaviour is necessary. Thus, a refined numerical model was developed to study the shear behaviour of the B-SCs. The numerical model, validated by push-out tests, was conducted to analyse the stress of the B-SCs and concrete slab during loading and to explore the failure mechanism of B-SCs. Then, a parametric study was performed to identify the key factors influencing the shear behaviour of the B-SCs. The concrete strength, and the thickness and the tensile strength of the shear plate were found to significantly influence the shear behaviour of B-SCs. According to the experiments and numerical analysis, calculation formulae for the ultimate shear resistance and slip modulus were proposed.

Pleurocidin-family cationic antimicrobial peptide NRC-03 exhibits potent and selective cytotoxicity towards cancer cells. However, the anticancer effect of NRC-03 in oral squamous cell carcinoma (OSCC) and the molecular mechanism of NRC-03 induced cancer cell death is still unclear. This study focused to investigate mitochondrial oxidative stress-mediated altered mitochondrial function involved in NRC-03-induced apoptosis of OSCC cells. NRC-03 entered the OSCC cells more easily than that of normal cells and bound to mitochondria as well as the nucleus, causing cell membrane blebbing, mitochondria swelling, and DNA fragmentation. NRC-03 induced high oxygen consumption, reactive oxygen species (ROS) release, mitochondrial dysfunction, and apoptosis in OSCC cells. Non-specific antioxidant N-acetyl-l-cysteine (NAC), or mitochondria-specific antioxidant mitoquinone (MitoQ) alleviated NRC-03-induced apoptosis and mitochondrial dysfunction indicated that NRC-03 exerts a cytotoxic effect in cancer cells via inducing cellular and mitochondrial oxidative stress. Moreover, the expression of cyclophilin D (CypD), the key component of mitochondrial permeability transition pore (mPTP), was upregulated in NRC-03-treated cancer cells. Blockade of CypD by siRNA-mediated depletion or pharmacological inhibitor cyclosporine A (CsA) significantly suppressed NRC-03-induced mitochondrial oxidative stress, mitochondrial dysfunction, and apoptosis. NRC-03 also activated MAPK/ERK and NF-κB pathways. Importantly, intratumoral administration of NRC-03 inhibited the growth of CAL-27 cells-derived tumors on xenografted animal models. Taken together, our study indicates that NRC-03 induces apoptosis in OSCC cells via the CypD-mPTP axis mediated mitochondrial oxidative stress.

Abstract Background Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. Methods RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety. Discussion This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer. Trial registration Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.

Autologous bone marrow-derived mesenchymal stem cells (BMSCs) are more easily available and frequently used for bone regeneration in clinics. Osteogenic differentiation of BMSCs involves complex regulatory networks affecting bone formation phenomena. Non-coding RNAs (ncRNAs) refer to RNAs that do not encode proteins, mainly including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, transfer RNA-derived small RNAs, etc. Recent in vitro and in vivo studies had revealed the regulatory role of ncRNAs in osteogenic differentiation of BMSCs. NcRNAs had both stimulatory and inhibitory effects on osteogenic differentiation of BMSCs. During the physiological condition, osteo-stimulatory ncRNAs are upregulated and osteo-inhibitory ncRNAs are downregulated. The opposite effects might occur during bone degenerative disease conditions. Intracellular ncRNAs and ncRNAs from neighboring cells delivered via exosomes participate in the regulatory process of osteogenic differentiation of BMSCs. In this review, we summarize the recent advances in the regulatory role of ncRNAs on osteogenic differentiation of BMSCs during physiological and pathological conditions. We also discuss the prospects of the application of modulation of ncRNAs function in BMSCs to promote bone tissue regeneration in clinics.

BackgroundAccumulating evidence suggests that dysregulation of Chordin-like 1 (CHRDL1) is associated with malignant biological behaviors in multiple cancers. However, the exact function and molecular mechanism of CHRDL1 in oral squamous cell carcinoma (OSCC) remain unclear.MethodsThe expression levels of CHRDL1 in OSCC tissues and CAL27 cells were determined by RT-qPCR. Immunohistochemical staining was applied to detect CHRDL1 protein expression in sample tissues from OSCC patients. Gain of function and knockdown by lentivirus were further used to examine the effects of CHRDL1 on cell proliferation, migration, invasion, and adhesion in OSCC. Tail vein injection of CAL27 cells with dysregulated CHRDL1 expression was further used to examine the effect of CHRDL1 on lung colonization. RNA sequencing was performed to explore the molecular mechanisms of CHRDL1 that underlie the progression of OSCC.ResultsCHRDL1 was significantly downregulated in OSCC tissues and CAL27 cells compared to controls. CHRDL1 knockdown enhanced migration, invasion, adhesion, and EMT, but not proliferation, in CAL27 cells. Overexpression of CHRDL1 had the opposite effects. Moreover, CHRDL1 was proven to inhibit tumor metastasis in vivo. Mechanistically, MAPK signaling pathway components, including ERK1/2, p38, and JNK, were found to regulate the malignant biological behaviors of CAL27 cells.ConclusionsOur results suggest that CHRDL1 has an inhibitory effect on OSCC metastasis via the MAPK signaling pathway, which provides a new possible potential therapeutic target against OSCC.

Serine incorporator (SERINC) proteins 1–5 (SERINC1-5) are involved in the progression of several diseases. SERINC2-4 are carrier proteins that incorporate the polar amino acid serine into membranes to facilitate the synthesis of phosphatidylserine and sphingolipids. SERINC genes are also differentially expressed in tumors. Abnormal expression of SERINC proteins occurs in human cancers of the breast, lung, colon, liver, and various glands, as well as in mouse testes. SERINC proteins also affect cleft lip and palate and nerve-related diseases, such as seizure Parkinsonism and borderline personality. Moreover, SERINC proteins have garnered significant interest as retroviral restriction factors, spurring efforts to define their function and elucidate the mechanisms through which they operate when associated with viruses. Human SERINC proteins possess antiviral potential against human immunodeficiency virus (HIV), SARS-COV-2, murine leukemia virus (MLV), equine infectious anemia virus (EIAV), and hepatitis B virus (HBV). Furthermore, the crystal structure is known, and the critical residues of SERINC5 that act against HIV have been identified. In this review, we discuss the most prevalent mechanisms by which SERINC3 and SERINC5 antagonize viruses and focus on the potential therapeutic applications of SERINC5/3 against HIV.

In this paper, we conduct a survey of the literature about reinforcement learning (RL)-based medium access control (MAC) protocols. As the scale of the wireless ad hoc network (WANET) increases, traditional MAC solutions are becoming obsolete. Dynamic topology, resource allocation, interference management, limited bandwidth and energy constraint are crucial problems needing resolution for designing modern WANET architectures. In order for future MAC protocols to overcome the current limitations in frequently changing WANETs, more intelligence need to be deployed to maintain efficient communications. After introducing some classic RL schemes, we investigate the existing state-of-the-art MAC protocols and related solutions for WANETs according to the MAC reference model and discuss how each proposed protocol works and the challenging issues on the related MAC model components. Finally, this paper discusses future research directions on how RL can be used to enable MAC protocols for high performance.

Many incentive schemes address the selfishness issue in opportunistic networks and show performance improvement by simulations. However, the insights of incentive schemes that affect network performance are not clear. Network capacity analysis can reveal how factors affect performance, which is a guideline for new designs. To analyze incentive schemes, a well-defined mathematical model is necessary, which cannot be achieved by existing analytical models based on empirical formulas or types of incentive schemes. First, this paper proposes such a model to show the incentive degree with the incentive scheme, cooperation degree, energy usage, buffer usage, and security based on a quantum game model. Verification compares the model with delivery ratios that show impacts on selfish nodes in simulations under two typical incentive schemes. Then, network capacity is analyzed with this model and a sparse clustering regime that has similar mobility to opportunistic networks in order to show factors for future designs.

BackgroundThe validity of lymphadenectomy of the lymph node along the superior mesenteric vein (LN14v) in gastric cancer remains controversial. The study investigated the characteristics and prognosis of gastric cancer with metastasis or micrometastasis to LN14v.MethodsA retrospective study of 626 patients undergoing radical gastrectomy in our center from January 2003 to December 2015 was analyzed. In total, 303 patients had lymphadenectomy of LN14v, and lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin nodes CK8/18. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis or metastasis on prognosis.ResultsThe metastatic rate of the LN14v lymph node was 15.8%, and the micrometastatic rate was 3.3%. Multivariate analysis showed site, Borrmann classification, postoperative lymph node metastasis (pN), and metastasis in LN6 and LN9 were predictive factors for LN14v micrometastasis or metastasis (P < 0.05). The 5-year survival rate in the positive group (LN14v micrometastasis or metastasis) was 12.4%. The prognosis of patients without LN14v lymph node micrometastasis was better than that of the positive group, whereas the difference between group of LN14v micrometastasis and LN14v metastasis was not obvious. In matched analysis, patients with stage III gastric cancer L/M area, pN2-3, and LN6(+) who underwent lymphadenectomy of LN14v had better survival than those without lymphadenectomy of LN14v.ConclusionLymph node micrometastasis may provide accurate prognostic information for patients with gastric cancer. Moreover, lymphadenectomy of LN14v might improve the survival of patients with stage III gastric cancer of L/M area, pN2-3, and LN6(+).

We constructed a prognostic risk model for colon adenocarcinoma (COAD) using microRNAs (miRNAs) as biomarkers. Clinical data of patients with COADs and miRNA-seq data were from TCGA, and the differential expression of miRNAs (carcinoma vs. para-carcinoma tissues) was assessed using R software. COAD data were randomly divided into Training and Testing Sets. A linear prognostic risk model was constructed using Cox regression analysis based on the Training Set. Patients were classified as high-risk or low-risk according to the score of the prognostic model. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate model performance. The gene targets in the prognostic model were identified and their biological functions were analyzed. Analysis of COAD and normal cell lines using qPCR was used to verify the model. There were 134 up-regulated and 140 down-regulated miRNAs. We used the Training Set to develop a prognostic model based on the expression of seven miRNAs. ROC analysis indicated this model had acceptable prediction accuracy (area under the curve=0.784). Kaplan-Meier survival analysis showed that overall survival was worse in the high-risk group. Cox regression analysis showed that the 7-miRNA Risk Score was an independent prognostic factor. The 2,863 predicted target genes were mainly enriched in the MAPK, PI3K-AKT, proteoglycans in cancer, and mTOR signaling pathways. For unknown reasons, expression of these miRNAs in cancerous and normal cells differed somewhat from model predictions. Regardless, the 7-miRNA Risk Score can be used to predict COAD prognosis and may help to guide clinical treatment.

Oral cancer constitutes approximately 2% of all cancers, while the most common type, oral squamous cell carcinoma (OSCC) represents 90% of oral cancers. Although the treatment of OSCC has improved recently, it still has a high rate of local recurrence and poor prognosis, with a 5-year survival rate of only 50%. Advanced stage OSCC tends to metastasize to lymph nodes. Thus, exploring new therapeutic strategies for OSCC is therefore an urgent priority. Exosomes, the small membrane vesicles derived from endosomes, have been detected in a wide array of bodily fluids. Exosomes contain a diversity of proteins, mRNAs, and non-coding RNAs, including microRNAs, long non-coding RNAs, piRNAs, circular RNAs, tsRNAs, and ribosomal RNAs, which are delivered to neighboring cells or even transported to distant sites. Exosomes have been associated with the tumorigenesis of OSCC, promote the proliferation, colonization, and metastasis of OSCC by transferring their contents to the target cells. Furthermore, exosomes are involved in the regulation of the tumor microenvironment to transform conditions favoring cancer progression in vivo. In this review, we summarize the crucial role of exosomes in the tumorigenesis and progression of OSCC and discuss the potential clinical application of exosomes in OSCC treatment.

Background Although sub‐Saharan Africa has a high prevalence of cardiovascular diseases (CVDs), there remains a lack of systematic and comprehensive assessment of risk factors and early CVD outcomes in adults in sub‐Saharan Africa. Methods and Results Using a stratified multistage random sampling method, we recruited 1106 men and women, aged >18 years, from the general population in Ghana to participate in a national health survey from 2016 to 2017. In Ghanaian adults, the age‐standardized prevalence of known CVD risk factors was 15.1% (95% CI, 12.9%–17.3%) for obesity, 6.8% (95% CI, 5.1%–8.5%) for diabetes mellitus, 26.1% (95% CI, 22.9%–29.4%) for hypertension, and 9.3% (95% CI, 7.1%–11.5%) for hyperuricemia. In addition, 10.1% (95% CI, 7.0%–13.2%) of adults had peripheral artery disease, 8.3% (95% CI, 6.7%–10.0%) had carotid thickening, 4.1% (95% CI, 2.9%–5.2%) had left ventricular hypertrophy, and 2.5% (95% CI, 1.5%–3.4%) had chronic kidney disease. Three CVD risk factors appeared to play prominent roles in the development of target organ damage, including obesity for peripheral artery disease (odds ratio [OR], 2.22; 95% CI, 1.35–3.63), hypertension for carotid thickening (OR, 1.92; 95% CI, 1.22–3.08), and left ventricular hypertrophy (OR, 5.28; 95% CI, 2.55–12.11) and hyperuricemia for chronic kidney disease (OR, 5.49; 95% CI, 2.84–10.65). Conclusions This comprehensive health survey characterized the baseline conditions of a national cohort of adults while confirming the prevalence of CVD risk factors, and early CVD outcomes have reached epidemic proportions in Ghana. The distinct patterns of risk factors in the development of target organ damage present important challenges and opportunities for interventions to improve cardiometabolic health among adults in Ghana.

Cellular activities, such as attachment, spreading, proliferation, migration, and differentiation are indispensable for the success of bone tissue engineering. Mesenchymal stromal cells (MSCs) are the key precursor cells to regenerate bone. Bioactive compounds from natural products had shown bone regenerative potential. Notoginsenoside R1 (NGR1) is a primary bioactive natural compound that regulates various biological activities, including cardiovascular protection, neuro-protection, and anti-cancer effects. However, the effect of NGR1 on migration, adhesion, spreading, and osteogenic differentiation of MSCs required for bone tissue engineering application has not been tested properly. In this study, we aimed to analyze the effect of NGR1 on the cellular activities of MSCs. Since human adipose-derived stromal cells (hASCs) are commonly used MSCs for bone tissue engineering, we used hASCs as a model of MSCs. The optimal concentration of 0.05 μg/mL NGR1 was biocompatible and promoted migration and osteogenic differentiation of hASCs. Pro-angiogenic factor VEGF expression was upregulated in NGR1-treated hASCs. NGR1 enhanced the adhesion and spreading of hASCs on the bio-inert glass surface. NGR1 robustly promoted hASCs adhesion and survival in 3D-printed TCP scaffold both in vitro and in vivo. NGR1 mitigated LPS-induced expression of inflammatory markers IL-1β, IL-6, and TNF-α in hASCs as well as inhibited the RANKL/OPG expression ratio. In conclusion, the biocompatible NGR1 promoted the migration, adhesion, spreading, osteogenic differentiation, and anti-inflammatory properties of hASCs.

Objective. Primary duodenum lymphoma (PDL) is extremely rare with limited data available in the literature. In this study, we sought to describe clinical features and identify factors affecting survival in patients with PDL using a large population cohort. Methods. The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2015. Results. A total of 1060 cases of PDLs were identified. Clinicopathological features as well as survival data of PDLs were analyzed and compared with 10573 primary gastric lymphomas (PGLs) and 3239 primary small intestinal lymphomas (PSILs) from the SEER database. PDL patients were younger in age (60.96 ± 15.205), and the proportion of stage I (53.21%) was higher in Ann Arbor staging. The proportion of PDLs treated by surgery (8.68%) is the lowest among PDLs, PGLs, and PSILs. The DSS of PDLs were significantly better than those of PGLs and PSILs, respectively (10-year survival rate: 21.24% vs. 20.40%, P=0.027; 10-year survival rate: 21.24% vs. 16.79%, P=0.001). Age, gender, Ann Arbor staging, and histological type were regarded as independent prognostic factor for the DSS by multivariate analysis (all P

The damage identification method based on macro-strain modality has shown good results for large-span flexible bridges. However, medium- and small-span bridges have a high stiffness, and the axle system is embodied. The strong time-varying vibration characteristics, coupled with the non-stationary characteristics of vehicle loads, make it difficult to accurately determine the stable strain modes of such bridges. To solve this problem, a damage localization index in the form of an amplitude vector matrix of the mutual energy density spectrum based on macro-strain was constructed using wavelet transform de-noising and reconstruction technology and cross-correlation function. The macro-static strain and macro-dynamic strain data obtained from a vehicle–bridge coupling experiment were reconstructed through wavelet transform, and the factors influencing the damage indices were analyzed. The results showed that the proposed indicators could help realize an accurate damage localization for medium- and small-span bridge systems with different damage degrees under the action of vehicle–bridge coupling.

The development of a successful vaccine, which should elicit a combination of humoral and cellular responses to control or prevent infections, is the first step in protecting against infectious diseases. A vaccine may protect against bacterial, fungal, parasitic, or viral infections in animal models, but to be effective in humans there are some issues that should be considered, such as the adjuvant, the route of vaccination, and the antigen-carrier system. While almost all licensed vaccines are injected such that inoculation is by far the most commonly used method, injection has several potential disadvantages, including pain, cross contamination, needlestick injury, under- or overdosing, and increased cost. It is also problematic for patients from rural areas of developing countries, who must travel to a hospital for vaccine administration. Noninvasive immunizations, including oral, intranasal, and transcutaneous administration of vaccines, can reduce or eliminate pain, reduce the cost of vaccinations, and increase their safety. Several preclinical and clinical studies as well as experience with licensed vaccines have demonstrated that noninvasive vaccine immunization activates cellular and humoral immunity, which protect against pathogen infections. Here we review the development of noninvasive immunization with vaccines based on live attenuated virus, recombinant adenovirus, inactivated virus, viral subunits, virus-like particles, DNA, RNA, and antigen expression in rice in preclinical and clinical studies. We predict that noninvasive vaccine administration will be more widely applied in the clinic in the near future.

FXIa is suggested as a major target for anticoagulant drug discovery because of reduced risk of bleeding. In this paper, we defined 5-phenyl-1H-pyrazole-3-carboxylic acid derivatives as privileged fragments for FXIa inhibitors’ lead discovery. After replacing the (E)-3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylamide moiety in compound 3 with 5-(3-chlorophenyl)-1H-pyrazole-3-carboxamide, we traveled from FXIa inhibitor 3 to a scaffold that fused the privileged fragments into a pharmacophore for FXIa inhibitors. Subsequently, we synthesized and assessed the FXIa inhibitory potency of a series of 5-phenyl-1H-pyrazole-3-carboxamide derivatives with different P1, P1′ and P2′moiety. Finally, the SAR of them was systematically investigated to afford the lead compound 7za (FXIa Ki = 90.37 nM, 1.5× aPTT in rabbit plasma = 43.33 μM) which exhibited good in vitro inhibitory potency against FXIa and excellent in vitro coagulation activities. Furthermore, the binding mode of 7za with FXIa was studied and the results suggest that the 2-methylcyclopropanecarboxamide group of 7za makes 2 direct hydrogen bonds with Tyr58B and Thr35 in the FXIa backbone, making 7za binds to FXIa in a highly efficient manner.

Jia-Jie Wang, Zhichao Zheng, Ying Zhang Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Ying Zhang, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China, Tel +86 18960810771, Email just4zhangying@hotmail.com; doctorzhangying@gdph.org.cnBackground: Metabolic dysfunction-associated steatotic liver disease (MASLD) increases the risk of cardiovascular disease and existing evidence indicates that MASLD affects the cardiovascular system through systemic inflammation. Our aim was to assess the association of hematological biomarkers of inflammation with the 10-year risk of major adverse cardiovascular events (MACE) and all-cause mortality in MASLD patients.Methods: A total of 1858 MASLD participants from the Atherosclerosis Risk in Communities cohort study at visit 2 (1990– 1992) were included. A total of 1338 non-MASLD participants were also included in the comparison. At baseline, hematological biomarkers of inflammation such as leukocytes, neutrophils, lymphocytes, monocytes, and C-reactive protein (CRP) were measured. Participants were followed up for MACE and all-cause mortality for a period of 10 years. Multivariate adjusted Cox models were used to estimate hazard ratios (HR).Results: The 10-year MACE was higher in MASLD participants than in non-MASLD participants (20.8% vs 9.3%). Monocytes (HR 1.114, [95% CI, 1.022– 1.216] per 1-SD, P=0.015) and CRP (HR 1.109 [95% CI, 1.032– 1.190] per 1-SD, P=0.005) were associated with an increased 10-year risk of MACE, independent of other cardiovascular risk factors. This association was specific to the MASLD population. None of these hematological biomarkers demonstrated a significant association with 10-year all-cause mortality.Conclusion: Increased levels of monocytes and CRP were associated with an increased 10-year risk of MACE in the MASLD population. Hematological biomarkers of inflammation may help identify MASLD populations at higher risk for cardiovascular events.Keywords: MASLD, biomarkers, inflammation, cardiovascular