Search

Low back pain (LBP) is a major public health problem worldwide and a significant health and economic burden. Intervertebral disc degeneration (IDD) is the reason for LBP. However, we have not identified effective therapeutic strategies to address this challenge. With accumulating knowledge on the role of circular RNAs in the pathogenesis of IDD, we realised that circular RNAs (circRNAs) may have tremendous therapeutic potential and clinical application prospects in this field. This review presents an overview of the current understanding of characteristics, classification, biogenesis, and function of circRNAs and summarises the protective and detrimental circRNAs involved in the intervertebral disc that have been studied thus far. This review is aimed to help researchers better understand the regulatory role of circRNAs in the progression of IDD, reveal their clinical therapeutic potential, and provide a theoretical basis for the prevention and targeted treatment of IDD.

Transboundary forests in the Himalayas are one of the world’s biodiversity hotspots, but exploring the patterns and influencing factors related to forest disturbance-recovery is still limited. In this study, we used a random forests model, a LandTrendr temporal segmentation algorithm and geographical detector to investigate the spatial and temporal evolution characteristics of forest disturbance and recovery and their influencing factors in the central Himalayas from 1995 to 2018. The results showed that forest disturbance was dominant (∼2.94 × 104 km2) and greater than recovery (∼0.56 × 104 km2). Both disturbance and recovery showed a significant decreasing trend (p

Background: Eurycomanone (EN) is a diterpenoid compound isolated from the roots of Eurycoma longifolia (E. longifolia). Previous studies have confirmed that E. longifolia can enhance bone regeneration and bone strength. We previously isolated and identified ten quassinoids from E. longifolia, and the result displayed that five aqueous extracts have the effects on promotion of bone formation, among whom EN showed the strongest activity. However, the molecular mechanism of EN on bone formation was unknown, and we further investigated in this study. Methods: After the verification of purity of extracted EN, following experiments were conducted. Firstly, the pharmacologic action of EN on normal bone mineralization and the therapeutic effect of EN on Dex-induced bone loss using zebrafish larvae. The mineralization area and integral optical density (IOD) were evaluated using alizarin red staining. Then the vital signaling pathways of EN relevant to OP was identified through network pharmacology analysis. Eventually in vitro, the effect of EN on cell viability, osteogenesis activities were investigated in human bone marrow mesenchymal stem cells (hMSCs) and C3H10 cells, and the molecular mechanisms by which applying AKT inhibitor A-443654 in hMSCs. Results: In zebrafish larvae, the administration in medium of EN (0.2, 1, and 5 μM) dramatically enhanced the skull mineralization area and integral optical density (IOD), and increased mRNA expressions of osteoblast formation genes (ALP, RUNX2a, SP7, OCN). Meanwhile, exposure of EN remarkably alleviated the inhibition of bone formation induced by dexamethasone (Dex), prominently improved the mineralization, up-regulated osteoblast-specific genes and down-regulated osteoclast-related genes (CTSK, RANKL, NFATc1, TRAF6) in Dex-treated bone loss zebrafish larvae. Network pharmacology outcomes showed the MAPK and PI3K-AKT signaling pathways are closely associated with 10 hub genes (especially AKT1), and AKT/GSK-3β/β-catenin was selected as the candidate analysis pathway. In hMSCs and C3H10 cells, results showed that EN at appropriate concentrations of 0.008–5 μM effectively increased the cell proliferation. In addition, EN (0.04, 0.2, and 1 μM) significantly stimulated osteogenic differentiation and mineralization as well as significantly increased the protein phosphorylation of AKT and GSK-3β, and expression of β-catenin, evidencing by the results of ALP and ARS staining, qPCR and western blotting. Whereas opposite results were presented in hMSCs when treated with AKT inhibitor A-443654, which effectively inhibited the pro-osteogenesis effect induced by EN, suggesting EN represent powerful potential in promoting osteogenesis of hMSCs, which may be closely related to the AKT/GSK-3β/β-catenin signaling pathway. Conclusions: Altogether, our findings indicate that EN possesses remarkable effect on bone formation via activating AKT/GSK-3β/β-catenin signaling pathway in most tested concentrations. The translational potential of this article: This study demonstrates EN is a new effective monomer in promoting bone formation, which may be a promising anabolic agent for osteoporosis (OP) treatment.

The development of coalbed methane resources in China has broad prospects, and the evolution process of coalbed water and its transportation law has important impacts on coalbed methane production capacity. This paper clarifies the composition, properties, sources and isotopic chronology of coal reservoir water, analyzes the expansion law of the pressure drop funnel and the inter-well interference mechanism during the water transport process, discusses the reservoir damage that may be caused by the water transport during drainage, and puts forward several suggestions for coalbed methane development according to the evolution of coal reservoir water and its transport and migration law during production. The results show that: (1) coal reservoir water is originated from primary sedimentary water, infiltration water, deep-forming water and diagenetic water, and the sodium-chlorine coefficient (rNa+/rCl−), Scholler coefficient (IBE), and mineralization degree of the original sedimentary water is0.129, and >10000 mg/L, respectively; corresponding values of infiltration water are the opposite of these relations; the δD and δ18O of deep-forming water is ranged from −80‰ to+40‰ and +7‰ to +9.5 ‰, respectively; the δD and δ18O of diagenetic water is ranged from −65‰ to −20‰ and +5‰ to+25‰, respectively; (2) the geochemical characteristics of coal reservoir water have important indicative significances for the enrichment and development of coalbed methane, and the high gas-containing areas of coalbed methane usually have the characteristics of low sodium-chlorine coefficient, low desulfurization coefficient, low magnesium-calcium coefficient, and high degree of metamorphism, correspondingly, the low gas-containing areas have the opposite characters; (3) the pressure drop funnel propagation during coal reservoir water transport and migration and the interference between wells are conducive to improve the coalbed methane production, and most of the coalbed methane wells in China are deployed by rectangular or diamond-shaped well networks, and the optimal well space is usually ranged between 250m and 400m; (4) the water transport of coal reservoirs can cause pulverized coal to block the formation, water lock damage, water sensitive damage, and velocity sensitive damage. To reduce reservoir damage, implementing reasonable drainage strength, optimizing the well network, and adding waterproof locking agent and pulverized coal dispersant to the incoming fluid are suggested. The research results can provide a certain theoretical basis for improving the exploration efficiency and coalbed methane yield in China.

The current article is concerned with the traveling fronts for a class of double degenerate equations with delay. We first show that the traveling fronts decay algebraically at one end, while those may decay exponentially or algebraically at the other end, which depend on the wave speed of traveling fronts. Based on the asymptotical behavior, the uniqueness and stability of traveling fronts are then proved. Of particular interest is the effect of the lower order term and higher order term on the critical speed. We mention that, under the double degenerate case, the nonlinear reaction is less competitive due to the appearance of degeneracy. This yields that the critical speed depends on the lower order term and higher order term, which is different from the nondegenerate case.

Abstract Background Acute coronary syndrome(ACS) is the leading cause of mortality and disability worldwide. Immune response has been confirmed to play a vital role in the occurrence and development of ACS. The objective of this prospective, multicenter, observational study is to define immune response and their relationship to the occurrence and progressive of ACS. Methods This is a multicenter, prospective, observational longitudinal cohort study. The primary outcome is the incidence of major adverse cardiovascular events (MACE) including in-stent restenosis, severe ventricular arrhythmia, heart failure, recurrent angina pectoris, and sudden cardiac death, and stroke one year later after ACS. Demographic characteristics, clinical data, treatments, and outcomes are collected by local investigators. Furthermore, freshly processed samples will be stained and assessed by flow cytometry. The expression of S100A4, CD47, SIRPα and Tim-3 on monocytes, macrophages and T cells in ACS patients were collected. Follow-up: during hospitalization, 3, 6 and 12 months after discharge. Discussion It is expected that this study will reveal the possible targets to improve the prognosis or prevent from occurrence of MACE in ACS patients. Since it’s a multicenter study, the enrollment rate of participants will be accelerated and it can ensure that the collected data are more symbolic and improve the richness and credibility of the test basis. Ethics and dissemination This study has been registered in Chinese Clinical Trial Registry Center. Ethical approval was obtained from the Affiliated Hospital of Guizhou Medical University. The dissemination will occur through the publication of articles in international peer-reviewed journals. Trial Registration Chinese Clinical Trial Registry: ChiCTR2200066382.

Abstract Mitochondria are hubs where bioenergetics, redox homeostasis, and anabolic metabolism pathways integrate through a tightly coordinated flux of metabolites. The contributions of mitochondrial metabolism to tumor growth and therapy resistance are evident, but drugs targeting mitochondrial metabolism have repeatedly failed in the clinic. Our study in pancreatic ductal adenocarcinoma (PDAC) finds that cellular and mitochondrial lipid composition influence cancer cell sensitivity to pharmacological inhibition of electron transport chain complex I. Profiling of patient-derived PDAC models revealed that monounsaturated fatty acids (MUFAs) and MUFA-linked ether phospholipids play a critical role in maintaining ROS homeostasis. We show that ether phospholipids support mitochondrial supercomplex assembly and ROS production; accordingly, blocking de novo ether phospholipid biosynthesis sensitized PDAC cells to complex I inhibition by inducing mitochondrial ROS and lipid peroxidation. These data identify ether phospholipids as a regulator of mitochondrial redox control that contributes to the sensitivity of PDAC cells to complex I inhibition.

Combustion of agricultural organic solid waste (AOSW) was an ideal solution for their resource utilization in view of their massive annual production and great potential for reduction of fossil fuel utilization. However, high alkali and alkaline earth metals (AAEMs) content in the feedstock can arose severe fouling and slagging issues and thus prohibiting its vast utilization. In this study, a semi-continuous water washing method was proposed to preliminarily remove AAEMs from agricultural organic solid waste and its effects on the combustion behaviors of washed solid product were investigated. Results showed that the combustion index S were improved to 2.63 × 10-6, over 68 % of the total ashes were removed from the cotton stalk, and 96.3 %, 89.0 % and 74.7 % of K, Na and Mg were effectively removed, respectively. Moreover, the softening temperature of low temperature ash from the washed sample was as high as 1450 °C, 538 °C higher than the low temperature ash from the original sample; the base acid ratio and fouling index were improved from high slagging and fouling risk (1.7 and 90.8) of the original organic solid waste to low and medium risk (0.4 and 3.5), respectively. All these results signified the contributing effect of proposed semi-continuous water washing method on the combustion of agricultural organic solid waste. In a word, this study provided a promising method for fouling and slagging inhibition during the agricultural organic solid waste combustion.

Oversampling techniques are widely used to rebalance imbalanced datasets. However, most of the oversampling methods may introduce noise and fuzzy boundaries for dataset classification, leading to the overfitting phenomenon. To solve this problem, we propose a new method (FSDR-SMOTE) based on Random-SMOTE and Feature Standard Deviation for rebalancing imbalanced datasets. The method first removes noisy samples based on the Tukey criterion and then calculates the feature standard deviation reflecting the degree of data discretization to detect the sample location, and classifies the samples into boundary samples and safety samples. Secondly, the K-means clustering algorithm is employed to partition the minority class samples into several sub-clusters. Within each sub-cluster, new samples are generated based on random samples, boundary samples, and the corresponding sub-cluster center. The experimental results show that the average evaluation value obtained by FSDR-SMOTE is 93.31% (93.16%, and 86.53%) in terms of the F-measure (G-mean, and MCC) on the 20 benchmark datasets selected from the UCI machine learning library.

Abstract Traumatic colon injury (TCI) is a typical injury with high mortality. Prolongation of the intervention time window is a potentially useful approach to improving the outcomes of TCI casualties. This study aimed to identify the pathological mechanisms of TCI and to develop effective strategies to extend the survival time. A semicircular incision was made to prepare a TCI model using C57BL/6 mice. An overview of microbiota dysregulation was achieved by metagenome sequencing. Protein expression reprogramming in the intestinal epithelium was investigated using proteomics profiling. The mice that were subjected to TCI died within a short period of time when not treated. Gut symbiosis showed abrupt turbulence, and specific pathogenic bacteria rapidly proliferated. The protein expression in the intestinal epithelium was also reprogrammed. Among the differentially expressed proteins, SERPINA3N was overexpressed after TCI modeling. Deletion of Serpina3n prolonged the posttraumatic survival time of mice with TCI by improving gut homeostasis in vivo. To promote the translational application of this research, the effects of melatonin (MLT), an oral inhibitor of the SERPINA3N protein, were further investigated. MLT effectively downregulated SERPINA3N expression and mitigated TCI‐induced death by suppressing the NF‐κB signaling pathway. Our findings prove that preventive administration of MLT serves as an effective regimen to prolong the posttraumatic survival time by restoring gut homeostasis perturbed by TCI. It may become a novel strategy for improving the prognosis of patients suffering from TCI.

BackgroundRetroperitoneal liposarcoma (RLS) is a rare but severe disease. Repeated postoperative recurrence with multiple tumors is a therapeutic dilemma. The clinical outcomes and survival predictors of recurrent RLS with multiple tumors remain to be explored.MethodsPatients with recurrent RLS were retrospectively analyzed. Univariate and multivariate analysis was performed to find independent prognostic factors that were correlated with Overall survival (OS) or progression-free survival (PFS). Factors significant in univariate analysis were further included into multivariate Cox proportional hazards regression model. The nomogram model was built to predict the survival status of patients. Variables that were significant in multivariable analysis were added to the internally validated nomogram models. The analysis of OS and PFS was performed by Kaplan–Meier analysis and log-rank test.ResultsA total of 113 recurrent RLS patients with multiple tumors were enrolled in the study. The 1-, 3-, and 5-years OS (PFS) rates were 70.7% (76.1%), 35.9% (76.1%), and 30.9% (76.1%), respectively. Univariate and multivariate analyses showed that number of surgeries, resection methods, tumor size, status of pathological differentiation, pathological subtypes, and recurrence patterns were important prognostic factors for OS or PFS (each p

Abstract Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) is refractory to heal mainly ascribed to the adverse remodeling of the penis induced by ineffectual microvascular perfusion, fibrosis, and neurotrophins scarcity in cavernosum. Phosphodiesterase type V inhibitors (PDE5i) have been regarded as an alternative candidate drug for avoiding penile neuropathy. However, the therapeutic efficacy is severely limited due to poor accumulation under systemic medication and endogenous nitric oxide (NO) deficiency in cavernosum. Herein, an innovative liposomal microbubble (MB) loaded with both Sildenafil (one of PDE5i) and NO was designed. Ultrasound‐targeted MB destruction (UTMD)‐mediated efficient release and integration erectogenic agents into corpus cavernosum with high biosafety. On a bilateral CNI rat model, the multifunctional MB‐cooperated UTMD improved microvascular perfusion in penis, simultaneously, alleviated hypoxia and oxidative stress, indicating successful activation of NO–cyclic guanosine monophosphate pathway. Also, evaluation of the endothelial/muscular composition, intracavernosal pressure, and neural integrity in the penis proved that coordinated intervention reversed the abnormal structural remodeling and promoted the recovery of functional erection. Our work demonstrates that MB loading Sildenafil and NO combined with UTMD hold great promise to “awaken” the efficacy of PDE5i in neurogenic ED, which provided a superior option for ensuring penile rehabilitation.

Abstract Background Health equity has persistently been a global concern. How to fairly and appropriately allocate health resources is a research hotspot. While Western China is relatively backward economically and presents difficulties for the allocation of health resources, little attention has been given to the equity of resource allocation there. This study analysed the equity of allocation of beds, physicians and nurses in Western China from 2014-2018 to provide targeted guidance for improving the equity of health resource allocation. Methods Data for 2014-2018 obtained from the Statistical Yearbook (2015-2019) of provinces (autonomous regions and municipalities) were used to analyse health resource allocation in terms of beds, physicians and nurses in Western China. The Lorenz curve and Gini coefficient were calculated to evaluate equity in the population dimension and geographic dimension. The Theil index was used to measure the inequity of the three indicators between minority and nonminority areas. Results The number of beds, physicians and nurses in Western China showed an increasing trend from 2014-2018. The Lorenz curve had a smaller curvature in the population dimension than in the geographic dimension. The Gini coefficients for health resources in the population dimension ranged from 0.044 to 0.079, and in the geographic dimension, the Gini coefficients ranged between 0.614 and 0.647. The above results showed that the equity of health resource allocation was better in the population dimension than in the geographic dimension. The Theil index ranged from 0.000 to 0.004 in the population dimension and from 0.095 to 0.326 in the geographic dimension, indicating that the inequity in health resource allocation was higher in the geographic dimension. The intergroup contribution ratios of the Theil index in both the population and geographic dimensions were greater than 60%, indicating that the inequity in resource allocation was mainly caused by intergroup differences, namely, the allocation of health resources within the province. Among them, the inequity of physicians and nurses allocation was the most obvious. Conclusions From 2014 to 2018, the total amount of health resources have improved in Western China. However, health resource allocation in Western China was still inequitable in the population and geographic dimensions, and the inequity of health resource allocation in the geographic dimension showed a tendency to worsen. Meanwhile, although the inequity of human recourse allocation was alleviated in 2018 compare with 2014, the inequity of human resource distribution within provinces was still obvious. The government can increase the number of health resources and improve the accessibility of health resources by increasing financial investment, strengthening humanistic care for health workers, and establishing internet hospitals.

Internet traffic is dramatically increasing with the development of network technologies and video streaming traffic accounts for large amount within the total traffic, which reveals the importance to guarantee the quality of content delivery service. Based on the network conditions, adaptive bitrate (ABR) control is utilized as a common technique which can choose the proper bitrate to ensure the video streaming quality. In this paper, new bitrate control method, QuDASH is proposed by taking advantage of the emerging quantum technology. In QuDASH, the adaptive control model is developed using the quadratic unconstrained binary optimization (QUBO), which aims at increasing the average bitrate and decreasing the video rebuffering events to maximize the user quality of experience (QoE). In order to formulate the video control model, first the QUBO terms of different factors are defined regarding video quality, bitrate change, and buffer condition. Then, all the individual QUBO terms are merged to generate an objective function. By minimizing the QUBO objective function, the bitrate choice is determined from the solution. The control model is solved by Digital Annealer, which is a quantum-inspired computing technology. The evaluation of the proposed method is carried out by simulation with the throughput traces obtained in real world under different scenarios and the comparison with other methods is conducted. Experiment results demonstrated that the proposed QuDASH method has better performance in terms of QoE compared with other advanced ABR methods. In 68.2% of the examined cases, QuDASH achieves the highest QoE results, which shows the superiority of the QuDASH over conventional methods.

Objective: To improve the prognosis of patients with gastric cancer (GC), more effective therapeutic targets are urgently needed. Increasing evidence indicates that miRNAs are involved in the progression of various tumors, and RAS-associated protein in the brain 31 (RAB31) is upregulated and promotes the progression of multiple malignant tumors. Here, we focused on identifying RAB31-targeted miRNAs and elucidating their potential mechanism in the progression of GC. Methods: RAB31 and miR-378a-3p expression levels were detected in paired fresh GC tissues and GC cell lines. Bioinformatics analysis was used to predict the miRNAs targeting RAB31 and the relationships between RAB31 and other genes. Dual-luciferase reporter assays were applied to verify the targeted interaction relationship. CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of GC cells. Tumorsphere formation assays were performed to assess the stemness of gastric cancer stem cells. Related proteins were detected by Western blot. Xenograft assays in nude mice were performed to explore the effect of miR-378a-3p in vivo. Results: We report the first evidence that miR-378a-3p is downregulated in GC, whereas its overexpression inhibits proliferation, invasion, and migration as well as promotes apoptosis in GC cells. Mechanistically, miR-378a-3p inhibits the progression of GC by directly targeting RAB31. Restoring RAB31 expression partially offsets the inhibitory effect of miR-378a-3p. Further research revealed that miR-378a-3p inhibits GLI1/2 in the Hedgehog signaling pathway and attenuates the stemness of gastric cancer stem cells. Finally, xenograft assays showed that miR-378a-3p inhibits GC tumorigenesis in vivo. Conclusions: MiR-378a-3p inhibits GC progression by directly targeting RAB31 and inhibiting the Hedgehog signaling pathway proteins GLI1/2.

Abstract Osteosarcoma (OS) is the most common primary malignant bone tumor in children and teenagers and is characterized by high malignant potential, rapid disease progression and high disability and mortality rates. Recently, noncoding RNAs (ncRNAs) have attracted the attention of many scholars due to their major regulatory roles in gene expression. Among them, lncRNA PVT1 and circPVT1 encoded by the PVT1 gene have been the focus of many studies; they are upregulated in OS, and abundant evidence indicates that lncRNA PVT1 and circPVT1 play key roles in the occurrence and development of OS. This review summarizes the mechanisms of action of lncRNA PVT1 and circPVT1 in regulating apoptosis, proliferation, glycolysis, invasion, migration and epithelial–mesenchymal transition (EMT) in OS and discusses their clinical applications in diagnosis, prognosis determination and drug resistance treatment, with the aim of helping researchers better understand the regulatory roles of lncRNA PVT1 and circPVT1 in OS progression and providing a theoretical basis for the development of early screening and accurate targeted treatment strategies and prognostic biomarkers for OS based on lncRNA PVT1 and circPVT1.

Abstract Background Gastric neuroendocrine neoplasm (g-NEN) is a rare but heterogeneous neoplasm, with an increasing incidence yearly. Conventional prognostic markers of g-NEN remain limited which could only be detected after surgery. There is an urgent need to explore new prognostic markers for g-NEN patients. This study aimed to investigate the prognostic value of platelet-to-lymphocyte, ratio (PLR) and the association between PLR and body mass index (BMI) in patients with gastric neuroendocrine neoplasms (g-NEN). Methods A retrospective cohort of patients with g-NEN from January 2001 through June 2016 was examined. The prognostic significance of PLR was determined by multiple regression analysis in different models. Stratified analysis was performed to examine the prognostic value of PLR at different BMI levels. Results In total, 238 patients were enrolled. Those with higher PLRs tended to undergo open surgery, had larger tumor sizes, were diagnosed more frequently with neuroendocrine carcinoma, and had higher tumor grades. PLR was significantly associated with the survival of patients with g-NEN. With PLR increased per standard deviation, the all-cause mortality risk of patients with g-NEN increased by 67%, 63%, and 54% in the crude (HR = 1.67, 95% CI 1.32–2.12, P < 0.001), minimally adjusted (HR = 1.63, 95% CI 1.28–2.08, P < 0.001), and fully adjusted (HR = 1.54, 95% CI 1.202–1.98, P = 0.001) models, respectively. Patients with higher PLR (quartile 4, ≥ 187) had a 1.8-fold increase in all-cause mortality risk compared with those with lower PLR (quartile 1–3, < 187). Furthermore, there was a significant interaction effect between BMI subgroups and PLR in predicting the survival of patients with g-NEN (PLR regarded as a continuous variable: all P for interaction < 0.05 in the crude, minimally adjusted, and fully adjusted models; PLR regarded as a categorical variable: P for interaction < 0.05 in the fully adjusted model). Patients with g-NEN with the characteristics of higher PLR (quartile 4, ≥ 187) and non-obesity (BMI < 25 kg/m2) had worse survival than others (P < 0.05). Conclusion The inflammation marker PLR has an independent prognostic value for patients with g-NENs, and high PLR combined with non-obesity increases the mortality risk of these patients.

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, a PPARα/γ target gene involved in tumor progression and chemoresistance, was significantly downregulated. Clinical analysis demonstrated a strong correlation between the protein levels of CES1 and SCD in HCC. Interference with lipid signaling by targeting the CES1-PPARα/γ-SCD axis sensitized HCC cells to cisplatin treatment. As a result, the growth of HCC xenograft tumors in NU/J mice was potently slowed by coadministration of cisplatin and CES1 inhibition. Our results, thus, suggest that CES1 is a promising therapeutic target for HCC treatment.

Real-time monitoring of microbial dynamics during fermentation is essential for wine quality control. This study developed a method that combines the fluorescent dye propidium monoazide (PMA) with CELL-qPCR, which can distinguish between dead and live microbes for Lactiplantibacillus plantarum. This method could detect the quantity of microbes efficiently and rapidly without DNA extraction during wine fermentation. The results showed that (1) the PMA-CELL-qPCR enumeration method developed for L. plantarum was optimized for PMA treatment concentration, PMA detection sensitivity and multiple conditions of sample pretreatment in wine environment, and the optimized method can accurately quantify 104–108 CFU/mL of the target strain (L. plantarum) in multiple matrices; (2) when the concentration of dead bacteria in the system is 104 times higher than the concentration of live bacteria, there is an error of 0.5–1 lg CFU/mL in the detection results. The optimized sample pretreatment method in wine can effectively reduce the inhibitory components in the qPCR reaction system; (3) the optimized PMA-CELL-qPCR method was used to monitor the dynamic changes of L. plantarum during the fermentation of Cabernet Sauvignon wine, and the results were consistent with the plate counting method. In conclusion, the live bacteria quantification method developed in this study for PMA-CELL-qPCR in L. plantarum wines is accurate in quantification and simple in operation, and can be used as a means to accurately monitor microbial dynamics in wine and other fruit wines.

BackgroundGuidelines widely recommend thyrotropin suppression to reduce the risk of recurrence in intermediate- and high-risk papillary thyroid cancer (PTC) after total thyroidectomy. However, an insufficient or excessive dosage may result in a number of symptoms/complications especially in older patients.Patients and methodsWe constructed a retrospective cohort including 551 PTC patient encounters. Using propensity score matching and logistic regression models, we determined the independent risk factors affecting levothyroxine therapy at different ages. Our outcomes included: expected TSH level and an unexpected TSH level, which was based on the initial thyroid-stimulating hormone (TSH) goal< 0.1 mIU/L with usual dosage of L-T4 (1.6 μg/kg/day).ResultsFrom our analysis, more than 70% of patients undergoing total thyroidectomy did not achieve the expected TSH level using an empirical medication regimen, and the effect of the drug was affected by age (odds ratio [OR], 1.063; 95% CI, 1.032-1.094), preoperative TSH level (OR, 0.554; 95% CI, 0.436-0.704) and preoperative fT3 level (OR, 0.820; 95% CI, 0.727-0.925). In patients with age < 55 years old, preoperative TSH level (OR, 0.588; 95% CI, 0.459-0.753), and preoperative fT3 level (OR, 0.859; 95% CI, 0.746-0.990) were two independent protective factors, while, in patients with age ≥ 55 years old, only preoperative TSH level (OR, 0.490; 95% CI, 0.278-0.861) was the independent protective factors to achieve expected TSH level.ConclusionOur retrospective analysis suggested the following significant risk factors of getting TSH suppression in PTC patients: age (≥55 years), lower preoperative TSH and fT3 levels.

Shale pore structure characterization is key to shale reservoir evaluation, sweet spot selection, and economic exploitation. It remains a challenge to accurately characterize shale micro-nano pores. Common experimental characterization methods for shale pore systems are listed, and advantages and weaknesses of each method are analyzed. An improved pore structure characterization method for shale is proposed by combining Helium and NMR. The new method does not affect shale samples and has a higher accuracy. The affecting factors for shale pore evolution for shale are also discussed, showing that organic matter content and maturity are key factors in total porosity development. Furthermore, a shale porosity–TOC maturity relationship chart is developed based on the experimental data of shale samples selected from six shale reservoirs. The application of this chart in Well X in the Gulong field of Songliao Basin proves its utility in evaluating shale reservoirs.

Abstract The rapid development of instant logistics services has brought not only convenience to people's life but also a great challenge to traffic management. Due to the limited delivery range of instant delivery systems, customers are usually recommended the meals nearby or pay much higher delivery fees for long‐distance delivery. This study proposes a novel order splitting strategy based on transfer stations for long‐distance meal orders to satisfy the diverse customer demands. The meal delivery routing problem is addressed with an order allocation strategy based on transfer stations through developing a three‐stage modelling framework consisting of order combination, splitting and delivery routing for the online‐to‐offline instant logistics services. Normal meal orders are combined by the DBSCAN algorithm, and the cross‐regional long‐distance orders are split by transfer stations. Based on order combination and splitting, a mixed integer programming model is constructed for the meal delivery routing problem and solved by the adaptive large neighbourhood search algorithm. The proposed algorithm converges quickly for the tested instances constructed based on real platform data. The proposed order allocation strategy can expand the delivery scopes of couriers effectively, stimulate more potential orders and guarantee the timeliness of meal delivery.

Abstract Objectives There are increasing numbers of studies of pleural tags (PTs). The purpose of this case series was to classify the PTs in patients with peripheral pulmonary adenocarcinoma based on radiologic-pathologic comparison and to study the prognosis. Methods The clinical, imaging, pathological and prognostic data of 161 patients with peripheral pulmonary adenocarcinoma in three hospitals were analyzed retrospectively. We classified PTs using computed tomography (CT) for pathologic comparison. Results According to the relationship between tumors and pleural on CT images, PTs were classified into four types: type 1, one or more linear pleural tag; type 2, one or more linear pleural tag with soft tissue component at the pleural end; type 3, one soft tissue cord-like pleural tag; type 4, directly abutting the visceral pleura, pulling or pushing the visceral pleura. In these PTs, the incidence of visceral pleural invasion (VPI) was high in type 2 (46.88%) and type 3 (56.41%) of PTs. Our prognostic analysis showed that micropapillary or solid histological subtype (HR = 5.766, 95% CI: 1.435–23.159, P = 0.014) and type 3 of PTs (HR = 11.058, 95% CI: 1.349–90.623, P = 0.025) were two independent risk factors for tumor progression. Conclusions PT is a risk factor for poor prognosis in patients with peripheral pulmonary adenocarcinoma, the presence of which on CT images can remind us to provide patients with a more reasonable treatment.

Military training is intense, difficult and often dangerous, so all kinds of injuries or diseases frequently occur during training. Most of the previous studies and reviews on military training-related injuries focused on musculoskeletal system, whereas there are no reviews of abdominal injuries and diseases. Although the incidence of military training-related abdominal injuries and diseases is relatively low, the patients’ condition is often critical especially in the presence of abdominal organ injury, leading to multi-organ dysfunction syndrome and even death. This paper elaborates on common types of military training-related abdominal injuries and diseases as well as the prevention and treatment measures, which provides some basis for scientific and reasonable training and improvement of medical security.

Abstract Background Traumatic colon injury (TCI) is a common disease during wartime. Prolongation of posttraumatic survival time is an effective approach to patient outcome improvement. However, there is a lack of basic research in this field. This study aimed to elucidate the mechanisms underlying TCI progression and to develop novel regimens to buy time for TCI patients on the battlefield. Methods A total of 669 Sprague–Dawley rats were used in this study. Surgical colon incision was performed to generate the TCI rat model. The landscape of colon microbiota compositions was depicted using 16S rRNA sequencing and metabolites in the intestinal contents were detected by metabolomics profiling. The signaling transduction in the intestinal epithelium was investigated using antibody microarrays and Western blotting. The enzyme-linked immunosorbent assay was conducted to measure the levels of interleukin-6 and tumor necrosis factor-α in intestines and plasma for the detection of inflammatory responses. Diamine oxidase, D-lactate and endotoxin in plasma and protein expression of zonula occludens 1 and occludin were selected as the indicators of intestinal barrier permeability. To investigate alterations of microbiota symbiosis, the relative abundances of specific bacterial genera were detected using quantitative real-time PCR. Results As a type of lethal injury, TCI induced acute disruption of intestinal homeostasis, characterized by inflammatory responses, intestinal barrier hyperpermeability and microbiota dysbiosis (P

Abstract Background Increasing evidence associates air pollution with thyroid dysfunction, whereas the potential relationship between exposure to ozone (O3) and Thyroid Nodules (TNs) is unclear. Methods This retrospective cohort study investigated the association between O3 exposure and TNs in Hunan province, enrolling 191,357 Chinese adults who lived in Hunan province from January 2009 to December 2019 and received voluntary medical examinations. Individual exposure levels to O3 from 2010 to 2019 were measured on account of participants’ residential addresses at the district level. Associations of O3 exposure with the risk of incidental TNs were assessed by restricted cubic splines and surveyed as odds ratios after adjusting for demographic factors. Results In total, 81,900 adults were newly diagnosed with TNs during the study period. Age-standardized TNs detection rate in Hunan province increased from 25.9 to 46.3% between 2010 and 2019, with the greatest annual percent change being 8.1 [95% CI, 7.3–8.8]. A similar trend has been found in all tumor sizes, ages, and both sexes. O3 exposure presented a statistically significant dose-dependent positive correlation (greater than 0.036 ppm) with TNs. Similarly, long-term exposure to high levels of O3 (1-year average O3 concentrations exceeding 0.0417 ppm) was found positively associated with increased TSH levels. Conclusions High-level O3 exposure in the long term was associated with an increase in TSH. Consequently, increased TSH was related to the increased risk of TNs. Being exposed to high-level O3 in the long term was related to the increased detection rates of TNs in Hunan province, which could be mediated by TSH.

To clarify the influence of yellow multicrystal rock sugar on the yield of jasmine flavor syrup, the jasmine flowers from Hengxian County, Guangxi Province were taken as raw materials, jasmine flavor syrup by impregnating jasmine flowers with yellow multicrystal rock sugar was prepared at low temperature in this paper. Taking the yield of jasmine flavor syrup as an indicator, on the basis of single-factor experiments, response surface analysis (RSM) was used to determine the optimal preparation process of flavor syrup. And the quality of the obtained jasmine flavor syrup was analyzed. Results showed that, the optimal conditions were: Impregnation time was 130.0 h, the mass ratio of flowers to sugar was 1:1.2 g/g, and the size of yellow multicrystal rock sugar was 0.780 mm through 21 mesh sieve. Under these conditions, the maximum yield of jasmine flavor syrup was 39.82%. RSM predicted that the order of the influence of various factors on the yield of jasmine flavor syrup as follows: Impregnation time > the mesh of yellow multicrystal rock sugar > the mass ratio of flower sugar. Through the experiment, the jasmine flavor syrup with high soluble solid content, moderate acidity, low water content, bright color, containing jasmine's natural flavor, color and some thermal nutrients, high flavor peak and pure syrup taste was obtained, which met the sensory requirements of concentrated liquid (juice and slurry) for national food industry.

BackgroundIncreasing evidence suggests that insulin resistance is linked to cardiovascular disease and atherosclerosis. The triglyceride–glucose (TyG) index has proven to be a convincing marker to quantitatively evaluate insulin resistance. However, there is no relevant information about the relationship between the TyG index and restenosis after carotid artery stenting.MethodsA total of 218 patients were enrolled. Carotid ultrasound and computed tomography angiography were used to evaluate in-stent restenosis. A Kaplan–Meier analysis and Cox regression method were performed to analyze the correlation between TyG index and restenosis. Schoenfeld residuals were used to determine the proportional-hazards assumption. A restricted cubic spline method was used to model and visualize the dose–response relationship between the TyG index and the risk of in-stent restenosis. Subgroup analysis was also performed.ResultsThirty-one participants (14.2%) developed restenosis. The preoperative TyG index had a time-varying effect on restenosis. Within 29 months post-surgery, an increasing preoperative TyG index was linked to a significant increased risk of restenosis (hazard ratio: 4.347; 95% confidence interval 1.886–10.023). However, after 29 months, the effect was decreased, although not statistically significant. The subgroup analysis showed that the hazard ratios tended to be higher in the age ≤ 71 years subgroup (p

Abstract Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract

Oxide-derived copper has been extensively studied as catalysts for CO2 electroreduction but its catalytic stability and selectivity still need to be improved. Here, the authors report ultrathin CuO nanoplate arrays for CO2 reduction with high ethylene selectivity and enhanced long-term stability.

Dispersants, serving as an essential raw material in the formulation of coal water slurry, offer an economical and convenient solution for enhancing slurry concentration, thus stimulating significant interest in the development of novel and efficient dispersants. This paper intends to illuminate the evolution of dispersants by examining both the traditional and the newly conceived types and elaborating on their respective mechanisms of influence on slurry performance. Dispersants can be classified into anionic, cationic, amphoteric, and non-ionic types based on their dissociation properties. They can be produced by modifying either natural or synthetic products. The molecular structure of a dispersant allows for further categorization into one-dimensional, two-dimensional, or three-dimensional structure dispersants. This document succinctly outlines dispersants derived from natural products, three-dimensional structure dispersants, common anionic dispersants such as lignin and naphthalene, and amphoteric and non-ionic dispersants. Subsequently, the adsorption mechanism of dispersants, governed by either electrostatic attraction or functional group effects, is elucidated. The three mechanisms through which dispersants alter the surface properties of coal, namely the wetting dispersion effect, electrostatic repulsion effect, and steric hindrance effect, are also explained. The paper concludes with an exploration of the challenges and emerging trends in the domain of dispersants.

Malaria is listed as one of the three most hazardous infectious diseases worldwide. Travelers and migrants passing through exit and entry ports are important sources of malaria pandemics globally. Developing accurate and rapid detection technology for malaria is important. Here, a novel hairpin-mediated amplification (HMA) technique was proposed for the detection of four Plasmodium species, including P. falciparum, P. vivax, P. malariae, and P. ovale. Based on the conserved nucleotide sequence of Plasmodium, specific primers and probes were designed for the HMA process, and the amplicon can be detected using lateral flow detection (LFD); the results can be read visually without specialized equipment. The specificity of HMA-LFD was evaluated using nucleic acids extracted from four different Plasmodium species and two virus species. The sensitivity of HMA-LFD was valued using 10× serial dilutions of plasmid containing the template sequence. Moreover, 78 blood samples were collected to compare HMA-LFD and qPCR. The HMA-LFD results were all positive for four different Plasmodium species and negative for the other two virus species. The sensitivity of HMA-LFD was tested to be near five copies/μL. The analysis of clinical samples indicated that the consistency of HMA-LFD and qPCR was approximately 96.15%. Based on these results, the HMA-LFD assay was demonstrated to be a rapid, sensitive, and specific technique for the detection of Plasmodium and has great advantages for on-site detection in low-resource areas and exit and entry ports.

Mycoplasma pneumoniae (M. pneumoniae) is an atypical bacterial pathogen responsible for community-acquired pneumonia primarily among school-aged children and young adults. Camellia oleifera (C. oleifera) has been used as a medicinal and edible plant in China for centuries, the constituents from which possessed various bioactivities. Notably, flavonoids existing in residues of C. oleifera defatted seeds exhibited significant anti-inflammatory activities. In the present study, we investigated the impact of total flavonoids from C. oleifera (TFCO) seed extract on M. pneumoniae pneumonia. TFCO was obtained using multiple column chromatography methods and identified as kaempferol glycosides via UPLC-HRESIMS. In a M. pneumoniae pneumonia mouse model, TFCO significantly reduced the lung damage, suppressed IL-1β, IL-6, and TNF-α production, and curbed TLR2 activation triggered by M. pneumoniae. Similarly, in RAW264.7 macrophage cells stimulated by lipid-associated membrane proteins (LAMPs), TFCO suppressed the generation of proinflammatory cytokines and TLR2 expression. Moreover, TFCO diminished the phosphorylation of IκBα, JNK, ERK, p38, and p65 nuclear translocation in vitro. In conclusion, TFCO alleviated M. pneumoniae-induced lung damage via inhibition of TLR2-mediated NF-κB and MAPK pathways, suggesting its potential therapeutic application in M. pneumoniae-triggered lung inflammation.

Due to the characteristics of multibody (MB) and finite element (FE) digital human body models (HBMs), the reconstruction of running pedestrians (RPs) remains a major challenge in traffic accidents (TAs) and new innovative methods are needed. This study presents a novel approach for reconstructing moving pedestrian TAs based on a humanoid robot method to improve the accuracy of analyzing dynamic vehicle–pedestrian collision accidents. Firstly, we applied the theory of humanoid robots to the corresponding joints and centroids of the TNO HBM and implemented the pedestrian running process. Secondly, we used rigid–flexible coupling HBMs to build pedestrians, which can not only simulate running but also analyze human injuries. Then, we validated the feasibility of the RP reconstruction method by comparing the simulated dynamics with the pedestrian in the accident. Next, we extracted the velocity and posture of the pedestrian at the moment of collision and further validated the modeling method through a comparison of human injuries and forensic autopsy results. Finally, by comparing two other cases, we can conclude that there are relative errors in both the pedestrian injury results and the rest position. This comparative analysis is helpful for understanding the differences in injury characteristics between the running pedestrian and the other two cases in TAs.

Studying the soil temperature field and its variation law is of great significance to the real-time service of agricultural production. To solve the problems of low detection efficiency and difficulty of distributed detection, a distributed detection method of soil temperature field using wavelength division multiplexing and space division multiplexing technologies based on fiber Bragg grating (FBG) sensor is proposed. In this scheme, the stainless steel tube encapsulating the FBG string was vertically buried in the measured soil, and the tunable laser method and the peak-seeking algorithm were used to demodulate the wavelength of each sensor of the FBG string. The soil temperature field measurement experiments were carried out in the farmland environment. The experimental results show that the proposed method can detect the soil temperature field in real time. The internal temperature of soil changes periodically with the periodic change of surface environment temperature. With the increase of depth, the influence of surface temperature on soil temperature gradually decreases, and the amplitude of soil temperature oscillation gradually decreases, but the hysteresis effect of temperature peak becomes more and more obvious. The ambient wind speed can reduce the temperature of soil surface and shallow layer. Soil moisture affects the speed of temperature transfer from the surface layer to the deep layers, and the hysteresis effect of temperature peak is more significant in the soil with higher moisture. Solar radiation has a great influence on the temperature of soil surface and shallow layer.

Visualizing cellular structures especially the cytoskeleton and the nucleus is crucial for understanding mechanobiology, but traditional fluorescence staining has inherent limitations such as phototoxicity and photobleaching. Virtual staining techniques provide an alternative approach to addressing these issues but often require substantial amount of user training data. In this study, we develop a generalizable cell virtual staining toolbox (termed CellVisioner) based on few-shot transfer learning that requires substantially reduced user training data. CellVisioner can virtually stain F-actin and nuclei for various types of cells and extract single-cell parameters relevant to mechanobiology research. Taking the label-free single-cell images as input, CellVisioner can predict cell mechanobiological status (e.g., Yes-associated protein nuclear/cytoplasmic ratio) and perform long-term monitoring for living cells. We envision that CellVisioner would be a powerful tool to facilitate on-site mechanobiological research.

Medulloblastoma is one of the most frequent malignant brain tumors in infancy and childhood. Early diagnosis and treatment are quite crucial for the prognosis. However, the pathogenesis of medulloblastoma is still not completely clarified. High-resolution mass spectrometry has enabled a comprehensive investigation on the mechanism of disease from the perspective of metabolism. Herein, we compared the difference of metabolic profiles of serum between medulloblastoma (n = 33) and healthy control (HC, n = 16) by using UPLC-Q/E-MS/MS. Principal component analysis and orthogonal projections to latent structures discriminant analysis (OPLS-DA) intuitively revealed the significantly distinct metabolic profiles between medulloblastoma and HC (p < 0.01 for permutation test on OPLS-DA model). Total of 25 significantly changed metabolites were identified. ROC analysis reported that six of them (Phosphatidic acid (8:0/15:0), 3'-Sialyllactose, Isocoproporphyrin, Acetylspermidine, Fructoseglycine and 3-Hydroxydodecanedioate) showed high specificity and precision to be potential diagnosis biomarkers (AUC > 0.98). Functional analysis discovered that there are four pathways notably perturbed for medulloblastoma. These pathways are related with the dysfunction of arachidonic acid metabolism, steroid hormone biosynthesis, and folate-related metabolism. The target intervention on these pathways may reduce the mortality of medulloblastoma.

BackgroundImmune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment.MethodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs).ResultsA total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%–25.5%] and 44.0% (95% CI, 34.1%–53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%–94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%–66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%–99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)].ConclusionThis systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population.

IntroductionAvailable phosphorus (P) scarcity in the highly weathered soils of the subtropical forests in southern China is a serious concern. To ensure whether inoculation of arbuscular mycorrhizal fungi (AMF) with Chinese fir (Cunninghamia lanceolata) under low P stress conditions could promote its growth and P utilization capacity, an indoor pot simulation experiment was carried out with the different P supply treatments and Chinese fir seedlings as the tested material.MethodsThe experiment had two P supply treatments, no P supply (P0, 0 mmol·L-1 KH2PO4) and normal P supply (P1, 1.0 mmol·L-1 KH2PO4). The seedling in each P supply treatment was inoculated with Glomus intraradices (Gi), a widespread species of AMF in the natural environment, and with no AMF inoculation as a control treatment (CK). The Gi infection rate in the root system, root cortex tissue dissolution rate, root morphological indexes and biomass, whole plant P use efficiency, and root P use efficiency of Chinese fir were determined under different treatment conditions.Results and DiscussionThe results showed that P0 treatment significantly increased the Gi infection rate (p< 0.05). After inoculating AMF with different P supply treatments, the root cortex tissue dissolution rate was considerably enhanced. In contrast, the Chinese fir’s root length and surface area were reduced; however, the root volume did not change significantly. The average root diameter in the P0 treatment and inoculated with AMF was significantly more prominent than in the uninoculated treatment (p< 0.05). The root biomass and root-to-shoot ratio at different P supply treatments were significantly higher in the Gi infection treatment than in the CK group. Under different P supply treatments, root inoculation with Gi promoted root P use efficiency and whole plant P use efficiency. In conclusion, low P stress condition promoted the colonization of AMF in the root system, increased the dissolution of root cortex tissue, root volume, and the average diameter, and promoted root biomass accumulation and P use efficiency.

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized metastatic melanoma (MM) treatment in just a few years. Ultraviolet (UV) in sunlight is the most significant environmental cause of melanoma, which is considered to be the main reason for tumor mutation burden (TMB) increase in melanoma. High TMB usually predicts that PD-1 inhibitors are effective. The sunlight exposure pattern of MM might be a clinical feature that matches TMB. The relationship between sunlight exposure patterns and immunotherapy response in MM is unclear. This study aims to investigate the correlation between sunlight exposure patterns and immunotherapy response in MM and establish nomograms that predict 3- and 5-year overall survival (OS) rate.MethodsWe searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled MM cases from 2005-2016. According to the advent of ICIs in 2011, the era was divided into the non-ICIs era (2005-2010) and the ICIs era (2011-2016). Patients were divided into three cohorts according to the primary site sunlight exposure patterns: head and neck in the first cohort, trunk arms and legs in the second cohort, and acral sites in the third cohort. We compared survival differences for each cohort between the two eras, performed stratified analysis, established nomograms for predicting 3- and 5-year OS rate, and performed internal validation.ResultsComparing the survival difference between the ICIs and non-ICIs era, head and neck melanoma showed the greatest improvement in survival, with 3- and 5-year OS rate increasing by 10.2% and 9.1%, respectively (P=0.00011). In trunk arms and legs melanoma, the 3- and 5-year OS rate increased by 4.6% and 3.9%, respectively (P

Purpose: To evaluate the early response of chemoradiotherapy (CRT) in nasopharyngeal carcinoma (NPC) based on intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional pseudo-continuous arterial spin labeling (3D pCASL). Materials and methods: Forty patients diagnosed with NPC were recruited and divided into complete remission (CR) and partial remission (PR) group after CRT. All patients underwent IVIM and ASL and the related parameters was obtained. These parameters include pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), average blood flow ( BFavg), minimum blood flow (BFmin), and maximum blood flow (BFmax). Student’s t test was used to compare the difference in ASL and IVIM derived parameters between CR and PR. The Areas under curve (AUC) of the receiver operating characteristic (ROC) was used to analyze the diagnostic performance of each parameter of ASL and IVIM to the treatment outcome. Results: the D value of IVIM in CR group was lower than that of the PR group ( P = 0.014),. Among the parameters of ASL, the BFavg and BFmax of the CR group were higher than those of the PR group(p = 0.004,0.013), but the BFmin had no statistical significance in the two groups（P = 0.54）. AUC of D, BFavg, and BFmax is about 0.731, 0.753, and 0.724, respectively, all of their combined AUC diagnosis was 0.812. Conclusion: The early response of NPC after CRT can predict by IVIM’s diffusion parameters and ASL-related blood flow parameters.

Abstract Purpose Marital status has emerged as an important influence on several cancer outcomes, but its role in medullary thyroid cancer (MTC) remains unclear. This study was to explore the effects of marital status on the prognosis of MTC patients and to determine whether its effects vary by age. Patients and methods We retrospectively extracted 1344 eligible patients diagnosed with MTC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the marital status, we divided those patients into married and unmarried groups. We compared the difference in overall survival (OS) and cancer‐specific survival (CSS) between married and unmarried via the Kaplan–Meier analysis. Univariate and multivariate Cox proportional models were performed to identify the prognostic factors of OS and CSS. Results There were 1344 MTC eligible patients in a total of which 883 (65.7%) were married and 461 (34.3%) were unmarried. The comparison observed between married and unmarried patients was as follows: male (45.2% vs. 28.0%), age (≥52 years) (55.9% vs. 44.6%), White (86.7% vs. 78.7%), and undergo surgery (97.7% vs. 93.3%). Multivariate analysis revealed unmarried status as a risk factor independently associated with worse OS (HR: 2.15, 95% CI: 1.59–2.92) rate and CSS (HR: 1.70, 95% CI: 1.17–2.47) rate. In a further analysis stratified by age, there was no significant difference in OS and CSS between married and unmarried patients younger than 52 years. For the remaining group with 52 years old and higher, unmarried patients showed significantly higher risk of OS and CSS than married patients at all stages of the pathology except M1 stage. Conclusion Married patients with MTC have a better prognosis than unmarried ones. Age can affect the association between marital status and the survival of MTC, and married elders may benefit more than youngers.

Abstract Background Fasting mimic diet is an effect approach for gastric cancer (GC) treatment. Exploring mechanisms of glucose deprivation-mediated GC suppression is required to develop novel therapeutic regimens. Farnesyltransferase 1 (FDFT1), as a novel target in basic research, has been reported to regulate malignant progression in some types of cancer. However, biological functions of FDFT1 in GC are still unclear. This study focused on biological functions of FDFT1 in GC and the association between glucose starvation (GS) and FDFT1. Methods The data derived from the Kaplan–Meier Plotter database were collected to identify the relationship between survival time and FDFT1 expression levels of GC patients. Bioinformatic analysis was performed to explore the biological functions of FDFT1. The expression levels of targeted genes and microRNAs (miRNAs) were detected with immunohistochemistry, quantitative real-time PCR and western blot. Malignant behaviors were measured using cell counting, cell counting kit-8, 5-ethynyl-2-deoxyuridine, wound healing, invasion transwell assays in vitro and constructions of subcutaneous and lung-metastatic tumors in vivo. The glycolysis of GC cells was determined by a series of metabolites, including lactate acid, pyruvic acid, ATP production, rates of glucose uptake, extracellular acidification rate and oxygen consumption rate. Results FDFT1 was downregulated in GC and negatively correlated with pathological T stage, pathological TNM stage and cancer differentiation. High expression of FDFT1 also indicated better prognosis of GC patients. FDFT1 upregulation attenuated proliferation, migration and invasion of GC. miR-216a-5p was identified as a critical suppressor of FDFT1 expression and miR-216a-5p/FDFT1 axis regulated malignant behaviors and glycolysis of GC cells. GS suppressed malignant behaviors of GC by targeting miR-216a-5p/FDFT1 axis both in vitro and in vivo. Conclusion This study illustrated novel mechanisms by which GS effectively suppresses GC. FDFT1 may become a potential prognostic indicator and novel target of GC therapy.

Abstract Background The antitoxin EndoAI is a TA system component that directly inhibits EndoA activity in vitro. The targeted activation of a TA system represents a potentially novel antimicrobial or antiviral strategy. However, whether the antitoxin functions alone and can induce plant disease resistance remain unknown. Results An endoAI was previously identified in the genome of Paenibacillus terrae NK3-4. It underwent a bioinformatics analysis, cloned and expressed in Escherichia coli. Then the functions of EndoAI inducing plant resistance to diseases as an elicitor were evaluated. The results showed that, EndoAI is a stable, alkaline, and hydrophilic protein, with a J-shaped three-dimensional structure in the absence of a ligand. It was clustered on the same branch with an antitoxin from Paenibacillus polymyxa SC2. Ectopically expressed EndoAI triggered a reactive oxygen species burst and a positive hypersensitive response (HR) in tobacco leaves. Moreover, 2 μmol EndoAI induced HR activity in tomato leaf, and it remained active after a 15-min exposure at 4–50 °C, and pH 6–8. Additionally, EndoAI induced plant systemic resistance against Alternaria alternata and tobacco mosaic virus, and the up-regulated transcription of PR genes, including PR1a, PR1b, PR5, PDF1.2, COL1, NPR1, and PAL. Conclusions These results imply that EndoAI may enhance the disease resistance of tobacco by promoting a series of early defense responses and up-regulating PR gene expression. These findings are relevant for future investigations on the mechanism underlying the EndoAI–plant interaction that leads to enhanced disease resistance. Furthermore, the endoAI may be useful for developing effective biocontrol agents to protect plants from diseases. Graphical Abstract

The influence of aridification and climatic oscillations on the genetic diversity and evolutionary processes of organisms during the Quaternary in northwestern China is examined using Haloxylon ammodendron. Based on the variation of two cpDNA regions (trnS-trnG and trnV) and one nDNA sequence (ITS1-ITS4) in 420 individuals from 36 populations, the spatial genetic structure and demographic history of H. ammodendron in arid China is examined. Median-joining network and Bayesian inference trees enabled the identification of three diverged lineages within H. ammodendron from 24 different haplotypes and 16 ribotypes, distributed across western (Xinjiang), eastern (Gansu and Inner Mongolia) and southern (Qinghai) regions. AMOVA analysis demonstrated that more than 80% of observed genetic variation related to lineage split was based on cpDNA and nDNA variation. Allopatric divergence among the three groups was mainly triggered by geographical isolation due to Xingxingxia rock and uplift of the Qilian Mountains during the Quaternary. Local adaptive differentiation among western, eastern and southern groups occurred due to gene flow obstruction resulting from arid landscape fragmentation accompanied by local environmental heterogeneity of different geographical populations. The southern margin of the Junggar Basin and the Tengger Desert possibly served as two independent glacial refugia for H. ammodendron. The distribution of genetic variation, coupled with SDMs and LCP results, indicated that H. ammodendron probably moved northward along the Junggar Basin and westward along Tengger Desert at the end of the last glacial maximum; postglacial re-colonization was probably westward and southward along the Hexi Corridor.

Abstract Background Enhanced recovery after surgery (ERAS) protocols were rapidly adopted in many surgeries such as fast-track arthroplasty. The study aimed to investigate the impact of ERAS protocols on the clinical effect of total knee arthroplasty (TKA) via the midvastus approach. Methods A total of 69 patients who underwent primary unilateral TKA via the midvastus approach from October 2018 to June 2019 were enrolled and randomly divided into two groups: ERAS group and Control group. The ERAS protocols were adopted for the ERAS group and consisted of pure juice drinking 2 h before the surgery, optimization of the preoperative anesthesia plan, phased use of tourniquets, and the use of tranexamic acid as well as a drug cocktail. The operative time, first postoperative walking time, first straight leg elevation time, postoperative hospitalization time, visual analogue scale score (VAS score), Hospital for Special Surgery score (HSS score), conventional Knee Society score (KSS), and knee range of motion (ROM) were used to assess the clinical effects in the two groups. All the included patients were followed up for 12 months. Results There were no significant differences in the basic demographic information and operation time between the ERAS and Control groups (P > 0.05). The first postoperative walking time (2.11 ± 0.11 h) and first postoperative straight leg elevation time (6.14 ± 1.73 h) in the ERAS group were significantly earlier than those in the Control group (P

Abstract Background Phosphoglucomutase 1 (PGM1) acts as an important regulator in glucose metabolism. However, the role of PGM1 in gastric cancer (GC) remains unclear. This study aims to investigate the role of PGM1 and develop novel regimens based on metabolic reprogramming in GC. Methods Correlation and enrichment analyses of PGM1 were conducted based on The Cancer Genome Atlas database. Data derived from the Kaplan–Meier Plotter database were analyzed to evaluate correlations between PGM1 expression and survival time of GC patients. Cell counting kit-8, 5-Ethynyl-2-deoxyuridine, flow cytometry assays, generation of subcutaneous tumor and lung metastasis mouse models were used to determine growth and metastasis in vitro and in vivo. Cell glycolysis was detected by a battery of glycolytic indicators, including lactate, pyruvic acid, ATP production and glucose uptake. Fatty Acid Synthase (FASN) activity and expression levels of lipid enzymes were determined to reflect on lipid metabolism. Results Correlation and enrichment analyses suggested that PGM1 was closely associated with cell viability, proliferation and metabolism. PGM1 was overexpressed in GC tissues and cell lines. High PGM1 expression served as an indicator of shorter survival for specific subpopulation of GC patients. It was also correlated with pathological tumor stage and pathological tumor node metastasis stage of GC. Under the glucose deprivation condition, knockdown of PGM1 significantly suppressed cell viability, proliferation and glycolysis, whereas lipid metabolism was enhanced. Orlistat, as a drug that was designed to inhibit FASN activity, effectively induced apoptosis and suppressed lipid metabolism in GC. However, orlistat conversely increased glycolytic levels. Orlistat exhibited more significant inhibitive effects on GC progression after knockdown of PGM1 under glucose deprivation due to combination of glycolysis and lipid metabolism both in vitro and in vivo. Conclusions Downregulation of PGM1 expression under glucose deprivation enhanced anti-cancer effects of orlistat. This combination application may serve as a novel strategy for GC treatment.

Systemic vasculitis are multisystem blood vessel disorders. However, Portal venous involvement is extremely rare, which represents a diagnostic and therapeutic challenge due to the heterogeneous nature, a lack of diagnostic criteria and limited effective therapy of vasculitis. We have reported a 48-year-old woman who was previously diagnosed with systemic vasculitis and was treated with prednisone, presented with gastrointestinal (GI) bleeding on admission. Further abdominal contrast-enhanced computed tomography (CT) with three-dimensional reconstruction suggested atrophic left hepatic lobe, enlarged spleen, and severe stenosis of main portal vein. Liver biopsy showed no evidence of fibrosis/cirrhosis. To prevent rebleeding, portal venous angioplasty by balloon dilation with collateral varices embolization was performed, and the GI hemorrhage was resolved completely. However, refractory ascites presented 8 months postoperatively. Abdominal CT angiography confirmed the recurrence of portal venous stenosis. Portal venous angioplasty by stent implantation was then performed to treat the portal hypertension (PHT)-related complications. After the intervention, the patient received anticoagulation therapy and continued immunosuppressive therapy. During the 5-year follow-up, the patient did not experience any onset of GI bleeding or ascites. Therefore, portal venous angioplasty with stent placement could be an effective treatment to prevent PHT-related complications when immunosuppression therapy failed.