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Disrupting effects of pollutants on symbiotic microbiota have been regarded as an important mechanism of host toxicity, with most current research focusing on the intestinal microbiota. In fact, the epidermal microbiota, which participates in the nutrient exchange between hosts and environments, could play a crucial role in host toxicity via community changes. To compare the contributions of intestinal and epidermal symbiotic microorganisms to host toxicity, this study designed single and combined scenarios of soil contamination [nano zero-valent iron (nZVI) and tris (2-chloroethyl) phosphate (TCEP)], and revealed the coupling mechanisms between intestinal/epidermal symbiotic bacterial communities and earthworm toxicological endpoints. Microbiome analysis showed that 15% of intestinal microbes were highly correlated with host endpoints, compared to 45% of epidermal microbes showing a similar correlation. Functional comparisons revealed that key species on the epidermis were mainly heterotrophic microbes with genetic abilities to utilize metal elements and carbohydrate nutrients. Further verifications demonstrated that when facing the co-contamination of nZVI and TCEP, certain symbiotic microorganisms became dominant and consumed zinc, copper, and manganese along with saccharides and amino acids, which may be responsible for the nutritional deficiencies in the host earthworms. The findings can enrich the understanding of the coupling relationship between symbiotic microorganisms and host toxicity, highlighting the importance of epidermal microorganisms in host resistance to environmental pollution.

The unique mining process of China's ion-adsorption rare earth (RE) mines has changed the structure of the mine ecosystem, and the interplay between the natural red soil characteristics and economic and social activities has exacerbated environmental problems such as the degradation of regional vegetation cover and soil erosion. These issues have had a profound and detrimental impact on the ecological security (ES) of the mining areas. The existing static evaluation study cannot comprehensively assess the ES status and dynamic evolution trend of the mining area, and cannot meet the needs of the complex ecosystem in the mining area. Therefore, this article constructs an ES evaluation index system based on the driver-pressure-state-impact-response-management causal framework model, and uses the variable weight (VW) theory to formulate a penalty-dominated state VW function to calculate the weight values of the indicators in different contexts of each year and evaluation unit. Finally, a dynamic evaluation of the spatial and temporal evolution trend of the ES of the Lingbei RE mining area is carried out during the period from 2000 to 2020. The geodetector model is then applied to reveal the driving factors impacting the ES of the mining area in different time periods. The results show that 1) Compared to the constant weight method, VW can provide a more detailed distribution of the ES level in the mining area, which has good application value in the small and dispersed ionic RE mining area. 2) The overall ES status of the Lingbei mining area shows a dynamic trend of deterioration followed by improvement and finally stabilization. 3) The vegetation health status is one of the most important driving factors of ES in the mine site, and the interaction between any two factors is greater than the explanatory power of the individual factors. This study provided insights into the ES and sustainable development of mining areas.

Category: Basic Sciences/Biologics; Diabetes Introduction/Purpose: Diabetes mellitus is a chronic metabolic disease that leads to serious complications including bone health and wound healing. Bone fractures commonly occur in diabetic patients, and are difficultly to heal due to prolonged inflammation, which leads to a higher risk of non-union. Fully reduced high mobility group box1 (frHMGB1) can play an important role in skeletal regeneration; however, the activity can be inhibited by Metformin; which is commonly used for the treatment of diabetes. The effect of frHMGB1 and Metformin on the bone fracture healing is largely unknown. In this study, we tested the hypothesis that frHMGB1 enhances healing in a nonunion bone fracture and Metformin inhibits the healing using a diabetic rat model. Methods: Diabetic fracture rat model was created by injection of streptozotocin into total 32 Sprague Dawley rats and confirmed by blood glucose levels.An incision was performed, tibia bones were fractured, followed by the muscle and skin wound closure.The rats were divided into four groups with 8 rats per group(Fig 1): Group-1 had no additional treatment;Group-2 were injected Metformin (IP, 160 mg/kg) daily;Group-3 were injected frHMGB1 into wound area (250 µg/kg) weekly;Group-4 were injected Metformin (IP, 160 mg/kg) daily and frHMGB1 into wound area (250 µg/kg) weekly. The rats were monitored postoperatively and sacrificed on postoperative day-28 and day-90. The blood samples were collected for HMGB1 & IL-1β.Tibia samples were also collected and examined by gross inspection, micro-CT images and histological analysis. Data was analyzed by One-way ANOVA followed by Fisher’s Least significance difference test. A p-value less than 0.05 was considered to be significantly different between the groups. Results: Metformin with frHMGB1 significantly decreased HMGB1 levels and decreased the enhanced expression of IL-1β compared to frHMGB1 alone. Micro-CT images showed completely healed at day-90 post-surgery in frHMGB1 rats while Metformin inhibited frHMGB1 enhanced bone fracture healing as evidenced by the gap in the fractured bone area(Fig 2). Histology analysis indicated that frHMGB1 enhanced fractured bone healing as evidenced by high density of the cells was found in the bone fracture area (Fig. 3). Safranin O and fast green staining along with Masson’s Trichrome staining confirmed the frHMGB1 local injection promoted fractured bone healing (Fig. 4) as evidenced by high quality bone tissue formation with collagen type I (red staining) and collagen type III (blue staining) in the fractured bone wound area. Conclusion: Fully reduced HMGB1 treatment enhanced healing in a nonunion diabetic rat model. The fracture site had high density of cells, quality bone tissue, and enhanced production of collagen I and III. However, Metformin inhibited frHMGB1-induced healing enhancement. In diabetic rats, nonunion bone fracture was present with evidence of inflammation showing elevated levels of HMGB1 and IL-1β.FrHMGB1 treatment enhanced healing of nonunion bone fracture by promoting cell proliferation and migration, limited HMGB1 concentration, increased collagen production. Although Metformin injection slowed down the bone fracture healing by inhibiting frHMGB1activity, it also blocked HMGB1 release and reduced the inflammation caused by HMGB1.

As a class of non-Newtonian fluids with yield stresses, Bingham fluids possess both solid and liquid phases separated by implicitly defined non-physical yield surfaces, which makes the standard numerical discretization challenging. The variational reformulation established by Duvaut and Lions, coupled with an augmented Lagrange method (ALM), brings about a finite element approach, whereas the inevitable local mesh refinement and preconditioning of the resulting large-scaled ill-conditioned linear system can be involved. Inspired by the mesh-free feature and architecture flexibility of physics-informed neural networks (PINNs), an ALM-PINN approach to steady-state Bingham fluid flow simulation, with dynamically adaptable weights, is developed and analyzed in this work. The PINN setting enables not only a pointwise ALM formulation but also the learning of families of (physical) parameter-dependent numerical solutions through one training process, and the incorporation of ALM into a PINN induces a more feasible loss function for deep learning. Numerical results obtained via the ALM-PINN training on one- and two-dimensional benchmark models are presented to validate the proposed scheme. The efficacy and limitations of the relevant loss formulation and optimization algorithms are also discussed to motivate some directions for future research.

The serine protease factor Xa (FXa) is upregulated in COVID-19 patients and functions in the coagulation pathway. Here, Dong et al characterise the basis of its antiviral activity in the context of SARS-CoV-2 pandemic variants.

The pupal stage of six Blaps species occurring in the northwest China are described and illustrated in detail: Blaps kiritshenkoi Semenov and Bogatchev, 1936, B. rugosa Gebler, 1825, B. miliaria Fischer von Waldheim, 1844, B. gobiensis Frivaldszky, 1889, B. caraboides caraboides Allard, 1882, and B. femoralis Fischer von Waldheim, 1844. A key to the pupae of Blaps is provided.

Prognosis of metastatic triple negative breast cancer (mTNBC) remains poor despite recent advances in therapeutic options. Trastuzumab deruxtecan (T-DXd) has shown promising efficacy in patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer, which is defined by immunohistochemistry (IHC) 1+ or 2+ and lack of HER2 amplification by fluorescence in situ hybridization (FISH) testing. The purpose of the study is to evaluate the safety and initial evidence of efficacy of intratumoral administration of CF33-hNIS-anti-PD-L1 (CHECKvacc) against mTNBC. Oncolytic virus CHECKvacc intratumoral injection is currently undergoing investigation in patients with mTNBC as a single agent (NCT05081492). The patient was enrolled on the clinical trial CHECKvacc for the Treatment of Metastatic Triple Negative Breast Cancer , received a single dose of CHECKvacc, and discontinued the study due to lack of immediate response. We report a case of a patient with mTNBC who was heavily pretreated and presented with extensive dermal metastasis. Two dermal metastasis biopsies in 2021 showed HER2 0 by IHC. The patient received a single dose of CHECKvacc and discontinued the study due to lack of immediate response. Twenty-five days later, the patient received treatment with T-DXd, and her tumor regressed significantly. The patient’s disease-free survival was 10 months (December 2021–October 2022). The sequential treatment with intratumoral injection of CHECKvacc followed by T-DXd may have significant clinical activity in select patients with heavily pretreated mTNBC. ClinicalTrials.gov NCT05081492.

Lipid-lowering agents are relevant in stroke prevention. Probucol (PU) is an antioxidative and lipid-lowering drug that has been used to treat atherosclerotic cardiovascular diseases and xanthomas. The drug penetrates the core of low-density lipoprotein cholesterol (LDL-C) particles, enhancing the activity of plasma cholesterol l ester transfer protein (CETP) and strengthening the liver scavenger receptor type I, resulting in reducing LDL-C; by increasing the activity of paraoxonase 1, upregulating the antioxidant function of high-density lipoprotein (HDL), and it decreases the serum HDL-cholesterol (HDL-C) level. This drug has been retired from the Western markets for lowering HDL-C levels and Q-interval prolongation. The latter side effect has been rarely reported and may be transient. Recent clinical evidence supports the effectiveness of PU in preventing cardiovascular events and in reducing mortality, irrespective of the reduction of HDL-C. Based on basic research and clinical studies, it appears that PU might be a valuable alternative when statins are ineffective or contraindicated, in patients at high risk of recurrence of cerebral ischemia and hemorrhage.

Tendon injuries, while prevalent, present significant challenges regarding their structural and functional restoration. Utilizing alpha-smooth muscle actin (α-SMA)-Ai9-scleraxis (Scx)-green fluorescent protein (GFP) transgenic mice, which exhibit both Scx (a tendon cell marker) and α-SMA (a myofibroblast marker), we explored the effects of metformin (Met) on tendon healing, repair, and its mechanisms of action. Our findings revealed that intraperitoneal (IP) injections of Met, administered before or after injury, as well as both, effectively prevented the release of HMGB1 into the tendon matrix and reduced circulating levels of HMGB1. Additionally, Met treatment increased and activated AMPK and suppressed TGF-β1 levels within the healing tendon. Tendon healing was also improved by blocking the migration of α-SMA+ myofibroblasts, reducing the prevalence of disorganized collagen fibers and collagen type III. It also enhanced the presence of collagen type I. These outcomes highlight Met’s anti-fibrotic properties in acutely injured tendons and suggest its potential for repurposing as a therapeutic agent to minimize scar tissue formation in tendon injuries, which could have profound implications in clinical practice.

Abstract Guidelines have shifted to now recommend endoscopic eradication therapy for Barrett’s esophagus (BE) with low and high-grade dysplasia. Previously, esophagectomy was the standard therapy for high-grade dysplasia. However, it is unclear to what degree ablation therapy has affected utilization of esophagectomy. In this retrospective observational cohort study of BE patients without cancer from the Premier Healthcare Database, the prevalence of utilization of endoscopic ablation therapy and of esophagectomy in BE were calculated and temporal trends were evaluated. A total of 938, 333 BE cases were included in the study. There was a significantly increasing trend of ablation over the period 2006 to 2010 (Annual Percentage Change (APC); 95% CI 0.56% [0.51%, 0.61%]), a significantly decreasing trend for the period 2011 to 2015 (APC; 95% CI − 0.15% [− 0.20%, − 0.11%]), and a shallow increasing trend for the period 2016 to 2019 (APC; 95% CI 0.09% [0.06%, 0.11%]). For esophagectomy, there was a significantly decreasing trend for the period 2006 to 2009 (APC; 95% CI − 0.03% [− 0.04%, − 0.02%]; P

Abstract The support for the membrane is the basis for the preparation and application of the zeolite membrane. Moreover, its cost and properties directly determine the performance of the zeolite membrane and its industrial applications. A novel porous silicon carbide (SiC) support for zeolite membrane bonded with needle-like mullite (3Al2O3·2SiO2) was prepared using SiC powders as the raw material and kaolin, Al(OH)3, and AlF3 as the needle-like mullite precursor additives via an in situ high-temperature reactions in an air atmosphere. Effects of the support material composition and the sintering temperature on the sintering behavior, pore structure, permeability, and microstructure of the resultant supports were extensively investigated. The needle-like mullite formation consumed silicon oxide (SiO2) and generated a rigid skeleton structure with a good pore structure and bonding phase. Hence, the porous SiC support exhibited high porosity, with relatively large pore size and mechanical strength, which helped improve the support performance. Notably, the porous SiC support sintered at 1480 °C with in situ inter-particle needle-like mullite bonding exhibited excellent filtration and permeability performance. The porous support materials and methods used in this work are suitable for designing and preparing a novel porous SiC support for zeolite membranes.

Abstract Background Regenerative endodontic procedures (REPs) have achieved clinical success on the immature permanent teeth with pulp necrosis, and can promote root development. However, preoperative factors and their effects on root development of REPs have not been definitely concluded. The aim of this study was to investigate the preoperative factors that may influence the root development of REPs. Methods A total of 116 teeth in 110 patients treated with REPs in the Paediatric Dentistry Department and Endodontics Department from 2013 to 2017 were included in this study. Preoperative factors including aetiology, age, diagnosis and initial root morphology were collected retrospectively, and the associations between these factors and root development after REPs were analysed by Fisher's exact test and multivariate logistic regression model. Results The overall rate of root development after REPs was 89.7%. The dens evaginatus group showed a higher rate (98.8%) in root development than the trauma group (67.6%) (P 0.05). And it showed in the trauma group that the teeth with apical foramen sizes larger than 3 mm significantly promoted root development than those smaller than 3 mm (P

Abstract Background Esophageal squamous cell carcinoma (ESCC) has poor prognosis mainly due to lacking of effective diagnostic biomarkers. Aberrant expression of secreted phosphoprotein 1 (SPP1) protein has been observed in several cancers. The purpose of this study is to assess the feasibility of serum autoantibody to SPP1 in detection of ESCC. Methods The SPP1 protein levels in 108 ESCC tissues and 72 adjacent normal tissues were analyzed by immunohistochemistry. Discovery group containing 62 serum samples from ESCC patients and 62 serum samples from normal controls (NC) were used to detect the levels of anti-SPP1 autoantibody by enzyme-linked immunosorbent assay (ELISA). Validation group containing another 100 ESCC and 100 NC serum samples were tested to confirm the levels of autoantibody to SPP1. Western blotting was performed to further confirm the results of ELISA. Results SPP1 protein was significantly overexpressed in ESCC tissues compared to adjacent normal tissues. ELISA results showed that serum autoantibody to SPP1 was significantly increased in ESCC compared to NC in both discovery and validation groups. Autoantibody to SPP1 could discriminate patients with ESCC from NC with the area under curve (AUC) values of 0.653 and 0.739 in discovery and validation group, respectively. The results of ELISA and the occurrence of immunoreactivity to SPP1 in ESCC sera were confirmed by western blotting. Conclusion Our study indicated the potential significance of anti-SPP1 autoantibody as a novel biomarker for detection of ESCC.

Abstract Solid polymer electrolytes (SPEs) have emerged as one of the most promising candidates for building solid‐state lithium batteries due to their excellent flexibility, scalability, and interfacial compatibility with electrodes. However, the low ionic conductivity and poor cyclic stability of SPEs do not meet the requirements for practical applications of lithium batteries. Here, a novel polymer dispersed ionic liquid‐based solid polymer electrolyte (PDIL‐SPE) is fabricated using the in situ polymerization‐induced phase separation (PIPS) method. The as‐prepared PDIL‐SPE possesses both outstanding ionic conductivity (0.74 mS cm−1 at 25°C) and a wide electrochemical window (up to 4.86 V), and the formed unique three‐dimensional (3D) co‐continuous structure of polymer matrix and ionic liquid in PDIL‐SPE can promote the transport of lithium ions. Also, the 3D co‐continuous structure of PDIL‐SPE effectively accommodates the severe volume expansion for prolonged lithium plating and stripping processes over 1000 h at 0.5 mA cm−2 under 25°C. Moreover, the LiFePO4//Li coin cell can work stably over 150 cycles at a 1 C rate under room temperature with a capacity retention of 90.6% from 111.1 to 100.7 mAh g−1. The PDIL‐SPE composite is a promising material system for enabling the ultrastable operation of solid‐state lithium‐metal batteries.

Abstract Stroke thrombolysis treatment is generally administered within 4.5 h, but a greater time window may be permitted depending upon the ischemic penumbra on neuroimaging. This observational cohort study investigated the outcomes of thrombolysis given within 12 h after symptom onset of lenticulostriate artery stroke. The population comprised 160 patients. Thrombolysis was administered via tissue plasminogen activator, alteplase (TPA). Thrombolysis was indicated by a mismatch between diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI), that is, an acute ischemic lesion on DWI without a corresponding lesion on T2WI. Demographics and medical history were compared with the modified Rankin scale (mRS) score, to reflect outcome. Patients with a favorable clinical outcome (mRS 0–1) had significantly lower hypertension, baseline NIH Stroke Scale (NIHSS) score, and admission systolic/diastolic blood pressure compared with patients with mRS 2–6. Lower admission systolic blood pressure and NIHSS score were significantly associated with favorable outcome. In patients either with IV-TPA within 4.5 h, or between 4.5 and 12 h, lower admission systolic blood pressure and/or NIHSS score similarly independently predict favorable outcome. However, in all groups, the onset-to-treatment time did not significantly influence the outcomes. We conclude that in our cohort higher admission systolic blood pressure and higher baseline NIHSS and not time were associated with poor outcome in patients with magnetic resonance-guided thrombolysis within 12 h of isolated lenticulostriate artery stroke, therefore loosening the traditionally perceived dependency of outcome on time.

Severe COVID-19 requires immediate and targeted intervention that is efficient against SARS-CoV-2 and its variants. Authors show here the therapeutic potential of engineered natural killer cells that simultaneously express a chimeric antigen receptor targeting the spike protein of SARS-CoV-2, and IL-15, a cytokine that enhances the function and survival of their own.

Abstract The performance of zeolite membrane supports directly determines the synthesis performance and industrial application of zeolite membranes. In this study, a novel and high permeation SiC supports for NaA zeolite membrane were prepared by carrying out in situ reaction bonding at high temperature in the air atmosphere to coat the SiC particles with aluminum sol. The effects of process parameters on the formation of porous structure of SiC supports were systematically investigated, and the underlying mechanism was explored. During the sintering process, high-temperature Al2O3 from aluminum sol reacted with SiO2 generated by oxidation of the surface of SiC particles to form mullite, which exhibited excellent chemical stability and improved the mechanical properties and chemical stability of the supports. The porous SiC supports for zeolite membrane displayed obvious three-dimensional connected pore structure, with smooth inner surface of the pores and obvious connection neck between the particles. The porous SiC supports for zeolite membrane showed good in situ mullite bonding between the particles, and high permeability. It has a porosity of 36.3%, an average pore size of 1.42 µm and a bending strength of 32.4 MPa. All these figures indicate good comprehensive properties that are consistent with the rigorous requirements of zeolite membrane synthesis and industrial application.

Food waste is a serious national and global problem. Milk is one of the most frequently wasted food items. This study aims to determine how long postexpiration-pasteurized milk may still be safe to consume and what is the relationship between bacterial growth from the milk and time after expiration. The experiments were carried out by incubating milk with agarose gel. The results showed that the bacterial growth was relatively low for at least the first few days after expiration. The more the days passed after the expiration date, the more the bacteria grew from the milk. There was no significant difference in the bacteria colony numbers in the whole milk samples opened either on day 0 or day 5 of expiration. None of the fat-free milk samples collected on the later (1–10) days showed any statistically significant difference in bacterial growth compared to the samples collected on the day after expiration (day 0). The bacterial growth increased with the increasing fat content of the milk. In addition, the rate of bacterial growth from the milk correlated with the acidity of the milk that is measured by pH. No significant sensory changes could be detected in any of the milk samples immediately after opening on the day of expiration or for up to 10 days after expiration when the unopened cartons were kept refrigerated. However, within 24 hours of opening the carton, whole milk that has expired for 6 or more days and 2% milk that has expired for 8 or more days developed a sour taste and mildly pungent smell. This sensory change was accompanied by the formation of lumps and fat-water separation. Fat-free milk samples remained unchanged under the same conditions. The experimental results suggest that whole and 2% skim milk may be safe for consumption up to 5-6 days after expiration. Fat-free milk may be safe for consumption up to 10 days after expiration, possibly longer. This study devised a way to show that milk is still safe for consumption after expiration; it will help reduce food waste.

Pinus koraiensis is famous for its high-quality timber production all the way and is much more famous for its high value health-care nut oil production potential since 1990’s, but the less understanding of its reproduction biology seriously hindered its nut productivity increase. Exploring the effects of reproduction on nutrient uptake, allocation and storage help to understand and modify reproduction patterns in masting species and high nut yield cultivar selection and breeding. Here, we compared seasonality in growth and in nitrogen ([N]) and phosphorus ([P]) concentrations in needles, branches and cones of reproductive (cone-bearing) and vegetative branches (having no cones) of P. koraiensis during a masting year. The growth of one- and two-year-old reproductive branches was significantly higher than that of vegetative branches. Needle, phloem and xylem [N] and [P] were lower in reproductive branches than in vegetative branches, although the extent and significance of the differences between branch types varied across dates. [N] and [P] in most tissues were high in spring, decreased during summer, and then recovered by the end of the growing season. Overall, [N] and [P] were highest in needles, lowest in the xylem and intermediate in the phloem. More than half of the N (73.5%) and P (51.6%) content in reproductive branches were allocated to cones. There was a positive correlation between cone number and N and P content in needles (R2 = 0.64, R2 = 0.73) and twigs (R2 = 0.65, R2 = 0.62) of two-year-old reproductive branches. High nutrient sink strength of cones and vegetative tissues of reproductive branches suggested that customized fertilization practices can help improve crop yield in Pinus koraiensis.

Abstract The ability of some animals to rapidly change their colors can greatly improve their chances of escaping predators or hunting prey. A classic example is cephalopods, which can rapidly shift through a wide range of colors. This ability is based on the synergetic effect of the change of pigmentary and structural colors exhibited by their own two categories of color‐changing cells: supernatant chromatophores offer various pigmentary colors and lower iridophores or leucophores reflect the different structural colors by adjusting their periodicities. Here, a mechanochromic liquid crystalline elastomer with force‐induced synergetic pigmentary and structural color change, whose mechanosensitivity is enhanced by the stress‐concentration induced by the doped nanoparticle, is presented. The materials have a large color‐changing gamut and high mechanochromic sensitivity, which exhibit great potential in the field of mechanical detectors, sensors, and anti‐counterfeiting materials.

Objective To analyze the epidemic of hepatitis C virus (HCV) in voluntary blood donors , and to assess the residual risk of HCV transmission by blood transfusion in Taiyuan. Methods The HCV screening results of voluntary blood donors in Taiyuan from 2016 to 2021 were collected by blood center information system, and the epidemiologic feature of first-time and repeated donors were analyzed. The incidence-window period model was used to assess the residual risk of HCV transmission by transfusion in first-time/repeated donors as well as that in repeated donors under different blood screening modes. Results Of the 662 705 samples in Taiyuan from 2016 to 2021, the HCV positive rate of the first-time donors was 1.83‰(595/325 009) and the residual risk of HCV transmission was 14.91/100 000. The HCV positive rate of the repeated donors was 0.04‰ (13/337 696) and the residual risk was 0.31/1 000 000. The total residual risk of HCV transmission was 7.47/1 000 000. A total of 337 696 blood samples of repeated blood donors were tested, the repeated blood donors’ residual risk of transfusion-transmitted HCV was 0.31/100 000 after dual ELISA tests , and 0.06/100 000 after dual ELISA and once NAT, which reduce by 80.65% since NAT were adopted. Conclusion The residual risk of HCV transmission from repeated donors was less than that from first-time donors. The blood screening mode of HCV by dual ELISA and once NAT can effectively reduce the residual risk of transfusion-transmitted HCV and improve blood safety. The rate of repeat blood donation needs to be increased by continuously optimizing the recruitment strategy of blood donors.

Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. In this article, we show that expression of abnormal spindle‐like microcephaly‐associated protein (ASPM) is up‐regulated in liver cancer samples, and this up‐regulation is significantly associated with tumor aggressiveness and reduced survival times of patients. Down‐regulation of ASPM expression inhibits the proliferation, invasion, migration and epithelial‐to‐mesenchymal transition of HCC cells in vitro and inhibits tumor formation in nude mice. ASPM interacts with disheveled‐2 (Dvl2) and antagonizes autophagy‐mediated Dvl2 degradation by weakening the functional interaction between Dvl2 and the lipidated form of microtubule‐associated proteins 1A/1B light chain 3A (LC3II), thereby increasing Dvl2 protein abundance and leading to Wnt/β‐catenin signaling activation in HCC cells. Thus, our results define ASPM as a novel oncoprotein in HCC and indicate that disruption of the Wnt–ASPM–Dvl2–β‐catenin signaling axis might have potential clinical value.

Oncolytic herpes simplex virus-1 lyses cancer cells while increases their immunogenicity. Blocking the CD47 “don’t eat me” signal on cancer cells promotes their phagocytosis by macrophages. Authors here show that oncolytic viruses expressing anti-CD47 antibodies improve glioblastoma survival in mouse models.

Abstract The membrane support is the basis for the preparation and application of the zeolite membrane and its cost and properties directly determine the performance of the zeolite membrane as well as its industrial applications. In this paper, the direct synthesis of NaA zeolite membrane on a novel low-cost support via an in situ reaction by utilizing natural clay can enable a significant reduction in manufacturing costs. During the preparation of the support for the NaA zeolite membrane, additives, such as Al2O3, Al(OH)3 and AlF3, were combined with kaolin clay and used as alumina precursors. Using the resulting porous mullite support, the effects of the firing temperature on the permeability and pore structure of the support were investigated extensively. The results of the experiment showed that silica in the natural clay was reacted by the Al2O3 precursor additives, producing a needle-like mullite in situ that served as a rigid skeleton porous structure for the support. Thus, a network porous structure of the mullite support could be formed during sintering process. The prepared network porous structure mullite supports exhibited a high pure water permeance of 3324 L m2 h1 bar1, open porosity of 41.8% and a mean pore size of 1.36 µm which was ideal for the preparation of the NaA zeolite membrane.

Abstract Background Complex kinase rearrangement, a mutational process involving one or two chromosomes with clustered rearrangement breakpoints, interferes with the accurate detection of kinase fusions by DNA-based next-generation sequencing (NGS). We investigated the characteristics of complex ALK rearrangements in non-small cell lung cancers using multiple molecular tests. Methods Samples of non-small cell lung cancer patients were analyzed by targeted-capture DNA-based NGS with probes tilling the selected intronic regions of fusion partner genes, RNA-based NGS, RT-PCR, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results In a large cohort of 6576 non-small cell lung cancer patients, 343 (5.2%) cases harboring ALK rearrangements were identified. Fourteen cases with complex ALK rearrangements were identified by DNA-based NGS and classified into three types by integrating various genomic features, including intergenic (n = 3), intragenic (n = 5) and “bridge joint” rearrangements (n = 6). All thirteen cases with sufficient samples actually expressed canonical EML4-ALK fusion transcripts confirmed by RNA-based NGS. Besides, positive ALK IHC was detected in 13 of 13 cases, and 9 of 11 cases were positive in FISH testing. Patients with complex ALK rearrangements who received ALK inhibitors treatment (n = 6), showed no difference in progression-free survival (PFS) compared with patients with canonical ALK fusions n = 36, P = 0.9291). Conclusions This study firstly reveals the molecular characteristics and clinical outcomes of complex ALK rearrangements in NSCLC, sensitive to ALK inhibitors treatment, and highlights the importance of utilizing probes tilling the selected intronic regions of fusion partner genes in DNA-based NGS for accurate fusion detection. RNA and protein level assay may be critical in validating the function of complex ALK rearrangements in clinical practice for optimal treatment decision.

Hepatocellular carcinomas remain as a global health threat given its high mortality rate. We have previously identified the selectivity of cold atmospheric plasma (CAP) against multiple types of malignant tumors and proposed it as a promising onco-therapeutic strategy. Here, we investigated its roles in controlling hepatocellular carcinoma malignancy and one possible driving molecular mechanism. By focusing on post-translational modifications including acetylation, phosphorylation, and ubiquitination, we identified the crosstalk between EGFR acetylation and EGFR(Tyr1068) phosphorylation and their collective roles in determining LC3B ubiquitination and proposed the EGFR/p-JNK/BIRC6/LC3B axis in CAP-triggered autophagy. Our study not only demonstrated the selectivity of CAP against hepatocellular carcinoma malignancy and confirmed its roles as an onco-therapeutic tool but also opened the horizon of translating CAP into clinics toward a broader scope that included human longevity and anti-aging.

Carotenoid cleavage oxygenases (CCOs) are key enzymes that function in degrading carotenoids into a variety of apocarotenoids and some other compounds. In this study, we performed genome-wide identification and characterization analysis of CCO genes in Cerasus humilis. Totally, nine CCO genes could be classified into six subfamilies, including carotenoid cleavage dioxygenase 1 (CCD1), CCD4, CCD7, CCD8, CCD-like and nine-cis-epoxycarotenoid dioxygenase (NCED), were identified. Results of gene expression analysis showed that ChCCOs exhibited diverse expression patterns in different organs and in fruits at different ripening stages. To investigate the roles of ChCCOs in carotenoids degradation, enzyme assays of the ChCCD1 and ChCCD4 were performed in Escerichia coli BL21(DE3) that can accumulate lycopene, β-carotene and zeaxanthin. The prokaryotic expressed ChCCD1 resulted in obvious degradation of lycopene, β-carotene and zeaxanthin, but ChCCD4 did not show similar functions. To further determine the cleaved volatile apocarotenoids of these two proteins, headspace gas chromatography/mass spectrometer analysis was performed. Results showed that ChCCD1 could cleave lycopene at 5, 6 and 5′, 6′ positions to produce 6-methy-5-hepten-2-one and could catalyze β-carotene at 9, 10 and 9′, 10′ positions to generate β-ionone. Our study will be helpful for clarifying the roles of CCO genes especially ChCCD1 in regulating carotenoid degradation and apocarotenoid production in C. humilis.

The clinical features of Parkinson’s disease (PD) include tremors and rigidity. However, paresthesia has not drawn clinical attention. PD involves the whole body and begins with gastrointestinal lesions, which do not start in the midbrain substantia nigra, but from the beginning of the medulla oblongata of the glossopharyngeal nerve nuclei, to the motor nerve dorsal nucleus of the vagus nerve, to the pons and midbrain, and finally to the neocortex. The human eye, ear, nose, tongue, and body perceive the external world. (1) Visual impairment in patients with PD can be easily confused with senile eye disease. This change in retinal pigment cells has many similarities to the degeneration of dopaminergic neurons in the substantia nigra in PD. (2) Selective high-frequency hearing impairment can cause a certain degree of communication barriers, only understanding the son’s bass but not the daughter’s soprano, and there is a certain relationship between hearing and body postural balance. (3) Olfactory loss is one of the earliest signs of PD and an important indicator for the early screening of PD. (4) Taste disorders, including loss of taste and taste memory, can cause cognitive impairment. (5) The body’s sense of touch, pressure, pain, temperature, and position abnormalities interfere with the motor symptoms of PD and seriously affect the quality of life of patients. This article discusses vision, hearing, smell, taste, touch, and analyses of neuroanatomy and pathology, revealing its clinical significance.

Sulforaphane (SFN), a natural anti-tumor compound from cruciferous vegetables, has been reported to induce protective autophagy to cancer cells, which might impair the anti-tumor efficiency of SFN. However, the accurate function and mechanism of SFN inducing autophagy in cancers are still obscure, especially in esophageal squamous cell carcinoma (ESCC), one of malignancies with high incidence in North China. Here, we mainly explored the potential function of autophagy upon SFN treatment in ESCC and molecular mechanism. We demonstrated that SFN could inhibit cell proliferation and induce apoptosis by activating caspase pathway. Moreover, we found activation of NRF2 pathway by SFN was responsible for the induction of autophagy and also a disadvantage element to the anti-tumor effects of SFN on ESCC, indicating that SFN might induce protective autophagy in ESCC. We, therefore, investigated effects of autophagy inhibition on sensitivity of ESCC cells to SFN and found that chloroquine (CQ) could neutralize the activation of SFN on NRF2 and enhance the activation of SFN on caspase pathway, thus improved the anti-tumor efficiency of SFN on ESCC in vitro and in vivo. Our study provides a preclinical rationale for development of SFN and its analogs to the future treatment of ESCC.

Abstract Background The Medicare population is increasing while the prevalence of obesity remains high. Bariatric surgery is the most efficacious treatment of obesity and its comorbidities. The objective of this investigation was to assess trends in utilization, readmission, mortality, and cost of bariatric surgery in the Medicare population. Methods Utilizing the Medicare Provider Analysis and Review database, patients with clinically severe obesity undergoing laparoscopic Roux‐en‐Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (SG), and laparoscopic adjustable gastric banding (LAGB) from 2011–2015 were identified. Trends in procedure selection, readmissions, mortality, and cost were examined. A multivariable logistic regression analysis to evaluate factors associated with readmission and mortality was performed. Results Of the 73,718 patients identified, 53,949 (73%) of patients were enrolled in Medicare due to disability, 19,191 (26%) due to age, and 578 (

Abstract Background We combined anatomy with imaging, transformed the 2D information of various imaging techniques into 3D information, and form the assessment system of real medical imaging cases in order to make up for the deficiencies in the current teaching of the medical imaging technology students. Methods A total of 460 medical imaging students were selected and randomly divided into two groups. The research group received the teaching of the fusion of the original CT and MR data 3D model and the original image combined with 3D anatomical image. CT and MRI data are imported through load DICOM of 3D slicer. Different tissues and organs are segmented by threshold and watershed algorithm of segment editor module. Models are exported through export / import models and label maps in segmentation. Save the NHDR file of the original data and Obj file of the corresponding model through save the NHDR and corresponding Obj files are loaded into probe 1.0 software. The software can give different colors to the three-dimensional models of different organs or tissues to display the stereo models and related data, and display the hook edges of organ models on coronal, sagittal and axial images. At the same time, annotation can be established in the corresponding anatomical position. Finally, it can be saved as a single file of Hwl, and the teaching can be opened at any time through the program of probe 1.0. Statistical analysis Academic self-efficacy scale and Self-directed learning ability scale was adopted by self-directed learning evaluation scale between two groups. Results Compare the theoretical scores and case analysis scores of the two groups. The scores of the study and control groups were significantly higher than those of the control group. Before the experiment, no significant difference was detected in the self-efficacy of learning ability and learning behavior between the two groups, while after the experiment, these differences between the two groups were statistically significan. Moreover, the learning ability self-efficacy and learning behavior of the two groups of students after the experiment was significantly higher than that before the experiment. The self-efficacy of the learning behavior of the control group was higher after the experiment than that before the experiment, albeit the difference was not statistically significant. Conclusions The modern, information-based and humanized experimental teaching mode will be constantly improved under the support of PACS system in order to optimize the medical imaging teaching activities for the development of modern medical education.

Abstract Background SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development. Methods Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across different tumors and among different breast cancer subtypes, we identify the tumor promotive role of SNRPD1 using multiple publicly available datasets. Through pathway, gene ontology enrichment analysis and network construction, we linked the onco-therapeutic role of SNRPD1 with cell cycle. Via a series of experimental studies including knockdown assay, qPCR, western blotting, cell cycle, drug response assay, we confirmed the higher expression of SNPRD1 at both gene and protein expression levels in triple negative breast cancer cells, as well as its roles in promoting cell cycle and chemotherapy response. Results Our study revealed that SNRPD1 over-expression was significantly associated with genes involved in cell cycle, cell mitosis and chromatin replication, and silencing SNRPD1 in breast cancer cells could lead to halted tumor cell growth and cell cycle arrest at the G0/G1 stage. We also found that triple negative breast cancer cells with reduced SNRPD1 expression lost certain sensitivity to doxorubicin whereas luminal cancer cells did not. Conclusions Our results suggested the prognostic value of SNRPD1 on breast cancer survival, its potential as the therapeutic target halting cell cycle progression for breast cancer control, and warranted special attention on the combined use of doxorubicin and drugs targeting SNRPD1.

Abstract Background CircRNAs with tissue-specific expression and stable structure may be good tumor prognostic markers. However, the expression of circRNAs in esophageal squamous cell carcinoma (ESCC) remain unknown. We aim to identify prognostic circRNAs and construct a circRNA-related signature in ESCC. Methods RNA sequencing was used to test the circRNA expression profiles of 73 paired ESCC tumor and normal tissues after RNase R enrichment. Bioinformatics methods, such as principal component analysis (PCA), t-distributed Stochastic Neighbor Embedding (t-SNE) algorithm, unsupervised clustering and hierarchical clustering were performed to analyze the circRNA expression characteristics. Univariate cox regression analysis, random survival forests-variable hunting (RSFVH), Kaplan–Meier analysis, multivariable Cox regression and ROC (receiver operating characteristic) curve analysis were used to screen the prognostic circRNA signature. Real-time quantitative PCR (qPCR) and fluorescence in situ hybridization(FISH) in 125 ESCC tissues were performed. Results Compared with normal tissues, there were 11651 differentially expressed circRNAs in cancer tissues. A total of 1202 circRNAs associated with ESCC prognosis (P

BackgroundCerebral edema forms immediately after blood flow interruption in ischemic stroke, which largely increased the death and disability. The glymphatic (glial-lymphatic) pathway is a major regulator of the brain liquid dynamics and homeostasis. This study aimed to investigate the transport kinetics of the glymphatic system after the appearance of ischemic edema.MethodsIn this study, a coated filament was attached to the left middle cerebral artery (MCA) of mice to establish a mouse model of permanent middle cerebral artery occlusion with an intact blood-brain barrier (BBB). The glymphatic function was then quantified using contrast-enhanced MRI (11.7T) by employing an injection of gadobenate dimeglumine (BOPTA-Gd) into the cisterna magna of mice. We then evaluated the expression and polarization of aquaporin-4 (AQP4) as a proxy for the physiological state of the glymphatic system.ResultsOur results revealed a positive correlation between the signal intensity in T1-weighted images and the corresponding apparent diffusion coefficient (ADC) values in the cortex, striatum, and periventricular zone, suggesting that impaired glymphatic transport kinetics in these regions is correlated to the cytotoxic edema induced by the occlusion of MCA. Furthermore, the increased depolarization of AQP4 in the parenchyma perivascular space (PVS) was consistent with glymphatic failure following the induced early cerebral ischemic edema.ConclusionsGlymphatic transport kinetics were suppressed between the onset of cytotoxic edema and the disruption of the BBB, which correlated with the diminishing ADC values that vary based on edema progression, and is associated with depolarization of AQP4 in the parenchyma PVSs.

Abstract Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Despite that high-risk factors have been identified, no test for early detection is available. This study aimed to identify circulating nucleic acid sequences associated with serum extracellular vesicle (EV) preparations at the time of OS diagnosis, as a step towards an OS early detection assay. Sequencing of small nucleic acids extracted from serum EV preparations revealed increased representation of diverse repetitive element sequences in OS patient versus control sera. Analysis of a validation cohort using qPCR of PEG-precipitated EV preparations revealed the over-representation of HSATI, HSATII, LINE1-P1, and Charlie 3 at the DNA but not RNA level, with receiver operating characteristic (ROC) area under the curve (AUC) ≥ 0.90. HSATI and HSATII DNAs co-purified with EVs prepared by precipitation and size exclusion chromatography but not by exosome immunocapture, indicative of packaging in a non-exosomal complex. The consistent over-representation of EV-associated repetitive element DNA sequences suggests their potential utility as biomarkers for OS and perhaps other cancers.

With the high pervasiveness of viral diseases, the battle against viruses has never ceased. Here we discuss five cellular processes, namely “autophagy”, “programmed cell death”, “immune response”, “cell cycle alteration”, and “lipid metabolic reprogramming”, that considerably guide viral replication after host infection in an orchestrated manner. On viral infection, “autophagy” and “programmed cell death” are two dynamically synchronized cell survival programs; “immune response” is a cell defense program typically suppressed by viruses; “cell cycle alteration” and “lipid metabolic reprogramming” are two altered cell housekeeping programs tunable in both directions. We emphasize on their functionalities in modulating viral replication, strategies viruses have evolved to tune these processes for their benefit, and how these processes orchestrate and govern cell fate upon viral infection. Understanding how viruses hijack host networks has both academic and industrial values in providing insights toward therapeutic strategy design for viral disease control, offering useful information in applications that aim to use viral vectors to improve human health such as gene therapy, and providing guidelines to maximize viral particle yield for improved vaccine production at a reduced cost.

Canine parvovirus (CPV) has been used in cancer control as a drug delivery vehicle or anti-tumor reagent due to its multiple natural advantages. However, potential host cell cycle arrest induced by virus infection may impose a big challenge to CPV associated cancer control as it could prevent host cancer cells from undergoing cell lysis and foster them regain viability once the virotherapy was ceased. To explore CPV-induced cell cycle arrest and the underlying mechanism toward improved virotherapeutic design, we focus on epidermal growth factor receptor (EGFR), a cellular receptor interacting with TfR that mediates CPV-host interactions, and alterations on its tyrosine phosphorylation sites in response to CPV infection. We found that CPV could trigger host G1/S cell cycle arrest via the EGFR (Y1086)/p27 and EGFR (Y1068)/STAT3/cyclin D1 axes, and EGFR inhibitor could not reverse this process. Our results contribute to our understandings on the mechanism of CPV-induced host cellular response and can be used in the onco-therapeutic design utilizing CPV by preventing host cancer cells from entering cell cycle arrest.

A novel malachite green molecularly imprinted membrane (MG-MIM) with specific selectivity for malachite green (MG) and leucomalachite green (LMG) was prepared using a hydrophobic glass fiber membrane as the polymer substrate, methyl violet as a template analog, 4-vinyl benzoic acid as the functional monomer, and ethyleneglycol dimethacrylate as the crosslinking agent. MG-MIM and non-imprinted membrane (NIM) were structurally characterized using scanning electron microscopy, surface area analyzer, Fourier-transform infrared spectrometer and synchronous thermal analyzer. The results showed that MG-MIM possessed a fluffier surface, porous and looser structure, and had good thermal stability. Adsorption properties of MG-MIM were investigated under optimal conditions, and adsorption equilibrium was reached in 20 min. The saturated adsorption capacities for MG and LMG were 24.25 ng·cm−2 and 13.40 ng·cm−2, and the maximum imprinting factors were 2.41 and 3.20, respectively. Issues such as “template leakage” and “embedding” were resolved. The specific recognition ability for the targets was good and the adsorption capacity was stable even after five cycles. The proposed method was successfully applied for the detection of MG and LMG in real samples, and it showed good linear correlation in the range of 0 to 10.0 μg·L−1 (R2 = 0.9991 and 0.9982), and high detection sensitivity (detection limits of MG and LMG of 0.005 μg/kg and 0.02 μg·kg−1 in shrimp, and 0.005 μg/kg and 0.02 μg/kg in fish sample). The recoveries and relative standard deviations were in the range of 76.31–93.26% and 0.73–3.72%, respectively. The proposed method provides a simple, efficient and promising alternative for monitoring MG and LMG in aquatic products.

ROS1 gene rearrangements have been reported in diverse cancer types including non‐small‐cell lung cancer (NSCLC), and with a notably higher prevalence in lung adenocarcinoma. The tyrosine kinase inhibitors, crizotinib, lorlatinib, and entrectinib, have demonstrated favorable efficacy in treating ROS1‐rearranged NSCLCs. Herein, we retrospectively reviewed 17 158 NSCLC patients whose tumor specimen and/or circulating cell‐free DNA underwent comprehensive genomic profiling. A total of 258 unique patients were identified with ROS1 rearrangements, representing an overall prevalence of approximately 1.5% of ROS1 fusions in newly diagnosed and relapsed NSCLC patients. CD74 (38%) was the most common fusion partner of ROS1, followed by EZR (13%), SDC4 (13%), SLC34A2 (10%), and other recurrent fusion partners with lower frequencies, including TPM3, MYH9, and CCDC6. Variant breakpoints occurred in ROS1 introns 33 (37%), 31 (25%), 32 (17%), and 34 (11%) with no obvious hotspots. CD74 (63%) and EZR (50%) were more frequently fused to ROS1 intron 33 than other introns, while ROS1 intron 31 was most frequently fused with SDC4 (79%) and SLC34A2 (81%). Crizotinib progression‐free survival (PFS) was not significantly different between fusion variants involving breakpoints in different ROS1 introns, nor was there a significant difference in PFS between CD74‐ROS1 and non‐CD74‐ROS1 groups of patients. Furthermore, TP53 was most frequently mutated in patients who progressed on crizotinib, and TP53 mutations were significantly associated with shorter crizotinib PFS. ROS1 mutations, including G2032R, were observed in approximately 33% of post‐crizotinib samples. Collectively, we report the prevalence of ROS1 fusions in a large‐scale NSCLC population and the efficacy of crizotinib in treating patients with ROS1‐rearranged NSCLC.

Abstract Recent studies have suggested that in addition to promoter region, DNA methylation in intragenic and intergenic regions also changes during physiological processes and disease. The current study showed that feeding of black raspberries (BRBs) to ApcMin mice suppressed colon and intestinal tumors. MBDCap‐seq suggested that dietary BRBs hypomethylated promoter, intragenic, and intergenic regions. Annotation of those regions highlighted genes in pathways involved in immune regulation, inflammatory signaling, production of nitric oxide and reactive oxygen species, and progression of colorectal cancer. BRB phytochemicals (e.g., ellagic acid, anthocyanins, oligosaccharides) and their gut bacterial metabolites (e.g., urolithin, protocatechuic acid, short‐chain fatty acids) inhibited DNMT1 and DNMT3B activities in a cell‐free assay. Our results suggest that BRBs’ hypomethylating activities result from the combined effects of multiple BRB phytochemicals and their gut bacterial metabolites. Because similar substances are found in many plant products, our results with BRBs might also apply to commonly consumed fruits and vegetables.

Immunoglobulin M (IgM) autoantibodies, as the early appearing antibodies in humoral immunity when stimulated by antigens, might be excellent biomarkers for the early detection of lung cancer (LC). We aimed to develop a multi-analyte integrative model combining IgM autoantibodies and a traditional tumor biomarker that could be a valuable and powerful auxiliary diagnostic tool and might improve the accuracy of early detection of lung adenocarcinoma (LUAD). A customized protein array based on cancer driver genes was constructed and applied in the discovery cohort consisting of 68 LUAD patients and 68 normal controls (NCs); 31 differentially expressed IgM autoantibodies were identified. The top 5 candidate IgM autoantibodies [based on the area under the receiver operating characteristic curve (AUC) ranking], namely, TSHR, ERBB2, survivin, PIK3CA, and JAK2, were validated in the validation cohort using enzyme-linked immunosorbent assay (ELISA), which included 147 LUAD samples, 72 lung squamous cell carcinoma (LUSC) samples, 44 small cell lung carcinoma (SCLC) samples, and 147 NCs. These indicators presented diagnostic capacity for LUAD, with AUCs of 0.599, 0.613, 0.579, 0.601, and 0.633, respectively (p

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck. In OSCC patients, the prognosis was dramatically different. In this research, we aimed to study the expressions and prognostic values of IgG Fc binding protein (FCGBP) in OSCC patients. The expression of FCGBP was analyzed using TCGA datasets and GEO datasets. FCGBP was evaluated for its predictive significance in OSCC patients by the use of a Kaplan-Meier and Cox regression model. Enrichment analysis for the GO and KEGG databases were conducted. CIBERSORT used TCGA datasets to show immune cell infiltration. In addition, researchers looked into the relationships between FCGBP and immune cells. The levels of FCGBP in OSCC cells was examined through the use of RT-PCR. FCGBP overexpression was tested for its effects on OSCC cell proliferation and invasion using CCK-8 and Transwell assays. We observed that FCGBP expressions were distinctly downregulated in OSCC specimens compared with nontumor tissues in both TCGA and GEO datasets, which was further confirmed by RT-PCR. OSCC patients with advanced clinical stages and poor prognoses had lower levels of FCGBP expression. Many immune-related biological activities and signaling pathways were found to be considerably abundant in KEGG tests and GO analysis results. The correlation analysis indicated that FCGBP was associated with a number of immune cells in a positive way. We found that FCGBP expressions were strongly and distinctly linked to the expressions of known immunological checkpoints, and FCGBP expression had significant positive connections with tumor mutational burden. FCGBP upregulation distinctly slowed the growth and invasion of OSCC cells in functional experiments. FCGBP has the potential to be a therapeutic target for OSCC and a biomarker for OSCC patients’ prognosis.

The agriculture sector is the backbone of the economies of many Asian countries such as India, China, and Bangladesh. The agriculture sector can contribute a major share to the GDP of such countries where the main occupation of the citizens is agriculture or the dependency of the citizens is mainly on the agricultural productivity. It is important to study the potential areas of agricultural economic resource development. The existing methods are not efficient enough to map the potential areas of agricultural productivity with economic resource development, and hence, it has motivated us to study the aspects which impact the economic resource development based on agricultural productivity. There are numerous factors such as low productivity, high irrigation amount, high labor charges, low proportion of planning optimization, and low crop yield that should be considered to study the correlation between economic development and agricultural productivity. Firstly, the spatial relationship of potential areas of agricultural economic resources development is analyzed in this paper. Secondly, the multiobjective linear programming model is proposed. Based on this multiobjective model, the optimal matching model for potential areas of agricultural economic resource development is constructed, and the improved genetic algorithm is used to solve the model to realize the optimal matching of potential areas of agricultural productivity and economic resource development. The experimental results show that the proposed method has high economic benefit, low irrigation amount, and high proportion of planning optimization with high crop yield.

Abstract Background The aim of this study was to identify prognostic long non-coding RNAs (lncRNAs) and develop a multi-lncRNA signature for suvival prediction in esophageal squamous cell carcinoma (ESCC). Methods The clinical and gene expression data from Gene Expression Omnibus database (GSE53624, n = 119) were obtianed as training set. A total of 98 paired ESCC tumor and normal tissues were detected by RNA sequencing and used as test set. Another 84 ESCC tissues were used for real-time quantitative PCR(qRT-PCR) and as an independent validation cohort. Survival analysis, Cox regression and Kaplan–Meier analysis were performed. Results We screened a prognostic marker of ESCC from the GSE53624 dataset and named it as the five-lncRNA signature including AC007179.1, MORF4L2-AS1, RP11-488I20.9, RP13-30A9.2, RP4-735C1.6, which could classify patients into high- and low-risk groups with significantly different survival(median survival: 1.75 years vs. 4.01 years, log rank P

Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Furthermore, we found that mTORC1/ mTORC2 inhibitor PP242 exhibited more efficacious anti-proliferative effect on ESCC cells than mTORC1 inhibitor RAD001 due to RAD001-triggered feedback activation of AKT signal. Another, we demonstrated that down-regulating expression of RICTOR in ECa109 and EC9706 cells inhibited proliferation and migration as well as induced cell cycle arrest and apoptosis. Noteworthy, knocking-down stably RICTOR significantly suppresses RAD001-induced feedback activation of AKT/PRAS40 signaling, and enhances inhibition efficacy of PP242 on the phosphorylation of AKT and PRAS40, thus potentiates the antitumor effect of RAD001 and PP242 both in vitro and in vivo. Our findings highlight that selective targeting mTORC2 could be a promising therapeutic strategy for future treatment of ESCC.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a low survival rate (9%). Epidemiologic studies show that healthy dietary patterns enriched of fruits and vegetables lower the risk of PDAC. We previously showed that supplementing black raspberries (BRBs) to patients with colorectal cancer increased tumor‐infiltrating NK cells and their cytotoxicity. We aimed to determine whether BRBs combat PDAC by modulating cancer immunity. NOD.SCID mice lacking T and B cells were injected with human Panc‐1‐Luc cells orthotopically, and immunocompetent KrasLSL.G12D/+‐Trp53LSL.R172H/+‐Pdx‐1‐Cre mice were fed BRBs. Peripheral blood mononuclear cells (PBMCs) from PDAC patients were treated with butyrate, a microbial metabolite of BRBs. The absence of T and B cells did not dampen BRBs’ antitumor effects in the NOD.SCID mice. In the KrasLSL.G12D/+‐Trp53LSL.R172H/+‐Pdx‐1‐Cre mice, BRBs significantly prolonged survival (189 days vs. 154 days). In both models, BRBs decreased tumor‐infiltrating CD11b+ cells and the expression of IL‐1β, sEH, and Ki67. BRBs also increased tumor‐infiltrating NKp46+ cells and the expression of CD107a, a functional marker of cytolytic NK and CD8+ T cells. In KrasLSL.G12D/+‐Trp53LSL.R172H/+‐Pdx‐1‐Cre mice, tumor infiltration of CD8+ T cells was increased by BRBs. Further using the PBMCs from PDAC patients, we show that butyrate decreased the population of myeloid‐derived suppressor cells (MDSCs). Butyrate also reversed CD11b+ cell‐mediated suppression on CD8+ T cells. Interestingly, there is a negative association between MDSC changes and patients’ survival, suggesting that the more decrease in MDSC population induced by butyrate treatment, the longer the patient had survived. Our study suggests the immune‐modulating potentials of BRBs in PDAC.

Abstract Esophageal carcinoma (EC) is a common malignant disease worldwide, especially in China. There is currently no specific blood test for detecting EC. Autoantibodies against tumor‐associated antigens (TAAbs) and microRNAs (miRNAs) are promising markers for cancer diagnosis and this study focuses on combining TAAbs and miRNAs to evaluate the diagnostic value in esophageal squamous cell carcinoma (ESCC). The expression levels of seven TAAbs and five microRNAs in plasmas from 125 patients diagnosed with ESCC and 125 healthy individuals were detected by enzyme‐linked immunosorbent assay (ELISA) and reverse transcription quantitative‐polymerase chain reaction (RT‐qPCR), respectively. The receiver operating characteristic (ROC) analysis was applied to estimate the diagnostic value of these markers for distinguishing ESCC patients from normal individuals. Logistic regression analysis was performed to generate prediction model and calculate the probability of individuals being diagnosed with ESCC. Three panels were established including four TAAbs, three miRNAs, and three TAAbs combined with three miRNAs. The panel consisting of three TAAbs (HCCR, C‐myc, and MDM2) and three miRNAs (miR‐21, miR‐223, and miR‐375) attained great diagnostic value for ESCC, with an area under the receiver operating characteristic curve (AUC) of 0.89 (95% CI: 0.85‐0.93) with the sensitivity of 69%, the specificity of 90%, the PPV of 83%, the NPV of 79%, and the coincidence rate of 81%. The optimal panel of six‐member markers was able to effectively discriminate the patients with ESCC from normal individuals, especially for early esophageal squamous cell carcinoma.