SIRT3 alleviates high glucose-induced chondrocyte injury through the promotion of autophagy and suppression of apoptosis in osteoarthritis progression.

A growing amount of epidemiological evidence proposes diabetes mellitus (DM) to be an independent risk factor for osteoarthritis (OA). Sirtuin 3 (SIRT3), which is mainly located in mitochondria, belongs to the family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases and is involved in the physiological and pathological processes of cell regulation. The aim of this study was to investigate the effects of SIRT3 on diabetic OA and underlying mechanisms in the prevention of type 2 DM (T2DM)-induced articular cartilage damage. High-fat and high-sugar diets combined with streptozotocin (STZ) injection were used for establishing an experimental T2DM rat model. The destabilization of medial meniscus (DMM) surgery was applied to induce the rat OA model. Primary rat chondrocytes were cultivated with a concentration of gradient glucose. Treatment with intra-articular injection of SIRT3 overexpression lentivirus was achieved in vivo, and intervention with SIRT3 knockdown was performed using siRNA transfection in vitro. High glucose content was found to activate inflammatory response, facilitate apoptosis, downregulate autophagy, and exacerbate mitochondrial dysfunction in a dose-dependent manner in rat chondrocytes, which can be deteriorated by SIRT3 knockdown. In addition, articular cartilage damage was found to be more severe in T2DM-OA rats than in DMM-induced OA rats, which can be mitigated by the intra-articular injection of SIRT3 overexpression lentivirus. Targeting SIRT3 is a potential therapeutic strategy for the alleviation of diabetic OA.

Preparation and Characterization of Multielement Composite Oxide Nanomaterials Containing Ce, Zr, Y, and Yb via Continuous Hydrothermal Flow Synthesis.

The synthesis of multielement composite oxide nanomaterials containing Ce, Zr, Y, and Yb was investigated using a micro confined jet mixer reactor operated in continuous mode under supercritical water conditions. The obtained nanoparticles were characterized using ICP-AES, SEM-EDS, FTIR, Raman spectroscopy, XRD, and TEM. All samples exhibited a uniform particle shape and a narrow particle size distribution. An analysis of the d-spacing results using selected electron area diffraction (SAED) patterns confirmed the production of cubic-phase crystals. A BET test was employed to determine the specific surface area of the prepared nanoparticles. OSC and TPR techniques were utilized to characterize the oxygen storage capacity and reduction performance of the obtained samples, with an analysis conducted to determine how the different proportions of elements affected the performance of multielement mixed oxides. The ionic conductivity of multielement composite oxide was measured using alternating current impedance spectroscopy (EIS), and the impact of Y, Ce, and Yb on the electrolyte material's ionic conductivity was analyzed.

Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting sirtuin 6.

Osteoarthritis (OA) is the most common type of arthritis and is an age-related joint disease that is particularly prevalent in subjects over 65 years old. The chronic rise of senescent cells has a close correlation with age-related diseases such as OA, and the senescence-associated secretory phenotype (SASP) is implicated in OA cartilage degeneration pathogenesis. Sirtuin 6 (SIRT6) is likely to be a key senescence-related regulator. Fisetin (FST) is a natural flavonol of the flavonoid family that is recommended as a senolytic drug to extend health and lifespan. However, the potential chondroprotective effects of FST on OA rats are largely unclarified. The aim of this study is to investigate the ameliorative effects of FST on OA joint cartilage and the relationship with SIRT6 and the detailed mechanisms from anti-inflammatory and anti-senescent perspectives. Rats were subjected to destabilization of the medial meniscus (DMM) surgery as a means of inducing the experimental OA model in vivo. Chondrocytes treated with IL-1ß were utilized for mimicking the OA cell model in vitro. Intra-articular injection of FST, OSS_128,167 (OSS, SIRT6 inhibitor), and MDL800 (MDL, SIRT6 agonist) in vivo or administering them in IL-1ß-induced rat chondrocytes in vitro were performed in order to determine the effects FST has on OA and the link with SIRT6. This study found SIRT6 level to be negatively correlated with OA severity. SIRT6 downregulation was validated in the joint cartilages of DMM rats and IL-1ß-treated chondrocytes. It was also notably demonstrated that FST can activate SIRT6. Both the administration of FST and activation of SIRT6 using MDL were found to rescue cartilage erosion, decrease extracellular matrix (ECM) degradation, prevent cartilage from apoptosis, and improve detrimental senescence-related phenotype. The alleviative effects of FST against inflammation, ECM degradation, apoptosis, and senescence in IL-1ß-stimulated chondrocytes were also confirmed. SIRT6 loss occurs in articular cartilage in OA pathogenesis, which is linked to aging. FST attenuates injury-induced aging-related phenotype changes in chondrocytes through the targeting of SIRT6.

Genetic algorithm-based semisupervised convolutional neural network for real-time monitoring of Escherichia coli fermentation of recombinant protein production using a Raman sensor.

As a non-destructive sensing technique, Raman spectroscopy is often combined with regression models for real-time detection of key components in microbial cultivation processes. However, achieving accurate model predictions often requires a large amount of offline measurement data for training, which is both time-consuming and labor-intensive. In order to overcome the limitations of traditional models that rely on large datasets and complex spectral preprocessing, in addition to the difficulty of training models with limited samples, we have explored a genetic algorithm-based semi-supervised convolutional neural network (GA-SCNN). GA-SCNN integrates unsupervised process spectral labeling, feature extraction, regression prediction, and transfer learning. Using only an extremely small number of offline samples of the target protein, this framework can accurately predict protein concentration, which represents a significant challenge for other models. The effectiveness of the framework has been validated in a system of Escherichia coli expressing recombinant ProA5M protein. By utilizing the labeling technique of this framework, the available dataset for glucose, lactate, ammonium ions, and optical density at 600 nm (OD600) has been expanded from 52 samples to 1302 samples. Furthermore, by introducing a small component of offline detection data for recombinant proteins into the OD600 model through transfer learning, a model for target protein detection has been retrained, providing a new direction for the development of associated models. Comparative analysis with traditional algorithms demonstrates that the GA-SCNN framework exhibits good adaptability when there is no complex spectral preprocessing. Cross-validation results confirm the robustness and high accuracy of the framework, with the predicted values of the model highly consistent with the offline measurement results.

Hsa_circ_0043603 promotes the progression of esophageal squamous cell carcinoma by sponging miR-1178-3p and regulating AADAC expression.

This study aims to investigate the regulatory impact of hsa_circ_0043,603, a circular RNA, on the progression of esophageal squamous cell carcinoma (ESCC), which ranks as the sixth leading cause of global mortality. We evaluated the expression, origin, and localization of hsa_circ_0043,603 in ESCC tumors using qRT-PCR, bioinformatics, and FISH analysis. Functional studies were conducted by manipulating the hsa_circ_0043,603 expression in Eca109 cells through overexpression and silencing plasmids. Additionally, xenografts derived from circ_0043,603-overexpressing Eca109 cells enabled us to investigate tumor growth, proliferation, and apoptosis. Through Starbase analysis, we identified miR-1178-3p as a target of circ_0043,603, which was validated using RIP and luciferase assays. Furthermore, we predicted arylacetamide deacetylase (AADAC) as a target of miR-1178-3p and examined its expression in ESCC tissues using Western blot. Lastly, we performed AADAC silencing and overexpression in Eca109 cells to study their impact on cellular phenotypic features, apoptosis, and their interaction with miR-1178-3p mimics and inhibitors. The low expression of hsa_circ_0043,603 in ESCC tissue was associated with poor prognosis. Overexpression of hsa_circ_0043,603 inhibited ESCC growth, invasion, migration, and proliferation, while promoting apoptosis in vitro and suppressing tumor growth in vivo. hsa_circ_0043,603 achieved these effects by targeting the oncogenic miR-1178-3p. Furthermore, AADAC was identified as a target of miR-1178-3p, and its reduced expression was confirmed in ESCC tissues. Overexpression of AADAC in Eca109 cells resulted in suppressed cell growth, proliferation, migration, and invasion by regulating miR-1178-3p. hsa_circ_0043,603 acts as a sponge for miR-1178-3p, leading to the regulation of AADAC expression and inhibition of ESCC development. These results suggest the potential of hsa_circ_0043,603 as a therapeutic and diagnostic target for ESCC.

Propensity score-matched analysis of enhanced recovery after surgery in total hip arthroplasty for displaced femoral neck fractures.

OBJECTIVE: The concept of enhanced recovery after surgery (ERAS) has been proposed in recent years, which indeed bring about evident convenience for the patients. This prospective cohort study was aimed to investigate the impact of ERAS on the clinical outcome of patients who undergoing total hip arthroplasty due to displaced femoral neck fractures. METHODS: Patients in two periods were included in our research, before ERAS (n = 194) and after ERAS (n = 65). The clinical outcome, such as patient statistics, details of perioperative management, length of stay (LOS), pain, Harris hip score, in-hospital complications, and interim postoperative survival were collected. This retrospective observational study addressed confounding bias using propensity score matching (PSM) analysis. RESULTS: With PSM, 55 pairs of well-matched patients were generated for comparison (conventional vs. ERAS). LOS decreased to 13.0 ± 3.2 days for the ERAS group, compared to 15.7 ± 3.5 days in the conventional group. VAS pain scores decreased significantly in both groups, and the decrease in the ERAS group was more significant than that in the conventional group at 3, 7, and 14 days postoperatively. The Harris scores of both groups significantly improved, but were better for the ERAS group than the conventional group at 7 and 14 days and 1 month postoperatively. However, no significant difference was observed at 6 months postoperatively. Additionally, the incidence of complications during hospitalization was lower in the ERAS group than that in the conventional group. No significant difference was observed in the medium-term survival between the two groups. CONCLUSIONS: ERAS apparently benefit patients in early rehabilitation by reducing complications and shortening hospital stays but not for the long-term hip function or survival.

Dapagliflozin suppress endoplasmic reticulum stress mediated apoptosis of chondrocytes by activating Sirt1.

OBJECTIVE: Osteoarthritis (OA) is a common joint disease characterized by inflammation and cartilage degeneration. Accumulating evidences support that endoplasmic reticulum (ER) stress induced OA chondrocytes apoptosis. The hypoglycemic and anti-inflammatory properties render Dapagliflozin (DAPA) effective in reducing ER stress on cells. However, its impact and potential mechanisms on the OA pathology are still obscure. The present study aimed to investigate whether DAPA attenuates ER stress in chondrocytes by activating sirt1 and delays the progression of OA. METHODS: In vitro, we first investigated the effect of DAPA on chondrocytes viability with IL-1ß or not for 24 or 48 h. Then, chondrocytes were treated with 10 ng/ml IL-1ß and 10 µM dapagliflozin with10 µM thapsigargin, 5 µM SRT1460 or not. Chondrocytes apoptosis in each group were detected by Tunel staining and flow cytometric. Immunofluorescence staining was applied to quantify the expression levels of cleaved caspase-3, Sirt1 and CHOP in chondrocytes. Inhibition of ER stress in chondrocytes associated with sirt1 activation were verified by PCR and western blotting. In addition, the effects of DAPA on cartilage were validated by a series of experiments in OA rat model, such as micro-CT, histological and immunohistochemical assay. RESULTS: The data demonstrated that DAPA alleviates IL-1ß induced ER stress related chondrocytes apoptosis, and PCR and western blotting data confirmed that DAPA inhibits the PERK-eIF2α-CHOP pathway by activating Sirt1. Besides, immunohistochemical results showed that DAPA enhanced the expression of Sirt1 and Collagen II in OA rats, and inhibited the expression of CHOP and cleaved caspase-3. Meanwhile, histological staining and micro-CT photography also confirmed that DAPA alleviated inflammation and cartilage degeneration in OA rat. CONCLUSIONS: The study demonstrated the relationship of ER stress and inflammation in the progression of OA, and verified that DAPA could inhibit PERK-eIF2α-CHOP axis of the ER stress response by activating Sirt1 in IL-1ß treated rat chondrocytes and potentially prevent the OA development.

Dissecting the role of lactate metabolism LncRNAs in the progression and immune microenvironment of osteosarcoma.

BACKGROUND: The process of lactate metabolism has been proved to play a critical role in the progression of various cancers and to influence the immune microenvironment, but its potential role in osteosarcoma remains unclear. METHODS: We have acquired transcriptomic and clinical data from 84 osteosarcoma samples and 70 normal bone samples from the TARGET and GTEx databases. We identified differentially expressed lactate metabolism-related LncRNAs (LRLs) in osteosarcoma and performed Cox regression and LASSO regression to establish LRLs prognostic signature (LRPS). The reliability of LRPS performance was examined by separate prognostic analysis, viability curves and receiver operating characteristic (ROC) curves. Furthermore, the effects of LRPS on the immune microenvironment of osteosarcoma were investigated, and the functions of the focal genes were experimentally validated. RESULT: A total of 856 differentially expressed LRLs were identified and 5 of them were selected to construct LRPS, which was a better prognostic predictor for osteosarcoma compared with other published prognostic signatures (AUC up to 0.947 and 0.839 in the training and test groups, respectively, with adj-p<0.05 for KM curves). We found that LRPS significantly affected the immune infiltration of osteosarcoma, while RP11-472M19.2 significantly promoted the metastasis of osteosarcoma, which was well validated experimentally. Encouragingly, a number of sensitive drugs were identified for LRPS and RP11-472M19.2 high-risk groups. CONCLUSION: Our study shows that lactate metabolism plays a crucial role in the development of osteosarcoma and has been well validated experimentally, providing extremely important insights into the clinical treatment and in-depth research of osteosarcoma.

Extracellular vesicles from human umbilical cord mesenchymal stem cells prevent steroid-induced avascular necrosis of the femoral head via the PI3K/AKT pathway.

Extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stem cells (hucMSC) have excellent therapeutic potential for many diseases. The aim of this study was to define the role of hucMSC-EVs in the prevention and treatment of steroid-induced avascular necrosis of the femoral head (SANFH). After establishing the SANFH rat model, the effects of hucMSC-EVs were assessed by measuring the microstructure of the femoral head using HE staining, micro-computed tomography (micro-CT), and TUNEL staining. The administration of hucMSC-EVs caused a significant reduction to glucocorticoids (GCs)-induced osteoblast apoptosis and empty lacuna of the femoral head, while effectively improving the microstructure. HucMSC-EVs rescued the deactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway induced by GCs, and reversed the proliferation and migration of osteoblasts inhibited by GCs. In addition, hucMSC-EVs attenuated the inhibitory effects of GCs on rat osteoblast osteogenesis, angiogenesis of endothelial cells, and prevented osteoblast apoptosis. However, the promoting effects of hucMSC-EVs were abolished following the blockade of PI3K/AKT on osteoblasts. hucMSC-EVs were found to prevent glucocorticoid-induced femoral head necrosis in rats through the PI3K/AKT pathway.

Gambogenic acid induces cell death in human osteosarcoma through altering iron metabolism, disturbing the redox balance, and activating the P53 signaling pathway.

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents with extremely poor prognosis. Gambogenic acid (GNA), one of the major bioactive ingredients isolated from Gamboge, has been shown to possess a multipotent antitumor effect, its activity on OS remains unclear yet. In this study, we found that GNA could trigger multiple cell death modalities, including ferroptosis and apoptosis in human OS cells, reduce the cell viability, inhibit the proliferation and invasiveness. Furthermore, GNA provoked oxidative stress leading to GSH depletion-inducing ROS generation and lipid peroxidation, altered iron metabolism represented by the induction of labile iron, mitochondrial membrane potential decreased, mitochondrial morphological changed, decreased the cell viability. In addition, ferroptosis inhibitors (Fer-1) and apoptosis inhibitors (NAC) can partially reversed GNA' s effects on OS cells. Further investigation showed that GNA augmented the expression of P53, bax, caspase 3 and caspase 9 and decreased the expression of Bcl-2, SLC7A11 and glutathione peroxidase-4 (GPX4). In vivo, GNA was showed to delay tumor growth significantly in axenograft osteosarcoma mouse model. In conclusion, this study reveals that GNA simultaneously triggers ferroptosis and apoptosis in human OS cells by inducing oxidative stress via the P53/SLC7A11/GPX4 axis.

CFD-PBM Simulation for Continuous Hydrothermal Flow Synthesis of Zirconia Nanoparticles in a Confined Impinging Jet Reactor.

Computational fluid dynamics (CFD) and population balance models (PBM) were coupled together for the first time to simulate the synthesis of zirconia nanoparticles in a continuous hydrothermal flow synthesis (CHFS) system with a self-designed confined impinging jet mixing (CJM) reactor. The hydrodynamic and thermodynamic behaviors within the CJM reactor strongly influenced the formation of the ZrO2 nanoparticles. Crucial parameters, such as velocities, temperatures, mixing conditions, and reaction rates, were analyzed under various supercritical conditions. Temperature and velocity measurements as functions of distance were also investigated. Normal particle size distribution (PSD) patterns were observed in all cases. The mean particle sizes in this study were calculated and compared using PBM aggregation analysis.

Effect of Emergency Percutaneous Coronary Intervention Combined with Sacubitril and Valsartan on the Cardiac Prognosis in Patients with Acute Myocardial Infarction.

Purpose: This study aimed to investigate the effect of emergency percutaneous coronary intervention (PCI) combined with sacubitril-valsartan (Entresto) on the cardiac prognosis in patients with acute myocardial infarction (AMI). Patients and Methods: A total of 78 AMI patients who were treated in our hospital between January 2020 and September 2021 were included and randomly divided into treatment group and control group (n=39 per group). In the control group, patients were treated with primary PCI combined with irbesartan; in the treatment group, patients were treated with primary PCI combined with Entresto; pharmacotherapy lasted for 3 months. The left ventricular remodeling indexes, serum N-terminal B-type natriuretic peptide precursor (NT-proBNP), serum homocysteine (HCY), cystatin C (CysC) and results of 6-minute walk test (6MWT) before and after treatment were compared between two groups. The incidence of major adverse cardiovascular events (MACE) was determined and compared between them. Results: (1) Before treatment, there were no marked differences in the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness (IVST), NT-proBNP, left ventricular ejection fraction (LVEF), HCY, CysC, and results of 6MWT between two groups (P>0.05). After treatment, the LVEDS, LVEDD, NT-proBNP, HCY and CysC in the control group were significantly higher than in the treatment group (P<0.05). The recovery of LVEF and 6MWT in the treatment group was significantly better than in the control group (P<0.05). After treatment, there was no significant difference in the IVST between two groups (P>0.05). (2) The incidence of MACE in the control group was significantly higher than in the treatment group (P<0.05). Conclusion: Compared with irbesartan, Entresto can further improve the cardiac function, prevent ventricular remodeling, and further optimize the clinical efficacy of PCI in AMI patients.

Astaxanthin attenuates osteoarthritis progression via inhibiting ferroptosis and regulating mitochondrial function in chondrocytes.

Ferroptosis is a novel form of regulated cell death that has a close association with mitochondrial dysfunction and is characterized by iron overload, the accumulation of reactive oxygen species (ROS), and lipid ROS. Chondrocytes ferroptosis accelerates the progression of osteoarthritis (OA). Astaxanthin (ATX) is a xanthophyll carotenoid that possesses anti-inflammatory and antioxidant properties and has been explored in research studies for the treatment of diabetes and cardiovascular disease. However, the role it plays in OA, particularly in chondrocyte ferroptosis, has not yet been reported. In this study, ferroptosis-related events were analyzed in rat chondrocytes in vitro. A surgical destabilized medial meniscus was performed for the establishment of in vivo OA model. The results showed that interleukin-1ß (IL-1ß) induced inflammatory injury in chondrocytes through the promotion of the expressions of inflammatory factors including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2). IL-1ß triggered chondrocyte ferroptosis by increasing the levels of intracellular ROS, lipid ROS, iron, and mitochondrial iron and inhibiting the expressions of SLC7A11/glutathione peroxidase 4 (GPX4) and Ferritin. The above indices were ameliorated by ferrostatin-1 (Fer-1, a classic ferroptosis inhibitor) and ATX. Furthermore, Fer-1 and ATX rescued the IL-1ß-induced down-regulating collagen type II (collagen Ⅱ) and up-regulating matrix metalloproteinase 13 (MMP13). Following treatment with IL-1ß, mitochondrial membrane potential decreased and the mitochondrial membrane was broken. At the same time, the mitochondrion shrank, becoming deformed as the mitochondrial cristae reduced and became disrupted. These changes were entirely consistent with ferroptosis features. All the aforementioned phenomena were reversed by Fer-1 and ATX. In addition, intra-articular injection of Fer-1 and ATX delayed articular cartilage degradation and OA progression. This study demonstrated that IL-1ß can induce inflammatory damage and ferroptosis in chondrocytes. Both Fer-1 and ATX have the ability to mitigate chondrocyte injury and osteoarthritis progression by inhibiting ferroptosis and the regulation of mitochondrial function. Targeting ferroptosis has the potential to be a promising future treatment method for OA.

Meta-analysis of the effect of low-level occupational benzene exposure on human peripheral blood leukocyte counts in China.

To investigate the effect of low-level occupational benzene exposure on human peripheral blood leukocyte counts of the workers, domestic and foreign published research data on the change of human peripheral blood leukocyte counts under low-level occupational benzene exposure from January 1990 to December 2020 were collected and analyzed. According to the literature inclusion and exclusion criteria, 18 independent studies from 12 publications were selected for meta-analysis to explore the effect of low-level occupational benzene exposure on human peripheral blood leukocyte counts. The results showed that the peripheral blood leukocyte counts abnormal rates of low-level occupational benzene exposure group were higher than those of the control group, and the difference was statistically significant. Low-level occupational benzene exposure could result in a relatively higher abnormal rate of peripheral blood leukocyte counts in the exposed population, indicating that low-level occupational benzene exposure at workplaces specified by the current benzene occupational exposure limit in China would affect the peripheral blood leukocyte counts of the workers, thus benzene with concentrations under the limit in the ambient air of workplace could be still harmful to the health of the exposed workers. The results of this study could provide a scientific basis for future revision of the benzene occupational exposure limit in China, and could also be a reference for the formulation of environmental standard concerning benzene in China in the future.

Long-chain alkanes in the atmosphere: A review.

As a representative species of intermediate volatile organic compounds (IVOCs), long-chain alkanes are considered to be important precursors of secondary organic aerosols (SOA) in the atmosphere. This work reviews the previous studies on long-chain alkanes in the atmosphere: (1) the detection methods and filed observations of long-chain alkanes in both gas and particle phases are summarized briefly; (2) the laboratory studies of long chain alkanes are reviewed, the kinetic data, reaction mechanism, SOA yields, and physicochemical properties of SOA are included in detail; (3) the research progress related to model simulations of long-chain alkanes are also discussed. In addition, based on available research results, several perspective contents are proposed that can be used as a guideline for future research plans.

Continuous Hydrothermal Flow Synthesis and Characterization of ZrO2 Nanoparticles Doped with CeO2 in Supercritical Water.

A confined jet mixing reactor operated in continuous hydrothermal flow synthesis was investigated for the synthesis of CeO2-ZrO2 (CZ) nanoparticles. The obtained ultrafine powders were characterized using scanning electron microscopy-energy dispersive spectrometry (SEM-EDS), inductively coupled plasma-atomic emission spectroscopy (ICP-AES), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscopy (TEM) coupled with selected area electron diffraction (SAED), a BET (Brunauer-Emmett-Teller)-specific surface area test and pore analysis, oxygen storage capacity (OSC) test, and a H2 temperature programmed reduction (H2-TPR) test. The XRD results show that all samples were composed of high-purity cubic CZ nanoparticles. High resolution transmission electron microscope (HR-TEM) analysis showed that CZ nanoparticles with uniform size and shape distributions were obtained in this investigation. The d-spacing values, determined based on the TEM-selected area electron diffraction (SAED) patterns, were in good agreements with the reference data. BET results showed that the prepared CZ samples had large specific surface areas. Pore volume and size distribution were obtained by pore analysis. Oxygen pulse adsorption technology was used to test the oxygen storage capacity of the sample. The redox capacity of the CZ material was determined by a H2 temperature-programmed reduction test.

Analysis of Threshold Change of Tumor Mutation Burden in Gastric Cancer.

BACKGROUND: The purpose of this study was to investigate the change of tumor mutation burden (TMB) in gastric cancer (GC) and its relationship with prognosis. METHODS: A total of 262 patients with GC from January 2018 to December 2019 were included in this study. All patients were in the advanced stage and were treated with surgical removal of D2 lymph nodes and dissection. Clinical data and gene expression profile data of the GC dataset in The Cancer Genome Atlas were collected. Patients were randomly divided into a high-level group and a low-level group according to the TMB of 8 mutations/Mb. TMB of GC was calculated based on cell mutation data. Cox regression model was used to evaluate the relationship between TMB and prognosis of GC patients. RESULTS: The total mutation rate of 262GC patients was 92.85%. The top 5 mutant genes were TP53, RB1, ARID1A, KMT2B, and RET. The expression level of TMB in GC patients was statistically significant with age, drinking history, and differentiation type. 94 of the 262 patients died, and 168 survived during the follow-up period. Patients with a high level of TMB had a worse prognosis than those with low level of TMB. The results of univariate and multivariate logistic analysis showed that the overall survival rate of GC patients was statistically significant with age, drinking history, clinical stage, differentiation type, and TMB. CONCLUSION: GC patients are often accompanied by changes in TMB, and its expression level is closely related to the degree of pathological differentiation, which is an independent factor affecting the prognosis of GC patients. High TMB value can evaluate the prognosis and provide a reference for the formulation of clinical treatment plans for GC patients.

Heavy ozone pollution episodes in urban Beijing during the early summertime from 2014 to 2017: Implications for control strategy.

Ground-level ozone (O3) has become the principal air pollutant in Beijing during recent summers. In this context, an investigation of ambient concentrations and variation characteristics of O3 and its precursors in May and June from 2014 to 2017 in a typical urban area of Beijing was carried out, and the formation sensitivity and different causes of heavy O3 pollution (HOP, daily maximum 8-h O3 (MDA8h O3)>124 ppbv) were analyzed. The results showed that the monthly assessment values of the O3 concentrations (the 90th percentile MDA8h O3 within one month) were highest in May or June from 2014 to 2017, and the values presented an overall increasing trend. During this period, the number of O3 pollution days (MDA8h O3 > 75 ppbv) also showed an increasing trend. During the HOP episodes, the concentrations of volatile organic compounds (VOCs), nitrogen oxides (NOX), and carbon monoxide (CO) were higher than their respective mean values in May and June, and the meteorological conditions were more conducive to atmospheric photochemical reactions. The HOP episodes were mainly caused by local photochemical formation. From 2014 to 2017, O3 formation during the HOP episodes shifted from VOC and NOX mixed-limited to VOC-limited conditions, and O3 formation was most sensitive to anthropogenic VOCs. Six categories of VOC sources were identified, among which vehicular exhaust contributed the most to anthropogenic VOCs. The VOC concentrations and OFPs of anthropogenic sources have decreased significantly in recent years, indicating that VOC control measures have been effective in Beijing. Nevertheless, NOX concentrations did not show an evident decreasing trend in the same period. Therefore, more attention should be devoted to O3 pollution control in May and June; control measure adjustments are needed according to the changes in O3 precursors, and coordinated control of VOCs and NOX should be strengthened in long-term planning.

A large-scale outdoor atmospheric simulation smog chamber for studying atmospheric photochemical processes: Characterization and preliminary application.

Understanding the formation mechanisms of secondary air pollution is very important for the formulation of air pollution control countermeasures in China. Thus, a large-scale outdoor atmospheric simulation smog chamber was constructed at Chinese Research Academy of Environmental Sciences (the CRAES Chamber), which was designed for simulating the atmospheric photochemical processes under the conditions close to the real atmospheric environment. The chamber consisted of a 56-m3 fluorinated ethylene propylene (FEP) Teflon film reactor, an electrically-driven stainless steel alloy shield, an auxiliary system, and multiple detection instrumentations. By performing a series of characterization experiments, we obtained basic parameters of the CRAES chamber, such as the mixing ability, the background reactivity, and the wall loss rates of gaseous compounds (propene, NO, NO2, ozone) and aerosols (ammonium sulfate). Oxidation experiments were also performed to study the formation of ozone and secondary organic aerosol (SOA), including α-pinene ozonolysis, propene and 1,3,5-trimethylbenzene photooxidation. Temperature and seed effects on the vapor wall loss and SOA yields were obtained in this work: higher temperature and the presence of seed could reduce the vapor wall loss; SOA yield was found to depend inversely on temperature, and the presence of seed could increase SOA yield. The seed was suggested to be used in the chamber to reduce the interaction between the gas phase and chamber walls. The results above showed that the CRAES chamber was reliable and could meet the demands for investigating tropospheric chemistry.

Silencing of Odorant-Binding Protein Gene OBP3 Using RNA Interference Reduced Virus Transmission of Tomato Chlorosis Virus.

Tomato chlorosis virus (ToCV) is widespread, seriously impacting tomato production throughout the world. ToCV is semi-persistently transmitted by Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Currently, insect olfaction is being studied to develop novel pest control technologies to effectively control B. tabaci and whitefly-borne virus diseases. Despite current research efforts, no report has been published on the role of odorant-binding proteins (OBPs) in insect preference under the influence of plant virus. Our previous research showed that viruliferous B. tabaci preferred healthy plants at 48 h after virus acquisition. In this study, we determined the effect of OBPs on the host preference interactions of ToCV and whiteflies. Our results show that with the increase in acquisition time, the OBP gene expressions changed differently, and the OBP3 gene expression showed a trend of first rising and then falling, and reached the maximum at 48 h. These results indicate that OBP3 may participate in the host preference of viruliferous whiteflies to healthy plants. When the expression of the OBP3 gene was knocked down by an RNA interference (RNAi) technique, viruliferous Mediterranean (MED) showed no preference and the ToCV transmission rate was reduced by 83.3%. We conclude that OBP3 is involved in the detection of plant volatiles by viruliferous MED. Our results provide a theoretical basis and technical support for clarifying the transmission mechanism of ToCV by B. tabaci and could provide new avenues for controlling this plant virus and its vectors.