Trends of older gastric cancer incidence, mortality, and survival in the highest gastric cancer risk area in China: 2010-2019 and prediction to 2024.

BACKGROUND: Gastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024. METHODS: The study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi's world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024. RESULTS: Based on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77-4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5-63.2%) in 2010 to 34.4% (95%CI, 32.1-36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5-55.1%) in 2010 to 34.2% (95%CI, 32.0-36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024. CONCLUSION: From 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years.

Application of Survival Quilts for prognosis prediction of gastrectomy patients based on the Surveillance, Epidemiology, and End Results database and China National Cancer Center Gastric Cancer database.

Objective: Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients. We aimed to develop and test 6-month, 1-, 2-, 3-, 5-, and 10-year overall survival (OS) and cancer-specific survival (CSS) prediction models for gastric cancer patients following gastrectomy. Methods: We derived and tested Survival Quilts, a machine learning-based model, to develop 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS prediction models. Gastrectomy patients in the development set (n = 20,583) and the internal validation set (n = 5,106) were recruited from the Surveillance, Epidemiology, and End Results (SEER) database, while those in the external validation set (n = 6,352) were recruited from the China National Cancer Center Gastric Cancer (NCCGC) database. Furthermore, we selected gastrectomy patients without neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis (TNM) stage. Prognostic performances of these OS and CSS models were assessed using the Concordance Index (C-index) and area under the curve (AUC) values. Results: The machine learning model had a consistently high accuracy in predicting 6-month, 1-, 2-, 3-, 5-, and 10-year OS in the SEER development set (C-index = 0.861, 0.832, 0.789, 0.766, 0.740, and 0.709; AUC = 0.784, 0.828, 0.840, 0.849, 0.869, and 0.902, respectively), SEER validation set (C-index = 0.782, 0.739, 0.712, 0.698, 0.681, and 0.660; AUC = 0.751, 0.772, 0.767, 0.762, 0.766, and 0.787, respectively), and NCCGC set (C-index = 0.691, 0.756, 0.751, 0.737, 0.722, and 0.701; AUC = 0.769, 0.788, 0.790, 0.790, 0.787, and 0.788, respectively). The model was able to predict 6-month, 1-, 2-, 3-, 5-, and 10-year CSS in the SEER development set (C-index = 0.879, 0.858, 0.820, 0.802, 0.784, and 0.774; AUC = 0.756, 0.827, 0.852, 0.863, 0.874, and 0.884, respectively) and SEER validation set (C-index = 0.790, 0.763, 0.741, 0.729, 0.718, and 0.708; AUC = 0.706, 0.758, 0.767, 0.766, 0.766, and 0.764, respectively). In multivariate analysis, the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set (hazard ratio [HR] = 14.59, 95% confidence interval [CI]: 1.872-2.774, P < 0.001), SEER validation set (HR = 2.28, 95% CI: 13.089-16.293, P < 0.001), and NCCGC set (HR = 1.98, 95% CI: 1.617-2.437, P < 0.001). We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients, and found that high-risk group remained as an independent CSS factor in the SEER development set (HR = 12.81, 95% CI: 11.568-14.194, P < 0.001) and SEER validation set (HR = 1.61, 95% CI: 1.338-1.935, P < 0.001). Conclusion: Survival Quilts could allow accurate prediction of 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS in gastric cancer patients following gastrectomy.

Sex disparity, prediagnosis lifestyle factors, and long-term survival of gastric cancer: a multi-center cohort study from China.

BACKGROUND: This multi-center cohort study aimed to investigate whether sex and prediagnosis lifestyle affect the prognosis of gastric cancer. METHODS: Patients with gastric cancer were from four gastric cancer cohorts of the National Cancer Center of China, The First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Provincial Cancer Hospital. Prediagnosis lifestyle factors in our study included body mass index (BMI) at diagnosis, usual BMI, weight loss, the history of Helicobacter pylori (Hp) infection, and the status of smoking and drinking. RESULTS: Four gastric cancer cohorts with 29,779 gastric cancer patients were included. In total patients, female patients had a better prognosis than male patients (HR = 0.938, 95%CI: 0.881-0.999, P = 0.046). For prediagnosis lifestyle factors, BMI at diagnosis, usual BMI and the amount of smoking were statistically associated with the prognosis of gastric cancer patients. Female patients with smoking history had a poorer survival than non-smoking females (HR = 0.782, 95%CI: 0.616-0.993, P = 0.044). Tobacco consumption > 40 cigarettes per day (HR = 1.182, 95%CI: 1.035-1.350, P = 0.013) was independent adverse prognostic factors in male patients. Obesity paradox was observed only in male patients (BMI < 18.5, HR = 1.145, 95%CI: 1.019-1.286, P = 0.023; BMI: 23-27.4, HR = 0.875, 95%CI: 0.824-0.930, P < 0.001; BMI ≥ 27.5, HR = 0.807, 95%CI: 0.735-0.886, P < 0.001). CONCLUSIONS: Sex and some prediagnosis lifestyle factors, including BMI at diagnosis, usual BMI and the amount of smoking, were associated with the prognosis of gastric cancer.

NQO1 promotes osteogenesis and suppresses angiogenesis in DPSCs via MAPK pathway modulation.

BACKGROUND: Influence on stem cells' angiogenesis and osteogenesis of NAD(P)H Quinone Dehydrogenase 1(NQO1) has been established, but its impact on dental pulp stem cells (DPSCs) is unexplored. An important strategy for the treatment of arteriosclerosis is to inhibit calcium deposition and to promote vascular repair and angiogenesis. This study investigated the function and mechanism of NQO1 on angiogenesis and osteogenesis of DPSCs, so as to provide a new ideal for the treatment of arteriosclerosis. METHODS: Co-culture of human DPSCs and human umbilical vein endothelial cells (HUVECs) was used to detect the angiogenesis ability. Alkaline phosphatase (ALP) activity, alizarin red staining (ARS), and transplantation of HA/tricalcium phosphate with DPSCs were used to detect osteogenesis. RESULTS: NQO1 suppressed in vitro tubule formation, migration, chemotaxis, and in vivo angiogenesis, as evidenced by reduced CD31 expression. It also enhanced ALP activity, ARS, DSPP expression and osteogenesis and boosted mitochondrial function in DPSCs. CoQ10, an electron transport chain activator, counteracted the effects of NQO1 knockdown on these processes. Additionally, NQO1 downregulated MAPK signaling, which was reversed by CoQ10 supplementation in DPSCs-NQO1sh. CONCLUSIONS: NQO1 inhibited angiogenesis and promoted the osteogenesis of DPSCs by suppressing MAPK signaling pathways and enhancing mitochondrial respiration.

[Advances in Research of the Effects and Mechanisms of Polyethylene Microplastics on Soil Nitrogen Transformation].

In the agricultural lands of China, polyethylene is the main component of microplastics （MPs）, with characteristics such as small size, wide distribution, easy accumulation, and difficult degradation. Therefore, it may have an impact on the elemental cycling process of the soil. On the basis of reviewing the key literatures in the past few years, this study systematically analyzed and summarized the key factors and processes of the polyethylene microplastics （PE-MPs） affecting soil nitrogen transformation. On the one hand, PE-MPs directly affected the activities of microorganisms and key enzymes related to soil nitrogen transformation by enriching microorganisms, selecting colonized microbial populations, and releasing additives. On the other hand, PE-MPs had indirect impacts on the activities of microorganisms and key enzymes related to soil nitrogen transformation by affecting soil physicochemical properties of soil and changing the microenvironment for microbial growth. Moreover, phthalates, an important additive of the MPs, may be the key factor affecting soil nitrogen transformation in the short-term. Finally, we posed key scientific issues that should be further studied in order to provide scientific support for nitrogen nutrition regulation and ecological risk assessment of soils contaminated by PE-MPs.

A Comparative Evaluation of Three Diagnostic Assays for the Detection of Human Monkeypox.

Accurate and early diagnosis of monkeypox virus (MPXV) is crucial for controlling epidemics and treating affected individuals promptly. This study aimed to assess the analytical and clinical performance of the MolecisionTM Monkeypox Virus qPCR Assay, Biorain Monkeypox Virus ddPCR Assay, and MAGLUMI® Monkeypox Virus Ag (chemiluminescence immunoassay, CLIA) Assay. Additionally, it aimed to compare the clinical application of antigen and nucleic acid assays to offer insights into using commercial monkeypox assay kits. Specimens from 117 clinical patients, serial diluted virus cell culture supernatant, and artificially created positive samples were tested to evaluate the performance of these assay kits for MPXV diagnostics. The Biorain Monkeypox Virus ddPCR Assay had a limit of detection (LoD) of 3.89 CCID50/mL, while the MolecisionTM Monkeypox Virus qPCR Assay had an LoD of 15.55 CCID50/mL. The MAGLUMI® Monkeypox Virus Ag (CLIA) Assay had an LoD of 0.500 pg/mL. The accuracy of the MolecisionTM Monkeypox Virus qPCR Assay was comparable to the Biorain Monkeypox Virus ddPCR Assay, and the MAGLUMI® Monkeypox Virus Ag (CLIA) Assay demonstrated high sensitivity. The specificity of all three MPXV diagnostic assays for clinical specimens with potential cross-reacting substances was 100%. In conclusion, this study provides valuable insights into the clinical application of monkeypox assays, supporting efforts to mitigate and control the spread of monkeypox.

Impact analysis of dust evolution pattern and determination of key ventilation parameters in highland highway construction tunnels.

In order to study the influence of ventilation parameters on the ventilation of plateau highway construction tunnels, a highway tunnel construction section in Yunnan is taken as the research background, and Fluent software is used for simulation. The results of the study show that: under the conditions of press-in ventilation, the wind speed in the center of the vortex area in the wind flow field is smaller than the wind speed in the surrounding area, and with the diffusion of the flow field, the average wind speed in the tunnel section gradually decreases, and ultimately stabilizes at the level of 0.5 m/s. After blasting, the dust mass concentration on the return side of the tunnel is higher than that on the duct side. Dust with a particle size of 30 µm or more settled rapidly within 100 m from the boring face, while dust with a particle size of 30 µm or less gradually diffused outward under the action of the wind flow. In the vicinity of the tunnel boring face, reducing the distance from the air outlet to the boring face and increasing the air velocity can improve the dust removal effect. This conclusion can provide theoretical basis and certain guidance for the evolution of dust and dust prevention in the tunnel construction process in plateau area.

The metabolic pathways of carbon assimilation and polyhydroxyalkanoate production by Rhodospirillum rubrum in response to different atmospheric fermentation.

The purple nonsulfur bacteria, Rhodospirillum rubrum, is recognized as a potential strain for PHAs bioindustrial processes since they can assimilate a broad range of carbon sources, such as syngas, to allow reduction of the production costs. In this study, we comparatively analyzed the biomass and PHA formation behaviors of R. rubrum under 100% CO and 50% CO gas atmosphere and found that pure CO promoted the PHA synthesis (PHA content up to 23.3% of the CDW). Hydrogen addition facilitated the uptake and utilization rates of CO and elevated 3-HV monomers content (molar proportion of 3-HV up to 9.2% in the presence of 50% H2). To elucidate the genetic events culminating in the CO assimilation process, we performed whole transcriptome analysis of R. rubrum grown under 100% CO or 50% CO using RNA sequencing. Transcriptomic analysis indicated different CO2 assimilation strategy was triggered by the presence of H2, where the CBB played a minor role. An increase in BCAA biosynthesis related gene abundance was observed under 50% CO condition. Furthermore, we detected the α-ketoglutarate (αKG) synthase, converting fumarate to αKG linked to the αKG-derived amino acids synthesis, and series of threonine-dependent isoleucine synthesis enzymes were significantly induced. Collectively, our results suggested that those amino acid synthesis pathways represented a key way for carbon assimilation and redox potential maintenance by R. rubrum growth under syngas condition, which could partly replace the PHA production and affect its monomer composition in copolymers. Finally, a fed-batch fermentation of the R. rubrum in a 3-l bioreactor was carried out and proved H2 addition indeed increased the PHA accumulation rate, yielding 20% ww-1 PHA production within six days.

Patients with advanced cancer were treated with immune checkpoint inhibitors and injected with COVID-19 vaccine to improve their prognosis without increasing pancreatic related adverse events.

To investigate immune checkpoint inhibitors (ICIs) induced pancreatic injury (ICIPI), the prognostic effect of COVID-19 vaccine on cancer patients, and whether COVID-19 vaccine increases the incidence of ICIPI. We conducted a retrospective study of 256 stage IV cancer patients treated with ICIs at The First Affiliated Hospital of Anhui Medical University from January 2020 to November 2022. Data collected included pancreatic enzyme levels, treatment outcomes, and vaccination status. Statistical significance was determined using the χ2 test and Kaplan-Meier method (p < .05). Compared to the control group, the vaccinated group (p < .0001) and the group with elevated pancreatic enzyme levels (p = .044) demonstrated higher disease control rates, indicating a direct benefit of vaccination and enzyme monitoring on treatment outcomes. Additionally, vaccinated patients demonstrated longer overall survival versus unvaccinated patients (23.9 months [95% CI, 22.3-25.5] vs 23.6 months [95% CI, 21.1-26.2], HR = 0.45 [95% CI, 0.24-0.86], p = .015) and progression-free survival (17.2 months [95% CI, 14.3-20.1] vs 13.7 months [95% CI, 11.3-16.1], HR = 0.54 [95% CI, 0.36-0.82], p = .004). Importantly, the analysis revealed no significant association between vaccination and pancreatic injury (p = .46). Monitoring pancreatic enzymes can effectively evaluate the therapeutic impact in patients using ICIs. Patients vaccinated against COVID-19 experience better immunotherapy outcomes without an increased risk of ICIPI.

STL Inhibited Angiogenesis of DPSCs Through Depressing Mitochondrial Respiration by Enhancing RNF217.

Angiogenesis is the determining factor during dental pulp regeneration. Six-twelve leukemia (STL) is identified as a key regulatory factor on the biological function of dental pulp stem cells (DPSCs) under hypoxic conditions, but its effect on angiogenesis is unclear. Co-culture of DPSCs and human umbilical vein endothelial cells (HUVECs) is used to detect tubule formation ability in vitro and the angiogenesis ability in vivo. RNA-seq and bioinformatic analyses are performed to screen differentially expressed genes. Seahorse Cell Mito Stress Test is proceeded to exam mitochondrial respiration. STL decreased tubule formation and mitochondrial respiration of DPSCs in vitro and restrained the number of blood vessels and the expression of VEGF in new formed tissue in vivo. Furthermore, pretreating STL-depleted DPSCs with rotenone, a mitochondrial respiration inhibitor, counteracted the promoting effect of STL knockdown on tubule formation. Then, RNA-seq and bioinformatic analyses identified some angiogenesis relevant genes and pathways in STL-depleted DPSCs. And STL enhanced expression of mRNA-ring finger protein 217 (RNF217), which inhibited the tubule formation and mitochondrial respiration of DPSCs. STL inhibited the angiogenesis of DPSCs through depressing mitochondrial respiration by enhancing RNF217, indicating that STL is a potential target for angiogenesis of DPSCs.

Risk Factors of Chemotherapy-Induced Thrombocytopenia After Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancies.

PURPOSE: Thrombocytopenia is among the most common chemotherapy-related hematologic toxicities. We aim to determine the predictors of oxaliplatin chemotherapy-induced thrombocytopenia in patients with gastrointestinal tumors to guide the clinic. METHODS: Clinical data of 750 patients with a malignant gastrointestinal tumor were included as the primary cohort. Basic clinical data, serological indices, and anthropometric indices of these patients were collected. According to the presence or absence of CIT, univariate analysis was performed to identify significant factors for multivariate analysis. In R language software, nomogram was constructed based on the results of multi-factor analysis, and the calibration curve and ROC curve were drawn. RESULTS: Univariate analysis identified 17 factors as closely related to CIT occurrence, namely age, lymph node metastasis (N) stage, metastasis (M) stage, lung metastasis, other site metastasis, chemotherapy regimen, course of treatment, total dose of oxaliplatin, AST, albumin, neutrophils, monocytes, baseline platelets, transferrin, natural killer (NK) cell, phase angle, and SMI (P < 0.10). The binary logistic multivariate regression analysis revealed five independent risk factors for developing CIT (P < 0.05), including the M stage, total dose of oxaliplatin, albumin, baseline thrombocyte count, and NK cell. Based on the results of multivariate logistic regression analysis, R software was used to establish a nomogram model. The calibration curve shows that the combined predictor has good consistency. The area under the ROC curve was 0.877 and the best cut-off value was 0.3579613 (sensitivity, 78.9%; specificity, 81.8%), which showed the better prediction efficiency. CONCLUSION: The total dose of oxaliplatin, M stage, albumin, baseline platelet count, and NK cell was independent risk factors for CIT. The sequentially constructed histogram model had a good predictive effect on the risk of thrombocytopenia caused by oxaliplatin chemotherapy in patients with gastrointestinal malignancies.

Blood transfusion might not be recommended for gastric cancer patients with pretransfusion minimum hemoglobin values higher than 90 g/L: a real-world study covering 20 years of 13470 patients.

BACKGROUND: There was no consistent evidence whether perioperative blood transfusion (PBT) affects the long-term survival of gastric cancer (GC) patients after undergoing gastrectomy. This study aimed to investigate the effects of PBT on long-term survival of GC patients, as well as to determine the threshold of PBT and provide evidence for future surgical practice. METHODS: We performed this real-world study of GC patients undergoing gastrectomy in China National Cancer Center from January 1, 2000 to December 30, 2019. Overall survival (OS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models were used to determine the risk factors for OS. RESULTS: In total, 13470 GC patients undergoing gastrectomy from 2000 to 2019 was included, of whom 3465 (34.6%) GC patients received PBT. PBT ratios declined from 29.1% (114/392) in 2000 to 11.2% in 2019 (149/1178), with the highest blood transfusion ratio in 2005 at 43.7% (220/504). For patients transfused with red blood cells, the median value of hemoglobin (Hb) before transfusion in the PBT group decreased from 110 g/L in 2000 to 87 g/L in 2019. Compared with patients who not receiving perioperative blood transfusion (NPBT), PBT group are more likely to be older (≥65, 39.1% vs. 30.1%, P<0.001), open operation (89.7% vs. 78.1%, P<0.001), higher ASA score (>2, 25.3% vs. 14.9%, P<0.001) and in the later pTNM stage (pTNM stage III, 68.5% vs. 51.5%, P<0.001). Results of multivariable Cox regression analysis showed that PBT was an independent prognostic factor for worse OS in GC patients undergoing gastrectomy (HR=1.106, 95% CI, 1.01-1.211, P=0.03). After stratified according to tumor stage, we found that PBT group had a worse prognosis only in pTNM stage III (HR=1.197, 95% CI, 1.119-1.281, P<0.001). OS was obviously poor in the PBT group when Hb levels were higher than 90 g/L (90 g/L120 g/L:HR= 1.207, 95% CI, 1.098-1.327, P<0.001), while there was no difference between the two groups when Hb levels were lower than or equal to 90 g/L (Hb≤90 g/L: HR=1.162, 95% CI, 0.985-1.370, P=0.075). CONCLUSION: In conclusion, PBT was an independent prognostic factor for worse OS. Blood transfusion might not be recommended for gastric cancer patients with perioperative minimum Hb values higher than 90 g/L.

Negative Regulation of LINC01013 by METTL3 and YTHDF2 Enhances the Osteogenic Differentiation of Senescent Pre-Osteoblast Cells Induced by Hydrogen Peroxide.

Senescent pre-osteoblasts have a reduced ability to differentiate, which leads to a reduction in bone formation. It is critical to identify the keys that regulate the differentiation fate of senescent pre-osteoblasts. LINC01013 has an essential role in cell stemness, differentiation, and senescence regulation. This study aims to examine the role and mechanism of LINC01013 in regulating osteogenic differentiation in senescent human embryonic osteoblast cell line (hFOB1.19) cells induced by hydrogen peroxide (H2O2). The results show that LINC01013 decreased alkaline phosphatase activity, mineralization of hFOB1.19 cells in vitro, and the expression of collagen II, osteocalcin, and bone sialoprotein. LINC01013 knockdown enhances the osteogenesis of hFOB1.19 cells and rescues osteogenic differentiation impaired by H2O2. METTL3 negatively regulates LINC01013 expression, enhancing hFOB1.19 cells' osteogenesis in vitro and in vivo. METTL3 overexpression can enhance hFOB1.19 cells' osteogenic differentiation impaired by H2O2. YTHDF2 promotes LINC01013 decay, facilitating osteogenic differentiation. YTHDF2 overexpression rescues hFOB1.19 cells osteogenic differentiation impaired by H2O2. Taken together, METTL3 upregulates osteogenic differentiation by inhibiting LINC01013, and YTHDF2 accelerates LINC01013 degradation, reducing its inhibitory effect. This study highlights LINC01013 as a key regulator in the fate switching process of senescent hFOB1.19 cells, impacting osteogenic differentiation.

miR615-3p inhibited FBLN1 and osteogenic differentiation of umbilical cord mesenchymal stem cells by associated with YTHDF2 in a m6A-miRNA interaction manner.

To investigate the role and mechanism of FBLN1 in the osteogenic differentiation and bone regeneration by using umbilical cord mesenchymal stem cells (WJCMSCs). We found that FBLN1 promoted osteogenic differentiation of WJCMSCs and WJCMSC-mediated bone regeneration. It was showed that there was an m6A methylation site in 3'UTR of FBLN1 mRNA, and the mutation of the m6A site enhanced the stability of FBLN1 mRNA, subsequently fostering the FBLN1 enhanced osteogenic differentiation of WJCMSCs. YTHDF2 was identified as capable of recognizing and binding to the m6A site, consequently inducing FBLN1 instability and repressed the osteogenic differentiation of WJCMSCs. Meanwhile, miR-615-3p negatively regulated FBLN1 by binding FBLN1 3'UTR and inhibited the osteogenic differentiation of WJCMSCs and WJCMSC-mediated bone regeneration. Then, we discovered miR-615-3p was found to regulate the functions of FBLN1 facilitated by YTHDF2 through an m6A-miRNA regulation mechanism. We demonstrated that FBLN1 is critical for regulating the osteogenic differentiation potentials of WJCMSCs and have identified that miR615-3p mediated the decay of FBLN1 mRNA which facilitated by m6A reading protein YTHDF2. This provided a novel m6A-miRNA epigenetic regulatory pattern for MSC regulation and bone regeneration.

Association of survival with adjuvant chemotherapy in patients with stage IB gastric cancer: a multicentre, observational, cohort study.

Background: Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. Methods: We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. Findings: Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52-1.00; DFS: HR, 0.91; 95% CI, 0.64-1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08-0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17-0.62; P < 0.001 for multiplicative interaction), or positive lymph nodes (HR, 0.17; 95% CI, 0.07-0.38; P < 0.001 for multiplicative interaction). The survival prediction models mainly based on variables associated with chemotherapy benefits in the subgroup analysis demonstrated good calibration and discrimination, with relatively high C-indexes. The C-indexes for OS were 0.74 for patients treated with adjuvant chemotherapy and 0.70 for patients treated with postoperative observation. Two nomograms were built from the models that can calculate individualized estimates of expected net survival gain attributable to adjuvant chemotherapy. Interpretation: In this cohort study, pathologic stage IB alone was not associated with survival benefits from adjuvant chemotherapy compared with postoperative observation in patients with early-stage GC. High-risk clinicopathologic features should be considered simultaneously when evaluating patients with stage IB GC for adjuvant chemotherapy. Funding: National Natural Science Foundation of China; the National Key R&D Program of China.

Evidence for the transportation of aggregated microplastics in the symplast pathway of oilseed rape roots and their impact on plant growth.

As an emerging contaminant, microplastics are absorbed by crops, causing diverse impacts on plants. Plants may have different physiological responses to different uptake modes of microplastics various stage of growth. In this study, the distribution of polystyrene (PS) microspheres in the roots of oilseed rape and the physiological responses at different growth stages were investigated by confocal laser scanning microscope, scanning electron microscopy, and biochemical analysis. This study, conducted via scanning electron microscopy, discovered that agglomerates of microspheres, rather than individual plastic pellets, were taken up by plant roots in solution for the first time. The agglomerates subsequently migrate into the vascular bundles of the root system. Moreover, this study provided the proof for the first time that PS is transported in plants via the symplast system. On the physiological and biochemical function, the exposure of PS at the flowering and bolting stages caused oxidative stress on oilseed rape. That is, the addition of PS with different particle sizes significantly increased peroxidase (POD), malondialdehyde (MDA), photosynthetic rate, chlorophyll content and inhibited superoxide dismutase (SOD) content in oilseed rape at different developmental stages. These changes regulated the chloroplast structure and chlorophyll synthesis, maintained a high photosynthetic rate, and mitigated the toxicity of PS. In addition, correlation analysis showed that MDA and citric acid contents were significantly positively correlated with chlorophyll contents (p < 0.05), which suggested that the 80 nm PS treatment stimulated organic acid secretion in oilseed rape at the bolting stage to maintain a higher chlorophyll content. This study expands the current understanding of the effects of microplastics on crop growth, and the results holding significant implications for exploring the impact of microplastics on vegetables during various developmental stages and for future risk assessment.

Geochemical Characteristics of the Middle Jurassic Coal-Bearing Mudstones in the Dameigou Area (Qaidam Basin, NW China): Implications for Paleoclimate, Paleoenvironment, and Organic Matter Accumulation.

The Qaidam Basin is a prominent oil and gas exploration and production base of NW China's Jurassic coal-bearing strata. Coal-bearing mudstones are important source rocks for unconventional reservoirs and can record valuable paleoenvironment and paleoclimate information. Here, geochemical analysis including total organic carbon (TOC), total sulfur, organic carbon isotopic composition, rock pyrolysis, X-ray diffraction, and major and trace elements were carried out on mudstone samples from the Middle Jurassic coal-bearing strata of the Dameigou section in the Qaidam Basin to reveal the paleoclimatic and paleoenvironmental conditions during the deposition of the strata and their controls on organic matter accumulation. Results show that the Middle Jurassic Dameigou and Shimengou formations include three significant stages based on their average TOC values of (3.32%, Stage I; 0.87%, Stage II; and 4.42%, Stage III) from the bottom to the top. The organic matter in mudstones in Stages I and II are mainly derived from terrestrial higher plants, while the organic matter has mixed sources of higher plant debris and lower aquatic organisms in Stage III. Paleoclimate parameters indicate that the mudstones in Stage I were deposited under humid and warm conditions, while the climate in Stage II changed to semiarid and warm conditions before turning dry and hot in Stage III. The varying paleoenvironmental characteristics under different paleoclimatic conditions have also been reconstructed. Our results suggest that the accumulation of organic matter in Stages I and II was primarily controlled by redox conditions, while paleoproductivity is the major controlling factor for organic matter accumulation in Stage III.

[Research Progress on Toxicity of Microplastics in Soil to Terrestrial Plants and Their Degradation Mechanism].

Microplastics(MPs), as a new type of environmental pollutants, have gradually attracted widespread attention since they were introduced by British scientists in 2004. Soil is an important accumulation site for microplastics, which can expand the scope of contamination and accumulate with agricultural practices such as irrigation and tillage. Microplastics in soil cause a variety of toxicities to terrestrial plants. The small particle size, difficult degradation, and strong adsorption capacity bring a challenge to the microplastic pollution treatment of soil. In this study, the toxicity of microplastics to terrestrial plants was reviewed in terms of their direct or indirect toxicity and combined effects with other pollutants, mainly in terms of mechanical injury, induction of oxidative stress, and cytotoxicity and genotoxicity to plants, resulting in plant growth and plant tissue metabolism obstruction. In general, the toxicity of microplastics depended on the polymer type, size, and dose; plant tolerance; and exposure conditions. In addition, the production of secondary microplastics and endogenous contaminants during their degradation in soil enhanced the biotoxicity of microplastics. Further, the physical, chemical, and microbial degradation mechanisms of microplastics were introduced in this study based on the current research. At first, the physical and chemical degradation of microplastics mainly occurred by changing the particle size and surface properties of microplastics and producing intermediates. Then, smaller-sized microplastics and their intermediates could eventually be converted to water and carbon dioxide through physical, chemical, and biological functions. Finally, further prospects regarding soil microplastics were introduced, and we provided information for future improvement and pollution control of microplastics.

FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies.

Drug therapy, including chemotherapy, targeted therapy, immunotherapy, and endocrine therapy, stands as the foremost therapeutic approach for contemporary human malignancies. However, increasing drug resistance during antineoplastic therapy has become a substantial barrier to favorable outcomes in cancer patients. To enhance the effectiveness of different cancer therapies, an in-depth understanding of the unique mechanisms underlying tumor drug resistance and the subsequent surmounting of antitumor drug resistance is required. Recently, F-box and WD Repeat Domain-containing-7 (FBXW7), a recognized tumor suppressor, has been found to be highly associated with tumor therapy resistance. This review provides a comprehensive summary of the underlying mechanisms through which FBXW7 facilitates the development of drug resistance in cancer. Additionally, this review elucidates the role of FBXW7 in therapeutic resistance of various types of human tumors. The strategies and challenges implicated in overcoming tumor therapy resistance by targeting FBXW7 are also discussed.

CO Diffusion Study and Spatial and Temporal Variation Modeling during the Construction Period of the Plateau Railroad Tunnel.

In order to investigate the diffusion law of CO gas in the vicinity of the tunnel boring face of the plateau long tunnel, to improve the efficiency of tunnel smoke exhaust, and to derive the spatial-temporal variation model of CO concentration for predicting the concentration of CO at different times and in different cross sections under specific environments, a CO diffusion model of a tunnel in Yunnan was established by using Ansys Fluent Fluid Simulation Software, and the CO transport characteristics under different conditions were simulated by taking the ventilation time, wind speed, and location of the air ducts as the influencing factors. The results show that the wind flows from the mouth of the wind pipe after the wind speed decreases, the diffusion area increases and arrives at the face of the direction of the rebound in the jet stream of new wind, and the return wind under the joint action of the vortex produced obviously, to reach the wind pipe mouth after the tunnel wind flow field, basically tends to stabilize. When the wind pipe mouth was arranged in the arch waist, 20 m away from the boring face, the inlet wind speed was 9 m/s and the ventilation time was 30 min; the CO concentration in the tunnel was reduced to below the maximum allowable concentration value. Moreover, the concentration of CO in the tunnel at the moment of 15 min of ventilation has a nonlinear positive correlation with the change of distance L from the boring face, while at the cross section of the air outlet of the wind pipe L = 20 m, the ventilation time is from 1 to 30 min and the concentration of CO at the cross section has a nonlinear decreasing trend with the ventilation time, which can be deduced according to the different space-time change models.