Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis.

BACKGROUND: The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78 years). METHODS: This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. RESULTS: Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. CONCLUSIONS: LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.

A nomogram of anastomotic stricture after rectal cancer: a retrospective cohort analysis.

BACKGROUND: Anastomotic stricture significantly impacts patients' quality of life and long-term prognosis. However, current clinical practice lacks accurate tools for predicting anastomotic stricture. This study aimed to develop a nomogram to predict anastomotic stricture in patients with rectal cancer who have undergone anterior resection. METHODS: A total of 1542 eligible patients were recruited for the study. Least absolute shrinkage selection operator (Lasso) analysis was used to preliminarily select predictors. A prediction model was constructed using multivariate logistic regression and presented as a nomogram. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration diagrams, and decision curve analysis (DCA). Internal validation was conducted by assessing the model's performance on a validation cohort. RESULTS: 72 (4.7%) patients were diagnosed with anastomotic stricture. Participants were randomly divided into training (n = 1079) and validation (n = 463) sets. Predictors included in this nomogram were radiotherapy, diverting stoma, anastomotic leakage, and anastomotic distance. The area under the ROC curve (AUC) for the training set was 0.889 [95% confidence interval (CI) 0.840-0.937] and for the validation set, it was 0.930 (95%CI 0.879-0.981). The calibration curve demonstrated a strong correlation between predicted and observed outcomes. DCA results showed that the nomogram had clinical value in predicting anastomotic stricture in patients after anterior resection of rectal cancer. CONCLUSION: We developed a predictive model for anastomotic stricture following anterior resection of rectal cancer. This nomogram could assist clinicians in predicting the risk of anastomotic stricture, thus improving patients' quality of life and long-term prognosis.

Survival and prognostic factors of primary retroperitoneal sarcomas after surgery: a single-center experience.

PURPOSE: The percentage of retroperitoneal sarcomas (RPS) among all soft tissue sarcomas ranges from 10 to 15%. Surgery remains the gold standard for RPS. In this study, we analyzed the impact of surgical treatment for primary RPS on recurrence and overall mortality at a Chinese institution and identified and evaluated prognostic variables. METHODS: Data from patients with RPS who underwent surgical treatment were retrospectively analyzed. The patients were treated at a single center from January 2000 to June 2018. Retrospectively collected demographic, clinicopathological, and surgical factors were examined. Overall survival (OS) and disease-free survival (DSF) were used as the primary endpoints. Predicted 5-year survival rates, encompassing both DFS and OS, were derived from the Sarculator prognostic nomogram. RESULTS: A total of 110 patients met the inclusion criteria. The median follow-up time after surgery for patients with primary RPS was 5.3 years. During this period, 59 patients died. The 5-year OS and DFS estimates were 63.5% and 35.3%, respectively. In a multivariate analysis, poor OS following surgical treatment of primary RPS was independently correlated with FNCLCC grade (p < 0.001) and surgical margin status (p = 0.016). FNCLCC grade (p = 0.001) and surgical margin status (p = 0.002) were also independently associated with poor DFS. The C-indices for 5-year OS and DFS survival utilizing the Sarculator prognostic nomogram were 0.71 and 0.73 respectively. CONCLUSION: The overall mortality rate of patients with RPS was considered acceptable. OS and DFS prognostic markers were established for primary RPS. Tumor grade and intraregional margins are other factors that affect survival and recurrence.

Alveolar bone morphology in patients with palatally-displaced maxillary lateral incisors before and after orthodontic treatment: A cone-beam computed tomography study.

INTRODUCTION: Palatal displacement of maxillary anterior teeth is common in clinical practice. Previous studies have reported that the labial bone around palatally-displaced incisors is thinner than that around normally-placed teeth. Therefore, it is necessary to elucidate alveolar bone changes after alignment to guide orthodontic treatment. In this study, we investigated the alveolar bone changes around palatally-displaced maxillary lateral incisors before and after treatment, and the effects of extraction and age using cone-beam computed tomography. METHODS: In this retrospective study, 55 patients with unilateral palatally-displaced maxillary lateral incisors were included. Three-dimensional alveolar bone changes were measured at three levels (25%, 50% and 75% of the root length) using cone-beam computed tomography. Group comparisons were made between displaced and control teeth, extraction and non-extraction groups, and adult and minor groups. RESULTS: After orthodontic treatment, labiopalatal and palatal alveolar bone widths decreased at all measured levels. Labial alveolar bone width increased significantly at P25, but decreased at P75. Concavity decreased, while tooth-axis angle, tooth length, B-CEJ and P-CEJ increased. Changes in LB and LP at P75, B-CEJ and P-CEJ were statistically significant. After treatment, the tooth-axis angle on the PD side increased by 9.46°. The change in tooth-axis angle on the PD side was significantly smaller, and LB and LP decreased more at P75, in the extraction group. CONCLUSIONS: Compared to the control teeth, alveolar bone thickness and height for the displaced teeth decreased more significantly after treatment. Tooth extraction and age also influenced alveolar bone changes.

FANCA facilitates G1/S cell cycle advancement, proliferation, migration and invasion in gastric cancer.

The present study explores the function of FANCA gene, a pivotal member of the Fanconi anaemia (FA) pathway crucial for preserving genomic stability and preventing cancer, particularly in the context of gastric cancer (GC). Using immunohistochemistry, quantitative real-time PCR, and western blot analysis, we evaluate FANCA mRNA and protein expressions in GC cell lines. The relationship between FANCA expression and clinicopathological characteristics is also explored. Various assays, including CCK8, colony formation, wound healing, and Transwell assays, are used to assess functional changes in cells associated with FANCA. Flow cytometry is utilized to evaluate alterations in the cell cycle resulted from FANCA knockdown and overexpression. Our findings show elevated FANCA expression in GC cell lines, with levels correlated with pathologic stage and lymphatic metastasis. FANCA knockdown impedes cell proliferation, migration, and invasion and induces G1/S phase cell cycle arrest. Conversely, FANCA overexpression stimulates cell proliferation, migration, and invasion. In vivo xenograft experiments confirm the promotional role of FANCA in GC tumor progression. Moreover, FANCA overexpression is associated with the activation of cell cycle. Collectively, our results suggest that FANCA drives malignant cell behaviors in GC through the cell cycle pathway, highlighting its potential as a therapeutic target for the treatment of GC.

PACSIN1 promotes immunosuppression in gastric cancer by degrading MHC-I.

Gastric cancer (GC) is a common gastrointestinal system malignancy. PACSIN1 functions as an oncogene in various cancers. This study aims to investigate the potential of PACSIN1 as a target in GC treatment. Gene expression is determined by RT-qPCR, immunofluorescence staining, and immunohistochemistry assay. FISH is performed to determine the colocalization of PACSIN1 and the major histocompatibility complex (MHC-I). Cytokine release and cell functions are analyzed by flow cytometry. In vivo assays are also conducted. Histological analysis is performed using H&E staining. The results show that PACSIN1 is overexpressed in GC patients, especially in those with immunologically-cold tumors. A high level of PACSIN1 is associated with poor prognosis. PACSIN1 deficiency inhibits autophagy but increases antigen presentation in GC cells. Moreover, PACSIN1 deficiency inhibits the lysosomal fusion and selective autophagy of MHC-I, increases CD8 + T-cell infiltration, and suppresses tumor growth and liver metastasis in vivo. Additionally, PACSIN1 knockout enhances the chemosensitivity of cells to immune checkpoint blockade. In summary, PACSIN1 mediates lysosomal fusion and selective autophagy of MHC-I and suppresses antigen presentation and CD8 + T-cell infiltration, thus inhibiting antitumor immunity in GC.

Laparoscopic versus open distal gastrectomy for advanced gastric cancer in elderly patients: a propensity-score matched analysis.

BACKGROUND: Scarce research has reported the efficacy and safety of laparoscopic distal gastrectomy in elderly patients. This retrospective study aimed to compare the outcomes of laparoscopic and open distal gastrectomy for advanced gastric cancer in elderly patients. METHODS: A total of 303 elderly patients who underwent distal gastrectomy for advanced gastric cancer from June 2017 to June 2021 were enrolled. Variables used to calculate propensity score matching included sex, age, body mass index, American Society of Anesthesiologists, history of diabetes, and history of hypertension. The statistical significance of continuous variables was tested using an independent sample t test. chi-square or Fisher's exact tests were used for categorical variables. Kaplan-Meier curve and log-rank test were used for the evaluation of 3-year overall survival and recurrence-free survival. RESULTS: After performing 1:1 propensity score matching, 248 patients were included for analysis (laparoscopic = 124, open = 124). Compared with the open group, the laparoscopic group showed significant advantages in estimated blood loss (P < 0.001), pain scale on the first postoperative day (P = 0.002), time to first flatus (P = 0.004), time to first liquid diet (P = 0.005), hospital stays (P < 0.001), and total complications (P = 0.011), but devoted much more operation time (P < 0.001). No statistical difference was observed between the two groups in 3-year recurrence-free survival (P = 0.315) or overall survival (P = 0.159). CONCLUSIONS: Our analysis demonstrated that laparoscopic surgery had the advantages of less intraoperative blood loss, fewer postoperative complications, and faster postoperative recovery in distal gastrectomy for advanced gastric, indicating that laparoscopic distal gastrectomy is safe and effective for treating elderly patients with distal gastric cancer.

The Discovery of Cyclic Lipopeptide Olenamidonins in a Deepsea-Derived Streptomyces Strain by Knocking Out a DtxR Family Regulator.

Three new cyclic lipopeptides, olenamidonins A-C (1-3), in addition to two previously reported metabolites (4 and 5), were accumulated in the ΔdtxRso deletion mutant of deepsea-derived Streptomyces olivaceus SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds 1-5 displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains Enterococcus faecalis CCARM 5172 and Enterococcus faecium CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56-6.25 µg/mL.

Modified Q-type purse-string suture duodenal stump embedding method for laparoscopic gastrectomy for gastric cancer.

OBJECTIVE: This study introduced the modified Q-type purse-string suture duodenal stump embedding method, a convenient way to strengthen the duodenum, and compared it to the conventional one to assess its efficacy and safety. METHODS: This retrospective analysis examined 612 patients who received laparoscopic gastrectomy for gastric Cancer at a single center. The patients were divided into Not Reinforced Group (n = 205) and Reinforced Group (n = 407) according to the surgical approach to the duodenal stump. The reinforced group was further divided into a modified Q-type purse-string suture embedding method group (QM, n = 232) and a conventional suture duodenal stump embedding method group (CM, n = 175) according to the methods of duodenal stump enhancement. Clinicopathological characteristics, operative variables, and short-term complications were documented and analyzed. RESULTS: The incidence of duodenal stump leakage(DSL) in the Not Reinforced Group was higher compared to the Reinforced Group, although the difference was not statistically significant [2.4% (5/205) vs 0.7% (3/407), p = 0.339]. Additionally, the Not Reinforced Group exhibited a higher rate of Reoperation due to DSL compared to the Reinforced Group [2 (1.0%) vs. 0, p = 0.046], with one patient in the Not Reinforced Group experiencing mortality due to DSL [1 (0.5%) vs 0, p = 0.158]. Subgroup analysis within the Reinforced Group revealed that the modified Q-type purse-string suture embedding group (QM) subgroup demonstrated statistically significant advantages over the conventional suture embedding group (CM) subgroup. QM exhibited shorter purse-string closure times (4.11 ± 1.840 vs. 6.05 ± 1.577, p = 0.001), higher purse-string closure success rates (93.1% vs. 77.7%, p = 0.001), and greater satisfaction with purse-string closure [224 (96.6%) vs 157 (89.7%), p = 0.005]. No occurrences of duodenal stump leakage were observed in the QM subgroup, while the CM subgroup experienced two cases [2 (1.1%)], though the difference was not statistically significant. Both groups did not exhibit statistically significant differences in secondary surgery or mortality related to duodenal stump leakage. CONCLUSION: Duodenal Stump Leakage (DSL) is a severe but low-incidence complication. There is no statistically significant relationship between the reinforcement of the duodenal stump and the incidence of DSL. However, laparoscopic reinforcement of the duodenal stump can reduce the severity of fistulas and the probability of Reoperation. The laparoscopic Q-type purse-string suture duodenal stump embedding method is a simple and effective technique that can, to some extent, shorten the operation time and enhance satisfaction with purse-string closure. There is a trend towards reducing the incidence of DSL, thereby improving patient prognosis to a certain extent.

Prediction model of anastomotic leakage after anterior resection for rectal cancer-based on nomogram and multivariate analysis with 1995 patients.

BACKGROUND: Postoperative anastomotic leakage for rectal cancer shows higher morbidity with grievous concomitant symptoms. Accurate assessment of the incidence of anastomotic leakage, multivariate analysis, and establishment of a scientific prediction model can be useful to dispose of its possible severe clinical consequences. METHODS: This retrospective study collected 1995 consecutive patients who underwent anterior resection of rectal cancer with primary anastomosis at Northern Jiangsu People's Hospital between January 2016 and June 2022. Independent risk factors associated with anastomotic leakage were analyzed by univariate and multivariate logistic regression. The chosen independent risk factors were used to construct a nomogram risk prediction model whose availability was evaluated by using a bootstrapped-concordance index and calibration plots with R software. RESULTS: A total of 1995 patients who underwent anterior resection for rectal cancer were included while 120 patients were diagnosed with anastomotic leakage, an incidence of 6.0%. Univariate analysis and its concomitant multivariate cox regression analysis indicated that independent risk factors associated with anastomotic leakage included male gender (odds ratio (OR) = 2.873), diabetes (OR = 2.480), neoadjuvant therapy (OR = 5.283), tumor's distance from the anus verge < 5 cm (OR = 5.824), tumor size ≥ 5 cm (OR = 4.888), and the blood lose > 50 mL (OR = 9.606).We established a nomogram prediction model with proper applicability (concordance index, 0.83) and the calibration curve to justify its predictive ability that the predicted occurrence probability keeps a high degree of consistency with the actual occurrence probability. Meanwhile, the area under the receiver operating characteristic (ROC) curve was 0.83. CONCLUSIONS: The characteristics of patients and tumor surgery-related conditions can affect the incidence of anastomotic leakage. However, whether the surgical method will affect morbidity is still controversial. Our nomogram can be seen as an effective instrument to predict anastomotic leakage after anterior resection for rectal cancer precisely.

Evaluation of the safety and efficacy of perform enterectomy in colorectal cancer patients aged 80 or older. A meta-analysis and a systematic review.

BACKGROUND: Colorectal cancer (CRC) is one of the four most common cancers in the world. At present, human beings have stepped into an aging society, and the number of over eighties colorectal cancer patients has increased year by year. However, few high-quality studies focused on the post-operation complications and long-term outcomes of octogenarian patients with colorectal cancer. This meta-analysis, based on published studies, aims to assess the safety of treating octogenarian CRC patients with surgery. METHODS: Databases, including PubMed, Embase, and Cochrane Library were searched until July 2022. The incidence of preoperative comorbidities, postoperative complications, and mortality was assessed using odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Furthermore, the hazard ratios (HRs) with 95% CIs were applied for survival outcomes. RESULTS: A total of 13,790 patients with CRC in 21 studies were included. Our results demonstrated that octogenarian patients were associated with a higher burden of comorbidities (OR = 3.03; 95% CI: 2.03, 4.53; P = .000), high incidences of overall postoperative complications (OR = 1.63; 95% CI: 1.29, 2.06; P = .000), high internal medicine postoperative complications (OR = 2.38; 95% CI: 1.76, 3.21; P = .000), high in-hospital mortality (OR = 4.01; 95% CI: 3.06, 5.27; P = .000) and poor overall survival (OR = 2.13; 95% CI: 1.78, 2.55; P = .000). But there is no statistical difference in surgery-related postoperative complications(OR = 1.16; 95% CI: 0.94, 1.43; P = .16) and DFS (OR = 1.03; 95% CI: 0.83, 1.29; P = .775). CONCLUSIONS: Extremely elderly patients with colorectal cancer have the high burden of comorbidities, high postoperative complications and mortality. However, survival outcomes (DFS) in patients 80 years and older are similar to younger patients. Clinicians should administer individualized treatment for such patients. Physiologic age rather than chronological age should determine cancer management for each individual.

OPN N-glycosylation promoted bone destruction.

OBJECTIVES: Exploring the role of OPN N-glycosylation in osteoblasts and osteoclasts. METHODS: Immunohistochemistry was used to detect the expression of OPN in mice with apical periodontitis. The asparagine at position 79 of the OPN protein was mutated to glutamine, and the above plasmids were transfected into osteoblasts and osteoclasts. The effect of OPN N-glycosylation on proliferation of osteoblasts and osteoclasts was detected by CCK8 assays. Western blotting was used to detect the expression of OPN N-glycosylation on osteoclasts and osteoblasts. Detection of N-glycosylation of OPN activated the NF-κB signaling pathway to regulate osteoblasts and osteoclasts. RESULTS: OPN increased the expression in a mice model of apical periodontitis. The expression curve of OPN resembled a reverse V shape. The OPN N-glycosylation site was identified as 79 by MS. N-glycosylation of OPN promoted the proliferation of osteoclasts. But the N79 glycosylation site of mutant OPN could not increase the proliferation of osteoblasts. OPN N-glycosylation modulated the expression of osteoclast- and osteoblast-associated factors through the NF-κB signaling pathway. N-glycosylation of OPN promoted nuclear translocation of NF-κB in osteoclasts and osteoblasts. CONCLUSIONS: The N-glycosylation site of OPN is 79. N-glycosylation of OPN played an important role in the biological function of OPN protein.

Evaluation of multiple biological indicators for the combined diagnosis of metastases from colorectal cancer-a retrospective study based on 1163 patients.

OBJECTIVE: This study aimed to investigate the efficacy of inflammatory markers (NLR, PLR) combined with tumor markers (CA50, CA199, CEA) in the diagnosis of colorectal cancer metastasis by a single-center retrospective study. METHODS: A total of 1163 CRC patients who received treatments in our hospital from January 2017 to December 2021 were enrolled retrospectively. Patients were grouped according to the absence of metastasis. The separate efficacy of tumor markers, NLR and PLR, was evaluated in the diagnosis of metastasis of colorectal cancer using ROC curve analysis, and their optimal cut-off values for distant metastases from colorectal cancer were determined. The area under the ROC curve (AUC) of the tumor markers combined with NLR and PLR was calculated by binary logistic regression analysis to evaluate the diagnostic efficacy of metastasis of colorectal cancer. In addition, patients were divided into two groups of high and low levels according to the optimal cut-off values, and the effects of NLR, PLR, and tumor markers on distant metastasis of colorectal cancer were evaluated using multiple logistic regression analysis. RESULT: The abnormal rate of CA50, CA199, CEA, NLR, and PLR in two subgroupsIt was statistically significant (P < 0.05). After AUC testifying, the diagnostic efficacy of NLR and PLR was equivalent to that of tumor marker (P > 0.05). In assessment of liver metastasis, peritoneal metastasis, and multiple metastasis, AUC of NLR and PLR with CRC-specific tumor markers showed higher predictive efficacy than AUC without combined NLR nor PLR. The CA50, CA199, CEA, PLR, and NLR were proved independently associated with metastasis using multiple logistic regression analysis (P < 0.05). CONCLUSION: NLR and PLR are noted tumor markers of colorectal cancer, which are characterized by noninvasive, high diagnostic efficacy, easy availability, and low cost. They can be combined with traditional tumor markers to evaluate and diagnose colorectal cancer metastasis by clinicians.

A nomogram for predicting the recurrence of small bowel obstruction after gastrectomy in patients with gastric cancer.

BACKGROUND: This study aimed to create a nomogram for predicting the recurrence of small bowel obstruction (SBO) after gastrectomy in patients with gastric cancer (GC) in order to provide better guidance for its diagnosis and treatment. METHODS: A total of 173 patients undergone gastrectomy and developed SBO from January 2015 to October 2022 were admitted into this case-control study. The risk factors of postoperative recurrent SBO were analyzed by univariate and multivariate regression, and a nomogram for predicting the recurrent SBO after gastrectomy was developed using R Studio. RESULTS: Thirty-nine cases of postoperative recurrent SBO occurred among the 173 GC patients who underwent radical gastrectomy, and the percentage of recurrent SBO was 22.54% (39/173). Age [odds ratio (OR) = 0.938, p = 0.026], WBC count (OR = 1.547, p < 0.001), tumor size (OR = 1.383, p = 0.024), postoperative metastasis (OR = 11.792, p = 0.030), and the interval from gastrectomy to first SBO (OR = 1.057, p < 0.001) were all identified as independent risk factors for postoperative recurrent SBO by logistic regression analysis. The receiver operating characteristic curve, the calibration curve, the model consistency index, and the decision curve analysis showed that the nomogram had good predictive performance. CONCLUSION: Based on these factors, we created a nomogram to predict the occurrence of postoperative recurrent SBO. This novel nomogram could serve as a crucial early warning indicator that would guide doctors to make informed decisions while managing patients with gastric cancer.

Contamination profiles and potential health risks of environmentally persistent free radicals in PM2.5 over typical central Chinese megacity.

As one of the most important transportation hubs and industrial bases in China, Zhengzhou has suffered from serious PM2.5 pollution for a long time. However, the investigation of contamination status and possible exposure risks of environmentally persistent free radicals (EPFRs) in PM2.5 from Zhengzhou is rare. In this work, a comprehensive study of pollution levels, seasonal variations, sources, and potential health risks of PM2.5-bound EPFRs in Zhengzhou was conducted for the first time. The atmospheric concentrations of EPFRs in PM2.5 from Zhengzhou ranged from 1.732 × 1012 spin m-3 to 7.182 × 1014 spin m-3 between 2019 and 2020. Relatively serious contamination was noticed in winter and spring. Primary fossil fuel combustion and Fe-mediated secondary formation were apportioned as possible sources of PM2.5-bound EPFRs in Zhengzhou. Moreover, to avert the bias of the toxicity assessment induced by utilization of incompletely extracted EPFRs from sample filter, simulatively generated EPFRs were applied to toxicological evaluations (cell viability and reactive oxygen species assays). Corresponding experimental dosages were based on the estimated adults' annual exposure amounts of EPFRs in real PM2.5 samples. The results elucidated that EPFRs might cause growth inhibition and oxidative stress of human lung cells, suggesting the possible exposure-induced health concerns for local people in Zhengzhou. This study provides practical information of real contamination status of PM2.5-bound EPFRs in Zhengzhou, which is favorable to local air pollution control and reduction of exposure risks on public health in central China.

Cadmium exposure exacerbates kidney damage by inhibiting autophagy in diabetic rats.

The incidence of diabetes mellitus (DM) is gradually increasing, making it a widespread global health concern. Cadmium (Cd) is a common toxic heavy metal in the environment, and cadmium exposure may be associated with diabetic nephropathy (DN). However, the mechanism of Cd-induced DN remains unclear. In this study, we aimed to determine the effect of cadmium on diabetic kidney injury and the underlying mechanism in diabetic rats and a renal tubular epithelial cell line (NRK-52E cells). Our results could provide novel insights on the nephrotoxic mechanism of cadmium. HE, PAS, and Masson staining were used to observe pathological renal injury. COL-I, COL-IV, CTSB, and CTSD protein levels were detected by immunohistochemistry and western blotting. Immunofluorescence was used to detect the fluorescence intensity of p62 and LC3 proteins in kidney tissue. TEM was used to observe the ultrastructure of mitochondria and number of autophagosomes. After cadmium exposure, DM rats showed a dramatic decrease in body weight compared to the unexposed DM group. Relative kidney weight showed a contrasting trend after cadmium exposure. Urinary microalbumin/creatinine significantly increased in normal and DM rats after cadmium exposure. However, the trend was clearer in the DM groups than in the control groups. Endogenous creatinine clearance exhibited a contrasting trend. After cadmium exposure in DM rats, MDA content significantly increased and GSH, CAT, SOD, and GSH-PX activation reduced compared to normal controls. Pathological damage was more pronounced, and the expression of autophagy related proteins and apoptosis and fibrosis proteins was significantly higher in vivo and vitro in the cadmium-exposed groups than in unexposed controls. Further, lysosomal protein levels were lower, and ROS content and autophagosome count significantly higher in the cadmium exposed groups compared to the unexposed controls. Therefore, Cadmium exposure aggravates diabetic kidney injury via autophagy inhibition.

Regulating Relative Nitrogen Locations of Diazine Functionalized Covalent Organic Frameworks for Overall H2 O2 Photosynthesis.

Nitrogen-heterocycle-based covalent organic frameworks (COFs) are considered promising candidates for the overall photosynthesis of hydrogen peroxide (H2 O2 ). However, the effects of the relative nitrogen locations remain obscured and photocatalytic performances of COFs need to be further improved. Herein, a collection of COFs functionalized by various diazines including pyridazine, pyrimidine, and pyrazine have been judiciously designed and synthesized for photogeneration of H2 O2 without sacrificial agents. Compared with pyrimidine and pyrazine, pyridazine embedded in TpDz tends to stabilize endoperoxide intermediate species, leading toward the more efficient direct 2e- oxygen reduction reaction (ORR) pathway. Benefiting from the effective electron-hole separation, low charge transfer resistance, and high-efficiency ORR pathway, an excellent production rate of 7327 µmol g-1 h-1 and a solar-to-chemical conversion (SCC) value of 0.62 % has been achieved by TpDz, which ranks one of the best COF-based photocatalysts. This work might shed fresh light on the rational design of functional COFs targeting photocatalysts in H2 O2 production.

Mutation of Leaf Senescence 1 Encoding a C2H2 Zinc Finger Protein Induces ROS Accumulation and Accelerates Leaf Senescence in Rice.

Premature senescence of leaves causes a reduced yield and quality of rice by affecting plant growth and development. The regulatory mechanisms underlying early leaf senescence are still unclear. The Leaf senescence 1 (LS1) gene encodes a C2H2-type zinc finger protein that is localized to both the nucleus and cytoplasm. In this study, we constructed a rice mutant named leaf senescence 1 (ls1) with a premature leaf senescence phenotype using CRISPR/Cas9-mediated editing of the LS1 gene. The ls1 mutants exhibited premature leaf senescence and reduced chlorophyll content. The expression levels of LS1 were higher in mature or senescent leaves than that in young leaves. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were significantly increased and catalase (CAT) activity was remarkably reduced in the ls1 plants. Furthermore, a faster decrease in pigment content was detected in mutants than that in WT upon induction of complete darkness. TUNEL and staining experiments indicated severe DNA degradation and programmed cell death in the ls1 mutants, which suggested that excessive ROS may lead to leaf senescence and cell death in ls1 plants. Additionally, an RT-qPCR analysis revealed that most senescence-associated and ROS-scavenging genes were upregulated in the ls1 mutants compared with the WT. Collectively, our findings revealed that LS1 might regulate leaf development and function, and that disruption of LS1 function promotes ROS accumulation and accelerates leaf senescence and cell death in rice.

Progress of Nanomaterials-Based Photothermal Therapy for Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the top 15 most prevalent cancers worldwide. However, the current treatment models for OSCC (e.g., surgery, chemotherapy, radiotherapy, and combination therapy) present several limitations: damage to adjacent healthy tissue, possible recurrence, low efficiency, and severe side effects. In this context, nanomaterial-based photothermal therapy (PTT) has attracted extensive research attention. This paper reviews the latest progress in the application of biological nanomaterials for PTT in OSCC. We divide photothermal nanomaterials into four categories (noble metal nanomaterials, carbon-based nanomaterials, metal compounds, and organic nanomaterials) and introduce each category in detail. We also mention in detail the drug delivery systems for PTT of OSCC and briefly summarize the applications of hydrogels, liposomes, and micelles. Finally, we note the challenges faced by the clinical application of PTT nanomaterials and the possibility of further improvement, providing direction for the future research of PTT in OSCC treatment.

Analysis of therapeutic targets and prognostic biomarkers of CXC chemokines in cervical cancer microenvironment.

BACKGROUND: The tumor microenvironment (TME) has received an increasing amount of attention. CXC chemokines can regulate immune cell transport and tumor cell activity to exert anti-tumor immunity. However, studies on the expression and prognosis of CXC chemokines in cervical cancer (CC) are more limited. METHODS: The study investigated the role of CXC chemokines in TME of CC by using public databases. Moreover, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) of CXC chemokines were performed to further verify. RESULTS: The transcriptional levels of CXCL1/3/5/6/8/9/10/11/13/16/17 in CC tissues were significantly elevated while the transcriptional levels of CXCL12/14 were significantly reduced. We reached a consistent conclusion that the expression of CXCL9/10/11/13 was verified by quantitative real-time PCR and immunohistochemistry. Moreover, CC patients with low transcriptional levels of CXCL1/2/3/4/5/8 were significantly associated with longer overall survival (OS). The CCL family was related to CXC chemokines neighboring alteration. RELA, NFKB1, LCK and PAK2 were the key transcription factors and kinase targets of CXC chemokines, respectively. We also found there were significant correlations between the expression of CXCL9/10/11 and the infiltration of immune cells (CD8+ T cell, CD4+ T cell, neutrophils and dendritic cells). CONCLUSIONS: In brief, we conducted a comprehensive analysis of CXC chemokines via clinical data and some online public databases. Our results may provide a new idea for the selection of immunotherapeutic targets and prognostic biomarkers for cervical cancer.