Climate change impacts on magnitude and frequency of urban floods under scenario and model uncertainties.

Many studies have confirmed that climate change leads to frequent urban flooding, which can lead to significant socioeconomic repercussions. However, most existing studies have not evaluated the impacts of climate change on urban flood from both event-scale and annual-scale dimensions. In addition, there are only few studies that simultaneously consider scenario and model uncertainties of climate change, and combine flood risk assessment and uncertainty analysis results to provide practical suggestions for urban drainage system management. This study uses the statistical downscaling method to calculate the design rainfall under ten rainfall return periods of four climate models and three climate change scenarios in 2040s, 2060s, and 2080s in various prefecture-level cities in China. The four climate models are HadGEM2- ES, MPI-ESM-MR, NorESM1-M and FGOALS-g2 models and the three climate change scenarios are constructed by different representative concentration pathways (RCP), namely RCP2.6, RCP4.5 and RCP8.5. On this basis, relying on the generated drainage systems using geographical information and other data, event-scale and annual-scale precipitation are combined to calculate the change ratio of annual flood volume expectation in prefecture-level cities in each future year compared with the current situation. Furthermore, the study evaluates scenario and model uncertainties of climate change, and then comprehensively integrates the flood risk and its uncertainties to provides suggestions for urban drainage system management.

Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

Current practice for the treatment of obstructive left-sided colon cancer in China: a nationwide cross-sectional survey.

PURPOSE: This study surveyed the current practice of surgical treatment of obstructive left-sided colon cancer (OLCC) in China. METHODS: All colorectal surgery departments at tertiary or secondary hospitals in China were invited to complete a web-based questionnaire between August 27 and September 2, 2020. RESULTS: Overall, completed questionnaire were received from 357 hospitals. Emergency surgery was the mainstay of treatment for OLCC, with the open approach accounting for up to 61.62%. The stoma rate of emergency surgery was up to 80%, mainly due to inadequate bowel preparation and severe edema of colon walls. Hartmann's procedure (61.62%) was the most preferred operation. A total of 243 hospitals (68.7%) reported that they would consider the use of a self-expanding metallic stent (SEMS) as a bridge for elective surgery. More than 50% of the hospitals participating in this study reported the success rate of SEMS placement, as well as the resolution rate of obstruction more than 80%, and the stent-related perforation rate was < 5%. A total of 126 hospitals considered carrying out a strategy of SEMS followed by neoadjuvant chemotherapy prior to elective surgery and believed that it might further improve treatment outcomes. CONCLUSIONS: SEMS is a feasible option for the treatment of OLCC in addition to traditional emergency surgery, and its clinical benefits have been preliminarily recognized.

[Efficacy and safety of black tomato concentrate in the treatment of erectile dysfunction: A prospective randomized controlled open trial].

OBJECTIVE: To evaluate the efficacy and safety of black tomato concentrate (BTC), which is rich in polyphenols, in the treatment of ED. METHODS: We conducted a prospective randomized open clinical study of 150 ED patients from December 2018 to February 2020, and treated the them with placebo (n = 50), BTC (n = 50) and Compound Xuanju Capsules (CXC) (n = 50), respectively, all for 8 weeks. Before and at 4 and 8 weeks after treatment, we obtained the scores of the patients on IIEF-5, Erection Hardness Score (EHS), Sexual Encounter Profile (SEP-2,3) and General Assessment Questionnaire (GAQ-1,2), related biochemical indexes and the T level, followed by comparison among the three groups. RESULTS: Totally, 120 of the patients completed the clinical trial, 37 in the placebo, 43 in the BTC and 40 in the CXC group. There were no statistically significant differences among the placebo, BTC and CXC groups in the baseline scores on IIEF-5 (12.03 �� 3.50 vs 11.70 �� 3.80 vs 11.42 �� 3.82), EHS, and SEP-2,3 (P > 0.05). At 8 weeks after treatment, the patients in the BTC group showed significant improvement in IIEF-5 (15.67 �� 3.63), EHS, SEP-2,3 and GAQ-1 positive response compared with those in the placebo group (P < 0.05) and similar improvement to that in the CXC group in IIEF-5 (15.67 �� 3.63 vs 15.65 �� 3.87), EHS, SEP-2,3 and GAQ-1,2 (P > 0.05). No statistically significant differences were observed in the incidence of adverse reactions among the placebo, BTC and CXC groups (4.7% vs 2.7% vs 5.0%, P > 0.05), and the symptoms were significantly relieved in the BTC group after change of the administration time to after meal. CONCLUSION: Black tomato concentrate is comparable to Compound Xuanju Capsules and better than placebo (P < 0.05) in improving the IIEF-5, EHS and SEP-2,3 scores of ED patients. And, with a high safety, it can be used as an alternative treatment of ED.

Icariin regulates miR-23a-3p-mediated osteogenic differentiation of BMSCs via BMP-2/Smad5/Runx2 and WNT/ß-catenin pathways in osteonecrosis of the femoral head.

Icariin is commonly used for the clinical treatment of osteonecrosis of the femoral head (ONFH). miR-23a-3p plays a vital role in regulating the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). The present study aimed to investigate the roles of icariin and miR-23a-3p in the osteogenic differentiation of BMSCs and an ONFH model. BMSCs were isolated and cultured in vitro using icariin-containing serum at various concentrations, and BMSCs were also transfected with a miR-23a inhibitor. The alkaline phosphatase (ALP) activity and cell viability as well as BMP-2/Smad5/Runx2 and WNT/ß-catenin pathway-related mRNA and protein expression were measured in BMSCs. Additionally, a dual-luciferase reporter assay and pathway inhibitors were used to verify the relationship of icariin treatment/miR-23a and the above pathways. An ONFH rat model was established in vivo, and a 28-day gavage treatment and lentivirus transfection of miR-23a-3p inhibitor were performed. Then, bone biochemical markers (ELISA kits) in serum, femoral head (HE staining and Digital Radiography, DR) and the above pathway-related proteins were detected. Our results revealed that icariin treatment/miR-23a knockdown promoted BMSC viability and osteogenic differentiation as well as increased the mRNA and protein expression of BMP-2, BMP-4, Runx2, p-Smad5, Wnt1 and ß-catenin in BMSCs and ONFH model rats. In addition, icariin treatment/miR-23a knockdown increased bone biochemical markers (ACP-5, BAP, NTXI, CTXI and OC) and improved ONFH in ONFH model rats. In addition, a dual-luciferase reporter assay verified that Runx2 was a direct target of miR-23a-3p. These data indicated that icariin promotes BMSC viability and osteogenic differentiation as well as improves ONFH by decreasing miR-23a-3p levels and regulating the BMP-2/Smad5/Runx2 and WNT/ß-catenin pathways.

Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses.

BACKGROUND: Pulmonary malignant neoplasms have a high worldwide morbidity and mortality, so the study of these malignancies using microRNAs (miRNAs) has attracted great interest and enthusiasm. The aim of this study was to determine the clinical effect of hsa-microRNA-204-5p (miR-204-5p) and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC). METHODS: Expression of miR-204-5p was investigated by real-time quantitative PCR (RT-qPCR). After data mining from public online repositories, several integrative assessment methods, including receiver operating characteristic (ROC) curves, hazard ratios (HR) with 95% confidence intervals (95% CI), and comprehensive meta-analyses, were conducted to explore the expression and clinical utility of miR-204-5p. The potential objects regulated and controlled by miR-204-5p in the course of NSCLC were identified by estimated target prediction and analysis. The regulatory network of miR-204-5p, with its target genes and transcription factors (TFs), was structured from database evidence and literature references. RESULTS: The expression of miR-204-5p was downregulated in NSCLC, and the downtrend was related to gender, histological type, vascular invasion, tumor size, clinicopathologic grade and lymph node metastasis (P<0.05). MiR-204-5p was useful in prognosis, but was deemed unsuitable at present as an auxiliary diagnostic or prognostic risk factor for NSCLC due to the lack of statistical significance in meta-analyses and absence of large-scale investigations. Gene enrichment and annotation analyses identified miR-204-5p candidate targets that took part in various genetic activities and biological functions. The predicted TFs, like MAX, MYC, and RUNX1, interfered in regulatory networks involving miR-204-5p and its predicted hub genes, though a modulatory loop or axis of the miRNA-TF-gene that was out of range with shortage in database prediction, experimental proof and literature confirmation. CONCLUSIONS: The frequently observed decrease in miR-204-5p was helpful for NSCLC diagnosis. The estimated target genes and TFs contributed to the anti-oncogene effects of miR-204-5p.

Expression of microRNA-99a-3p in Prostate Cancer Based on Bioinformatics Data and Meta-Analysis of a Literature Review of 965 Cases.

BACKGROUND microRNAs (miRNAs) have a role as biomarkers in human cancer. The aim of this study was to use bioinformatics data, and review of cases identified from the literature, to investigate the role of microRNA-99a-3p (miR-99a-3p) in prostate cancer, including the identification of its target genes and signaling pathways. MATERIAL AND METHODS Meta-analysis from a literature review included 965 cases of prostate cancer. Bioinformatics databases interrogated for miR-99a-3p in prostate cancer included The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and ArrayExpress. Twelve computational predictive algorithms were developed to integrate miR-99a-3p target gene prediction data. Bioinformatics analysis data from Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analysis were used investigate the possible pathways and target genes for miR-99a-3p in prostate cancer. RESULTS TCGA data showed that miR-99a was down-regulated in prostate cancer when compared with normal prostate tissue. Receiver-operating characteristic (ROC) curve area under the curve (AUC) for miR-99a-3p was 0.660 (95% CI, 0.587-0.732) or a moderate level of discriminations. Pathway analysis showed that miR-99a-3p was associated with the Wnt and vascular endothelial growth factor (VEGF) signaling pathways. The PPP3CA and HYOU1 genes, selected from the PPI network, were highly expressed in prostate cancer tissue compared with normal prostate tissue, and negatively correlated with the expression of miR-99a-3p. CONCLUSIONS In prostate cancer, miR-99a-3p expression was associated with the Wnt and VEGF signaling pathways, which might inhibit the expression of PPP3CA or HYOU1.

[Intestinal absorption properties of ponicidin by single pass perfusion model in rats].

To determine the absorption properties and study the intestinal absorption kinetics of poncidin in rats. In situ single pass perfusion model was combined with High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS/MS) method to investigate the intestinal absorption characteristics and calculate absorption parameters with aspects of drug absorption, concentration and perfusion medium. The absorption of poncidin under acid condition at pH 6.5 was more stable, where intestinal enzymes showed little influence on metabolism, and the absorption was significantly higher than that in pH alkaline condition at pH 8.0 (P<0.05). Drug concentrations had no significant influence on absorption rate constant of the same intestinal segment Ka and apparent permeability coefficient Papp values of poncidin. Different concentrations of poncidin showed no significant differences in the Ka and Papp values among duodenum, jejunum and colon, but the values were significantly lower than ileum absorption parameters, with significant differences (P<0.05). There was no significant effect of verapamil on intestinal absorption of poncidin. The results showed that poncidin could be absorbed at all the studied intestinal segments while ileum seemed to be the best absorption segment in the concentration range of 10-1 000 µg·L⁻¹. The absorption was characterized by a linear dynamic process of passive transport, without absorption saturation. Weak acid environment was helpful for the intestinal absorption of poncidin, and ponicidin was not a substrate of P-glycoprotein (P-gp).

BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation.

Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6 secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls (HC). Interestingly, BTLA-expressing CD11c APCs from ATB patients displayed lower expression of HLA-DR and less IL-6 secretion, but higher expression of CD86 than those from HC volunteers. Mixed lymphocyte reaction suggests that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c APCs stimulatory capacity. This role is impaired in ATB patients manifested by low expression of HLA-DR and low production of IL-6. This previous unappreciated role for BTLA may have implications in the prevention and treatment of patients with ATB.

ctPath: Demixing pathway crosstalk effect from transcriptomics data for differential pathway identification.

Identifying differentially expressed pathways (DEPs) plays important roles in understanding tumor etiology and promoting clinical treatment of cancer or other diseases. By assuming gene expression to be a sparse non-negative linear combination of hidden pathway signals, we propose a pathway crosstalk-based transcriptomics data analysis method (ctPath) for identifying differentially expressed pathways. Biologically, pathways of different functions work in concert at the systematic level. The proposed method interrogates the crosstalks between pathways and discovers hidden pathway signals by mapping high-dimensional transcriptomics data into a low-dimensional pathway space. The resulted pathway signals reflect the activity level of pathways after removing pathway crosstalk effect and allow a robust identification of DEPs from inherently complex and noisy transcriptomics data. CtPath can also correct incomplete and inaccurate pathway annotations which frequently occur in public repositories. Experimental results on both simulation data and real-world cancer data demonstrate the superior performance of ctPath over other popular approaches. R code for ctPath is available for non-commercial use at the URL http://micblab.iim.ac.cn/Download/.

[Interaction and mechanism between poinicidin and BSA].

To establish a sensitive and specific LC-MS/MS method for determination of the binding conditions of ponicidin with bovine serum albumin (BSA) and analysis of its mechanism. The protein binding rates and related binding constants of ponicidin in BSA samples were determined by ultrafiltration and LC-MS/MS. Scatchard equation was used to calculate the binding constant (Ka) of ponicidin in BSA samples as well as the number of binding sites (n), and the mechanism on ponicidin binding with BSA was explored. The results showed that the average protein binding rate of ponicidin with BSA was 57.2%, mainly as grade Ⅰ intensive binding, and the relevant binding constant was 2.54×104 L•µg⁻¹, with a binding site number of n=0.75. The binding of ponicidin with BSA had no concentration dependence within the investigated concentrations. The established method in this study showed high sensitivity, specificity, simple operation and met the analysis requirements, and the calculation of binding constant laid foundation for the clinical drug interactions and pharmacokinetics research.

[Effects of Climatic Factors on Contents of Major Medical Components in Smilax china from Different Regions in Western Hunan].

OBJECTIVE: To study the impact of climatic factors on the major medical component in Smilax china, and to supply a scientific and standard operation protocol on the introduction and cultivation. METHODS: Detect the content of major medical components, such as baicalin and astibin, in Smilax china from eight counties of Xiangxi Autonomous Prefecture. And establish their relationship with annual average temperature, Jan average temp, Jul average temp, valid accumulative temp (≥ 10 degress C), annual maximum temp, annual minimum temp, annual precipitation, annual sunshine amount, non-frost period and relative humidity by using the methods of partial least squares regression analysis (PLS). RESULTS: Relative humidity, annual minimum temp and annual precipitation are the dominant factors. Annual minimum temp, annual average temp and valid accumulative temp were significantly correlated to the content of major medical components, thus, relative humidity, annual precipitation and non-frost period were negatively related to them. CONCLUSION: This study provides a scientific basis for resources protection,introduction and cultivation of Smilax china.

[Efficacies of gefitinib versus paclitaxel/carboplatin for patients with advanced pulmonary adenocarcinoma].

OBJECTIVE: To compare the clinical efficacies of gefitinib versus paclitaxel/carboplatin in patients with advanced pulmonary adenocarcinoma. METHODS: A total of 51 advanced pulmonary adenocarcinoma patients were recruited from Guangdong General Hospital during October 2006 to September 2007. Eligible patients were ≥ 18 years old, either non-smokers or former light smokers and receiving no prior chemotherapy or biological/immunological therapy. According to performance status, smoking status and gender, they were selected with dynamic equilibrium randomized method 1: 1 to receive first-line gefitinib (250 mg/d) in gefitinib arm or carboplatin/paclitaxel (carboplatin, area under the curve 5 mg × ml⁻¹ × min⁻¹, 21-day cycle; paclitaxel, 200 mg/m², 21-day cycle in chemotherapy arm. The primary endpoint was progression free survival (PFS). And the secondary endpoints were objective response rate (ORR) and overall survival (OS). RESULTS: They were randomized into gefitinib arm (n = 25) and paclitaxel/carboplatin arm (n = 26). The median PFS was 4.2 months in gefitinib arm and 8.3 months in paclitaxel/carboplatin arm (P = 0.422); ORR 36.0% in gefitinib arm and 42.3% in paclitaxel/carboplatin arm (P = 0.645); Median OS 14.4 months in gefitinib arm and 15.0 months in paclitaxel/carboplatin arm (P = 0.290). Multifactorial Cox regression analysis showed that age (P = 0.004), epidermal growth factor receptor (EGFR) gene mutation status (P = 0.012) and subsequent treatments (platinum-based chemotherapy, P = 0.001; EGFR-tyrosine kinase inhibitors (TKI), P = 0.005) were the significant predictors of OS. CONCLUSIONS: No significant differences exist in terms of efficacy and survival between first-line gefitinib and paclitaxel/carboplatin for Chinese patients with pulmonary adenocarcinoma who are non-smokers or former light smokers. And age, EGFR gene mutation status and subsequent treatments are significant predictor of OS. However, first-line gefitinib should not be recommended for advanced non-small cell lung cancer (NSCLC) patients only based on clinical factors, due to a very small sample-size in our study.

Tofacitinib treatment for plaque psoriasis and psoriatic arthritis: A meta-analysis of randomised controlled trials.

Objectives Tofacitinib is used as an oral Janus-associated kinase (JAK) inhibitor acting on JAK1 and JAK3, in treating psoriatic disease. However, there is still no consensus on the optimal dosage and duration of tofacitinib. In this study, we aimed to evaluate the effects of tofacitinib in treating psoriatic disease. Methods and Materials A literature search was done utilising Cochrane library, Medline, EMBASE, Wiley Online library, Web of Science and BIOSIS Previews through December 18, 2022. We performed a meta-analysis of published original studies to assess the impact of tofacitinib in plaque psoriasis or psoriatic arthritis therapy based on seven randomised controlled trials (RCTs) involving 2,672 patients (receiving tofacitinib) and 853 controls (receiving placebo). Results Compared with placebo, the treatment of 5 mg twice-daily (BID) tofacitinib for 12 weeks is sufficient to significantly alleviate the main clinical manifestations of psoriasis [≥75% decrease in Psoriasis Area and Severity Index score (PASI 75): Risk ratio (RR)=4.38 (95% Confidence interval (CI) 2.51 to 7.64); ≥90% decrease in PASI score (PASI 90): RR=21.68 (95% CI 4.20 to 111.85); Physician's Global Assessment of 'clear' or 'almost clear' (PGA 0/1): RR=3.93 (95%CI 3.03 to 5.09)]. Interestingly, there was no significant difference in improvement in PGA 0/1 with 5 mg BID tofacitinib given for 16 weeks when compared with 5 mg BID tofacitinib for 12 weeks [RR=1.11 (95%CI 0.98 to 1.25)]. Additionally, the 5 mg BID tofacitinib for 16 weeks treatment schedule significantly increased the incidence of upper respiratory tract infection (URTI) [RR=1.89 (95%CI 1.06 to 3.38)] as compared to 5 mg BID tofacitinib for 12 weeks treatment schedule [RR=1.15 (95%CI 0.60 to 2.20)]. Conclusion The 5 mg BID tofacitinib for 12 weeks treatment significantly improved psoriasis without causing too many specific adverse events. This indicated that tofacitinib is an effective treatment plan for psoriatic disease by reasonably controlling dosage and dosing time.

Relationship between platelet count and severity of neonatal respiratory distress syndrome.

BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is a primary cause of morbidity and mortality in premature infants. Platelets have a unique role in lung repair and remodeling. This study aimed to determine the relationship between platelet count and NRDS severity. METHODS: The study included 234 newborns diagnosed with NRDS from January 2019 to August 2023. This study employed two methods of grouping: the first based on platelet count, dividing participants into thrombocytopenia (platelet count < 150 × 109/L, n = 50) and non-thrombocytopenia groups (platelet count ≥ 150 × 109/L, n = 184), and the second based on the severity of NRDS, categorizing them into severe (n = 24) and mild-moderate (n = 210) groups. Within the first grouping method, the thrombocytopenia group was further subdivided into moderate-severe group (platelet count < 100 × 109/L, n = 4) and mild group (platelet count was between 100.0 × 109/L and 150.0 × 109/L, n = 46). This study aimed to analyze the clinical characteristics of NRDS with thrombocytopenia, explore the correlation between platelet count and clinical indicators of NRDS. Binary Logistic regression analysis was employed to identify independent risk factors for thrombocytopenia in NRDS. RESULTS: A higher proportion of newborns in the severe group exhibited thrombocytopenia (severe group = 41.7%, mild-moderate group = 19.0%). Hospital stay, ventilation time, oxygen therapy duration were longer in the thrombocytopenia group compared to the non-thrombocytopenia group. Hospital stay, ventilation time, oxygen therapy duration, chest radiography score, and C-reactive protein (CRP) levels were inversely associated with platelet count. Conversely, Apgar scores at 1 and 5 min, gestational age, and birth weight showed positive correlations with platelet count. Point-biserail correlation showed that thrombocytopenia was more likely to occur in newborns whose mothers had gestational hypertension, and the lower platelet count, the more severe NRDS. Oxygen therapy duration, birth weight < 1500 g, gestational hypertension and CRP levels emerged as independent risk factors for thrombocytopenia in NRDS. All differences were statistically significant (p all < 0.05). CONCLUSION: NRDS accompanied by thrombocytopenia indicates a more severe condition and poorer clinical outcomes. It is hypothesized that NRDS with thrombocytopenia involves a complex multifactorial etiology, including severe lung inflammation.

Microbiological Mechanisms of Collaborative Remediation of Cadmium-Contaminated Soil with Bacillus cereus and Lawn Plants.

Severe cadmium contamination poses a serious threat to food security and human health. Plant-microbial combined remediation represents a potential technique for reducing heavy metals in soil. The main objective of this study is to explore the remediation mechanism of cadmium-contaminated soil using a combined approach of lawn plants and microbes. The target bacterium Bacillus cereus was selected from cadmium-contaminated soil in mining areas, and two lawn plants (Festuca arundinacea A'rid III' and Poa pratensis M'idnight II') were chosen as the target plants. We investigated the remediation effect of different concentrations of bacterial solution on cadmium-contaminated soil using two lawn plants through pot experiments, as well as the impact on the soil microbial community structure. The results demonstrate that Bacillus cereus promotes plant growth, and the combined action of lawn plants and Bacillus cereus improves soil quality, enhancing the bioavailability of cadmium in the soil. At a bacterial suspension concentration of 105 CFU/mL, the optimal remediation treatment was observed. The removal efficiency of cadmium in the soil under Festuca arundinacea and Poa pratensis treatments reached 33.69% and 33.33%, respectively. Additionally, the content of bioavailable cadmium in the rhizosphere soil increased by up to 13.43% and 26.54%, respectively. Bacillus cereus increased the bacterial diversity in the non-rhizosphere soil of both lawn plants but reduced it in the rhizosphere soil. Additionally, the relative abundance of Actinobacteriota and Firmicutes, which have potential for heavy metal remediation, increased after the application of the bacterial solution. This study demonstrates that Bacillus cereus can enhance the potential of lawn plants to remediate cadmium-contaminated soil and reshape the microbial communities in both rhizosphere and non-rhizosphere soils.

Hsa-miR-483-5p/mRNA network that regulates chemotherapy resistance in locally advanced rectal cancer identified through plasma exosome transcriptomics.

BACKGROUND: Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. However, the underlying mechanisms remain elusive. AIM: To detect the differential expression profiles of plasma exosomal microRNAs (miRNAs) in poor and good responders and explore the potential mechanisms of chemoresistance. METHODS: In this study, the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses (poor/good responders) and treatment courses (pre/post-nCRT) using RNA sequencing. RESULTS: Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT. Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways, such as the MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, Toll-like receptor signaling pathway, VEGF signaling pathway, and mTOR signaling pathway. Further analysis indicated that MAPK3, RAX2, and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer, and the profiles of MAPK3, TSPYL5, and ZNF417 were correlated with tumor stage. In addition, the expression profiles of MAPK3, RNF165, and ZNF417 were negatively correlated with inhibitory concentration 50 values. Accordingly, an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed. CONCLUSION: This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs. However, further research is required within the framework of our established miRNA-mRNA network.

Machine Learning-Enabled Tomographic Imaging of Chemical Short-Range Atomic Ordering.

In solids, chemical short-range order (CSRO) refers to the self-organization of atoms of certain species occupying specific crystal sites. CSRO is increasingly being envisaged as a lever to tailor the mechanical and functional properties of materials. Yet quantitative relationships between properties and the morphology, number density, and atomic configurations of CSRO domains remain elusive. Herein, it is showcased how machine learning-enhanced atom probe tomography (APT) can mine the near-atomically resolved APT data and jointly exploit the technique's high elemental sensitivity to provide a 3D quantitative analysis of CSRO in a CoCrNi medium-entropy alloy. Multiple CSRO configurations are revealed, with their formation supported by state-of-the-art Monte-Carlo simulations. Quantitative analysis of these CSROs allows establishing relationships between processing parameters and physical properties. The unambiguous characterization of CSRO will help refine strategies for designing advanced materials by manipulating atomic-scale architectures.

PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial.

No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%). The sample size was calculated by optimal two-stage design. The primary endpoint was the objective response rate (ORR). The study included 71 patients (sintilimab arms, n = 35; pembrolizumab arms, n = 36) and met its primary endpoint, with a confirmed ORR of 51.4% (18/35) in the sintilimab arms. The confirmed ORR (95% confidence interval) was 46.2% (19.2%, 74.9%) and 42.9% (17.7%, 71.1%) for patients treated with sintilimab and pembrolizumab monotherapy; and 54.5% (32.2%, 75.6%) and 45.4% (24.4%, 67.8%) for those treated with sintilimab- and pembrolizumab-based combination therapies. The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies. The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies. Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies. However, the incidence of rash was higher with sintilimab than pembrolizumab monotherapy. This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab.

Clinical characteristics and risk factors of post-operative intestinal flora disorder following laparoscopic colonic surgery: A propensity-score-matching analysis.

BACKGROUND: Intestinal flora disorder (IFD) poses a significant challenge after laparoscopic colonic surgery, and no standard criteria exists for its diagnosis and treatment. AIM: To analyze the clinical features and risk factors of IFD. METHODS: Patients with colon cancer receiving laparoscopic surgery were included using propensity-score-matching (PSM) methods. Based on the occurrence of IFD, patients were categorized into IFD and non-IFD groups. The clinical characteristics and treatment approaches for patients with IFD were analyzed. Multivariate regression analysis was performed to identify the risk factors of IFD. RESULTS: The IFD incidence after laparoscopic surgery was 9.0% (97 of 1073 patients). After PSM, 97 and 194 patients were identified in the IFD and non-IFD groups, respectively. The most common symptoms of IFD were diarrhea and abdominal, typically occurring on post-operative days 3 and 4. All patients were managed conservatively, including modulation of the intestinal flora (90.7%), oral/intravenous application of vancomycin (74.2%), and insertion of a gastric/ileus tube for decompression (23.7%). Multivariate regression analysis identified that pre-operative intestinal obstruction [odds ratio (OR) = 2.79, 95%CI: 1.04-7.47, P = 0.041] and post-operative antibiotics (OR = 8.57, 95%CI: 3.31-23.49, P < 0.001) were independent risk factors for IFD, whereas pre-operative parenteral nutrition (OR = 0.12, 95%CI: 0.06-0.26, P < 0.001) emerged as a protective factor. CONCLUSION: A stepwise approach of probiotics, vancomycin, and decompression could be an alternative treatment for IFD. Special attention is warranted post-operatively for patients with pre-operative obstruction or early use of antibiotics.