Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Leveraging functional genomic annotations and genome coverage to improve polygenic prediction of complex traits within and between ancestries.

We develop a method, SBayesRC, that integrates genome-wide association study (GWAS) summary statistics with functional genomic annotations to improve polygenic prediction of complex traits. Our method is scalable to whole-genome variant analysis and refines signals from functional annotations by allowing them to affect both causal variant probability and causal effect distribution. We analyze 50 complex traits and diseases using ∼7 million common single-nucleotide polymorphisms (SNPs) and 96 annotations. SBayesRC improves prediction accuracy by 14% in European ancestry and up to 34% in cross-ancestry prediction compared to the baseline method SBayesR, which does not use annotations, and outperforms other methods, including LDpred2, LDpred-funct, MegaPRS, PolyPred-S and PRS-CSx. Investigation of factors affecting prediction accuracy identifies a significant interaction between SNP density and annotation information, suggesting whole-genome sequence variants with annotations may further improve prediction. Functional partitioning analysis highlights a major contribution of evolutionary constrained regions to prediction accuracy and the largest per-SNP contribution from nonsynonymous SNPs.

Safety and benefit of modified mesohepatectomy in the treatment of bilobar involvement congenital biliary dilatation.

BACKGROUND: The diseased bile duct in bilobar congenital biliary dilatation is extensive and often requires major hepatectomy or liver transplantation associated with a higher risk. We aimed to evaluate the safety and benefit of modified mesohepatectomy, in comparison with trisectionectomy, to treat bilobar congenital biliary dilatation. METHODS: This study included 28 patients with type IV and V bilobar congenital biliary dilatation. An innovative mesohepatectomy comprising the hepatectomy technique beyond the P/U point and bile duct shaping was applied to 14 patients to address the extensively diseased bile duct and difficulty in hepaticojejunostomy. Another 14 patients received trisectionectomy. The perioperative and long-term outcomes of these patients were compared. RESULTS: The ratio of residual liver volume to standard liver volume in the mesohepatectomy group was higher (78.68% vs. 40.90%, p = 0.005), while the resection rate of the liver parenchyma was lower (28.25% vs. 63.97%, p = 0.000), than that in trisectionectomy group. The mesohepatectomy group had a lower severe complication (>Clavein III, 0% vs. 57.70%, p = 0.019) and incidence of posthepatectomy liver failure (7.14% vs. 42.86%, p = 0.038). No significant difference was observed in blood loss and bile leakage (p > 0.05). All the patients in the mesohepatectomy group achieved optimal results in the long-term follow-up. CONCLUSIONS: mesohepatectomy provides an efficient treatment option for bilobar congenital biliary dilatation and can achieve radical resection, retain more liver parenchyma, and reduce the difficulty of hepaticojejunostomy, especially for patients that are not eligible for major hepatectomy and liver transplantation.

Unravelling the complex causal effects of substance use behaviours on common diseases.

BACKGROUND: Substance use behaviours (SUB) including smoking, alcohol consumption, and coffee intake are associated with many health outcomes. However, whether the health effects of SUB are causal remains controversial, especially for alcohol consumption and coffee intake. METHODS: In this study, we assess 11 commonly used Mendelian Randomization (MR) methods by simulation and apply them to investigate the causal relationship between 7 SUB traits and health outcomes. We also combine stratified regression, genetic correlation, and MR analyses to investigate the dosage-dependent effects. RESULTS: We show that smoking initiation has widespread risk effects on common diseases such as asthma, type 2 diabetes, and peripheral vascular disease. Alcohol consumption shows risk effects specifically on cardiovascular diseases, dyslipidemia, and hypertensive diseases. We find evidence of dosage-dependent effects of coffee and tea intake on common diseases (e.g., cardiovascular disease and osteoarthritis). We observe that the minor allele effect of rs4410790 (the top signal for tea intake level) is negative on heavy tea intake ( b ̂ G W A S = - 0.091 , s . e . = 0.007 , P = 4.90 × 10 - 35 ) but positive on moderate tea intake ( b ̂ G W A S = 0.034 , s . e . = 0.006 , P = 3.40 × 10 - 8 ) , compared to the non-tea-drinkers. CONCLUSION: Our study reveals the complexity of the health effects of SUB and informs design for future studies aiming to dissect the causal relationships between behavioural traits and complex diseases.

Many people smoke or consume alcohol, coffee and tea. The relationship between using these types of substance and the development of different diseases is not well understood. Previous studies have suggested that differences in genetics, i.e. inherited characteristics, could have an impact on how each substance impacts a particular person's health. We used a method called Mendelian Randomization to look at the impact of consuming tobacco, alcohol, coffee and tea on the development of various common diseases using genetic information. We found that relationships were complicated and many were dosage-dependent, but that consumption of a large amount of all substances tended to have negative health impacts regardless of lifestyle, behavioural or inherited characteristics.

[Effects of Straw Returning and Biochar Addition on Greenhouse Gas Emissions from High Nitrate Nitrogen Soil After Flooding in Rice-vegetable Rotation System in Tropical China].

In rice-vegetable rotation systems in tropical areas, a large amount of nitrate nitrogen accumulates after fertilization in the melon and vegetable season, which leads to the leaching of nitrate nitrogen and a large amount of N2O emission after the seasonal flooding of rice, which leads to nitrogen loss and intensification of the greenhouse effect. How to improve the utilization rate of nitrate nitrogen and reduce N2O emissions has become an urgent problem to be solved. Six treatments were set up [200 mg·kg-1 KNO3 (CK); 200 mg·kg-1 KNO3 + 2% biochar addition (B); 200 mg·kg-1 KNO3+1% peanut straw addition (P); 200 mg·kg-1 KNO3 + 2% biochar + 1% peanut straw addition (P+B); 200 mg·kg-1 KNO3 + 1% rice straw addition (R); 200 mg·kg-1 KNO3 + 2% biochar+1% rice straw addition (R+B)] and cultured at 25℃ for 114 d to explore the effects of organic material addition on greenhouse gas emissions and nitrogen use after flooding in high nitrate nitrogen soil. The results showed that compared with that in CK, adding straw or combining straw with biochar significantly increased soil pH (P<0.05). The B and P treatments significantly increased the cumulative N2O emissions by 41.6% and 28.5% (P<0.05), and the P+B, R, and R+B treatments significantly decreased the cumulative N2O emissions by 14.1%, 24.7%, and 36.7% (P<0.05), respectively. The addition of straw increased the net warming potential of greenhouse gases (NGWP). The addition of coir biochar significantly reduced the effect of straw on NGWP (P<0.05). The combined application of straw and biochar decreased NGWP, and P+B significantly decreased NGWP, but that with R+B was not significant (P>0.05). Adding straw or biochar significantly increased soil microbial biomass carbon (MBC) (P<0.05), and that of P+B was the highest (502.26 mg·kg-1). The combined application of straw and biochar increased soil microbial biomass nitrogen (MBN), and that of P+B was the highest. The N2O emission flux was negatively correlated with pH (P<0.01) and positively correlated with NH4+-N and NO3--N (P<0.01). The cumulative emission of N2O was negatively correlated with MBN (P<0.05). There was a significant negative correlation between NO3--N and MBN (P<0.01), indicating that the reduction in NO3--N was likely to be held by microorganisms, and the increase in the microbial hold of NO3--N also reduced N2O emission. In conclusion, the combined application of peanut straw and coconut shell biochar could significantly inhibit N2O emission and increase soil MBC and MBN, which is a reasonable measure to make full use of nitrogen fertilizer, reduce nitrogen loss, and slow down N2O emission after the season of Hainan vegetables.

Osthole Activates the Cholinergic Anti-Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses.

Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.

Comprehensive analysis reveals the prognostic and immunogenic characteristics of DNA methylation regulators in lung adenocarcinoma.

DNA methylation regulators (DMRs) play a key role in DNA methylation, thus mediating tumor occurrence, metastasis, and immunomodulation. However, the effects of DMRs on clinical outcomes and immunotherapy response remain unexplored in lung adenocarcinoma (LUAD). In this study, eight LUAD cohorts and one immunotherapeutic cohort of lung cancer were utilized. We constructed a DNA methylation regulators-related signature (DMRRS) using univariate and multivariate COX regression analysis. The DMRRS-defined low-risk group was preferentially associated with favorable prognosis, tumor-inhibiting microenvironment, more sensitivity to several targeted therapy drugs, and better immune response. Afterward, the prognostic value and predictive potential in immunotherapy response were validated. Collectively, our findings uncovered that the DMRRS was closely associated with the tumor immune microenvironment and could effectively predict the clinical outcome and immune response of LUAD patients.

Fully biobased hydrogel based on chitosan and tannic acid coated cotton fabric for underwater superoleophobicity and efficient oil/water separation.

Underwater superoleophobic (UWSO) materials have garnered significant attention in separating oil/water mixtures. But, the majority of these materials are made from non-degradable and non-renewable raw materials, polluting the environment and wasting scarce resources while using them. Against this backdrop, this study aimed to fabricate an environmental-friendly UWSO textile using biobased materials. To achieve this, hydrogel consisting of chitosan (CS) and poly(tannic acid) (PTA) were formed and coated on cotton fabric (CTF) via dip-coating followed by oxidative polymerization. CS&PTA hydrogel endowed the CTF with a rough surface and high surface energy, leading to an UWSO CTF with an underwater oil contact angle as high as 166.84°. The CS&PTA/CTF had excellent separation capability toward various oil/water mixtures, showing separation efficiency above 99.84 % and water flux higher than 23, 999 L m-2 h-1. Moreover, CS&PTA/CTF possessed excellent mechanical and environmental stability with underwater superoleophobicity unchanged after sandpaper friction, ultrasonication, organic solvents, NaCl (m/v, 30 %) solution, and acid/base solution immersion, due to the strong interaction between the hydrogel and cotton fabric generated by the mussel-inspired adhesion owing to the presence of PTA. The fully biobased UWSO CTF exhibits great promising to be an alternative to traditional superwetting materials for separation of oil/water mixtures.

Enhanced efficacy of a novel aspirator in uniportal video-assisted thoracoscopic mediastinal lymph node dissection: a non-randomized prospective clinical trial.

Background: Video-assisted thoracoscopic surgery (VATS) is the standard approach in early-stage non-small cell lung cancer (NSCLC) and surgical aspirators play a crucial role. Traditional aspirators lack the ability to pull and lift tissue and cannot achieve optimal exposure. Therefore, we designed a new surgical aspirator that combined the function of thoracoscopic forceps. In this study, we aimed to validate the efficacy and safety of this new surgical aspirator. Methods: We performed a prospective non-randomized intervention trial and enrolled 504 consecutive patients scheduled for uniportal VATS in early NSCLC requiring mediastinal lymph node dissection. A novel aspirator we developed with a clamping function via a front pliers-like structure was implemented in intervention group, whereas traditional aspirator was used in control group. Time spent for nodal dissection in No. 2/4R and No. 7R/L (No. 7 lymph nodes resected through right or left side) lymph nodes and perioperative adverse events related to lymph node dissection were recorded. Mann-Whitey U test was applied to analyze sex and pathological type, an independent-samples t-test was applied to analyze surgery time and age. Results: In total, 250 of enrolled patients were allocated into traditional aspirator group and 254 of them were allocated into new aspirator group. Surgeons spent 544.71±120.80 (range, 332-917, median 541) seconds dissecting No. 2/4R lymph nodes with traditional aspirators and 507.54±100.00 (range, 348-702, median 520) seconds dissecting with new aspirators (P=0.008). The traditional aspirator group had an average surgery time of 507.11±104.61 (range, 310-785, median 510) seconds for No. 7R lymph nodes and 608.47±128.50 (range, 397-919, median 606) seconds for No. 7L lymph nodes, while that in the new aspirator group was 465.09±94.94 (range, 271-744, median 476) seconds (P=0.001) and 549.39±102.11 (range, 368-782, median 538) seconds (P<0.001). The new aspirator showed an efficacy advantage in mediastinal lymph node dissection in VATS, without additional risk. Conclusions: This is the first report about a new suction device combining the functions of both traditional surgical aspirators and forceps, which can effectively shorten the time of mediastinal lymph node dissection and improve the efficiency of thoracoscopic surgery without increasing lymph node dissection-related adverse events.

A radiomics nomogram for predicting postoperative recurrence in esophageal squamous cell carcinoma.

Purpose: To establish and validate a radiomics nomogram for predicting recurrence of esophageal squamous cell carcinoma (ESCC) after esophagectomy with curative intent. Materials and methods: The medical records of 155 patients who underwent surgical treatment for pathologically confirmed ESCC were collected. Patients were randomly divided into a training group (n=109) and a validation group (n=46) in a 7:3 ratio. ​Tumor regions are accurately segmented in computed tomography images of enrolled patients. Radiomic features were then extracted from the segmented tumors. We selected the features by Max-relevance and min-redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) methods. A radiomics signature was then built by logistic regression analysis. To improve predictive performance, a radiomics nomogram that incorporated the radiomics signature and independent clinical predictors was built. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses (DCA). Results: We selected the five most relevant radiomics features to construct the radiomics signature. The radiomics model had general discrimination ability with an area under the ROC curve (AUC) of 0.79 in the training set that was verified by an AUC of 0.76 in the validation set. The radiomics nomogram consisted of the radiomics signature, and N stage showed excellent predictive performance in the training and validation sets with AUCs of 0.85 and 0.83, respectively. Furthermore, calibration curves and the DCA analysis demonstrated good fit and clinical utility of the radiomics nomogram. Conclusion: We successfully established and validated a prediction model that combined radiomics features and N stage, which can be used to predict four-year recurrence risk in patients with ESCC who undergo surgery.

Gold-semiconductor nanohybrids as advanced phototherapeutics.

Phototherapeutics is gaining momentum as a mainstream treatment for cancer, with gold-semiconductor nanocomposites showing promise as potent phototherapeutic agents due to their structural tunability, biocompatibility and functional diversity. Such nanohybrids possess plasmonic characteristics in the presence of gold and the catalytic nature of semiconductor units, as well as the unexpected physicochemical properties arising from the contact interface. This perspective provides an overview of the latest research on gold-semiconductor nanocomposites for photodynamic, photothermal and photocatalytic therapy. The relationship between the spatial configuration of these nanohybrids and their practical performance was explored to deliver comprehensive insights and guidance for the design and fabrication of novel composite nanoplatforms to enhance the efficiency of phototherapeutics, promoting the development of nanotechnology-based advanced biomedical applications.

Air embolism after CT-guided localization of pulmonary ground-glass nodules.

OBJECTIVE: To investigate the incidence of air embolism (AE) related to CT-guided localization of pulmonary ground-glass nodules (GGNs) prior to video-assisted thoracoscopic surgery (VATS). METHODS: The data of all patients who received CT-guided localization of GGNs before VATS from May 2020 to October 2021 were retrospectively analyzed. RESULTS: A total of 1395 consecutive patients with 1553 GGNs were enrolled. AEs occurred in seven patients (0.5%). In four of the seven patients with AE, the embolism was detected before the patients left the CT table and emergency treatments were carried out. Among them, one patient had chest tightness and unilateral limb dyskinesia, one patient had convulsions and transient loss of consciousness, and two patients had no definite clinical symptoms. After a short-term high-flow oxygen inhalation, the clinical symptoms of two patients with symptomatic AE disappeared and two patients with asymptomatic AE did not show any symptoms. In the remaining three patients with AE, the embolism were detected retrospectively when evaluating the images in the PACS for this study. Fortunately, these three patients never developed clinical symptoms related to AE. All seven patients with AE underwent VATS on the day of localization and all GGNs were successfully removed under the guidance of markers. CONCLUSION: The incidence of AE related to CT-guided localization of GGNs was 0.5%, which was significantly higher than expected. Post-localization whole thoracic CT should be performed and observed carefully so as to avoid missed AE and delayed treatment. ADVANCES IN KNOWLEDGE: The incidence of AE related to CT-guided localization of GGNs was 0.5%. In order to timely detect AE, whole thoracic CT scan rather than local CT in the lesion area should be performed after localization. A small amount of AE may be missed if the post- localization CT images are not carefully observed.

Isolation and Identification of a Novel Anti-Dry Eye Peptide from Tilapia Skin Peptides Based on In Silico, In Vitro, and In Vivo Approaches.

Tilapia skin is a great source of collagen. Here, we aimed to isolate and identify the peptides responsible for combating dry eye disease (DED) in tilapia skin peptides (TSP). In vitro cell DED model was used to screen anti-DED peptides from TSP via Sephadex G-25 chromatography, LC/MS/MS, and in silico methods. The anti-DED activity of the screened peptide was further verified in the mice DED model. TSP was divided into five fractions (TSP-I, TSP-II, TSP-III, TSP-IV, and TSP-V), and TSP-II exerted an effective effect for anti-DED. A total of 131 peptides were identified using LC/MS/MS in TSP-II, and NGGPSGPR (NGG) was screened as a potential anti-DED fragment in TSP-II via in silico methods. In vitro, NGG restored cell viability and inhibited the expression level of Cyclooxygenase-2 (COX-2) protein in Human corneal epithelial cells (HCECs) induced by NaCl. In vivo, NGG increased tear production, decreased tear ferning score, prevented corneal epithelial thinning, alleviated conjunctival goblet cell loss, and inhibited the apoptosis of corneal epithelial cells in DED mice. Overall, NGG, as an anti-DED peptide, was successfully identified from TSP, and it may be devoted to functional food ingredients or medicine for DED.

Joint analysis of GWAS and multi-omics QTL summary statistics reveals a large fraction of GWAS signals shared with molecular phenotypes.

Molecular quantitative trait loci (xQTLs) are often harnessed to prioritize genes or functional elements underpinning variant-trait associations identified from genome-wide association studies (GWASs). Here, we introduce OPERA, a method that jointly analyzes GWAS and multi-omics xQTL summary statistics to enhance the identification of molecular phenotypes associated with complex traits through shared causal variants. Applying OPERA to summary-level GWAS data for 50 complex traits (n = 20,833-766,345) and xQTL data from seven omics layers (n = 100-31,684) reveals that 50% of the GWAS signals are shared with at least one molecular phenotype. GWAS signals shared with multiple molecular phenotypes, such as those at the MSMB locus for prostate cancer, are particularly informative for understanding the genetic regulatory mechanisms underlying complex traits. Future studies with more molecular phenotypes, measured considering spatiotemporal effects in larger samples, are required to obtain a more saturated map linking molecular intermediates to GWAS signals.

Using clinical and radiomic feature-based machine learning models to predict pathological complete response in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation.

OBJECTIVE: This study aimed to build radiomic feature-based machine learning models to predict pathological clinical response (pCR) of neoadjuvant chemoradiation therapy (nCRT) for esophageal squamous cell carcinoma (ESCC) patients. METHODS: A total of 112 ESCC patients who underwent nCRT followed by surgical treatment from January 2008 to December 2018 were recruited. According to pCR status (no visible cancer cells in primary cancer lesion), patients were categorized into primary cancer lesion pCR (ppCR) group (N = 65) and non-ppCR group (N = 47). Patients were also categorized into total pCR (tpCR) group (N = 48) and non-tpCR group (N = 64) according to tpCR status (no visible cancer cells in primary cancer lesion or lymph nodes). Radiomic features of pretreatment CT images were extracted, feature selection was performed, machine learning models were trained to predict ppCR and tpCR, respectively. RESULTS: A total of 620 radiomic features were extracted. For ppCR prediction models, radiomic model had an area under the curve (AUC) of 0.817 (95% CI: 0.732-0.896) in the testing set; and the combination model that included rad-score and clinical features had a great predicting performance, with an AUC of 0.891 (95% CI: 0.823-0.950) in the testing set. For tpCR prediction models, radiomic model had an AUC of 0.713 (95% CI: 0.613-0.808) in the testing set; and the combination model also had a great predicting performance, with an AUC of 0.814 (95% CI: 0.728-0.881) in the testing set. CONCLUSION: This study built machine learning models for predicting ppCR and tpCR of ESCC patients with favorable predicting performance respectively, which aided treatment plan optimization. CLINICAL RELEVANCE STATEMENT: This study significantly improved the predictive value of machine learning models based on radiomic features to accurately predict response to therapy of esophageal squamous cell carcinoma patients after neoadjuvant chemoradiation therapy, providing guidance for further treatment. KEY POINTS: • Combination model that included rad-score and clinical features had a great predicting performance. • Primary tumor pCR predicting models exhibit better predicting performance compared to corresponding total pCR predicting models.

Molluscicidal activity of Nicotiana tabacum extracts on the invasive snail Pomacea canaliculata.

Botanical molluscicides for controlling the invasive snail Pomacea canaliculata have attracted worldwide attention because of their cost and environmental friendliness. Aqueous extracts from discarded tobacco leaf (Nicotiana tobacum) were evaluated for molluscicidal activity against different-sized P. canaliculata under laboratory conditions. The results showed that over 90% of the snails died in 1 g/L tobacco extract within 4 days, and the survival of P. canaliculata was inversely proportional to the snail size, tobacco extract concentration and length of exposure time. Adult males were more susceptible to tobacco extract than females. The snails had few chances to feed or mate in 0.5 g/L tobacco extract, and reproduction was greatly limited in 0.2 g/L. The growth of juvenile snails was inhibited in 0.2 g/L tobacco extract, but adults were unaffected. The antioxidant capacity of P. canaliculata in response to tobacco extract can be size- and sex-dependent, and the activities of superoxide dismutase, catalase, and acetylcholinesterase and the contents of glutathione and malondialdehyde were increased in adult males. These results suggest that discarded tobacco leaves can be useful as a molluscicide for controlling the invasive snail P. canaliculata based on its effects on survival, behaviour, food intake, growth performance and antioxidant capacity.

Modified ulnar lengthening for correction of the Masada type 2 forearm deformity in hereditary multiple exostosis.

Few articles have reported on the treatment of Masada type 2 forearm deformities in hereditary multiple exostosis, possibly because of the high redislocation rate and other complications. This study precisely declares the use of modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities. 20 children with Masada type 2 forearm deformities were admitted for surgical treatment at our hospital from February 2014 to February 2021. There were 13 girls and 7 boys, ranging in age from 3.5 to 15 years (mean: 9 years) at the time of operation. We removed the prominent osteochondromas of the distal ulna and the proximal radius, positioned a classic Ilizarov external fixator on the forearm and then performed ulnar transverse one-third proximal diaphyseal subperiosteal osteotomy. We adopted modified ulnar lengthening postoperatively. The effects of surgical correction of deformity and functional improvement of the limb were assessed via regular follow-up and X-ray. The patients were followed up for 36 months, and the ulna was lengthened 26.99 mm on average; all radial heads remained relocated. The radiographic evaluations, including relative ulnar shortening, radial articular angle, and carpal slip, were improved. The functions of the elbow and forearm were all improved after surgery. Modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities in hereditary multiple exostoses has been proven to be an effective and reliable technique in the early stage.

Circular circRANGAP1 Contributes to Non-small Cell Lung Cancer Progression by Increasing COL11A1 Expression Through Sponging miR-653-5p.

Numerous studies have discovered that hsa_circ_0063526 (also known as circRANGAP1) is an oncogenic circular RNA (circRNA) in some human tumors, including non-small cell lung cancer (NSCLC). However, the concrete molecular mechanism of circRANGAP1 involved in NSCLC is not completely elucidated. CircRANGAP1, microRNA-653-5p (miR-653-5p), and Type XI collagen (COL11A1) contents were determined via real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative ability, migration, and invasion were measured using 5-ethynyl-2'-deoxyuridine (EdU), colony formation, wound healing, and transwell assays. E-cadherin, N-cadherin, Vimentin, and COL11A1 protein levels were detected via western blot assay. After Starbase software prediction, the binding between miR-653-5p and circRANGAP1 or COL11A1 was verified using a dual-luciferase reporter assay. Besides, the role of circRANGAP1 on tumor cell growth was analyzed using a xenograft tumor model in vivo. Increased circRANGAP1 and COL11A1, and reduced miR-653-5p were found in NSCLC tissues and cell lines. Furthermore, circRANGAP1 absence might hinder NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Mechanically, circRANGAP1 functioned as a sponge of miR-653-5p to increase COL11A1 expression. In vivo experiments illustrated that circRANGAP1 knockdown repressed tumor growth. CircRANGAP1 silencing might suppress NSCLC cell malignant biological behaviors, at least in part, through the miR-653-5p/COL11A1 axis. These results provided a promising strategy for treating NSCLC malignancies.

Leveraging base-pair mammalian constraint to understand genetic variation and human disease.

Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.

Manganese and copper additions differently reduced cadmium uptake and accumulation in dwarf Polish wheat (Triticum polonicum L.).

This study investigated the effects of manganese (Mn) and copper (Cu) on dwarf Polish wheat under cadmium (Cd) stress by evaluating plant growth, Cd uptake, translocation, accumulation, subcellular distribution, and chemical forms, and the expression of genes participating in cell wall synthesis, metal chelation, and metal transport. Compared with the control, Mn deficiency and Cu deficiency increased Cd uptake and accumulation in roots, and Cd levels in root cell wall and soluble fractions, but inhibited Cd translocation to shoots. Mn addition reduced Cd uptake and accumulation in roots, and Cd level in root soluble fraction. Cu addition did not affect Cd uptake and accumulation in roots, while it caused a decrease and an increase of Cd levels in root cell wall and soluble fractions, respectively. The main Cd chemical forms (water-soluble Cd, pectates and protein integrated Cd, and undissolved Cd phosphate) in roots were differently changed. Furthermore, all treatments distinctly regulated several core genes that control the main component of root cell walls. Several Cd absorber (COPT, HIPP, NRAMP, and IRT) and exporter genes (ABCB, ABCG, ZIP, CAX, OPT, and YSL) were differently regulated to mediate Cd uptake, translocation, and accumulation. Overall, Mn and Cu differently influenced Cd uptake and accumulation; Mn addition is an effective treatment for reducing Cd accumulation in wheat.