Developing and validating a nomogram for early predicting the need for intestinal resection in pediatric intussusception.

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis. Patients & methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model. Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908). Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.

Diagnosis of cervical lymphoma using a YOLO-v7-based model with transfer learning.

To investigate the ability of an auxiliary diagnostic model based on the YOLO-v7-based model in the classification of cervical lymphadenopathy images and compare its performance against qualitative visual evaluation by experienced radiologists. Three types of lymph nodes were sampled randomly but not uniformly. The dataset was randomly divided into for training, validation, and testing. The model was constructed with PyTorch. It was trained and weighting parameters were tuned on the validation set. Diagnostic performance was compared with that of the radiologists on the testing set. The mAP of the model was 96.4% at the 50% intersection-over-union threshold. The accuracy values of it were 0.962 for benign lymph nodes, 0.982 for lymphomas, and 0.960 for metastatic lymph nodes. The precision values of it were 0.928 for benign lymph nodes, 0.975 for lymphomas, and 0.927 for metastatic lymph nodes. The accuracy values of radiologists were 0.659 for benign lymph nodes, 0.836 for lymphomas, and 0.580 for metastatic lymph nodes. The precision values of radiologists were 0.478 for benign lymph nodes, 0.329 for lymphomas, and 0.596 for metastatic lymph nodes. The model effectively classifies lymphadenopathies from ultrasound images and outperforms qualitative visual evaluation by experienced radiologists in differential diagnosis.

Alcohol and colorectal cancer risk subclassified by mutational signatures of DNA mismatch repair deficiency.

BACKGROUND: We examined whether the association between alcohol consumption and CRC incidence was stronger for tumors with higher contributions of defective MMR (dMMR)-related tumor mutational signatures (TMSs). METHODS: We used data from 227,916 men and women who participated in the Nurses' Health Study (1980-2016), the Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2016). Dietary data was collected every 4 years through validated food frequency questionnaires. Relative contributions of two dMMR-related TMSs (c-dMMRa/SBS15 and c-dMMRb/SBS26) were quantified using whole-exome sequencing data in a subset of incident CRC cases. Duplication-method Cox proportional hazards regression models were used to assess the association between alcohol consumption and the risk of CRC subtypes according to different contributions of the TMSs. All statistical tests were 2-sided. RESULTS: We documented 825 incident CRC cases with available TMS data over 26-36 years of follow-up. The association between alcohol consumption and CRC incidence was stronger for tumors with higher contributions of c-dMMRb/SBS26 (P-heterogeneitytrend = 0.02) compared to tumors with lower contributions of this TMS. Compared with nondrinkers, drinkers with ≥15 g/d of alcohol had a high risk of c-dMMRb/SBS26-high CRC [multivariable-adjusted HR: 2.43 (95% CI: 1.55-3.82)], but not c-dMMRb/SBS26-low CRC [0.86 (95% CI: 0.57-1.28)] or c-dMMRb/SBS26-moderate CRC [1.14 (95% CI: 0.76-1.71)]. No significant differential associations were observed for c-dMMRa/SBS15 (P-heterogeneitytrend = 0.41). CONCLUSIONS: High alcohol consumption was associated with an increased incidence of CRC containing higher contributions of c-dMMRb/SBS26, suggesting that alcohol consumption may be involved in colorectal carcinogenesis through the DNA mismatch repair pathway.

Intestinal epithelial Krüppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability.

Maintenance of intestinal barrier function contributes to gastrointestinal homeostasis and therefore cardiovascular diseases. A number of studies show that intestinal permeability is affected by excessive inflammatory responses. Krüppel-like factor (KLF) 4 is one of the critical transcriptional factors, which controls multiple immune responses. In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found that overexpression of epithelial Klf4 in atherosclerotic mice significantly increased intestinal tight junction expression and ameliorated endotoxemia, whereas replenishment of LPS abolished these benefits. Overexpression of Klf4 reversed LPS-induced permeability and downregulation of ZO-1 and Occludin in Caco-2 cells in vitro. HFHC diet stimulated the expression of epithelial microRNA-34a, whereas silence of epithelial Klf4 abolished the benefits of microRNA-34a sponge, a specific miR-34a inhibitor, on intestinal permeability and atherosclerotic development. A clinical cohort of 24 atherosclerotic patients supported colon KLF4/NF-κB/tight junction protein axis mediated intestine/cardiovascular interaction in patients with atherosclerosis. Taken together, intestinal epithelial KLF4 protects against intestinal inflammation and barrier dysfunction, ameliorating atherosclerotic plaque formation.

Post-diagnostic multivitamin supplement use and colorectal cancer survival: A prospective cohort study.

BACKGROUND: Use of multivitamin supplements has been associated with lower incidence of colorectal cancer (CRC). However, its influence on CRC survival remains unknown. METHODS: Among 2424 patients with stage I-III CRC who provided detailed information about multivitamin supplements in the Nurses' Health Study and Health Professionals Follow-up Study, the authors calculated multivariable hazard ratios (HRs) of multivitamin supplements for all-cause and CRC-specific mortality according to post-diagnostic use and dose of multivitamin supplements. RESULTS: During a median follow-up of 11 years, the authors documented 1512 deaths, among which 343 were of CRC. Compared to non-uses, post-diagnostic users of multivitamin supplements at a dose of 3-5 tablets/week had lower CRC-specific mortality (HR, 0.55; 95% confidence interval [CI], 0.36-0.83, p = .005), and post-diagnostic users at doses of 3-5 and 6-9 tablets/week had lower all-cause mortality (HR, 0.81; 95% CI, 0.67-0.99, p = .04; HR, 0.79; 95% CI, 0.70-0.88), p < .001). The dose-response analysis showed a curvilinear relationship for both CRC-specific (pnonlinearity < .001) and all-cause mortality (pnonlinearity  = .004), with the maximum risk reduction observed at 3-5 tablets/week and no further reduction at higher doses. Compared to non-users in both pre- and post-diagnosis periods, new post-diagnostic users at dose of <10 tablets/week had a lower all-cause mortality (HR, 0.81; 95% CI, 0.71-0.94, p = .005), whereas new users at a dose of ≥10 tablets/week (HR, 1.58; 95% CI, 1.07-2.33) and discontinued users (HR, 1.35; 95% CI, 1.14-1.59) had a higher risk of mortality. CONCLUSIONS: Use of multivitamin supplements at a moderate dose after a diagnosis of nonmetastatic CRC is associated with lower CRC-specific and overall mortality, whereas a high dose (≥10 tablets/week) use is associated with higher CRC-specific mortality.

Targeting the IRE1α-XBP1s axis confers selective vulnerability in hepatocellular carcinoma with activated Wnt signaling.

Liver-specific Ern1 knockout impairs tumor progression in mouse models of hepatocellular carcinoma (HCC). However, the mechanistic role of IRE1α in human HCC remains unclear. In this study, we show that XBP1s, the major downstream effector of IRE1α, is required for HCC cell survival both in vitro and in vivo. Mechanistically, XBP1s transactivates LEF1, a key co-factor of ß-catenin, by binding to its promoter. Moreover, XBP1s physically interacts with LEF1, forming a transcriptional complex that enhances classical Wnt signaling. Consistently, the activities of XBP1s and LEF1 are strongly correlated in human HCC and with disease prognosis. Notably, selective inhibition of XBP1 splicing using an IRE1α inhibitor significantly repressed the viability of tumor explants as well as the growth of tumor xenografts derived from patients with distinct Wnt/LEF1 activities. Finally, machine learning algorithms developed a powerful prognostic signature based on the activities of XBP1s/LEF1. In summary, our study uncovers a key mechanistic role for the IRE1α-XBP1s pathway in human HCC. Targeting this axis could provide a promising therapeutic strategy for HCC with hyperactivated Wnt/LEF1 signaling.

Development of Inverse-Opal-Structured Charge-Deficient Co9S8@nitrogen-Doped-Carbon to Catalytically Enable High Energy and High Power for the Two-Electron Transfer I+/I- Electrode.

The iodine (I) electrode involving two-electron transfer chemistry by converting between I+ and I-, has the potential to deliver theoretically doubled capacity and higher working voltage platforms, thus achieving higher energy density. However, owing to the slow kinetics of the cascade two-electron transfer reactions, the system suffers from large overpotentials and low power density, especially at high working currents and low temperatures. Here, an inverse-opal-structured cobalt sulfide@nitrogen-doped-carbon (Co9S8@NC) catalyst with unique charge-deficient states is developed to promote the reaction kinetics of the I-/I+ electrode. The charge-deficient Co9S8@NC catalyst not only enables strong physicochemical adsorption with the iodine species but also significantly reduces the activation energy and interfacial charge transfer resistance of the cascade I+/I0/I- conversion reaction. Consequently, the prototypical Zn‖I+/I0/I- battery equipped with the Co9S8@NC catalyst can deliver a high energy density of 554 Wh kg-1 and a stable cycle life of 5000 cycles at 30 °C. Moreover, at a subzero temperature of -30 °C, the battery can exhibit enhanced kinetics and a high power density of 1514 W kg-1, high energy density of 485 Wh kg-1.

Bidirectional Association Between Cardiovascular Disease and Lung Cancer in a Prospective Cohort Study.

INTRODUCTION: The study aimed to prospectively investigate the bidirectional association between cardiovascular disease (CVD) and lung cancer, and whether this association differs across genetic risk levels. METHODS: This study prospectively followed 455,804 participants from the United Kingdom Biobank cohort who were free of lung cancer at baseline. Cox proportional hazard models were used to estimate the hazard ratio (HR) for incident lung cancer according to CVD status. In parallel, similar approaches were used to assess the risk of incident CVD according to lung cancer status among 478,756 participants free of CVD at baseline. The bidirectional causal relations between these conditions were assessed using Mendelian randomization analysis. Besides, polygenic risk scores were estimated by integrating genome-wide association studies identified risk variants. RESULTS: During 4,007,477 person-years of follow-up, 2006 incident lung cancer cases were documented. Compared with participants without CVD, those with CVD had HRs (95% confidence interval [CI]) of 1.49 (1.30-1.71) for NSCLC, 1.80 (1.39-2.34) for lung squamous cell carcinoma (LUSC), and 1.25 (1.01-1.56) for lung adenocarcinoma (LUAD). After stratification by smoking status, significant associations of CVD with lung cancer risk were observed in former smokers (HR = 1.44, 95% CI: 1.20-1.74) and current smokers (HR = 1.38, 95% CI: 1.13-1.69), but not in never-smokers (HR = 0.98, 95% CI: 0.60-1.61). In addition, CVD was associated with lung cancer risk across each genetic risk level (pheterogeneity = 0.336). In the second analysis, 32,974 incident CVD cases were recorded. Compared with those without lung cancer, the HRs (95% CI) for CVD were 2.33 (1.29-4.21) in NSCLC, 3.66 (1.65-8.14) in LUAD, and 1.98 (0.64-6.14) in LUSC. In particular, participants with lung cancer had a high risk of incident CVD at a high genetic risk level (HR = 3.79, 95% CI: 1.57-9.13). No causal relations between these conditions were observed in Mendelian randomization analysis. CONCLUSIONS: CVD is associated with an increased risk of NSCLC including LUSC and LUAD. NSCLC, particularly LUAD, is associated with a higher CVD risk. Awareness of this bidirectional association may improve prevention and treatment strategies for both diseases. Future clinical demands will require a greater focus on cardiac oncology.

Development, Validation, and Comparison of 2 Ultrasound Feature-Guided Machine Learning Models to Distinguish Cervical Lymphadenopathy.

ABSTRACT: The objective of this study is to develop and validate the performance of 2 ultrasound (US) feature-guided machine learning models in distinguishing cervical lymphadenopathy. We enrolled 705 patients whose US characteristics of lymph nodes were collected at our hospital. B-mode US and color Doppler US features of cervical lymph nodes in both cohorts were analyzed by 2 radiologists. The decision tree and back propagation (BP) neural network were developed by combining clinical data (age, sex, and history of tumor) and US features. The performance of the 2 models was evaluated by calculating the area under the receiver operating characteristics curve (AUC), accuracy value, precision value, recall value, and balanced F score (F1 score). The AUC of the decision tree and BP model in the modeling cohort were 0.796 (0.757, 0.835) and 0.854 (0.756, 0.952), respectively. The AUC, accuracy value, precision value, recall value, and F1 score of the decision tree in the validation cohort were all higher than those of the BP model: 0.817 (0.786, 0.848) vs 0.674 (0.601, 0.747), 0.774 (0.737, 0.811) vs 0.702 (0.629, 0.775), 0.786 (0.739, 0.833) vs 0.644 (0.568, 0.720), 0.733 (0.694, 0.772) vs 0.630 (0.542, 0.718), and 0.750 (0.705, 0.795) vs 0.627 (0.541, 0.713), respectively. The US feature-guided decision tree model was more efficient in the diagnosis of cervical lymphadenopathy than the BP model.

Increased Levels of Urine Volatile Organic Compounds Are Associated With Diabetes Risk and Impaired Glucose Homeostasis.

CONTEXT: Volatile organic compounds (VOCs) are pervasive environmental pollutants that have been linked to various adverse health effects. However, the effect of ambient VOCs, whether individually or in mixtures, on diabetes remains uncertain and requires further investigation. OBJECTIVE: This study investigates the effects of ambient VOCs exposure, whether single or mixed, on diabetes mellitus and glucose homeostasis in the general population. METHODS: Urinary concentrations of VOC metabolites were obtained from the National Health and Nutrition Examination Survey. Survey-weighted logistic regression and generalized linear regression were used to explore the associations between individual VOC exposure and diabetes risk and glucose homeostasis indicators, respectively. Weighted quantile sum (WQS) regression models were applied to assess the combined effects of VOC mixtures. RESULTS: Out of 8468 participants, 1504 had diabetes mellitus. Eight VOC metabolites showed positive associations with diabetes mellitus (OR, 1.15-1.43; all P < .05), insulin resistance (IR) (OR, 1.02-1.06; P < .05), and other glucose homeostasis indicators (ß, 0.04-2.32; all P < .05). Mixed VOC models revealed positive correlations between the WQS indices and diabetes risk (OR = 1.52; 95% CI, 1.29-1.81), IR (OR = 1.36; 95% CI, 1.14-1.62), and other glucose homeostasis indicators (ß, 0.17-2.22; all P < .05). CONCLUSION: Urinary metabolites of ambient VOCs are significantly associated with an increased diabetes risk and impaired glucose homeostasis. Thus, primary prevention policies aimed at reducing ambient VOCs could attenuate diabetes burden.

Adaptive integral alternating minimization method for robust learning of nonlinear dynamical systems from highly corrupted data.

This paper proposes an adaptive integral alternating minimization method (AIAMM) for learning nonlinear dynamical systems using highly corrupted measured data. This approach selects and identifies the system directly from noisy data using the integral model, encompassing unknown sparse coefficients, initial values, and outlier noisy data within the learning problem. It is defined as a sparse robust linear regression problem. An adaptive threshold parameter selection method is proposed to constrain model fitting errors and select appropriate threshold parameters for sparsity. The robustness and accuracy of the proposed AIAMM are demonstrated through several numerical experiments on typical nonlinear dynamical systems, including the van der Pol oscillator, Mathieu oscillator, Lorenz system, and 5D self-exciting homopolar disc dynamo. The proposed method is also compared to several advanced methods for sparse recovery, with the results indicating that the AIAMM demonstrates superior performance in processing highly corrupted data.

Preparation, Characterization, and Properties of UV-Curable Coating Doped with Nano-SiO2.

In this study, a hydrophobic, wear-resistant ultraviolet (UV)-curable coating was investigated as an alternative to traditional coatings with low hardness and high susceptibility to scratching. The SiO2 nanoparticles were ground and modified using high-energy ball milling, during which the surface energy of nano-SiO2 particles rapidly increased as their particle size decreased. Different proportions of modified nano-SiO2 particles were added to the coating and cured into a film. The structure of the composite coating was analyzed via infrared spectroscopy, scanning electron microscopy, and X-ray diffraction, which confirmed the successful preparation of the composite coating. The mechanical and optical property tests of the coating were investigated. With a 5% nano-SiO2 content, the hardness of the coating reached 5H, whereas the adhesion was poor (2B), and the flexibility was 1. The overall comprehensive performance of the coating was best when the addition amount was 3%. The coating exhibited good hardness, flexibility, and adhesion. The hardness of the coating reached 4H, the adhesion was 4B, the flexibility was 5, the coating haze was 12.38 HZ, and the contact angle was 118°.

Integrative Analysis Reveals STC2 as a Prognostic Biomarker of Laryngeal Squamous Cell Carcinoma.

Stanniocalcin 2 (STC2) is involved in many tumour types, but it remains unclear what its biological function is in laryngeal squamous cell carcinoma (LSCC). Therefore, we investigated STC2's expression, potential function, and prognostic significance of in LSCC. The expression and prognosis of STC2 in LSCC were described using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In the TCGA database, the relationship between STC2 and immune infiltration, expression of immune cell chemokine and receptor genes, immune cell molecular marker genes, and epithelial‒mesenchymal transition (EMT) marker genes were analysed. The biological processes involved in STC2 and its expression-related genes were analysed comprehensively using bioinformatics. The single-gene ceRNA network of STC2 was constructed in the TCGA database. Finally, LSCC patients' tumour tissue STC2 expression was verified. STC2 silencing with the RNAi technique was used for the determination of cellular functions in a laryngeal cancer cell line. STC2 expression was higher in most tumours, including LSCC, than in normal tissues and was associated with poor prognosis. The relative proportions of naïve B, plasma, follicular helper T, and macrophage M0 cells in LSCC and normal samples differed significantly. STC2 expression correlated significantly positively with that of TGFB1 (biomarker of Tregs) and significantly negatively with that of D79A and CD19 (biomarkers of B cells). Furthermore, STC2 affected chemokine and receptor gene expression in immune cells. STC2 expression correlated with EMT marker gene expression in LSCC. STC2 was enriched in the PI3K/AKT signalling pathway, extracellular matrix (ECM) organisation, ECM-receptor interaction, and other tumour-related signalling pathways. STC2 was highly expressed in our clinical samples. N-cadherin and vimentin expression were decreased in the TU686 cell line after successful silencing of STC2, indicating that high STC2 expression may prompt LSCC cells to adopt a mesenchymal cell phenotype. STC2 silencing substantially reduced proliferation and migration in the TU686 cell line. STC2 may be a promising predictive biomarker for tumours, providing new approaches for LSCC diagnosis and treatment monitoring.

Simultaneous Single-Position Lateral Lumbar Interbody Fusion Surgery and Unilateral Percutaneous Pedicle Screw Fixation for Spondylolisthesis.

OBJECTIVE: To evaluate the clinical and radiological efficacy of a combine of lateral single screw-rod and unilateral percutaneous pedicle screw fixation (LSUP) for lateral lumbar interbody fusion (LLIF) in the treatment of spondylolisthesis. METHODS: Sixty-two consecutive patients with lumbar spondylolisthesis who underwent minimally invasive (MIS)-TLIF with bilateral pedicle screw (BPS) or LLIF-LSUP were retrospectively studied. Segmental lordosis angle (SLA), lumbar lordosis angle (LLA), disc height (DH), slipping percentage, the cross-sectional areas (CSA) of the thecal sac, screw placement accuracy, fusion rate and foraminal height (FH) were used to evaluate radiographic changes postoperatively. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the clinical efficacy. RESULTS: Patients who underwent LLIF-LSUP showed shorter operating time, less length of hospital stay and lower blood loss than MIS-TLIF. No statistical difference was found between the 2 groups in screw placement accuracy, overall complications, VAS, and ODI. Compared with MIS-TLIF-BPS, LLIF-LSUP had a significant improvement in sagittal parameters including DH, FH, LLA, and SLA. The CSA of MIS-TLIF-BPS was significantly increased than that of LLIF-LSUP. The fusion rate of LLIF-LSUP was significantly higher than that of MIS-TLIF-BPS at the follow-up of 3 months postoperatively, but there was no statistical difference between the 2 groups at the follow-up of 6 months, 9 months, and 12 months. CONCLUSION: The overall clinical outcomes and complications of LLIF-LSUP were comparable to that of MIS-TLIF-BPS in this series. Compared with MIS-TLIF-BPS, LLIF-LSUP for lumbar spondylolisthesis represents a significantly shorter operating time, hospital stay and lower blood loss, and demonstrates better radiological outcomes to maintain lumbar lordosis, and reveal an overwhelming superiority in the early fusion rate.

[Effects of Long-term Tillage on Soil Bacterial Community Structure and Physicochemical Properties of Dryland Wheat Fields in Northern China].

To explore the effects of long-term tillage on bacterial community structure in different soil layers of dryland wheat fields and its relationship with soil physicochemical properties, a long-term field experiment was conducted from 2016 to 2021 in Wenxi Experimental Demonstration Base of Shanxi Agricultural University, Shanxi Province. We studied the effects of no-tillage (NT), subsoiling-tillage (ST), and deep plowing (DP) on soil physicochemical properties; α and ß diversity of the bacterial community; and dominant and different species of phyla and genera in different soil layers. Additionally, PICRUSt2 was used to predict the metabolic function of soil bacterial community. The results revealed that subsoiling-tillage and deep plowing significantly increased the soil water content in the 20-40 cm soil layer and significantly decreased the soil organic carbon content in the 0-20 cm soil layer compared with that under no-tillage for five consecutive years. Compared with that under deep plowing, subsoiling-tillage significantly increased soil water content, soil organic carbon content, dissolved organic carbon content, and dissolved organic nitrogen content in the 0-20 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing increased the α diversity of the soil bacterial community in the 0-40 cm soil layer, and subsoiling-tillage was higher than deep plowing. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundances of Acidobacteria and Nitrospirae in the 0-20 cm soil layer and Acidobacteria, Chloroflexi, Gemmatimonadetes, Rokubacteria, GAL15, and Nitrospirae in the 20-40 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundance of Nitrospira in the 0-20 cm soil layer and Rubrobacter and Streptomyces in the 20-40 cm soil layer. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundance of Acidobacteria and Gemmatimonadetes in the 0-40 cm soil layer. Redundancy analysis demonstrated that the contents of soil organic carbon, dissolved organic carbon, and dissolved organic nitrogen in the 0-20 cm soil layer exerted positive effects on Actinobacteria and Blastococcus, and the soil water content in the 0-40 cm soil layer exerted positive effects on Acidobacteria, Chloroflexi, and Gemmatimonadetes under subsoiling-tillage. The results of PICRUSt2 prediction showed that subsoiling-tillage and deep plowing significantly increased the relative abundance of amino acid metabolism and the metabolism of cofactors and vitamins but decreased the relative abundance of lipid metabolism of bacterial communities in the 20-40 cm soil layer compared with that under no-tillage. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundances of amino acid metabolism in the 0-40 cm soil layer and other amino acid metabolism in the 0-20 cm soil layer. In conclusion, subsoiling-tillage or deep plowing could increase the soil water content, α diversity of the soil bacterial community, and their metabolic capacity in the dryland wheat fields during the summer fallow period. The relative abundance of Acidobacteria and Gemmatimonadetes and the ability of amino acid metabolism of the bacterial community were increased by subsoiling-tillage, and thus the contents of soil dissolved organic carbon and dissolved nitrogen can be increased.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

Four undescribed pyrethrins from seeds of Pyrethrum cinerariifolium and their aphidicidal activity.

Four undescribed pyrethrins C-F (1-4) as well as four known pyrethrins (5-8) were isolated from seeds of Pyrethrum cinerariifolium Trev. The structures of compounds 1-4 were elucidated by UV, HRESIMS, and NMR (1H and 13C NMR, 1H-1H COSY, HSQC, HMBC and ROESY), among which the stereostructure of compound 4 was determined by calculated ECD. Furthermore, compounds 1-4 were evaluated for their aphidicidal activities. The insecticidal assay results showed that 1-4 exhibited moderate aphidicidal activities at the concentration of 0.1 mg/mL with the 24 h mortality rates ranging from 10.58 to 52.98%. Among them, pyrethrin D (2) showed the highest aphidicidal activity, with the 24 h mortality rate of 52.98%, which was slightly lower than the positive control (pyrethrin II, 83.52%).

In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Cancer Incidence in Adulthood: A Prospective Cohort Study.

OBJECTIVE: To evaluate the association of early-life tobacco smoke exposure, especially interacting with cancer genetic variants, with adult cancer. PARTICIPANTS AND METHODS: We examined the associations of in utero tobacco smoke exposure, age of smoking initiation, and their interaction with genetic risk levels with cancer incidence in 393,081 participants from the UK Biobank. Information on tobacco exposure was obtained by self-reported questionnaires. A cancer polygenic risk score was constructed by weighting and integrating 702 genome-wide association studies-identified risk variants. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for overall cancer and organ-specific cancer incidence. RESULTS: During 11.8 years of follow-up, 23,450 (5.97%) and 23,413 (6.03%) incident cancers were included in the analyses of in utero exposure and age of smoking initiation, respectively. The HR (95% CI) for incident cancer in participants with in utero exposure to tobacco smoke was 1.04 (1.01-1.07) for overall cancer, 1.59 (1.44-1.75) for respiratory cancer, and 1.09 (1.03-1.17) for gastrointestinal cancer. The relative risk of incident cancer increased with earlier smoking initiation (Ptrend<.001), with the HR (95% CI) of 1.44 (1.36-1.51) for overall cancer, 13.28 (11.39-15.48) for respiratory cancer, and 1.72 (1.54-1.91) for gastrointestinal cancer in smokers with initiation in childhood compared with never smokers. Importantly, a positive additive interaction between age of smoking initiation and genetic risk was observed for overall cancer (Padditive=.04) and respiratory cancer (Padditive=.003) incidence. CONCLUSION: In utero exposure and earlier smoking initiation are associated with overall and organ-specific cancer, and age of smoking initiation interaction with genetic risk is associated with respiratory cancer.

Interaction of metabolism-related pathway gene variants with bisphenol A exposure on serum lipid profiles.

Bisphenol A (BPA) can be metabolized by metabolic enzymes and may induce abnormal lipid metabolism. We hypothesized that BPA exposure and its interaction with metabolism-related genes might be associated with serum lipid profiles. We performed a two-stage study among 955 middle-aged and elderly participants in Wuhan, China. Urinary BPA level was estimated without (BPA, µg/L) or with (BPA/Cr, µg/g) adjustments for urinary creatinine and ln-transformed values (ln-BPA or ln-BPA/Cr) were used to normalize the asymmetrical distributions. A total of 412 metabolism-related gene variants were selected and used for gene-BPA interaction analysis. Multiple linear regression was used to analyze the interactions between BPA exposure and metabolism-related genes on serum lipid profiles. In the discovery stage, both ln-BPA and ln-BPA/Cr was associated with decreased high-density lipoprotein cholesterol (HDL-C). Gene-urinary BPA interaction for IGFBP7 rs9992658 was observed to associate with HDL-C levels in both discovery and validation stages, with Pinteraction equal to 9.87 × 10-4 (ln-BPA) and 1.22 × 10-3 (ln-BPA/Cr) in combined analyses. In addition, the inverse association of urinary BPA with HDL-C levels was only observed among individuals carrying rs9992658 AA genotype, but not in individuals carrying rs9992658 AC or CC genotypes. The interaction between BPA exposure and metabolism-related gene IGFBP7 (rs9992658) was associated with HDL-C levels.

HSPA12A was identified as a key driver in colorectal cancer GWAS loci 10q26.12 and modulated by an enhancer-promoter interaction.

Although genome-wide association studies (GWASs) have identified over 100 colorectal cancer (CRC) risk loci, an understanding of causal genes or risk variants and their biological functions in these loci remain unclear. Recently, genomic loci 10q26.12 with lead SNP rs1665650 was identified as an essential CRC risk loci of Asian populations. However, the functional mechanism of this region has not been fully clarified. Here, we applied an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk loci 10q26.12. Notably, HSPA12A had the most significant effect among the identified genes and functioned as a crucial oncogene facilitating cell proliferation. Moreover, we conducted an integrative fine-mapping analysis to identify putative casual variants and further explored their association with CRC risk in a large-scale Chinese population consisting of 4054 cases and 4054 controls and also independently validated in 5208 cases and 20,832 controls from the UK biobank cohort. We identified a risk SNP rs7093835 in the intron of HSPA12A that was significantly associated with an increased risk of CRC (OR 1.23, 95% CI 1.08-1.41, P = 1.92 × 10-3). Mechanistically, the risk variant could facilitate an enhancer-promoter interaction mediated by the transcriptional factor (TF) GRHL1 and ultimately upregulate HSPA12A expression, which provides functional evidence to support our population findings. Collectively, our study reveals the important role of HSPA12A in CRC development and illustrates a novel enhancer-promoter interaction module between HSPA12A and its regulatory elements rs7093835, providing new insights into the etiology of CRC.