Hydrogeochemical features, genesis, and quality appraisal of confined groundwater in a typical large sedimentary plain.

The confined groundwater of arid sedimentary plains has been disturbed by long-term anthropogenic extraction, and its hydrochemical quality is required for sustainable development. The present research investigates the hydrochemical characteristics, formation, potential health threats, and quality suitability of the confined groundwater in the central North China Plain. Results show that the confined groundwater has a slightly alkaline nature in the study area, predominantly dominated by fresh-soft Cl-Na and HCO3-Na types. Water chemistry is governed by water-rock interactions, including dissolution of evaporites and cation exchange. Approximately 97% of the sampled confined groundwaters exceed the prescribed standard for F-. It is mainly due to geological factors such as mineral dissolution, cation exchange, and competitive adsorption of HCO3 - and may also be released from compacted soils because of groundwater extraction. Enriched F- in the confined groundwater can pose an intermediate and higher non-carcinogenic risk to more than 90% of the population. It poses the greatest health threat to the population in the north-eastern part of the study area, especially to infants and children. For sustainable development, the long-term use of confined groundwater for irrigation in the area should be avoided, and attention should also be paid to the potential soil salinization and infiltration risks. In the study area, 97% of the confined groundwaters are found to be excellent or good quality for domestic purposes based on Entropy-weighted Water Quality Index. However, the non-carcinogenic health risk caused by high contents of F- cannot be ignored. Therefore, it is recommended that differential water supplies should be implemented according to the spatial heterogeneity of confined groundwater quality to ensure the scientific and rational use of groundwater resources. PRACTITIONER POINTS: The hydrochemistry quality of confined groundwater in an arid sedimentary plain disturbed by long-term anthropogenic extraction was investigated. The suitability of confined groundwater for multiple purposes such as irrigation and drinking were evaluated. The hydrochemical characteristics and formation mechanism of confined groundwater under the influence of multiple factors were revealed.

Prediction of lateral lymph node metastasis in rectal cancer patients based on MRI using clinical, deep transfer learning, radiomic, and fusion models.

Introduction: Lateral lymph node (LLN) metastasis in rectal cancer significantly affects patient treatment and prognosis. This study aimed to comprehensively compare the performance of various predictive models in predicting LLN metastasis. Methods: In this retrospective study, data from 152 rectal cancer patients who underwent lateral lymph node (LLN) dissection were collected. The cohort was divided into a training set (n=86) from Tianjin Union Medical Center (TUMC), and two testing cohorts: testing cohort (TUMC) (n=37) and testing cohort from Gansu Provincial Hospital (GSPH) (n=29). A clinical model was established using clinical data; deep transfer learning models and radiomics models were developed using MRI images of the primary tumor (PT) and largest short-axis LLN (LLLN), visible LLN (VLLN) areas, along with a fusion model that integrates features from both deep transfer learning and radiomics. The diagnostic value of these models for LLN metastasis was analyzed based on postoperative LLN pathology. Results: Models based on LLLN image information generally outperformed those based on PT image information. Rradiomics models based on LLLN demonstrated improved robustness on external testing cohorts compared to those based on VLLN. Specifically, the radiomics model based on LLLN imaging achieved an AUC of 0.741 in the testing cohort (TUMC) and 0.713 in the testing cohort (GSPH) with the extra trees algorithm. Conclusion: Data from LLLN is a more reliable basis for predicting LLN metastasis in rectal cancer patients with suspicious LLN metastasis than data from PT. Among models performing adequately on the internal test set, all showed declines on the external test set, with LLLN_Rad_Models being less affected by scanning parameters and data sources.

Ubiquitin-specific protease 38 promotes atrial fibrillation in diabetic mice by stabilizing iron regulatory protein 2.

BACKGROUND: Atrial fibrillation (AF) is a common cardiovascular disease often observed in diabetes mellitus, and there is currently no satisfactory therapeutic option. Ubiquitin-specific protease 38 (USP38) has been implicated in the degradation of numerous substrate proteins in the myocardium. Herein, we aim to investigate the role of USP38 in AF induced by diabetes. METHODS: Cardiac-specific transgenic USP38 mice and cardiac-specific knockout USP38 mice were constructed, and streptozotocin was used to establish diabetic mouse model. Functional, electrophysiological, histologic, biochemical studies were performed. RESULTS: The expression of USP38 was upregulated in atrial tissues of diabetic mice and HL-1 cells exposed to high glucose. USP38 overexpression increased susceptibility to AF, accompanied by aberrant expression of calcium-handling protein, heightened iron load and oxidation stress in diabetic mice. Conversely, USP38 deficiency reduced vulnerability to AF by hampering ferroptosis. Mechanistically, USP38 bound to iron regulatory protein 2 (IRP2), stabilizing it and remove K48-linked polyubiquitination chains, thereby increasing intracellular iron overload, lipid peroxidation, and ultimately contributing to ferroptosis. In addition, reduced iron overload by deferoxamine treatment alleviated oxidation stress and decreased vulnerability to AF in diabetic mice. CONCLUSION: Overall, our findings reveal the detrimental role of USP38 in diabetes-related AF, manifested by increased level of iron overload and oxidation stress.

Early-stage voiding function following uni- versus bilateral inferior vesical vessel resection during therapeutic lateral lymph node dissection with autonomic nerve sparing for advanced low rectal cancer (with video).

Introduction: Lateral lymph node dissection (LLND) has now been widely accepted as the optimal procedure to minimize lateral local recurrence (LLR) for selected cases with advanced lower rectal cancer in Asian countries. However, there is still controversy over the preservation or resection of the inferior vesical vessels (IVVs) during LLND due to concerns of impaired post-operative urinary function. Moreover, the standardized procedure for autonomic nerve preservation has not yet been established. Aim: To evaluate the early-stage postoperative voiding function in patients who underwent LLND with uni- versus bilateral resection of the IVVs and to introduce an autonomic nerve sparing technique with a fascial space priority approach (FSPA). Material and methods: LLND was performed in 106 consecutive patients with advanced low rectal cancer at Tianjin Union Medical Center from May 2017 to October 2022. Prospectively collected clinical data were retrospectively compared between patients who received uni-lateral and bilateral LLND. A video with narration was provided to introduce the stepwise procedure of autonomic nerve preservation during IVV resection. Results: The unilateral lymph node dissection (LND) group and the bilateral LND group included 75 and 31 cases, respectively. All LLNDs were performed with FSPA with IVV resection as a standard procedure. No significant differences were observed in overall catheterization days (p = 0.336) and re-catheterization rate (p = 0.575) between groups. No patients in either group suffered from long-term (≥ 30 days) voiding dysfunction. Conclusions: Autonomic nerve sparing is achievable with resection of IVVs during LLND. Satisfactory early-stage voiding function could be obtained with IVV resection on both sides.

Laparoscopic Ureteric Reconstruction After Partial Ureterectomy for Locally Advanced and Recurrent Pelvic Malignancies (with Video).

BACKGROUND: The urinary tract is one of the most frequently involved organs in advanced non-urologic pelvic malignances. Extensive resection of ureteric organs is mandatory during a curative surgery. Urinary reconstruction after partial ureterectomy, the most challenging situation, is associated with a higher incidence of complication than cystectomy, especially when performed with laparoscopy. Furthermore, to date, no generally accepted strategy for urinary reconstruction after extensive tumor resection with partial ureterectomy has been established. METHODS: The study identified and scrutinized intraoperative videos and clinical records of patients with locally advanced or recurrent pelvic malignancies who underwent segmental ureterectomy during en bloc resection of advanced tumors between February 2020 and February 2024. RESULTS: The study enrolled nine patients, including four cases managed by ureteroureteral anastomosis, two cases managed by ureteroneocystomy, two cases managed by Boari flap reconstruction, and one case managed by ileal interposition. In all nine cases, R0 margins were obtained, and no case needed conversion to laparotomy. No clinical evidence of postoperative urinary leakage was identified. The median follow-up period was 14 months (range, 5-19 months). In three of the nine cases, recurrence was identified, at the 3rd, 18th, and 19th month follow-up evaluations, respectively. One patient died of systemic metastasis. CONCLUSIONS: Laparoscopic ureteric reconstruction is feasible for patients who undergo segmental ureterectomy during extensive surgery for locally advanced or recurrent pelvic malignancies. A low anastomotic leakage rate and favorable postoperative renal function could be achieved in this study when anastomosis was performed laparoscopically.

USP38 exacerbates pressure overload-induced left ventricular electrical remodeling.

BACKGROUND: Ubiquitin-specific protease 38 (USP38), belonging to the USP family, is recognized for its role in controlling protein degradation and diverse biological processes. Ventricular arrhythmias (VAs) following heart failure (HF) are closely linked to ventricular electrical remodeling, yet the specific mechanisms underlying VAs in HF remain inadequately explored. In this study, we examined the impact of USP38 on VAs in pressure overload-induced HF. METHODS: Cardiac-specific USP38 knockout mice, cardiac-specific USP38 transgenic mice and their matched control littermates developed HF induced by aortic banding (AB) surgery. After subjecting the mice to AB surgery for a duration of four weeks, comprehensive investigations were conducted, including pathological analysis and electrophysiological assessments, along with molecular analyses. RESULTS: We observed increased USP38 expression in the left ventricle of mice with HF. Electrocardiogram showed that the USP38 knockout shortened the QRS interval and QTc, while USP38 overexpression prolonged these parameters. USP38 knockout decreased the susceptibility of VAs by shortening action potential duration (APD) and prolonging effective refractory period (ERP). In addition, USP38 knockout increased ion channel and Cx43 expression in ventricle. On the contrary, the increased susceptibility of VAs and the decreased expression of ventricular ion channels and Cx43 were observed with USP38 overexpression. In both in vivo and in vitro experiments, USP38 knockout inhibited TBK1/AKT/CAMKII signaling, whereas USP38 overexpression activated this pathway. CONCLUSION: Our data indicates that USP38 increases susceptibility to VAs after HF through TBK1/AKT/CAMKII signaling pathway, Consequently, USP38 may emerge as a promising therapeutic target for managing VAs following HF.

Tirzepatide protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and inflammation via PI3K/Akt signaling.

BACKGROUND: Doxorubicin (DOX) is a highly effective and widely used cytotoxic agent with application for various malignancies, but it's clinically limited due to its cardiotoxicity Oxidative stress and inflammation were reported to take part in DOX-induced cardiotoxicity. Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist has been approved to treat type 2 diabetes. However, its role in DOX-induced cardiotoxicity and the underlying mechanisms has not been explored. METHODS: The cardioprotective properties of Tirzepatide against DOX-induced cardiotoxicity are examined in this work both in vivo and in vitro. For four weeks, an intraperitoneal injection of 4 mg/kg DOX was used to cause cardiotoxicity in C57BL/6 mice. To ascertain the cardioprotective function and underlying mechanisms of Tirzepatide against DOX-induced cardiotoxicity, mice and H9c2 cells were treated with and without Tirzepatide. RESULTS: Tirzepatide treatment significantly inhibited DOX-induced oxidative stress, inflammation and cardiac injury. Mechanistically, PI3K/Akt signaling pathway contributes to the protective effect of Tirzepatide against DOX-induced cardiotoxicity and inhibited PI3K/Akt signaling pathway with LY294002 almost blocked its therapeutic effect. CONCLUSIONS: Collectively, Tirzepatide could alleviate DOX-induced oxidative stress, inflammation and cardiac injury via activating PI3K/Akt signaling pathway and Tirzepatide may be a novel therapeutic target for DOX-induced cardiotoxicity.

Precise Regulation in Chain-Edge Structural Microenvironments of 1D Covalent Organic Frameworks for Photocatalysis.

Covalent organic frameworks (COFs) constitute a promising research topic for photocatalytic reactions, but the rules and conformational relationships of 1D COFs are poorly defined. Herein, the chain edge structure is designed by precise modulation at the atomic level, and the 1D COFs bonded by C, O, and S elements is directionally prepared for oxygen-tolerant photoinduced electron transfer-atom transfer radical polymerization (PET-ATRP) reactions. It is demonstrated that heteroatom-type chain edge structures (─O─, ─S─) lead to a decrease in intra-plane conjugation, which restricts the effective transport of photogenerated electrons along the direction of the 1D strip. In contrast, the all-carbon type chain edge structure (─C─) with higher intra-plane conjugation not only reduces the energy loss of photoexcited electrons but also enhances the carrier density, which exhibits the optimal photopolymerization performance. This work offers valuable guidance in the exploitation of 1D COFs for high photocatalytic performance. This work offers valuable guidance in the exploitation of 1D COFs for high photocatalytic performance.

Sorafenib plus transarterial chemoembolization vs sorafenib alone for patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Although the past decade has seen remarkable advances in treatment options for hepatocellular carcinoma (HCC), the dismal overall prognosis still envelops HCC patients. Several comparative trials have been conducted to study whether transarterial chemoembolization (TACE) could improve clinical outcomes in patients receiving sorafenib for advanced HCC; however, the findings have been inconsistent. AIM: To study the potential synergies and safety of sorafenib plus TACE vs sorafenib alone for treating advanced HCC, by performing a systematic review and meta-analysis. METHODS: This study was conducted following the PRISMA statement. A systematic literature search was conducted using the Cochrane Library, Embase, PubMed, and Web of Science databases. Data included in the present work were collected from patients diagnosed with advanced HCC receiving sorafenib plus TACE or sorafenib alone. Data synthesis and meta-analysis were conducted using Review Manager software. RESULTS: The present study included 2780 patients from five comparative clinical trials (1 was randomized control trial and 4 were retrospective studies). It was found that patients receiving sorafenib plus TACE had better prognoses in terms of overall survival (OS), with a combined hazard ratio (HR) of 0.65 [95% confidence interval (95%CI): 0.46-0.93, P = 0.02, n = 2780]. Consistently, progression free survival (PFS) and time to progression (TTP) differed significantly between the sorafenib plus TACE arm and sorafenib arm (PFS: HR = 0.62, 95%CI: 0.40-0.96, P = 0.03, n = 443; TTP: HR = 0.73, 95%CI: 0.64-0.83, P < 0.00001, n = 2451). Disease control rate (DCR) was also significantly increased by combination therapy (risk ratio = 1.36, 95%CI: 1.02-1.81, P = 0.04, n = 641). Regarding safety, the incidence of any adverse event (AE) was increased due to the addition of TACE; however, no significant difference was found in grade ≥ 3 AEs. CONCLUSION: The combination of sorafenib with TACE has superior efficacy to sorafenib monotherapy, as evidenced by prolonged OS, PFS, and TTP, as well as increased DCR. Additional high-quality trials are essential to further validate the clinical benefit of this combination in the treatment of advanced HCC.

Identification of hydrochemical fingerprints, quality and formation dynamics of groundwater in western high Himalayas.

Identifying hydrochemical fingerprints of groundwater is a challenge in areas with complex geological settings. This study takes the Gilgit-Baltistan, a complex geological area in west high Himalayas, Pakistan, as the study area to get insights into the hydrochemcial genesis and quality of groundwater in complex geological mountainous regions. A total of 53 samples were collected across the area to determine the hydrochemical characteristics and formation of groundwater. Results revealed groundwater there is characterized by slightly alkaline and soft fresh feature. Groundwater is dominated by the hydrochemical facies of HCO3·SO4-Ca·Mg type. The factor method yields three components (PCs) of principal component analysis, which together explain 75.71% of the total variances. The positive correlation of EC, TDS, Ca2+, SO42-, K+ in PC1, and NO3-, Cl- in PC2 indicate that a combination of natural and anthropogenic activities influences groundwater hydrochemistry. Water-rock interaction is the main mechanism governing the natural hydrochemistry of groundwater. The negative correlation of Cl-, SO42-, Ca2+, and Na+ with NDVI attributes to inorganic salt uptake by plant roots. Groundwater chemical composition is also affected by the type of land use. Groundwater is characterized as excellent and good water quality based on the entropy-weighted water quality index assessment, and is suitable for drinking purposes except for very few samples, while aqueous fluoride would pose potential health threats to water consumers in western high Himalayas, and infants are most at risk compared to other populations. This study will help to deepen the hydrochemial formation mechanism and exploitation suitability of groundwater resources in the mountainous areas that undergone the combined actions of nature and human activities, and provide insights into the characteristics of water environmental quality in western Himalayas area.

Prediction of ROS1 and TRKA/B/C occupancy in plasma and cerebrospinal fluid for entrectinib alone and in DDIs using physiologically based pharmacokinetic (PBPK) modeling approach.

PURPOSE: Entrectinib (ENT) is a potent c-ros oncogene 1(ROS1) and neurotrophic tyrosine receptor kinase (NTRKA/B/C) inhibitor. To determine the optimum dosage of ENT using ROS1 and NTRKA/B/C occupancy in plasma and cerebrospinal fluid (CSF) in drug-drug interactions (DDIs), physiologically-based pharmacokinetic (PBPK) models for healthy subjects and cancer population were developed for ENT and M5 (active metabolite). METHODS: The PBPK models were built using the modeling parameters of ENT and M5 that were mainly derived from the published paper on the ENT PBPK model, and then validated by the observed pharmacokinetics (PK) in plasma and CSF from healthy subjects and patients. RESULTS: The PBPK model showed that AUC, Cmax, and Ctrough ratios between predictions and observations are within the range of 0.5-2.0, except that the M5 AUC ratio is slightly above 2.0 (2.34). Based on the efficacy (> 75% occupancy for ROS1 and NTRKA/B/C) and safety (AUC < 160 µM·h and Cmax < 8.9 µM), the appropriate dosing regimens were identified. The appropriate dosage is 600 mg once daily (OD) when administered alone, reduced to 200 mg and 400 mg OD with itraconazole and fluconazole, respectively. ENT is not recommended for co-administration with rifampicin or efavirenz, but is permitted with fluvoxamine or dexamethasone. CONCLUSION: The PBPK models can serve as a powerful approach to predict ENT concentration as well as ROS1 and NTRKA/B/C occupancy in plasma and CSF.

A radiomics model based on T2WI and clinical indexes for prediction of lateral lymph node metastasis in rectal cancer.

OBJECTIVE: The aim of this study was to explore the clinical value of a radiomics prediction model based on T2-weighted imaging (T2WI) and clinical indexes in predicting lateral lymph node (LLN) metastasis in rectal cancer patients. METHODS: This was a retrospective analysis of 106 rectal cancer patients who had undergone LLN dissection. The clinical risk factors for LLN metastasis were selected by multivariable logistic regression analysis of the clinical indicators of the patients. The LLN radiomics features were extracted from the pelvic T2WI of the patients. The least absolute shrinkage and selection operator algorithm and backward stepwise regression method were adopted for feature selection. Three LLN metastasis prediction models were established through logistic regression analysis based on the clinical risk factors and radiomics features. Model performance was assessed in terms of discriminability and decision curve analysis in the training, verification and test sets. RESULTS: The model based on the combined T2WI radiomics features and clinical risk factors demonstrated the highest accuracy, surpassing the models based solely on either T2WI radiomics features or clinical risk factors. Specifically, the model achieved an AUC value of 0.836 in the test set. Decision curve analysis revealed that this model had the greatest clinical utility for the vast majority of the threshold probability range from 0.4 to 1.0. CONCLUSION: Combining T2WI radiomics features with clinical risk factors holds promise for the noninvasive assessment of the biological characteristics of the LLNs in rectal cancer, potentially aiding in therapeutic decision-making and optimizing patient outcomes.

Dapansutrile Ameliorates Atrial Inflammation and Vulnerability to Atrial Fibrillation in HFpEF Rats.

BACKGROUND: Numerous studies have demonstrated that NLRP3 inflammasomes are key players in the progression of atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF). This study aimed to analyse the effect of pharmacological inhibition of NLRP3 inflammasomes using dapansutrile (DAPA), an oral NLRP3-specific inhibitor. METHODS: Dahl salt-sensitive rats were fed a high-salt diet (HSD, 8% NaCl) to induce HFpEF. Either DAPA (200 mg/kg/day) or saline was administered daily via gavage for 4 weeks. Electrophysiological studies were performed to assess the AF inducibility. Confocal fluorescence microscopy and western blot analysis were used to study calcium handling. RESULTS: The DAPA-treated HFpEF rats were less prone to AF induction by programmed electrical stimulation. Atrial fibrosis and inflammation were attenuated in DAPA-treated HFpEF hearts. Dapansutrile treatment showed an increase in the Ca2+ transient sarcoplasmic reticulum-Ca2+ load, and protein expression of SERCA2; NCX1 and phosphorylation of PLB at Thr17 were decreased following DAPA treatment. The increased frequency of spontaneous Ca2+ spark in the HFpEF rats was related to the hyperphosphorylation of RyR2 at Ser2814, which was blunted in DAPA treatment. Dapansutrile treatment also decreased the phosphorylation of CaMKII expression in the HFpEF rats. Mechanistically, DAPA exerts an anti-arrhythmic effect, mainly by inhibiting activation of the NLRP3 inflammasome. CONCLUSION: These data provide evidence that the beneficial cardiac effects of DAPA are associated with reduced atrial inflammation and improved CaMKII-dependent Ca2+-handling abnormalities via blunting activation of the NLRP3 inflammasome, and DAPA may be beneficial in a rat model of HFpEF-induced AF.

Low-intensity pulsed ultrasound treatment mitigates ventricular arrhythmias via inhibiting microglia-mediated neuroinflammation in heart failure rat model.

BACKGROUND: Sympathetic overactivation plays an important role in heart failure (HF)-induced ventricular arrhythmias (VAs). Microglia-mediated neuroinflammation could contribute to sympathetic overactivation. A previous study demonstrated that low-intensity pulsed ultrasound (LIPUS) could inhibit neuroinflammation. However, whether LIPUS could attenuate HF-induced VAs via inhibiting microglia-mediated neuroinflammation remains largely unknown. METHODS: Forth Sprague-Dawley male rats were averagely randomized into four groups: CTL (control) group, CTL + LIPUS group, HF group and HF + LIPUS. Surgical ligation of the coronary artery was used for induction of HF. In vivo electrophysiological study was performed to check VAs susceptibility. Left stellate ganglion (LSG) neural activity and heart rate variability (HRV) were used to test sympathetic nerve activity. RESULTS: Compared to the HF group, LIPUS treatment significantly ameliorated HF-induced cardiac hypertrophy, fibrosis, and dysfunction. In addition, LIPUS treatment markedly inhibited HF-induced VAs susceptibility and reversed gap junction remodeling. LIPUS treatment obviously inhibited microglial activation and neuroinflammation in PVN, sympathetic hyperactivity in the LSG and proinflammatory cytokines releases in the ventricle. P2X7/NLRP3 signaling pathway may be involved in the anti-arrhythmic effect of LIPUS treatment following HF. CONCLUSIONS: Our data demonstrated that LIPUS treatment protected against HF-induced VAs via alleviating microglia-mediated neuroinflammation, sympathetic overactivation and proinflammatory cytokines releases through inhibiting P2X7/NLRP3 signaling. This study provides novel insight into the therapeutic potential of LIPUS.

Case report of radiotherapy combined with anlotinib and immunotherapy for a patient with esophageal cancer and esophageal fistula.

BACKGROUND: Esophageal cancer (EC) is a frequent gastrointestinal malignancy. The most common types of EC pathology worldwide are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Although surgical resection is still the main treatment modality for EC, most patients are already lost to surgery at the time of presentation due to the late stage. In recent years, the development of radiation therapy (RT) combined with targeted therapy (TT) and immunization therapy (IT) has brought more options for the treatment of EC. During radiation therapy, the radiation therapy area is very close to the trachea and esophagus, so radiation therapy may cause damage to the tissues of the trachea and esophagus, which is also known as a tracheoesophageal fistula (TF). We present the case of an EC patient who developed TF during radiation therapy and gradually improved after a combination of anlotinib and immunotherapy. METHODS: The patient was diagnosed with poorly differentiated ESCC by pathological biopsy and treated with "lobaplatin + Tegafur Gimeracil Oteracil Porassium Capsule" for 5 cycles. RESULTS: CT scan of the chest showed progression after treatment. During RT, the patient developed radiotherapy-related adverse effects, which were relieved by symptomatic support therapy. At the end of RT, the patient developed TF, but we chose to let the patient continue his radiation treatment plan with the anti-angiogenic drug "anlotinib." CONCLUSION: After radiation therapy, the patient continued to be treated with anlotinib and immunotherapy with camrelizumab, and the patient's lesion improved.

An Analysis of the Gene Expression Associated with Lymph Node Metastasis in Colorectal Cancer.

Objective: This study aimed to explore the genes regulating lymph node metastasis in colorectal cancer (CRC) and to clarify their relationship with tumor immune cell infiltration and patient prognoses. Methods: The data sets of CRC patients were collected through the Cancer Gene Atlas database; the differentially expressed genes (DEGs) associated with CRC lymph node metastasis were screened; a protein-protein interaction (PPI) network was constructed; the top 20 hub genes were selected; the Gene Ontology functions and the Kyoto Encyclopedia of Genes and Genomes pathways were enriched and analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression method was employed to further screen the characteristic genes associated with CRC lymph node metastasis in 20 hub genes, exploring the correlation between the characteristic genes and immune cell infiltration, conducting a univariate COX analysis on the characteristic genes, obtaining survival-related genes, constructing a risk score formula, conducting a Kaplan-Meier analysis based on the risk score formula, and performing a multivariate COX regression analysis on the clinical factors and risk scores. Results: A total of 62 DEGs associated with CRC lymph node metastasis were obtained. Among the 20 hub genes identified via PPI, only calcium-activated chloride channel regulator 1 (CLCA1) expression was down-regulated in lymph node metastasis, and the rest were up-regulated. A total of nine characteristic genes associated with CRC lymph node metastasis (KIF1A, TMEM59L, CLCA1, COL9A3, GDF5, TUBB2B, STMN2, FOXN1, and SCN5A) were screened using the LASSO regression method. The nine characteristic genes were significantly related to different kinds of immune cell infiltration, from which three survival-related genes (TMEM59L, CLCA1, and TUBB2B) were screened. A multi-factor COX regression showed that the risk scores obtained from TMEM59L, CLCA1, and TUBB2B were independent prognostic factors. Immunohistochemical validation was performed in tissue samples from patients with rectal and colon cancer. Conclusion: TMEM59L, CLCA1, and TUBB2B were independent prognostic factors associated with lymphatic metastasis of CRC.

Influence laws of air gap structure manipulation of covalent organic frameworks on dielectric properties and exciton effects for photopolymerization.

Boosting the dissociation of excitons is essential to enhance the photocatalytic efficiency. However, the relationship between the structure of the catalyst and the exciton effect on the photocatalytic activity is still unclear as the main problem. Here, it is proposed that as a descriptive factor, an experimentally measurable dielectric constant (εr) is available to quantitatively describe its relationship with exciton binding energy (Eb) and photocatalytic activity. With tuning the linker of covalent organic frameworks (COFs), the "air gap" structure is oriented to shrink, leading to an increased εr of COFs and a lower Eb to facilitate exciton dissociation. Meanwhile, taking "water-/oxygen-fueled" photo-induced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization as a demonstration platform, it can be seen that COFs with a small "air gap" structure have relatively superior photocatalytic activity. This provides important implications for the evolution of efficient photocatalysts.

Proteoglycan Extracted from Ganoderma lucidum Ameliorated Diabetes-Induced Muscle Atrophy via the AMPK/SIRT1 Pathway In Vivo and In Vitro.

Muscle atrophy often occurs in type 2 diabetes (T2D) and leads to an increase in physical disability and insulin resistance. However, there are very few studies that have investigated potential natural products used for this condition. In this study, we demonstrated that FYGL (Fudan-Yueyang-G. lucidum), a proteoglycan extracted from Ganoderma lucidum, ameliorated muscle atrophy in rat and mouse models of diabetes. Histopathological analysis of muscle revealed that oral administration of FYGL significantly prevented reduction of the cross-sectional area of muscle fibers and overexpression of muscle atrophic factors in diabetic rats and mice. Muscle RNA-seq analysis in vivo indicated that FYGL regulated genes related to myogenesis, muscle atrophy, and oxidative phosphorylation. Also, FYGL activated AMPK in vivo. Furthermore, the underlying molecular mechanisms were studied in palmitate-induced C2C12 muscle cells using immunofluorescence staining and Western blotting, which revealed that FYGL inhibited muscle atrophy by stimulating ATP production and activating the AMPK/SIRT1 pathway, thus promoting oxidative metabolism. This result rationalized the in vivo findings. These results suggest FYGL as a promising functional food ingredient for the prevention of T2D-induced muscle atrophy.

Diagnostic value of a radiomics model based on CT and MRI for prediction of lateral lymph node metastasis of rectal cancer.

This study aimed to develop a radiomics model for predicting lateral lymph node (LLN) metastasis in rectal cancer patients using MR-T2WI and CT images, and assess its clinical value. This prospective study included rectal cancer patients with complete MR-T2WI and portal enhanced CT images who underwent LLN dissection at Tianjin Union Medical Center between June 2017 and November 2022. Primary lesions and LLN were segmented using 3D slicer. Radiomics features were extracted from the region of interest using pyradiomics in Python. Least absolute shrinkage and selection operator algorithm and backward stepwise regression were employed for feature selection. Three LLN metastasis radiomics prediction models were established via multivariable logistic regression analysis. The performance of the model was evaluated using receiver operating characteristic curve analysis, and the area under the curve (AUC), sensitivity, specificity were calculated for the training, validation, and test sets. A nomogram was constructed for visualization, and decision curve analysis (DCA) was performed to evaluate clinical value. We included 94 eligible patients in the analysis. For each patient, we extracted a total of 1344 radiomics features. The CT combined with MR-T2WI model had the highest AUC for all sets compared to CT and MR-T2WI models. AUC values for the CT combined with MR-T2WI model in the training, validation, and test sets were 0.957, 0.901, and 0.936, respectively. DCA revealed high prediction value for the combined MR-T2WI and CT model. A radiomics model based on CT and MR-T2WI data effectively predicted LLN metastasis in rectal cancer patients preoperatively.