Internal loading regulates the phosphorus concentration in a diversion input shallow lake in the semi-humid region of North China: Differentiated processes in littoral wetland and open water areas.

Diversion input lakes usually have a low catchment area/lake area ratio and pulsing pollution input. Various pollutants might accumulate in the lake continuously owing to the concentration effect under high evaporation but low precipitation over the entire area, typically for sedimentary cyclic elements such as phosphorus (P). However, the detailed transportation, sedimentation, and internal release mechanisms of P in the diversion input lakes remain unclear. This study conducted a year-long investigation of the littoral wetlands and open water areas of the shallow Lake Hengshui in the semi-humid region of North China. Results revealed that the average total P concentrations in the water and surficial sediment reached as high as 0.202 mg L-1 and 878.21 mg kg-1 in summer. The high water P levels in the lake were mainly regulated by the high internal P loading during summer and autumn, with the internal P loading being approximately nine times the external P loading. The littoral wetland area serves as a higher sedimentation sink and release source of P than the open water area. The concentrated P was continuously transported to the littoral wetland area through detritus burial, coprecipitation, and deposition of suspended particles. The release of P was mainly controlled by the dissolution of redox-sensitive Fe-P and Org-P at high temperatures and organic matter mineralization in the sediment, accompanied by the potential release capacity of apatite P (Ca-P). Future management of eutrophication and P levels in similar diversion input lakes should pay more attention to the high internal P loading in the sediment and the differentiated sedimentation and release processes in the littoral wetland and open water areas.

Microstructure and interaction in aluminum hydrides@polydopamine composites and interfacial improvement with GAP adhesive.

The reduction of interfacial interaction and the deterioration of processing properties of aluminum hydrides (AlH3) is the main challenges preventing its practical application. Here, a simple and effective core-shell structure aluminum hydrides@polydopamine (AlH3@PDA) complex was constructed through in-situ polymerization. The evolution of element states on the surface of AlH3 conducted by X-ray photoelectron spectroscopy indicated the successful introduction of PDA to form the core@shell structure, the thickness of the PDA coated layer increased with the increasing PDA dosage from 0.1 to 1.6% in mass fraction, and the maximum of thickness is 50 nm in TEM testing. Py GC/MS results proved that the increase of dopamine concentration leads to higher proportions of self-assemble units, whereas lower dopamine concentrations favor higher levels of chemical bonded components. Regarding whether PDA is a covalent polymer or a noncovalent aggregate of some species, the formation of intermediates, such as dopaminechrome and 5,6-dihydroxyindole played an important role to coordination interaction with AlH3 in FTIR, Raman, and UV-Vis spectra testing. Compared with pure AlH3, the formation of organic PDA coating improved AlH3 heat resistance. The adhesion work with GAP adhesive was also improved from 107.02 J/m2 of pure AlH3 to 111.13 mJ/m2 of AlH3@PDA-5 complex. This paper provides well support for further practical application of AlH3 in solid propellants.

Modeling alcohol-associated liver disease in humans using adipose stromal or stem cell-derived organoids.

Alcohol-associated liver disease (ALD) is a prevalent liver disease, yet research is hampered by the lack of suitable and reliable human ALD models. Herein, we generated human adipose stromal/stem cell (hASC)-derived hepatocellular organoids (hAHOs) and hASC-derived liver organoids (hALOs) in a three-dimensional system using hASC-derived hepatocyte-like cells and endodermal progenitor cells, respectively. The hAHOs were composed of major hepatocytes and cholangiocytes. The hALOs contained hepatocytes and nonparenchymal cells and possessed a more mature liver function than hAHOs. Upon ethanol treatment, both steatosis and inflammation were present in hAHOs and hALOs. The incubation of hALOs with ethanol resulted in increases in the levels of oxidative stress, the endoplasmic reticulum protein thioredoxin domain-containing protein 5 (TXNDC5), the alcohol-metabolizing enzymes ADH1B and ALDH1B1, and extracellular matrix accumulation, similar to those of liver tissues from patients with ALD. These results present a useful approach for understanding the pathogenesis of ALD in humans, thus facilitating the discovery of effective treatments.

Temperature, humidity, and ionisation effect of iodine oxoacid nucleation.

Iodine oxoacids are recognised for their significant contribution to the formation of new particles in marine and polar atmospheres. Nevertheless, to incorporate the iodine oxoacid nucleation mechanism into global simulations, it is essential to comprehend how this mechanism varies under various atmospheric conditions. In this study, we combined measurements from the CLOUD (Cosmic Leaving OUtdoor Droplets) chamber at CERN and simulations with a kinetic model to investigate the impact of temperature, ionisation, and humidity on iodine oxoacid nucleation. Our findings reveal that ion-induced particle formation rates remain largely unaffected by changes in temperature. However, neutral particle formation rates experience a significant increase when the temperature drops from +10 °C to -10 °C. Running the kinetic model with varying ionisation rates demonstrates that the particle formation rate only increases with a higher ionisation rate when the iodic acid concentration exceeds 1.5 × 107 cm-3, a concentration rarely reached in pristine marine atmospheres. Consequently, our simulations suggest that, despite higher ionisation rates, the charged cluster nucleation pathway of iodic acid is unlikely to be enhanced in the upper troposphere by higher ionisation rates. Instead, the neutral nucleation channel is likely to be the dominant channel in that region. Notably, the iodine oxoacid nucleation mechanism remains unaffected by changes in relative humidity from 2% to 80%. However, under unrealistically dry conditions (below 0.008% RH at +10 °C), iodine oxides (I2O4 and I2O5) significantly enhance formation rates. Therefore, we conclude that iodine oxoacid nucleation is the dominant nucleation mechanism for iodine nucleation in the marine and polar boundary layer atmosphere.

The causal relationship between COVID-19 and ten esophageal diseases: a study utilizing Mendelian randomization.

Background: Clinical signs of dysphagia, pancreatic achalasia, and esophagitis have been reported in patients with COVID-19. However, the causal relationship between COVID-19 and esophageal diseases is not clear. Therefore, we utilized Mendelian randomization to explore the potential association between COVID-19 and esophageal diseases. Methods: The summary statistics for a Genome-wide association study (GWAS) were obtained from The COVID-19 Host Genetics Initiative, encompassing four types of COVID-19 as exposure: severe COVID-19, hospitalized COVID-19 versus ambulatory COVID-19, hospitalized COVID-19 versus uninfected, and confirmed COVID-19. Additionally, summary statistics for ten esophageal diseases as outcomes were sourced from the GWAS Catalog and FinnGen databases. Univariate Mendelian randomization (MR) analysis was utilized to thoroughly investigate and validate the potential causal association between COVID-19 and various esophageal conditions, including esophageal varices, Barrett's esophagus, esophagitis, esophageal obstruction, esophageal ulcer, esophageal perforation, gastroesophageal reflux, congenital esophageal malformations, benign esophageal tumors, and esophageal adenocarcinoma. Results: An inverse variance-weighted (IVW) model was utilized for univariate Mendelian randomization (MR) analysis, which revealed that genetic liability in patients with confirmed COVID-19 was associated with esophageal obstruction (OR [95% CI]: 0.5275458 [0.2822400-0.9860563]; p-value = 0.0450699). Furthermore, a suggestive causal association was found between genetic liability and a reduced risk of benign esophageal tumors (OR [95% CI]: 0.2715453 [0.09368493-0.7870724]; p-value = 0.0163510), but with a suggestively increased risk of congenital esophageal malformations (OR [95% CI]: 6.959561 [1.1955828-40.51204]; p-value = 0.03086835). Additionally, genetic liability in hospitalized COVID-19 patients, compared to non-hospitalized COVID-19 patients, was suggestively associated with an increased risk of esophagitis (OR [95% CI]: 1.443859 [1.0890568-1.914252]; p-value = 0.01068201). The reliability of these causal findings is supported by Cochran's Q statistic and the MR-Egger intercept test. Conclusion: The results of this study suggest the existence of a causal relationship between COVID-19 and esophageal diseases, highlighting differing risk effects of COVID-19 on distinct esophageal conditions.

Advances and challenges in thermal runaway modeling of lithium-ion batteries.

The broader application of lithium-ion batteries (LIBs) is constrained by safety concerns arising from thermal runaway (TR). Accurate prediction of TR is essential to comprehend its underlying mechanisms, expedite battery design, and enhance safety protocols, thereby significantly promoting the safer use of LIBs. The complex, nonlinear nature of LIB systems presents substantial challenges in TR modeling, stemming from the need to address multiscale simulations, multiphysics coupling, and computing efficiency issues. This paper provides an extensive review and outlook on TR modeling technologies, focusing on recent advances, current challenges, and potential future directions. We begin with an overview of the evolutionary processes and underlying mechanisms of TR from multiscale perspectives, laying the foundation for TR modeling. Following a comprehensive understanding of TR phenomena and mechanisms, we introduce a multiphysics coupling model framework to encapsulate these aspects. Within this framework, we detail four fundamental physics modeling approaches: thermal, electrical, mechanical, and fluid dynamic models, highlighting the primary challenges in developing and integrating these models. To address the intrinsic trade-off between computational accuracy and efficiency, we discuss several promising modeling strategies to accelerate TR simulations and explore the role of AI in advancing next-generation TR models. Last, we discuss challenges related to data availability, model scalability, and safety standards and regulations.

Protective effects of COVID-19 vaccination in splenectomized patients with immune thrombocytopenia.

Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.

Efficient preparation of icariin from epimedin C by recyclable biphasic enzymatic hydrolysis.

Icariin is the most bioactive ingredient of Epimedium L. and a quality marker of Herba Epimedii. Conventional methods for production of Icariin are known to be inefficient, resulting in low yields and significant environmental pollution. This study aimed to develop a sustainable and effective biphasic enzymatic hydrolysis system for the efficient conversion of epimedin C to icariin. The biphasic system was created using butyl acetate and phosphate buffer (pH 4.5) at a ratio of 3:1 (V/V) along with α-L-rhamnosidase/epimedin C (2 U/1 mg) at 50 °C for 12 h. Consequently, 98.21% of epimedin C was hydrolysed to icariin, with 95.62% of the product being transferred to the organic phase. Even after four cycles of use, the conversion ratio remained high at 75.28%. Furthermore, this novel strategy was also used for the conversion of Epimedium brevicornu Maxim. extracts. The biphasic system represents a sustainable and effective method for icariin production, offering potential benefits for industrial applications.

Infrared image target detection for substation electrical equipment based on improved faster region-based convolutional neural network algorithm.

Substation electrical equipment generates a massive number of infrared images during operation. However, the overall quality of the infrared images is low and it lacks image detail information. When using traditional target detection algorithms for detection, feature extraction poses great difficulties. Therefore, to address this problem, this paper proposes a target detection algorithm based on the improved faster region-based convolutional neural network (Faster R-CNN). It achieves the correct identification of different types of electrical equipment in infrared images. First, the algorithm improves the backbone network of Faster R-CNN for feature extraction. An InResNet structure is proposed to replace the residual block structure of the original ResNet-34 network, which enhances the richness of feature extraction. Second, the rectified linear unit activation function in the original feature extraction network is replaced by the exponential linear unit activation function, and group normalization is used instead of batch normalization as the network normalization method. Then, the dense connection structure is introduced into the ResNet-34 network, and the whole network is called residual dense connection network. Finally, the improved Faster R-CNN is compared to the original Faster R-CNN, a single-shot multibox detector, and you only look once v3 plus spatial pyramid pooling. The experimental results show that the improved algorithm has the highest mean average precision and average recall for most of the substation electrical equipment in infrared images. Moreover, from the confidence level of the detected electrical equipment and the accuracy of the prediction box, the improved Faster R-CNN has the best performance.

Hypoxia-Responsive Hydrogen-Bonded Organic Framework-Mediated Protein Delivery for Cancer Therapy.

The efficient delivery of therapeutic proteins to tumor sites is a promising cancer treatment modality. Hydrogen-bonded organic frameworks (HOFs) have been successfully used for the protective encapsulation of proteins; however, easy precipitation and lack of controlled release of existing HOFs limit their further application for protein delivery in vivo. In this study, a hypoxia-responsive HOF, self-assembled from azobenzenedicarboxylate/polyethylene glycol-conjugated azobenzenedicarboxylate and tetrakis(4-amidiniumphenyl)methane through charge-assisted hydrogen-bonding, is developed for systemic protein delivery to tumor cells. The newly generated HOF platform efficiently encapsulates representative cytochrome C, demonstrating good dispersibility under physiological conditions. Moreover, it can respond to overexpressed reductases in the cytoplasm under hypoxic conditions, inducing fast intracellular protein release to exert therapeutic effects. The strategy presented herein can be applied to other therapeutic proteins and can be expanded to encompass more intrinsic tumor microenvironment stimuli. This offers a novel avenue for utilizing HOFs in protein-based cancer therapy. This article is protected by copyright. All rights reserved.

Sustained oxidation of Tea-Fe(III)/H2O2 simultaneously achieves sludge reduction and carbamazepine removal: The crucial role of EPS regulation.

Establishing an economic and sustained Fenton oxidation system to enhance sludge dewaterability and carbamazepine (CBZ) removal rate is a crucial path to simultaneously achieve sludge reduction and harmless. Leveraging the principles akin to "tea making", we harnessed tea waste to continually release tea polyphenols (TP), thus effectively maintaining high level of oxidation efficiency through the sustained Fenton reaction. The results illustrated that the incorporation of tea waste yielded more favorable outcomes in terms of water content reduction and CBZ removal compared to direct TP addition within the Fe(III)/hydrogen peroxide (H2O2) system. Concomitantly, this process mainly generated hydroxyl radical (•OH) via three oxidation pathways, effectively altering the properties of extracellular polymeric substances (EPS) and promoting the degradation of CBZ from the sludge mixture. The interval addition of Fe(III) and H2O2 heightened extracellular oxidation efficacy, promoting the desorption and removal of CBZ. The degradation of EPS prompted the transformation of bound water to free water, while the formation of larger channels drove the discharge of water. This work achieved the concept of treating waste with waste through using tea waste to treat sludge, meanwhile, can provide ideas for subsequent sludge harmless disposal.

Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model.

BACKGROUND: Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years. However, the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study. In order to determine the association between adverse reaction factors and prognosis, the aim of this study was to conduct a systematic prognostic analysis. By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy, a nomogram model will be established to predict the survival status of patients more accurately. AIM: To explore the characteristics and predictors of immune-related adverse reactions (irAEs) in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1 (PD-1) inhibitors and to analyze the correlation between irAEs and patient prognosis. METHODS: A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected. Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred. Clinical features, manifestations, and prognosis of irAEs in the two groups were collected and analyzed. A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs, and the prediction model of irAEs was established. The receiver operating characteristic (ROC) curve was used to evaluate the ability of different indicators to predict irAEs. A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis. The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients. RESULTS: A total of 132 patients were followed up, of whom 63 (47.7%) developed irAEs. We looked at the two groups' clinical features and found that the two groups were statistically different in age ≥ 65 years, Ki-67 index, white blood cell count, neutrophil count, and regulatory T cell (Treg) count (all P < 0.05). Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence (P = 0.030). The ROC curve indicated that Treg + Ki-67 + age (≥ 65 years) combined could predict irAEs well (area under the curve = 0.753, 95% confidence interval: 0.623-0.848, P = 0.001). Results of the Kaplan-Meier survival curve showed that progression-free survival (PFS) was longer in the irAEs group than in the non-irAEs group (P = 0.001). Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS (P = 0.006). CONCLUSION: The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy. irAEs can affect the patients' PFS and result in longer PFS. Treg + Ki-67 + age (≥ 65 years old) combined can better predict the occurrence of adverse reactions.

Irisin alleviates obesity-induced bone loss by inhibiting interleukin 6 expression via TLR4/MyD88/NF-κB axis in adipocytes.

INTRODUCTION: Obesity-induced bone loss affects the life quality of patients all over the world. Irisin, one of the myokines, plays an essential role in bone and fat metabolism. OBJECTIVE: Investigate the effects of irisin on bone metabolism via adipocytes in the bone marrow microenvironment. METHODS: In this study, we fed fibronectin type III domain-containing protein 5 (FNDC5, the precursor protein of irisin) knockout mice (FNDC5-/-) with a high-fat diet (HFD) for 10 weeks. The quality of bone mass was assessed by micro-CT analysis, histological staining, and dynamic bone formation. In vitro, the lipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assayed by Oil Red O staining, and the osteogenic differentiation was assayed by alkaline phosphatase staining. Meanwhile, the gene expression in the BMSC-differentiated adipocytes by RNA sequence and the involved pathway of irisin were determined by western blot and qRT-PCR were performed. RESULTS: The FNDC5-/- mice fed with a HFD showed an increased body weight, fat content of the bone marrow and bone, and a decreased bone formation compared with those with a standard diet (SD). In vitro, irisin inhibited the differentiation of BMSCs into adipocytes and alleviated the inhibition of osteogenesis derived from BMSCs by the adipocyte supernatant. RNA sequence and blocking experiment showed that irisin reduced the production of interleukin 6 (IL-6) in adipocytes through downregulating the TLR4/MyD88/NF-κB pathway. Immunofluorescence staining of bone marrow further confirmed an increased IL-6 expression in the FNDC5-/- mice fed with HFD compared with those fed with SD, which suffered serious bone loss. CONCLUSION: Irisin downregulates activation of the TLR4/MyD88/NF-κB pathway, thereby reducing IL-6 production in adipocytes to enhance the osteogenesis of BMSCs. Thus, the rescue of osteogenesis of BMSCs, initially inhibited by IL-6, is a potential therapeutic target to mitigate obesity-induced osteoporosis.

Safety, tolerability, and pharmacokinetics of aildenafil citrate tablets, a novel oral PDE5 inhibitor, in healthy Chinese volunteers after multiple-dose administration.

Background: Aildenafil citrate is a potent and selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, developed for the treatment of erectile dysfunction (ED). Aim: This study aimed to assess the pharmacokinetics, safety, and tolerability of aildenafil citrate tablets after multiple doses in healthy Chinese males. Methods: Twenty participants were divided into 2 groups, 10 participants each. Participants were administered multiple doses of aildenafil citrate tablets at 30 and 60 mg. Outcomes: The safety evaluation was based on clinical symptoms and adverse events. Concentrations of aildenafil and its key metabolites (M1, M5, and M12) in human serum were measured by liquid chromatography-tandem mass spectrometry. Results: Pharmacokinetic analysis showed rapid absorption and elimination of aildenafil, with a median time to maximum serum concentration of 1 hour and mean terminal half-lives of 2.75 and 3.26 hours in the respective dose groups. The mean maximum concentration was proportional to the aildenafil dose in the range of 30 to 60 mg, although the area under the curve was not proportional for serum concentration vs time 0 to the last measurable time point (24 hours). Multiple doses of aildenafil were well tolerated, with 60.0% of men experiencing treatment-emergent adverse events, notably myalgia and fatigue, particularly in the 60-mg group. Clinical Implications: Aildenafil citrate tablets demonstrated favorable tolerability with once-daily administration over the clinical dose range. The occurrence of myalgia and fatigue was more prevalent in the 60-mg group. From a pharmacokinetic perspective, optimal administration of aildenafil citrate tablets appears to be 1 hour before sexual intercourse in men with ED. Strengths and Limitations: This study presents robust safety and pharmacokinetic data at expected therapeutic doses, unaffected by clinical factors. The efficacy of aildenafil citrate tablets warrants further validation in individuals with ED. Conclusion: Aildenafil citrate tablets exhibited good tolerability in healthy Chinese males following multiple doses at 30 and 60 mg. The 60-mg group showed an increased incidence of myalgia and fatigue, suggesting the need for heightened clinical vigilance. The mean maximum concentration, but not the area under the curve, displayed dose proportionality within the 30- to 60-mg dose range, and no significant drug accumulation was observed with repeated daily administration. Clinical Trial Registration: CTR20192473 (http://www.chinadrugtrials.org.cn).

Unveiling the Link: Minimum Inferior Vena Cava Diameter and Thrombosis Risk.

RATIONALE AND OBJECTIVES: This study aimed to investigate the relationship between minimum inferior vena cava (IVC) diameter magnification percentage and in-situ IVC thrombosis (iIVCT) after inferior vena cava filter (IVCF) placement in lower extremity deep vein thrombosis (LEDVT). METHODS: This was a single center retrospective study. Study sample consisted of patients with LEDVT who received computed tomography venography of IVC both before and after IVCF placement between January 2019 and October 2023. A propensity score matching (PSM) was also used in covariates including age, hypertension, and thrombus limbs. Multivariate Cox regression analyses were performed to mitigate the impact of selection bias and control for potential confounding variables. The incremental changes associated with minimum IVC diameter magnification percentage and iIVCT were evaluated with restricted cubic spines (RCS). RESULTS: 113 LEDVT patients (age 58.8 ± 17.8 years, 57.5% male) were included. Multivariate Cox regression analyses revealed a significant positive association between the minimum IVC diameter magnification percentage and the incidence of iIVCT after adjusting for the age, hypertension, and thrombus limbs (adjusted hazard risk [HR] = 1.02, 95% CI, 1.01 to 1.02, p < .001), suggesting minimum IVC diameter magnification percentage was an independent risk factor for iIVCT. Moreover, after using PSM, the association remained significant (HR=1.01, 95% CI, 1.01 to 1.02, p < .001). RCS analysis showed a non-linear dose-response association (s-shaped fitting curve) between minimum IVC diameter magnification percentage and iIVCT risk (nonlinear p = .041). The fitting curve indicated a threshold effect (overall p = .005), with a smaller magnification percentage being negatively associated with the incidence of iIVCT, presenting continuously decreasing HR at levels of magnification percentage < 37.3%. CONCLUSION: A decreasing minimum IVC diameter magnification percentage is consistently associated with a decreasing risk of iIVCT following IVCF placement when the percentage is < 37.3%, indicating that it is a protective factor against iIVCT incidence. WHAT THIS PAPER ADDS?: This single-center retrospective study, which designed to investigate the relationship between minimum inferior vena cava diameter magnification percentage and in-situ inferior vena cava thrombosis (iIVCT) following inferior vena cava filter (IVCF) placement in lower extremity deep vein thrombosis in 113 patients, demonstrated that decreasing minimum IVC diameter magnification percentage is consistently associated with a decreasing risk of iIVCT following IVCF placement when the percentage is < 37.3%, indicating that it is a protective factor against iIVCT incidence.

Characterization and risk factors of inferior vena cava thrombosis in situ detected by computed tomography venography following filter placement: A single-center retrospective cohort study.

OBJECTIVE: This study aimed to characterize radiographic characteristics on computed tomography venography and risk factors of inferior vena cava thrombosis (IVCT) in situ after retrievable vena cava filter (VCF) placement. METHODS: Between September 2018 and June 2023, a single-center retrospective cohort study was conducted in patients with or without IVCT in situ following VCF placement. Patient baseline demographics, presentation of lower extremity deep vein thrombosis (LEDVT), thrombus characteristics, concurrent pulmonary embolism, comorbidities and risk factors for LEDVT, and IVC and VCF-related information were collected and analysed. Univariable analysis followed by multivariable analysis was performed to evaluate the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: One hundred and seventeen eligible patients were included, regionally isolated filling-defect surrounding the support pillars of VCF and contacting IVC wall on computed tomography venography images were identified, clots were more frequently found on the minor axis or anterior wall of IVC. Univariable analyses suggested that the incidence of IVCT in situ (31.6%, 37/117) was closely associated with age (P = .001), thrombus limb (left (P = .001) and bilateral side (P = .001)), hypertension (P = .008), filter shapes (P < .001), short IVC diameter (P = .009) or magnification percentage (P = .004), and long IVC diameter (P = .006). Multivariable analyses suggested that bilateral side LEDVT (OR, 4.92; 95% CI, 1.56-15.51; P = .007) and increased short IVC magnification percentage (OR, 1.01; 95% CI, 1.00-1.03; P = .013) statistically significant increase the IVCT in situ risk, whereas increased age (OR, 0.96; 95% CI, 0.94-0.99; P = .013) and short IVC diameter (OR, 0.87; 95% CI, 0.77-0.98; P = .026) were associated with decreased odds against IVCT in situ. CONCLUSIONS: IVCT in situ represents regionally isolated filling-defect at points of filter contact with IVC wall. Bilateral side LEDVT and increased short IVC magnification percentage may be potential risk factors impacting the occurrence of IVCT in situ, while increased age and short IVC diameter may decrease the incidence of IVCT in situ and seem to be protective factor against IVCT in situ emergence.

Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies.

Traditional Chinese medicine (TCM) has been widely used for several centuries for metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). At present, NAFLD has become the most prevalent form of chronic liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. However, there is still a lack of effective treatment strategies in Western medicine. The development of NAFLD is driven by multiple mechanisms, including genetic factors, insulin resistance, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, gut microbiota dysbiosis, and adipose tissue dysfunction. Currently, certain drugs, including insulin sensitizers, statins, vitamin E, ursodeoxycholic acid and betaine, are proven to be beneficial for the clinical treatment of NAFLD. Due to its complex pathogenesis, personalized medicine that integrates various mechanisms may provide better benefits to patients with NAFLD. The holistic view and syndrome differentiation of TCM have advantages in treating NAFLD, which are similar to the principles of personalized medicine. In TCM, NAFLD is primarily classified into five types based on clinical experience. It is located in the liver and is closely related to spleen and kidney functions. However, due to the multi-component characteristics of traditional Chinese medicine, its application in the treatment of NAFLD has been considerably limited. In this review, we summarize the advances in the pathogenesis and treatment of NAFLD, drawn from both the Western medicine and TCM perspectives. We highlight that Chinese and Western medicine have complementary advantages and should receive increased attention in the prevention and treatment of NAFLD.

The Fanconi anemia pathway repairs colibactin-induced DNA interstrand cross-links.

Colibactin is a secondary metabolite produced by bacteria present in the human gut and is implicated in the progression of colorectal cancer and inflammatory bowel disease. This genotoxin alkylates deoxyadenosines on opposite strands of host cell DNA to produce DNA interstrand cross-links (ICLs) that block DNA replication. While cells have evolved multiple mechanisms to resolve ("unhook") ICLs encountered by the replication machinery, little is known about which of these pathways promote resistance to colibactin-induced ICLs. Here, we use Xenopus egg extracts to investigate replication-coupled repair of plasmids engineered to contain site-specific colibactin-ICLs. We show that replication fork stalling at a colibactin-ICL leads to replisome disassembly and activation of the Fanconi anemia ICL repair pathway, which unhooks the colibactin-ICL through nucleolytic incisions. These incisions generate a DNA double-strand break intermediate in one sister chromatid, which can be repaired by homologous recombination, and a monoadduct ("ICL remnant") in the other. Our data indicate that translesion synthesis past the colibactin-ICL remnant depends on Polη and a Polκ-REV1-Polζ polymerase complex. Although translesion synthesis past colibactin-induced DNA damage is frequently error-free, it can introduce T>N point mutations that partially recapitulate the mutation signature associated with colibactin exposure in vivo. Taken together, our work provides a biochemical framework for understanding how cells tolerate a naturally-occurring and clinically-relevant ICL.