Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses.

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.

An Insulin-Modified pH-Responsive Nanopipette Based on Ion Current Rectification.

The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes.

DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer.

Purpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism. Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression. Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P<0.05), and high DSG2 expression suggested poor overall survival (P<0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P<0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P<0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P<0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05). Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.

Exserolide J ameliorates lipid accumulation in vitro by regulating liver X receptor alpha and peroxisome proliferator-activated receptor alpha proteins.

Exserolides are isocoumarin derivatives containing lactone moiety. Recently, some isocoumarins have been demonstrated to ameliorate hyperlipidemia, a major factor for inducing cardiovascular diseases. However, the effects and mechanisms of action of exserolides on hyperlipidemia are not known. The aim of this study is to investigate whether the marine fungus Setosphaeria sp.-derived exserolides (compounds I, J, E, and F) exert lipid-lowering effects via improving reverse cholesterol transport (RCT) in vitro. RAW264.7 macrophages and HepG2 cells were used to establish lipid-laden models, and the levels of intracellular lipids and RCT-related proteins were determined by assay kits and Western blotting, respectively. We observed that exserolides (at a 5 µM concentration) significantly decreased intracellular cholesterol and triglyceride levels in oxidized low-density lipoprotein-laden RAW264.7 cells and markedly improved [3H]-cholesterol efflux. Among the four tested compounds, exserolide J increased the protein levels of ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor α (PPARα), and liver X receptor α (LXRα). Furthermore, treatment with exserolides significantly decreased oleic acid-laden lipid accumulation in HepG2 hepatocytes. Mechanistically, exserolides enhance PPARα protein levels; furthermore, compound J increases cholesterol 7 alpha-hydroxylase A1 and LXRα protein levels. Molecular docking revealed that exserolides, particularly compound J, can interact with PPARα and LXRα proteins. These data suggest that the terminal carboxyl group of compound J plays a key role in lowering lipid levels by stimulating LXRα and PPARα proteins. In conclusion, compound J exhibits powerful lipid-lowering effects in vitro. However, its hypolipidemic effects in vivo should be investigated in the future.

Glucagon Receptor Antagonist for Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is an emerging major unmet need and one of the most significant clinic challenges in cardiology. The pathogenesis of HFpEF is associated with multiple risk factors. Hypertension and metabolic disorders associated with obesity are the 2 most prominent comorbidities observed in patients with HFpEF. Although hypertension-induced mechanical overload has long been recognized as a potent contributor to heart failure with reduced ejection fraction, the synergistic interaction between mechanical overload and metabolic disorders in the pathogenesis of HFpEF remains poorly characterized. METHOD: We investigated the functional outcome and the underlying mechanisms from concurrent mechanic and metabolic stresses in the heart by applying transverse aortic constriction in lean C57Bl/6J or obese/diabetic B6.Cg-Lepob/J (ob/ob) mice, followed by single-nuclei RNA-seq and targeted manipulation of a top-ranked signaling pathway differentially affected in the 2 experimental cohorts. RESULTS: In contrast to the post-trans-aortic constriction C57Bl/6J lean mice, which developed pathological features of heart failure with reduced ejection fraction over time, the post-trans-aortic constriction ob/ob mice showed no significant changes in ejection fraction but developed characteristic pathological features of HFpEF, including diastolic dysfunction, worsened cardiac hypertrophy, and pathological remodeling, along with further deterioration of exercise intolerance. Single-nuclei RNA-seq analysis revealed significant transcriptome reprogramming in the cardiomyocytes stressed by both pressure overload and obesity/diabetes, markedly distinct from the cardiomyocytes singularly stressed by pressure overload or obesity/diabetes. Furthermore, glucagon signaling was identified as the top-ranked signaling pathway affected in the cardiomyocytes associated with HFpEF. Treatment with a glucagon receptor antagonist significantly ameliorated the progression of HFpEF-related pathological features in 2 independent preclinical models. Importantly, cardiomyocyte-specific genetic deletion of the glucagon receptor also significantly improved cardiac function in response to pressure overload and metabolic stress. CONCLUSIONS: These findings identify glucagon receptor signaling in cardiomyocytes as a critical determinant of HFpEF progression and provide proof-of-concept support for glucagon receptor antagonism as a potential therapy for the disease.

Necroptosis plays a role in TL1A-induced airway inflammation and barrier damage in asthma.

BACKGROUND: Airway epithelial cell (AEC) necroptosis contributes to airway allergic inflammation and asthma exacerbation. Targeting the tumor necrosis factor-like ligand 1 A (TL1A)/death receptor 3 (DR3) axis has a therapeutic effect on asthmatic airway inflammation. The role of TL1A in mediating necroptosis of AECs challenged with ovalbumin (OVA) and its contribution to airway inflammation remains unclear. METHODS: We evaluated the expression of the receptor-interacting serine/threonine-protein kinase 3(RIPK3) and the mixed lineage kinase domain-like protein (MLKL) in human serum and lung, and histologically verified the level of MLKL phosphorylation in lung tissue from asthmatics and OVA-induced mice. Next, using MLKL knockout mice and the RIPK3 inhibitor GSK872, we investigated the effects of TL1A on airway inflammation and airway barrier function through the activation of necroptosis in experimental asthma. RESULTS: High expression of necroptosis marker proteins was observed in the serum of asthmatics, and necroptosis was activated in the airway epithelium of both asthmatics and OVA-induced mice. Blocking necroptosis through MLKL knockout or RIPK3 inhibition effectively attenuated parabronchial inflammation, mucus hypersecretion, and airway collagen fiber accumulation, while also suppressing type 2 inflammatory factors secretion. In addition, TL1A/ DR3 was shown to act as a death trigger for necroptosis in the absence of caspases by silencing or overexpressing TL1A in HBE cells. Furthermore, the recombinant TL1A protein was found to induce necroptosis in vivo, and knockout of MLKL partially reversed the pathological changes induced by TL1A. The necroptosis induced by TL1A disrupted the airway barrier function by decreasing the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin, possibly through the activation of the NF-κB signaling pathway. CONCLUSIONS: TL1A-induced airway epithelial necroptosis plays a significant role in promoting airway inflammation and barrier dysfunction in asthma. Inhibition of the TL1A-induced necroptosis pathway could be a promising therapeutic strategy.

Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence.

BACKGROUND: The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation. RESEARCH DESIGN AND METHODS: Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group. Kaplan-Meier recovery analysis and Cox proportional hazards models were used to evaluate the recovery time and hazard ratios. Additionally, study-level pooled analyses for multiple clinical outcomes were performed. RESULTS: In the 115-patient cohort, UDCA treatment was significantly associated with a reduced recovery time. The subgroup analysis suggests that the 300 mg subgroup had a significant (adjusted hazard ratio: 1.63 [95% CI, 1.01 to 2.60]) benefit with a shorter duration of fever. The results of pooled analyses also show that UDCA treatment can significantly reduce the incidence of severe/critical diseases in COVID-19 (adjusted odds ratio: 0.68 [95% CI, 0.50 to 0.94]). CONCLUSIONS: UDCA treatment notably improves the recovery time following an Omicron strain infection without observed safety concerns. These promising results advocate for UDCA as a viable treatment for COVID-19, paving the way for further large-scale and prospective research to explore the full potential of UDCA.

Cytochrome P450 Enzyme Design by Constraining the Catalytic Pocket in a Diffusion Model.

Although cytochrome P450 enzymes are the most versatile biocatalysts in nature, there is insufficient comprehension of the molecular mechanism underlying their functional innovation process. Here, by combining ancestral sequence reconstruction, reverse mutation assay, and progressive forward accumulation, we identified 5 founder residues in the catalytic pocket of flavone 6-hydroxylase (F6H) and proposed a "3-point fixation" model to elucidate the functional innovation mechanisms of P450s in nature. According to this design principle of catalytic pocket, we further developed a de novo diffusion model (P450Diffusion) to generate artificial P450s. Ultimately, among the 17 non-natural P450s we generated, 10 designs exhibited significant F6H activity and 6 exhibited a 1.3- to 3.5-fold increase in catalytic capacity compared to the natural CYP706X1. This work not only explores the design principle of catalytic pockets of P450s, but also provides an insight into the artificial design of P450 enzymes with desired functions.

Gasdermin D silencing alleviates airway inflammation and remodeling in an ovalbumin-induced asthmatic mouse model.

Emerging evidence demonstrates that pyroptosis has been implicated in the pathogenesis of asthma. Gasdermin D (GSDMD) is the pyroptosis executioner. The mechanism of GSDMD in asthma remains unclear. The aim of this study was to elucidate the potential role of GSDMD in asthmatic airway inflammation and remodeling. Immunofluorescence staining was conducted on airway epithelial tissues obtained from both asthma patients and healthy controls (HCs) to evaluate the expression level of N-GSDMD. ELISA was used to measure concentrations of cytokines (IL-1ß, IL-18, IL-17A, and IL-10) in serum samples collected from asthma patients and healthy individuals. We demonstrated that N-GSDMD, IL-18, and IL-1ß were significantly increased in samples with mild asthma compared with those from the controls. Then, wild type and Gsdmd-knockout (Gsdmd-/-) mice were used to establish asthma model. We performed histopathological staining, ELISA, and flow cytometry to explore the function of GSDMD in allergic airway inflammation and tissue remodeling in vivo. We observed that the expression of N-GSDMD, IL-18, and IL-1ß was enhanced in OVA-induced asthma mouse model. Gsdmd knockout resulted in attenuated IL-18, and IL-1ß production in both bronchoalveolar lavage fluid (BALF) and lung tissue in asthmatic mice. In addition, Gsdmd-/- mice exhibit a significant reduction in airway inflammation and remodeling, which might be associated with reduced Th17 inflammatory response and M2 polarization of macrophages. Further, we found that GSDMD knockout may improve asthmatic airway inflammation and remodeling through regulating macrophage adhesion, migration, and macrophage M2 polarization by targeting Notch signaling pathway. These findings demonstrate that GSDMD deficiency profoundly alleviates allergic inflammation and tissue remodeling. Therefore, GSDMD may serve as a potential therapeutic target against asthma.

Tanreqing Injection Inhibits Activation of NLRP3 Inflammasome in Macrophages Infected with Influenza A Virus by Promoting Mitophagy.

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1ß (IL-1ß) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1ß (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION: TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1ß, and attenuating the inflammatory response.

Quantitative assessment and correlational analysis of subjective and objective indicators in patients with allergic rhinitis.

Background: The diagnosis of allergic rhinitis is mainly based on the typical medical history, clinical manifestations, and corresponding allergen test results of the patients. However, there are often clinical inconsistencies among the 3. Objective: To study the clinical characteristics of patients with allergic rhinitis from both subjective and objective aspects to determine the correlations between the quantitative assessment outcomes of subjective and objective indicators. Methods: A total of 111 patients with allergic rhinitis who visited our outpatient clinic from June 2022 to December 2022 were selected. The 22-item sino-nasal outcome test (SNOT-22) and the visual analog scale (VAS) for the severity of the disease were used to score the subjective indicators of allergic rhinitis. The objective indicators of allergic rhinitis were evaluated by serum inhalant allergens immunoglobulin E test, nasal endoscopy modified Lund-Kennedy (MLK) scoring method, and acoustic rhinometry. Results: SNOT-22 score, total VAS score for symptoms, and the VAS score for nasal itching were positively correlated with the number of positive allergens (r = 0.266, P = 0.005, r = 0.576, P < 0.001, and r = 0.271, P = 0.004, respectively). No differences were found in all subjective indicators scores between the total immunoglobulin E positive and negative groups (P > 0.05). SNOT-22 score, total VAS score for symptoms, and the VAS score for nasal congestion were positively correlated with MLK total score of nasal endoscopy (r = 0.343, P < 0.001, r = 0.438, P < 0.001, and r = 0.225, P = 0.018, respectively). Parameters of acoustic rhinometry were not correlated with the subjective indicators scores of allergic rhinitis (P > 0.05). Conclusion: A multifaceted quantitative assessment of allergic rhinitis using a combination of subjective and objective methods can help physicians make an accurate diagnosis and create reasonable treatment plans.

Mechanism of Qiguiyin Decoction Sensitizing Levofloxacin Against Multidrug-Resistant Pseudomonas aeruginosa Infection Based on PK-PD and Antibody Chip Technology.

Background: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection. Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD. Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 ß, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group. Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.

Targeting lysyl oxidase like 2 attenuates OVA-induced airway remodeling partly via the AKT signaling pathway.

BACKGROUND: Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma. METHODS: The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor. RESULTS: Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-ß1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression. CONCLUSIONS: Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.

Catechol compounds as dual-targeting agents for fish protection against Ichthyophthirius multifiliis infections.

Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.

Nanoconfinement steers nonradical pathway transition in single atom fenton-like catalysis for improving oxidant utilization.

The introduction of single-atom catalysts (SACs) into Fenton-like oxidation promises ultrafast water pollutant elimination, but the limited access to pollutants and oxidant by surface catalytic sites and the intensive oxidant consumption still severely restrict the decontamination performance. While nanoconfinement of SACs allows drastically enhanced decontamination reaction kinetics, the detailed regulatory mechanisms remain elusive. Here, we unveil that, apart from local enrichment of reactants, the catalytic pathway shift is also an important cause for the reactivity enhancement of nanoconfined SACs. The surface electronic structure of cobalt site is altered by confining it within the nanopores of mesostructured silica particles, which triggers a fundamental transition from singlet oxygen to electron transfer pathway for 4-chlorophenol oxidation. The changed pathway and accelerated interfacial mass transfer render the nanoconfined system up to 34.7-fold higher pollutant degradation rate and drastically raised peroxymonosulfate utilization efficiency (from 61.8% to 96.6%) relative to the unconfined control. It also demonstrates superior reactivity for the degradation of other electron-rich phenolic compounds, good environment robustness, and high stability for treating real lake water. Our findings deepen the knowledge of nanoconfined catalysis and may inspire innovations in low-carbon water purification technologies and other heterogeneous catalytic applications.

Prevalence, treatment efficacy, and risk factors of vascular complications in acute pancreatitis: A case-control study.

OBJECTIVE: We aimed to investigate the prevalence of vascular complications in acute pancreatitis (AP), to compare patient outcomes using various treatments, and to explore the related risk factors. METHODS: Consecutive AP patients admitted from January 2010 to July 2017 were retrospectively included. Demographics, vascular complications, laboratory indices, and imaging findings were collected. Univariate and multivariate analyses were used to explore potential risk factors of vascular complications. RESULTS: Of 3048 AP patients, 808 (26.5%) had vascular complications, including visceral vein thrombosis, sinistral portal hypertension, and arterial complications. And 38 (4.7%) patients received anticoagulant therapy and had a higher rate of recanalization (P < 0.001). Bleeding occurred in 95 (11.8%) patients, who received further treatment. Multivariate analysis identified male gender (odds ratio [OR] 1.650, 95% confidence interval [CI] 1.101-2.472), hyperlipidemia (OR 1.714, 95% CI 1.356-2.165), disease recurrence (OR 3.727, 95% CI 2.713-5.118), smoking (OR 1.519, 95% CI 1.011-2.283), hemoglobin level (OR 0.987, 95% CI 0.981-0.993), white blood cell (WBC) count (OR 1.094, 95% CI 1.068-1.122), non-vascular local complications (OR 3.018, 95% CI 1.992-4.573), computed tomography severity index (CTSI) (OR 1.425, 95% CI 1.273-1.596), and acute physiology and chronic health evaluation (APACHE) II score (OR 1.057, 95% CI 1.025-1.090) were related to vascular complications. CONCLUSIONS: Vascular complications in AP is prevalent and their treatment is challenging. Further investigations are warranted to determine the optimal treatment strategy. Independent risk factors included male gender, hyperlipidemia, disease recurrence, smoking, WBC count, non-vascular local complications, CTSI, and APACHE II score.

Strategy to Efficient Photodynamic Therapy for Antibacterium: Donor-Acceptor Structure in Hydrogen-Bonded Organic Framework.

While the construction of a donor-acceptor (D-A) structure has gained great attention across various scientific disciplines, such structures are seldomly reported within the field of hydrogen-bonded organic frameworks (HOFs). Herein, a D-A based HOF is synthesized, where the adjacent D-A pairs are connected by hydrogen bonds instead of the conventionally employed covalent bonds. This structural feature imparts material with a reduced energy gap between excited state and triplet state, thereby facilitating the intersystem crossing (ISC) and boosting the generation rate of single oxygen (quantum yield = 0.98). Consequently, the resulting material shows high performance for antimicrobial photodynamic therapy (PDT). The impact of D-A moiety is evident when comparing this finding to a parallel study conducted on an isoreticular HOF without a D-A structure. The study presented here provides in-depth insights into the photophysical properties of D-A pair in a hydrogen-bonded network, opening a new avenue to the design of innovative materials for efficient PDT.

Construction of a Model for Predicting the Risk of pT3 Based on Perioperative Characteristics in cT1 Renal Cell Carcinoma: A Retrospective Study at a Single Institution.

INTRODUCTION: This study explored the predictors of upstaging and multiple sites of extension, and constructed a predictive model based on perioperative characteristics to calculate the risk of upstaging of cT1 renal cell carcinoma to pT3. METHODS: We retrospectively reviewed 1012 patients diagnosed with cT1 renal cell carcinoma who underwent surgical treatment at the Affiliated Hospital of Qingdao University between June 2016 and August 2021. The continuous and categorical variables were analyzed using the Mann-Whitney U test and Chi-square test, respectively. After randomly dividing patients into a training set and an internal validation set with a ratio of 7:3, univariate and multivariate logistic regression analyses were used to explore the predictors of upstaging and multiple sites of extension. A nomogram model was established based on the predictors of upstaging and was validated. RESULTS: Ninety-one cases (8.99%) of renal cell carcinoma were upstaged to pT3. In the training set, multivariate logistic regression identified the following predictors of upstaging: maximum tumor diameter, hilus involvement, tumor necrosis, tumor edge irregularity, symptoms, smoking, and platelet-lymphocyte ratio. A nomogram model was established based on the predictors. The area under the receiver operating characteristic curve was 0.810 in the training set, and 0.804 in the validation set. A 10-fold internal cross-validation conducted 200 times showed that the mean area under the curve was 0.797. The calibration curve and decision curve analysis suggested that the nomogram had robust clinical predictive power. Analyses showed higher neutrophil-lymphocyte ratio and tumor necrosis were associated with multiple sites of extrarenal extension in patients with pT3a renal cell carcinoma. CONCLUSIONS: We identified 7 predictors of upstaging to pT3 and 2 predictors of multiple sites of extension. A nomogram model was constructed with satisfactory accuracy for predicting upstaging to pT3.

A new evaluation system for drug-microbiota interactions.

The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug-microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug-microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug-microbiota interactions.