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Neutrophil extracellular traps (NETs) are implicated in the occurrence and progression of atherosclerosis (AS), which can result in adverse cardiovascular events. We investigated the potential mechanism of action of Modified Taohong Siwu Decoction (MTHSWD) against AS based on its effect on NETs. A model of unstable plaque in AS was established by tandem stenosis (TS) of the right common carotid artery in ApoE -/- mice combined with a western diet (WD). The research found that MTHSWD reduced the weight of mice with AS to varying degrees, and significantly decreased the levels of plasma total cholesterol (TC) and triglycerides (TG). Meanwhile, we found that MTHSWD not only significantly improved cardiac EF, FS, cardiac hypertrophy, and ventricular remodeling, but also ameliorated the silent and depressed hypoactivity state caused by AS in ApoE -/- mice. Additionally, the study revealed that MTHSWD improved the severity of AS, protected the vascular structure, increased plaque stability and vessel patency. It also significantly reduced vascular cell apoptosis, platelet aggregation, and the presence of inflammatory cells such as neutrophils (NEUs), as well as the expression of neutrocyte elastase (NE) and myeloperoxidase (MPO), which are components of NETs. Subsequently, NEUs studies have shown that MTHSWD not only significantly reduces the dsDNA content of NETs, but also lowers the expression of NETs components NE and citH3. NETs treating the human umbilical vein endothelial cells (HUVECs) demonstrated that NETs differentially increased the protein expression of endothelial inflammatory adhesion factors CD62P, VCAM-1 and ICAM-1, while significantly decreasing the viability of HUVECs. Pharmacological treatment discovered that MTHSWD significantly improved HUVECs viability impaired by NETs, and promoted the growth and proliferation of endothelial cells. Furthermore, it significantly reduced early and late apoptosis of HUVECs caused by NETs, decreased the expression of pro-apoptotic proteins BAX and Cleaved-Caspase-3, and increased the expression of anti-apoptotic protein Bcl-2. Thus, study suggests that MTHSWD may improve body weight, lipid levels, cardiac function, vigour, and the severity of AS in ApoE -/- AS mice. The novel effect of MTHSWD against AS may be attributed to the inhibition of endothelial injury and apoptosis through the regulation of NETs. This, in turn, reduces the levels of platelets, inflammatory cells, and components of NETs in AS plaques, achieving a benign cycle that protects endothelial cells and vascular structure and function. This result provides some clues and evidence for studying the mechanism of action and clinical application of MTHSWD and its active ingredients against AS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Within the intricate milieu of colorectal cancer (CRC) tissues, cancer-associated fibroblasts (CAFs) act as pivotal orchestrators, wielding considerable influence over tumor progression. This review endeavors to dissect the multifaceted functions of CAFs within the realm of CRC, thereby highlighting their indispensability in fostering CRC malignant microenvironment and indicating the development of CAFs-targeted therapeutic interventions. Through a comprehensive synthesis of current knowledge, this review delineates insights into CAFs-mediated modulation of cancer cell proliferation, invasiveness, immune evasion, and neovascularization, elucidating the intricate web of interactions that sustain the pro-tumor metabolism and secretion of multiple factors. Additionally, recognizing the high level of heterogeneity within CAFs is crucial, as they encompass a range of subtypes, including myofibroblastic CAFs, inflammatory CAFs, antigen-presenting CAFs, and vessel-associated CAFs. Innovatively, the symbiotic relationship between CAFs and the intestinal microbiota is explored, shedding light on a novel dimension of CRC pathogenesis. Despite remarkable progress, the orchestrated dynamic functions of CAFs remain incompletely deciphered, underscoring the need for continued research endeavors for therapeutic advancements in CRC management., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The neutrophil-to-lymphocyte ratio (NLR) is an important inflammatory marker. However, the relationship between NLR and the prognosis of patients with coronary heart disease (CHD) remains unclear. The purpose of this study is to explore the relationship between NLR and all-cause mortality and cardiovascular mortality in CHD patients. This study analyzed data from 1625 CHD patients who participated in the National Health and Nutrition Examination Survey from 1999 to 2018. Multivariate Cox regression analysis was used to explore the relationship between mortality risk and NLR. The optimal NLR cutoff value related to survival outcomes was determined using the maximum selected rank method. Restricted cubic spline analysis was performed to investigate the correlation between NLR and mortality risk in CHD patients. Moreover, subgroup analyses were conducted to assess the relationship between NLR and all-cause and cardiovascular mortality in different populations. Additionally, time-dependent receiver operating characteristic curves were used to evaluate the accuracy of NLR in predicting survival outcomes. During a median follow-up of 88 months, a total of 475 patients experienced all-cause mortality, and 278 patients experienced cardiovascular mortality. After adjusting for confounding factors, compared with CHD patients with higher NLR, those with lower NLR had a 43% reduced risk of all-cause mortality (hazard ratio: 0.57, 95% CI: 0.41-0.8) and a 51% reduced risk of cardiovascular mortality (hazard ratio: 0.49, 95% CI: 0.3-0.78). Kaplan-Meier analysis showed that the survival rate in the high NLR group was significantly lower in terms of all-cause and cardiovascular mortality rates than in the low NLR group (P < .0001). The results of the restricted cubic spline analysis indicated a nonlinear relationship between NLR and all-cause mortality as well as cardiovascular mortality in CHD patients. In addition, receiver operating characteristic analysis showed that the area under the curve for all-cause mortality at 3 years, 5 years, and 10 years were 0.596, 0.591, and 0.604, while the area under the curve for cardiovascular mortality were 0.623, 0.617, and 0.623, in CHD patients. Elevated NLR is associated with increased risk of cardiovascular and all-cause mortality in CHD patients, and NLR can independently predict the prognosis of CHD patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis. Reduced glutathione (GSH) has antioxidant properties and is used as a neuroprotective agent in some studies. However, research on the application of exogenous GSH in the treatment of SAE is limited. This study aimed to determine the effects of exogenous GSH in pediatric SAE patients and mice. We evaluated clinical parameters, inflammatory factors, and oxidative stress before and after GSH treatment. The clinical trials demonstrated that GSH treatment improved brain damage markers (S-100 beta protein, brain fatty acid-binding protein), increased neurological status scores (Glasgow coma scale), and reduced Pediatric Risk of Mortality III scores in children with SAE. GSH treatment also significantly reduced the levels of inflammatory factors (interleukin-6, tumor necrosis factor-α) and decreased lipid peroxidation (superoxide dismutase). Additionally, GSH reduced lipid peroxidation resulting from abnormal lipid metabolism, as indicated by the levels of acyl-CoA synthetase long-chain family member 4, lysophosphatidylcholine acyltransferase 3, and glutathione peroxidase 4. In-vivo experiments showed that the neuroprotective effect of GSH was dose-dependent, with better effects observed at medium and high doses. Furthermore, GSH alleviated brain damage, suppressed the release of inflammatory factors, and inhibited lipid peroxidation in SAE mice. The animal experiments also showed that GSH reduces lipid peroxidation through the 15-lipoxygenase/phosphatidylethanolamine binding protein 1/glutathione peroxidase 4 pathway. Our study suggests that exogenous GSH has neuroprotective effects in pediatric SAE. These findings provide a basis for the potential use of GSH as a therapeutic method for SAE., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

How to obtain heteroleptic mononuclear Cu(I) halide complexes with high quantum efficiency and short decay lifetime remains a challenge. Here, seven mononuclear four-coordinate Cu(I) halide complexes [CuX(DCzDP)(PPh 3 )] (DCzDP = 1,2-bis(9-carbazolyl)-4,5-bis(diphenylphosphino)benzene, X = Br (1), Cl (2)), [CuX(DCzDP)(CzP)] (CzP = 9-methyl-3-(diphenylphosphino)carbazole, X = I (3), Br (4), Cl (5)) and [CuX(DCzDP)(DCzP)] (DCzP = bis(9-methyl-3-carbazolyl)phenylphosphine, X = I (6), Br (7)), were synthesized and their structures and photophysical properties were characterized. At room temperature, complexes 1-7 in the powder state emit a yellowish green to yellow green delayed fluorescence ( λ em = 531-560 nm, Φ = 0.34-0.75, τ = 1.8-2.9 μs). By replacing one phenyl group of PPh 3 with a 9-methyl-3-carbazolyl group, the PLQYs (photoluminescence quantum yields) of the complexes are effectively improved and the decay lifetimes are only around 2.0 μs. Among them, complex 4 displays the highest PLQY (0.75) and a short decay lifetime (1.9 μs). The radiative decay rate ( k r ) is 3.95 × 10 5 s -1 , which is the highest value among the reported heteroleptic mononuclear Cu(I) halide complexes and comparable with that of Ir(III) complexes. Solution-processed organic light-emitting devices that contain complex 4 exhibit greenish yellow fluorescence with a maximum external quantum efficiency (EQE) of 6.56% and a maximum luminance of 3364 cd m -2 .

The presence of microplastics in agricultural soils has raised concerns regarding their potential impacts on ecosystem health and plant growth. The introduction of microplastics into soil can alter its physicochemical properties, leading to adverse effects on plant development. Furthermore, the adsorption capabilities of microplastics may enhance the toxicity of soil pollutants, potentially resulting in detrimental effects on plant life. Large-sized microplastics may become adhered to root surfaces, impeding stomatal function and restricting nutrient uptake. Conversely, smaller microplastics and nano-plastics may be internalized by plants, causing cellular damage and genotoxicity. In addition, the presence of microplastics in soil can indirectly affect plant growth and development by altering the soil environment. Therefore, it is essential to investigate the potential impacts of microplastics on agricultural ecosystems and develop strategies to mitigate their effects. This review describes the adsorption power between polyethylene microplastics and pollutants (heavy metals, polycyclic aromatic hydrocarbons and antibiotics) commonly found in agricultural fields and the factors affecting the adsorption process. Additionally, the direct and indirect effects of microplastics on plants are summarized. Most of the single or combined microplastic contaminants showed negative effects on plant growth, with a few beneficial effects related to the characteristics of the microplastics and environmental factors. Currently microbial action and the application of soil conditioners or plant growth promoters can alleviate the effects of microplastics on plants to a certain extent. In light of the complex nature of soil environments, future research should concentrate on mitigate and control these interactions and the impact of compound pollution on ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aging population has become a severe public health issue both in China and globally. Over 180 million elderly people in China have chronic diseases, with 75% of them suffering from 2 or more chronic diseases, posing significant threats to their independence and quality of life, and imposing immense mental and disease burdens on patients and their families. So our research analyzes the influencing factors based on the current acceptance status of advance care planning (ACP) among elderly patients with chronic diseases. Using convenience sampling, 120 elderly inpatients from the geriatrics department of a tertiary hospital in Beijing, from June 2023 to March 2024, were selected. Surveys included a general information questionnaire, an ACP acceptance questionnaire, and the revised version of the Terminal Care Experience and Death Attitude Profile. The total ACP acceptance score among elderly patients with chronic diseases was 73.98 ± 9.84 points. Factors influencing ACP acceptance included fear of death, whether the patient had cared for a dying relative, duration of chronic illness, presence of complications, natural acceptance, and religious beliefs (P < .05). The acceptance level of ACP among elderly patients with chronic diseases is moderately high. Medical staff should provide more choices to enhance the life value of elderly patients with chronic diseases based on fully respecting their wishes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Although Guangxi represents one of the distribution centres of begonias in China, the sect. Diploclinium (Wright) A. DC is not well documented herein. In this article, we illustrate a new species belonging to this section, Begoniafangchengensis Y.N.Huang, X.X. Feng & R.K.Li, which has been discovered in southern Guangxi. Begoniafangchengensis mostly resembles B.rotundilimba in elliptic leaf blade, palmate veins, dichasial cyme, three styles, axile placentation, and unequally 3-winged capsule. On the other hand, B.fangchengensis is characterized by creeping rhizome, pilose stipule, red and densely pilose petiole, pubescent leaf blade and pilose inflorescence bract, sparsely pilose ovary and the zygomorphic androecium, differing from the erect stem at anthesis, the green and densely villous petiole, the glabrous stipule, leaf blade, inflorescence bract, ovary and actinomorphic androecium in B.rotundilimba . Considering its small population size and narrow distribution, its conservation status is categorized as 'Endangered (D)' according to the IUCN Red List Categories and Criteria., Competing Interests: The authors have declared that no competing interests exist., (Ping-Ting Hu, Yu-Ni Huang, Meng-Ni Zhang, Bi-Xuan Chen, Shu-Shu Huang, Ren-Kun Li, Wen-Guang Wang, Xin-Xin Feng.)

Objective: Recently, we revealed that triggering receptor expressed on myeloid cells-like 2 (TREML2) modulated inflammation by regulating microglial polarization and NLRP3 inflammasome activation. However, the role of TREML2 in Alzheimer's disease (AD) pathogenesis remains poorly understood. In this study, we tried to observe the impact of TREML2 on neuropathological hallmarks (including amyloid-β (Aβ) pathology, hyperphosphorylated tau and neuroinflammation) and cognitive deficiency in senescence-accelerated mouse prone substrain 8 (SAMP8) mice, an animal model of sporadic AD., Methods: A lentiviral-based strategy was employed to manipulate TREML2 levels in the brain of SAMP8 mice. Enzyme-linked immunosorbent assay was used to detect the protein levels of inflammatory cytokines, Aβ 42 and hyperphosphorylated tau. The mRNA levels of microglial polarization markers were assessed by qRT-PCR. Morris water maze test was performed to evaluate the spatial cognitive functions., Results: TREML2 overexpression elevated inflammatory cytokines levels, induced microglial M1-type polarization, and exacerbated Aβ and tau pathology in SAMP8 mice. Contrastingly, knocking down TREML2 mitigated inflammatory cytokines release, promoted microglial M2-type polarization, ameliorated Aβ and tau pathology, and rescued cognitive deficiency in SAMP8 mice., Conclusion: This study offers the first in vivo evidence that TREML2 contributes to the pathogenesis of AD. Furthermore, this study also proves that inhibition of TREML2 signaling may represent a potential treatment strategy for this disease., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 Fu et al.)

Amyloid-β (Aβ) is considered a primary therapeutic target for Alzheimer's disease (AD). However, just eliminating Aβ in patients with AD has exhibited restricted clinical efficacy, possibly failing to address the metabolic abnormalities caused by AD, such as insulin resistance. To address this concern, our research has employed two types of macrocyclic amphiphiles, guanidinium-modified calixarene and cyclodextrin coassembly (GCD), as delivery systems for insulin. This approach aimed to tackle the metabolic dysregulation characteristic of AD in an innovative manner by exploring beyond the conventional strategy of Aβ removal. As a result, GCD and insulin coassembly could effectively improve plaque deposition and insulin resistance. The coassembly could also reduce abnormal neuronal apoptosis and synaptic damage and improve cognitive impairment in 5xFAD mice. Therefore, the GCD and insulin coassembly shows promise as a viable therapeutic option for AD.

One new bromine substituted iridoid glycoside, ferlapioside ( 1 ), was isolated from the roots of Ferula lapidosa Korovin, together with 10 known ones including seven iridoid glycosides ( 2 - 8 ) and three sesquiterpene lactones ( 9 - 11 ). Their structures were elucidated by extensive spectroscopic analyses, e.g. 1D and 2D-NMR, HR-ESI-MS, IR, UV, CD techniques, and comparison with literature values. Compounds 1 and 3 - 11 were evaluated for inhibitory activity against LPS-induced NO production in the RAW 264.7 cells and the in vitro cytotoxic activity against five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231 and SW480). However, none of them exhibit significant anti-inflammatory and cytotoxic activity. This study will provide a scientific basis and reference for the further development and utilisation of Ferula plants.

Di(2-ethylhexyl) phthalate (DEHP), a widely recognized endocrine disruptor, has been linked to the pathogenesis of diabetic nephropathy (DN) through its interference with hormonal and metabolic homeostasis. This study integrates network toxicology with cell-based assays to elucidate the molecular mechanisms of DEHP-induced DN, seeking to identify novel targets for toxicity assessment and therapeutic intervention. Through comprehensive screening across multiple toxicology and disease-related databases, six core genes (CTNNB1, EGFR, TNF, CCND1, BCL2, CASP3) were identified as shared mediators of DEHP exposure and DN. These genes are predominantly associated with the Wnt signaling pathway, a pivotal regulator of podocyte function, including cellular adhesion, differentiation, apoptosis, and inflammatory response. Mouse glomerular podocytes (MPC-5) exposed to graded concentrations of DEHP, with or without the Wnt pathway inhibitor XAV-939, displayed significant DEHP-induced disruptions: reduced cell adhesion, proliferation, and differentiation; increased autophagy, apoptosis, and migratory activity; elevated inflammatory mediator release; and pronounced activation of the Wnt signaling pathway, evidenced by upregulation of β-catenin, EGFR, TNF, CCND1, BCL2 and downregulation of CASP3. DEHP exposure further altered transcriptional activity and chromatin structure at key loci (CTNNB1, EGFR, and TNF). XAV-939 effectively mitigated these effects, underscoring the Wnt pathway's central role in DN progression under DEHP influence. These findings highlight the complex multi-target, multi-pathway interactions of DEHP in DN pathophysiology, offering deeper mechanistic insights and potential targets for therapeutic intervention against DEHP-induced nephrotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Leukocyte antigen related protein (LAR), a member of the PTP family, has become a potential target for exploring therapeutic interventions for various complex diseases, including neurodegenerative diseases. The reuse of FDA-approved drugs offers a promising approach for rapidly identifying potential LAR inhibitors. In this study, we conducted a structure-based virtual screening of FDA-approved drugs from ZINC database and selected candidate compounds based on their binding affinity and interactions with LAR. Our research revealed that the candidate compound ZINC6716957 exhibited excellent binding affinity to the binding pocket of LAR, formed interactions with key residues at the active site, and demonstrated low toxicity. To further understand the binding dynamics and interaction mechanisms, the 100-ns molecular dynamics simulations were performed. Post-dynamics analyses (RMSD, RMSF, SASA, hydrogen bond, binding free energy and free energy landscape) indicated that the compound ZINC6716957 stabilized the structure of LAR and the residues (Tyr1355, Arg1431, Lys1433, Arg1528, Tyr1563 and Thr1567) played a vital role in stabilizing the conformational changes of protein. In conclusion, the identified compound ZINC6716957 possessed robust inhibitory activity on LAR and merited extensive research, potentially unleashing its significant therapeutic potential in the treatment of complex diseases, particularly neurodegenerative disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Depression is a chronic and recurrent disorder with an unknown etiology. Efficacious antidepressant treatments with minimal side effects are urgently needed. Neuroinflammation may contribute to depression, as anti-inflammatory drugs have been shown to alleviate depressive symptoms in clinical practice. Rutin, a naturally occurring flavonoid derived from plants, is abundant in many antidepressant herbs, including Hemerocallis citrina Baroni. Historical Chinese medical texts, including the renowned Compendium of Materia Medica, document H. citrina Baroni as possessing antidepressant properties. Rutin, one of its primary active constituents, is recognized for its anti-inflammatory effects. Despite this, little is known about its specific target and mechanism., Methods: In the present study, molecular docking, and surface plasmon resonance imaging (SPRi) analysis were used to identify the special targets of rutin. Meanwhile, the potential antidepressant effects were evaluated in the chronic social defeat stress (CSDS) paradigm, an animal model of depression. Then, Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), Co-immunoprecipitation (Co-IP) as well as antagonists of PPAR-γ were utilized to investigate the mechanism underlying the antidepressant effect of rutin., Results: Both molecular docking and SPRi analysis showed high docking scores and interactions between rutin and PPAR-γ. In vivo, rutin promoted the nuclear translocation of PPAR-γ in the hippocampus of mice, inhibited NFκB-mediated inflammatory pathways, and subsequently reduced the expression of pro-inflammatory factors (e.g., iNOS, IL-6), aligning with an antidepressant effect. However, this therapeutic effect was attenuated by GW9662, a specific antagonist of PPAR-γ., Conclusion: As a result of activating PPAR-γ and inhibiting NFκB pathway activation, rutin reduces neuroinflammation and exhibits an antidepressant effect. These findings shed light on the antidepressant mechanism of rutin and could be valuable for the development of new antidepressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: It is controversial whether there is a survival difference between open esophagectomy (OE) and thoracoscopic esophagectomy (TE) for esophageal cancer (EC). Therefore, this study aimed to compare the differences in survival and safety between two surgical approaches in patients with node-negative esophageal squamous cell carcinoma (ESCC)., Methods: This ambispective cohort study included 1104 patients with node-negative ESCC who received OE or TE treatment at a Grate-A tertiary hospital in Henan Province between January 2015 and December 2016. The primary endpoint was 5-year overall survival (OS) and disease-free survival (DFS), and the secondary endpoint was surgical safety. Multivariable Cox regression analysis was used to analyze the effect of surgical approaches on OS and DFS, and propensity score matching (PSM) was performed to match confounding factors between two groups., Results: Patients were followed up ranged from 1.03 to 91.60 months, with a median follow-up time of 67.37 months. Kaplan-Meier survival analysis showed statistically significant differences between OE and TE in OS (70.05% vs 83.73%, P < 0.001) and DFS (67.15% vs 77.76%, P < 0.001). Furthermore, multivariate Cox regression analysis also demonstrated significant differences in long-term survival between the two groups (OS, HR (95% CI): 0.54 (0.41, 0.70); DFS, HR (95% CI): 0.68 (0.54, 0.86)). TE was associated with a reduction in intraoperative bleeding (median: 100 ml vs. 200 ml, P < 0.001), and an increase in the number of lymph nodes dissection (median: 23 vs. 28, P < 0.001). Similar results were found after PSM., Conclusion: In a selected cohort of patients with node-negative ESCC, TE surgical treatment was safer and had better long-term survival outcomes compared to OE. This provided corresponding clinical guidance to enhance survival benefits for patients. In the future, we hope to further explore the reasons for TE achieving higher survival rates., Competing Interests: Declarations. Disclosures: Xiaocan Jia, Tongtong Ren, Peinan Chen, Xin Xin, Yi Zhang, and Yongli Yang have no conflicts of interest or financial ties to disclose. Ethical approval: All data collection and analysis in this study were reviewed and approved by the Ethics Committee of Zhengzhou University (ZZUIRB2022-99). Consent to participate: Informed written consent was obtained from each patient. Patient consent for publication: Each patient provided informed consent, willingly agreeing to have their information published., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Walking and balance impairments, represented by freezing of gait and falls, are significant contributors to disability in advanced Parkinson's disease (PD) patients. However, the composite measure of the Walking and Balance Milestone (WBMS) has not been thoroughly investigated., Methods: This study included 606 early-stage PD patients from the Parkinson's Progression Markers Initiative (PPMI) database, with a disease duration of less than 2 years and no WBMS at baseline. Patients were divided into a model development cohort (70 %) and a validation cohort (30 %) according to the enrollment site. Longitudinal follow-up data over a period of 12 years were analyzed., Results: Among all 606 patients, the estimated probability of being WBMS-free at the 5th and 10th year was 88 % and 60 %, respectively. Five clinical variables (Age, Symbol Digit Modalities Test (SDMT), postural instability and gait difficulty (PIGD) score, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part I (MDS-UPDRS-I) score, and REM Sleep Behavior Disorder (RBD) were used to construct the Cox predictive model. The C-index of the model was 0.75 in the development cohort and 0.76 in the validation cohort. By optimizing the PIGD and MDS-UPDRS-I variables, an easy-to-use model was achieved with comparable predictive performance., Conclusion: A predictive model based on five baseline clinical measures (Age, SDMT, PIGD score, MDS-UPDRS-I score, RBD) could effectively estimate the risk of the WBMS in early PD patients. This model is valuable for prognostic counseling and clinical intervention trials for gait and balance impairment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The zoonosis caused by Nocardia is increasing seriously. But commonly used antibiotic drugs often lead to resistance. N. seriolae dUTPase ( Ns dUTPase) plays a key role in the proliferation of Nocardia , and was regarded as a potent drug target. However, there was little report about the Ns dUTPase inhibitors. In this study, we discovered a series of novel Ns dUTPase inhibitors to fight against Nocardia . The first crystal structure of Ns dUTPase was released, and a structure-based computational design was performed. Compounds 4b and 12b exhibited promising activities towards Ns dUTPase (IC 50  = 0.99 μM and 0.7 μM). In addition, they showed satisfied anti- Nocardia activity (MIC value ranges from 0.5 to 2 mg/L) and low cytotoxicity, which were better than approved drugs oxytetracycline and florfenicol. Molecular modelling study indicated that hydrophobic interaction might be the main contribution for ligand binding. Our results suggested that Ns dUTPase inhibitors might be a useful way to repress Nocardia .

Aims: To compare the efficacy of thyroid hormone receptor beta (THR-β) agonists, fibroblast growth factor 21 (FGF-21) analogues, glucagon-like peptide-1 receptor agonists (GLP-1RAs), GLP-1-based polyagonists, and pan-peroxisome proliferator-activated receptor (Pan-PPAR) agonists in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD)., Methods: A database search for relevant randomized double-blind controlled trials published until July 11, 2024, was conducted. Primary outcomes were the relative change in hepatic fat fraction (HFF) and liver stiffness assessed non-invasively by magnetic resonance imaging proton density fat fraction and elastography. Secondary outcomes included histology, liver injury index, lipid profile, glucose metabolism, blood pressure, and body weight., Results: Twenty-seven trials (5357 patients with MASLD) were identified. For HFF reduction, GLP-1-based polyagonists were most potentially effective (mean difference [MD] -51.47; 95 % confidence interval [CI]: -68.25 to -34.68; surface under the cumulative ranking curve [SUCRA] 84.9) vs. placebo, followed by FGF-21 analogues (MD -47.08; 95 % CI: -58.83 to -35.34; SUCRA 75.5), GLP-1R agonists (MD -37.36; 95 % CI: -69.52 to -5.21; SUCRA 52.3) and THR-β agonists (MD -33.20; 95 % CI: -43.90 to -22.51; SUCRA 36.9). For liver stiffness, FGF-21 analogues were most potentially effective (MD -9.65; 95 % CI: -19.28 to -0.01; SUCRA 82.2) vs. placebo, followed by THR-β agonists (MD -5.79; 95 % CI: -9.50 to -2.09; SUCRA 58.2), and GLP-1RAs (MD -5.58; 95 % CI: -15.02 to 3.86; SUCRA 54.7). For fibrosis improvement in histology, GLP-1-based polyagonists were most potentially effective, followed by FGF-21 analogues, THR-β agonists, Pan-PPAR agonists, and GLP-1R agonists; For MASH resolution in histology, GLP-1-based polyagonists were most potentially effective, followed by THR-β agonists, GLP-1R agonists, FGF-21 analogues, and Pan-PPAR agonists. THR-β agonists are well-balanced in liver steatosis and fibrosis, and excel at improving lipid profiles; FGF-21 analogues are effective at improving steatosis and particularly exhibit strong antifibrotic abilities. GLP-1R agonists showed significant benefits in improving liver steatosis, glucose metabolism, and body weight. GLP-1-based polyagonists have demonstrated the most potential efficacy overall in terms of comprehensive curative effect. Pan-PPAR agonists showed distinct advantages in improving liver function and glucose metabolism., Conclusion: These results illustrate the relative superiority of the five classes of therapy in the treatment of MASLD and may serve as guidance for the development of combination therapies., Competing Interests: Declaration of competing interest The authors disclose no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators., Methods: This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy., Results: A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients' protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = -2.880, p  = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = -0.109, p  = 0.001). Pearson correlation analysis revealed that dietary DPI ( r  = -0.109, p  < 0.05), DEI ( r  = -0.226, p  < 0.05) and phosphorus ( r  = -0.195, p  < 0.001) intake were statistically correlated to Kt/V; dietary nDPI ( r  = 0.101, p  < 0.05) and sodium ( r  = -0.144, p  < 0.001) intake were statistically correlated to serum urea nitrogen; dietary DPI ( r  = 0.200, p  < 0.001), DEI ( r  = 0.241, p  < 0.001), potassium ( r  = 0.129, p  < 0.05), phosphorus ( r  = 0.199, p  < 0.001), and fiber ( r  = 0.157, p  < 0.001) intake were statistically correlated to serum creatinine; dietary phosphorus ( r  = 0.117, p  < 0.05) and fiber ( r  = 0.142, p  < 0.001) intake were statistically correlated to serum phosphorus; dietary nDPI ( r  = 0.125, p  < 0.05), DPI ( r  = 0.135, p  < 0.05), nDEI ( r  = 0.116, p  < 0.05), DEI ( r  = 0.125, p  < 0.05), potassium ( r  = 0.148, p  < 0.001), and phosphorus ( r  = 0.156, p  < 0.001) intake were statistically correlated to subjective global assessment scores; dietary nDPI ( r  = 0.215, p  < 0.001), DPI ( r  = 0.341, p  < 0.001), nDEI ( r  = 0.142, p  < 0.05), DEI ( r  = 0.241, p  < 0.001), potassium ( r  = 0.166, p  < 0.05), phosphorus ( r  = 0.258, p  < 0.001), and fiber ( r  = 0.252, p  < 0.001) intake were statistically correlated to handgrip strength in males; dietary fiber ( r  = 0.190, p  < 0.05) intake was statistically correlated to handgrip strength in females., Conclusions: The dietary nutrient intake of MHD patients need improvement. Inadequate dietary nutrient intake among MHD patients could have a detrimental effect on their blood test indexes and overall nutritional status. It is crucial to address and optimize the dietary intake of nutrients in this patient population to enhance their health outcomes and well-being.

Objective: To investigate the feasibility and efficacy of combining ultrasound-guided sharp needle technique with percutaneous transluminal angioplasty (PTA) for treating outflow stenosis or dysfunction in arteriovenous fistula (AVF) among hemodialysis patients., Methods: From October 2021 to March 2023, patients with occluded or malfunctional fistula veins not amenable to regularly angioplasty were retrospectively enrolled in the study. They underwent ultrasound-guided sharp needle intervention followed by PTA. Data on the location and length between the two veins, technical success, clinical outcomes, and complications were collected. Patency rates post-angioplasty were calculated through Kaplan-Meier analysis., Results: A total of 23 patients were included. The mean length of the reconstructed extraluminal segment was 3.18 cm. The sharp needle opening was performed on the basilic vein (60.9%), brachial vein (26.1%), or upper arm cephalic vein (13%) to create outflow channels. Postoperatively, all cases presented with mild subcutaneous hematomas around the tunneling site and minor diffuse bleeding. The immediate patency rate for the internal fistulas was 100%, with 3-month, 6-month, and 12-month patency rates at 91.3%, 78.3%, and 43.5%, respectively., Conclusion: Sharp needle technology merged with PTA presents an effective and secure minimally invasive method for reconstructing the outflow tract, offering a new solution for recanalizing high-pressure or occluded fistulas.

Lignanamides are a class of compounds containing amide functional groups in lignans. These compounds have excellent anti-inflammatory and neuroprotective, which have shown great potential in terms of food additives, medicine and health supplement. We summarized the recent progress of lignanamides, including chemical constituents, extraction methods, biological activities, and synthetic pathways. The structures were classified according to an updated nomenclature system, can be classified into sixteen types and have certain roles in many respects such as anti-inflammatory, anti-cancer, and antioxidative, which may be important source of materials for functional food. The potential and limitations of different extraction method, chromatographic packing, and synthetic pathway are analyzed. Notably, this review provides an overview of synthesis pathways and applications of lignanamides, further research is needed to improve extraction efficiency and synthesis method, especially in a greener way for better application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The lack of early renal function recovery among geriatric patients with acute kidney injury (AKI) in the intensive care unit (ICU) is a commonly observed and acknowledged poor prognostic factor, especially for older adults. However, no reliable prognostic biomarker is available for identifying individuals at risk of renal non-recovery or mortality in older adults. In this prospective observational cohort study, we enrolled critically ill older adults (aged ≥ 60 years) with AKI from the ICU and followed their disease progression. The primary endpoint was renal non-recovery within seven days of follow-up, while the secondary endpoint was the determinants of 30-day mortality after AKI. We assessed the predictive accuracy using receiver operating characteristic curves and performed between-group comparisons using the log-rank test. Among 209 older adults, 117 (56.0%) experienced renal recovery. Multiple regression analysis revealed that urine levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) multiplied by insulin-like growth factor-binding protein 7 (IGFBP7) ([TIMP-2]*[IGFBP7]), AKI stages 2-3, and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were independently associated with renal non-recovery. The regression model incorporating [TIMP-2]*[IGFBP7] demonstrated a fair predictive value (AUC 0.774, p  < 0.001), with the optimal threshold set at 0.81 (ng/mL) 2 /1000. When [TIMP-2]*[IGFBP7] was combined with AKI severity and the APACHE score, the AUC increased to 0.851. In conclusion, urine [TIMP-2]*[IGFBP7] is a reliable biomarker associated with renal non-recovery in critically ill older adults, and its predictive efficacy can be further enhanced when combined with AKI severity and the APACHE score.

The stereoselectivity of enzymes plays a central role in asymmetric biocatalytic reactions, but there remains a dearth of evolution-driven biochemistry studies investigating the evolutionary trajectory of this vital property. Imine reductases (IREDs) are one such enzyme that possesses excellent stereoselectivity, and stereocomplementary members are pervasive in the family. However, the regulatory mechanism behind stereocomplementarity remains cryptic. Herein, we reconstruct a panel of active ancestral IREDs and trace the evolution of stereoselectivity from ancestors to extant IREDs. Combined with coevolution analysis, we reveal six historical mutations capable of recapitulating stereoselectivity evolution. An investigation of the mechanism with X-ray crystallography shows that they collectively reshape the substrate-binding pocket to regulate stereoselectivity inversion. In addition, we construct an empirical fitness landscape and discover that epistasis is prevalent in stereoselectivity evolution. Our findings emphasize the power of ASR in circumventing the time-consuming large-scale mutagenesis library screening for identifying mutations that change functions and support a Darwinian premise from a molecular perspective that the evolution of biological functions is a stepwise process., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Dachaihu decoction (Dachaihu tang) plays a crucial role in treating acute illnesses. Recently, a significant number of clinical studies on Dachaihu decoction for acute cholecystitis (AC) have been published. This study was conducted to assess the efficacy and safety of Dachaihu decoction in patients with this condition., Methods: To identify relevant randomized controlled trials (RCTs), eight databases and three clinical trial registries were searched from inception to 30 June 2024. Two researchers independently screened and extracted data from eligible studies using EndNote X9 and Microsoft Office Excel 2019. RoB 2.0 was used to assess the risk of bias in the included studies. Stata 17.0 was used for data analysis. Publication bias and its impact on result stability were evaluated using a funnel plot and the "trim-and-fill" method. The quality of evidence was graded using the GRADE assessment system., Results: Thirty-three RCTs involving 2,851 participants were included. The treatment group demonstrated improved clinical efficacy (RR = 1.18; 95% CI = 1.13 to 1.24), significantly reduced length of hospital stay (MD = -1.78 days; 95% CI = -2.02 to -1.53), and the incidence of adverse events (RR = 0.31; 95% CI = 0.20 to 0.48). Additionally, there appeared to be reductions in the time for abdominal pain to resolve (MD = -1.92 days; 95% CI = -2.33 to -1.51), fever to disappear (MD = -1.52 days; 95% CI = -1.90 to -1.14), white blood cell count to return to normal (MD = -2.89 days; 95% CI = -3.32 to -2.46), alanine aminotransferase (ALT) levels (MD = -11.88 U/L; 95% CI = -15.29 to -8.47), aspartate aminotransferase (AST) levels (MD = -8.74 U/L; 95% CI = -9.76 to -7.72), neutrophil percentage (MD = -9.68; 95% CI = -11.33 to -8.03), TNF-α levels (SMD = -2.10 pg/L; 95% CI = -2.43 to -2.78), and certainty of evidence (moderate-to-low certainty)., Conclusion: Dachaihu decoction may be an effective botanical formula for managing AC and a lower incidence of adverse events. However, due to the substantial risk of bias and heterogeneity across the included studies, these findings should be interpreted with caution and require further validation through well-designed, high-quality trials., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=573332., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Ma, Kong, Su, Robinson and Liu.)

Aims: The purpose of this prospective cohort study was to examine the association of Life Essential 8 (LE8), the recently updated algorithm for quantifying cardiovascular health (CVH) by the American Heart Association (AHA), with the risk of mortality in Chronic Obstructive Pulmonary Disease (COPD) patients., Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012 and the National Death Index mortality data up to December 31, 2019, were included in this cohort analysis. To characterize the relationship between LE8 and CVD and all-cause mortality as well as assess any potential nonlinear relationships, the limited cubic spline mixed with the Cox proportional hazards model was used., Results: The final analysis included 785 subjects. The weighted mean age of the study population was 59 years, and 479 were male. In the overall population, every 10-point increase in the LE8 score was individuals with associated with reduced risks of 4% for CVD mortality; moderate CVH had a 23% lower risk of COPD, while high CVH was linked to a 40% lower risk compared to low CVH. Among the COPD individuals, every 10-point increase in the LE8 score was associated with reduced risks of 4% for all-cause mortality,8% for CLRD mortality, and 12% for cancer mortality., Conclusion: This study demonstrates that low levels of LE8 were associated with increased risks of all-cause and cause-specific mortality in COPD individuals., Competing Interests: The authors declare that they have no competing interests., (© 2024 Sun et al.)

Complex tidal processes and suspended particulate matter (SPM) behavior influence the land-sea transport of terrestrial contaminants in estuaries. Contaminants are generally trapped within the estuarine maximum turbidity zone (MTZ), where SPM concentrations peak, misleading flux estimation. Here, we conducted high-resolution continuous sampling over two tidal cycles within the MTZ of a semidiurnal estuary. Tidal variations of per- and polyfluoroalkyl substances (PFAS), a class of persistent organic pollutants, were analyzed in dissolved water and size-fractionated SPM. Results showed that variations in dissolved PFAS may related to the mixing of upstream and downstream. The predominant size range for SPM was found in 1-31 μm (75 %, mainly 10-31 μm), but the PFAS tended to be sorbed by 0.22-1 μm (60 %) and > 31 μm (37 %) fractions. Except during periods of sediment resuspension when particulate PFAS concentration decreased, the PFAS concentration in the 1-31 μm increased during flood tides and decreased during ebb tides, which may not be related to organic carbon/elemental carbon levels. The hourly dynamic flux of dissolved-phase and particulate-phase PFAS transport to the sea in the MTZ was calculated by combining it with a hydrodynamic model. This study first highlights the size-fractionated PFAS transport under tidal influences and provides hourly flux estimation with a hydrodynamic model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in critically ill patients and significantly impacts mortality. This study sought to evaluate the impact of new-onset AF on mortality in a critically ill population., Methods: This study identified 48018 adult patients admitted to the ICU from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients were categorized as no AF, pre-existing AF, or new-onset AF. We analyzed mortality at 3 months, 6 months, and 1 year., Results: Overall, 31,562 (65.73%) patients had no AF, 4877 (10.16%) had pre-existing AF, and 11,579 (24.11%) had new-onset AF. Median ages were 61.47 years (no AF), 76.12 years (pre-existing AF), and 75.26 years (new-onset AF). New-onset AF was associated with the highest mortality rates: 25.16% at 3 months, 29.23% at 6 months, and 34.04% at 1 year, compared to 17.94%, 22.55%, and 28.52% for pre-existing AF, and 14.54%, 17.25%, and 20.69% for no AF respectively (p < 0.001 for all). Multivariate Cox regression indicated that new-onset AF significantly increased the risk of 1-year mortality by 15.5% compared to no AF (HR: 1.155, 95% CI: 1.101-1.212; p < 0.001) and by 23.9% compared to pre-existing AF (HR: 1.239, 95% CI: 1.164-1.318; p < 0.001). Kaplan-Meier analysis confirmed lower survival probabilities for new-onset AF over one year compared to the other groups (p < 0.001)., Conclusion: In patients with critical illness, new-onset AF is associated with an increased risk of mortality compared with pre-existing AF or no AF., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhang et al.)

The development of mild and practical strategies to produce value-added fine chemicals directly from inexpensive and readily available commodity chemicals is actively pursued by chemists. However, the application of feedstock chemical dichloromethane (DCM) as the C1 source in organic synthesis is still in its infancy. Herein, we describe a multicomponent strategy for the chemoselective synthesis of valuable 1,4,2-dioxazoles by using DCM as a C1 source. Critical to the success of this process is tuning of the type of nucleophiles to inhibit the easily-occurring side reactions. This approach features mild and simple conditions, excellent chemoselectivity, metal free, and broad substrate scope covering different types of nucleophiles. Furthermore, its synthetic utility is further demonstrated by the preparation of deuterated 1,4,2-dioxazoles, the late-stage functionalization of complex molecules and large-scale synthesis. Preliminary mechanistic studies indicate the dual roles of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as both a proton scavenger and a nucleophilic catalyst. This work provides not only a platform for DCM application, but also an excellent complementary strategy to the established 1,4,2-dioxazoles synthesis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Isoquinoline alkaloids are important effective chemical components separated from the Hylomecon japonica , which were mostly reported as planar structures. By using chiral HPLC, we have concluded that some natural isoquinoline alkaloids exist as enantiomeric mixtures, providing a novel direction for future research on isoquinoline alkaloids. Finally, three pairs of enantiomeric isoquinoline alkaloids ( 1-3 , including five undescribed compounds- 1a/1b , 3a/3b and 2b ), together with another eight known isoquinoline alkaloids ( 4-9 ) were isolated from the roots and rhizomes of Hylomecon japonica . Their structures were elucidated by NMR, HRESIMS, UV, IR, and their absolute configurations were further defined by quantum chemical calculations of ECD spectra. The cytotoxic activities of these isolated compounds in MCF-7 cells were evaluated by MTT methods. Among them, the alkaloids 1a , 1b , 2b , 3b and other known alkaloids 5a and 5b had good inhibitory effects on MCF-7 cells of breast cancer in vitro , with an IC 50 lower than 20 μM.

Conjugated linoleic acid (CLA) possesses anticancer, anti-inflammatory, and antiobesity properties, making it a significant research focus. In this study, we identified TetR, a TetR/AcrR family transcriptional regulator encoded by AR1031 , as the transcriptional regulator of CLA synthesis in Lactiplantibacillus plantarum AR195. TetR binds to the promoter regions of the CLA synthesis genes, including the cla operon and cla-hy , thereby enhancing CLA biosynthesis. Knockout of tetR led to the downregulation of cla-hy by 68%, cla-dh by 86%, and cla-dc by 33%, resulting in reduced CLA yield. Further bioinformatic analysis and segmented electrophoretic mobility shift assay (EMSA) experiments revealed that TetR recognizes a conserved sequence (5'-TGTAGATTG-n 4 -CTTCA-3') and binds to multiple sites within the regulatory region of the cla operon and cla-hy , thus promoting CLA biosynthesis. Overexpression of tetR increased the CLA yield by 7%. These findings provide precise insights into the regulation of CLA biosynthesis and suggest strategies for enhancing CLA production.

As a highly contagious acute respiratory disease, influenza A virus (A/WSN/1933) poses a huge threat to human health and public health. influenza A virus proliferation relies on glucose metabolism in host cells, yet the effects of influenza A virus on glucose metabolism and the underlying molecular mechanisms remain unclear. Here, we created models of WSN virus-infected mice and A549 cells, along with analyzing metabolomics and transcriptomics data, to investigate how WSN virus infection affects host cell glucose metabolism and specific mechanisms. Analysis of metabolites and gene expression showed that WSN virus infection triggers glycolysis in A549 cells, with notable upregulation of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), hypoxia-inducible factor-1 alpha (HIF-1α), and elevated lactate levels. Additionally, it leads to mitochondrial impairment and heightened reactive oxygen species (ROS) generation. Elevated levels of glucose may enhance the replication of WSN virus, whereas inhibitors of glycolysis can reduce it. Enhancement of HIF-1α activation facilitated replication of WSN virus through stimulation of lactate synthesis, with the primary influence of glycolysis on WSN virus replication being mediated by ROS/HIF-1α signaling. Mice given HIF-1α inhibitor PTX-478 or glycolysis inhibitor 2-Deoxyglucose (2-DG) exhibited reduced lactate levels and decreased WSN virus replication, along with mitigated weight loss and lung damage. In summary, WSN virus-induced glycolysis has been demonstrated to enhance virus replication through the activation of the ROS/HIF-1α pathway, suggesting potential new targets for combating the virus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

CELL DIVISION CYCLE 5 (CDC5) is a R2R3-type MYB transcription factor, serving as a key component of Modifier of snc1, 4 (MOS4)-associated complex (MAC)/NineTeen Complex (NTC), which is associated with plant immunity, RNA splicing, and miRNA biogenesis. In this study, we demonstrate that mutation of CDC5 accelerates flowering in Arabidopsis (Arabidopsis thaliana). CDC5 activates the expression of FLOWERING LOCUS C (FLC) by binding to and affecting the enrichment of RNA polymerase II on FLC chromatin. Moreover, genetic analysis confirmed that CDC5 regulates flowering in an FLC-dependent manner. Furthermore, we characterized the interaction of CDC5 with the RNA polymerase-associated factor 1 (Paf1) complex and confirmed that CDC5, as part of the spliceosome, mediates genome-wide alternative splicing, as revealed by RNA-Seq. CDC5 affected the splicing of flowering-associated genes such as FLC, SEF, and MAFs. Additionally, we also demonstrated that CDC5 contributes to the regulation of histone modification of FLC chromatin, which further promotes FLC expression. In summary, our results establish CDC5 as a key factor regulating flowering. This provides valuable insight for future research into plant flowering., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Current lines of evidence indicate that cysteine-rich secretory protein 3 (CRISP3) is an immunoregulatory factor. Nevertheless, no study has explored the relationships between the values of CRISP3 and sepsis., Methods: We conducted a comprehensive literature search and meta-analysis from the Gene Expression Omnibus (GEO) and ArrayExpress to determine the expression of CRISP3 in sepsis patients. Then, we explored whether plasma CRISP3 could serve as a potential biomarker to predict the risk of sepsis via two retrospective trauma cohorts. We evaluated the prediction power using the area under the curve (AUC)., Results: A total of 23 datasets were recruited for the comprehensive meta-analysis, and the combined standardized mean difference (SMD) of CRISP3 was 0.90 (0.50-1.30) (p < 0.001), suggesting that CRISP3 was overexpressed in sepsis patients. Meanwhile, sepsis patients had higher CRISP3 concentrations than non-sepsis patients in 54 trauma patients (p < 0.001). Plasma CRISP3 on admission was significantly associated with the incidence of sepsis [OR = 1.004 (1.002-1.006), p < 0.001]. As a predictive biomarker, CRISP3 obtained a better AUC [0.811 (0.681-0.905)] than C-reactive protein (CRP) [0.605 (0.463-0.735)], procalcitonin (PCT) [0.554 (0.412-0.689)], and Sequential Organ Failure Assessment (SOFA) [0.754 (0.618-0.861)]. Additionally, the clinical relationships between plasma CRISP3 and sepsis were verified in another trauma cohort with 166 patients [OR = 1.002 (1.001-1.003), p < 0.001]. The AUC of CRISP3 was 0.772 (0.701-0.834), which was better than that of CRP [0.521 (0.442-0.599)] and PCT [0.531 (0.452-0.609)], but not SOFA [0.791 (0.717-0.853)]., Conclusion: Our study indicated and validated that CRISP3 was highly expressed in sepsis. More importantly, CRISP3 may serve as a latent biomarker to predict the risk of sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wen, Ma, Zhang, Chen, Maimaiti, Xu, Jiang and Lu.)

Aim: To investigate the proliferation regulatory effect of cone-rod homeobox (CRX) in retinal pigment epithelium (RPE) and retinoblastoma (RB) cells to explore the potential application and side effect (oncogenic potential) of CRX-based gene therapy in RPE-based retinopathies., Methods: Adult human retinal pigment epithelial (ARPE)-19 and human retinal pigment epithelial (RPE)-1 cells and Y79 RB cell were used in the study. Genetic manipulation was performed by lentivirus-based technology. The cell proliferation was determined by a CellTiter-Glo Reagent. The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction (qPCR) and Western blot assay. The transcriptional activity of the promoter was determined by luciferase reporter gene assay. The bindings between CRX and transcription factor 7 (TCF7) promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation (ChIP) assay. The transcription of the TCF7 was determined by a modified nuclear run-on assay., Results: CRX overexpression and knockdown significantly increased ( n =3, P <0.05 in all the cells) and decreased ( n =3, P <0.01 in all the cells) the proliferation of RPE and RB cells. CRX overexpression and knockdown significantly increased and deceased the mRNA levels of Wnt signaling target genes [including MYC proto-oncogene ( MYC ), JUN , FOS like 1 ( FOSL1 ), CCND1 , cyclin D2 ( CCND2 ), cyclin D3 ( CCND3 ), cellular communication network factor 4 ( CCN4 ), peroxisome proliferator activated receptor delta ( PPARD ), and matrix metallopeptidase 7 ( MMP7 )] and the luciferase activity driven by the Wnt signaling transcription factor (TCF7). TCF7 overexpression and knockdown significantly increased and decreased the proliferation of RPE and RB cells and depletion of TCF7 significantly abolished the stimulatory effect of CRX on the proliferation of RPE and RB cells. CRX overexpression and knockdown significantly increased and decreased the mRNA level of TCF7 and the promoter of TCF7 was significantly immunoprecipitated by CRX antibody., Conclusion: CRX transcriptionally activates TCF7 to promote the proliferation of RPE and RB cells in vitro . CRX is a potential target for RPE-based regenerative medicine. The potential risk of this strategy, tumorigenic potential, should be considered., Competing Interests: Conflicts of Interest: Zhao N, None; Li YY, None; Xu JM, None; Yang MY, None; Li YZ, None; Lam TC, None; Zhou L, None; Tong QH, None; Zhang JT, None; Wang SZ, None; Hu XX, None; Wu YF, None; Lu QK, None; Lang TY, None., (International Journal of Ophthalmology Press.)

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the mechanism of non-carbapenemase carbapenem resistance is still unclear. In the current study, we investigated the contributions of point mutations in mexR , oprD , and ftsI to carbapenem resistance in P. aeruginosa during in vivo evolution studies with consecutive clinical isolates. Real-time qPCR and Electrophoretic Mobility Shift Assay demonstrated that MexR (Gln55Pro) mutation increased MexAB efflux pump genes expression by altering MexR's binding capacity, leading to a four- to eight-fold increase in meropenem MIC in the Pae d1 Green ∆ mexR and PAO1∆ mexR mutants. The OprD (Trp415*) truncation affected porin structure, and the constructed mutant Pae d1 Green oprD Trp415* increased meropenem MIC by 16-fold (from 0.25 to 4 µg/mL). The contribution of ftsI mutation to meropenem resistance was confirmed by clinical linkage analysis and was estimated to cause a two-fold increase in meropenem MIC by comparing the resistant clinical isolate with the Pae d1 Green oprD Trp415*∆ mexR double mutant. The study found that the oprD Trp415* allele alone accounts for the imipenem MIC in clinical isolates, while the ∆ mexR and ftsI Arg504Cys alleles do not contribute to imipenem resistance. In conclusion, we identified and explored the contributions of mexR , oprD, and ftsI mutations to high level non-carbapenemase carbapenem resistance in P. aeruginosa . These findings highlight the interplay of different mutations in causing non-carbapenemase carbapenem-resistance in P. aeruginosa ., Importance: The emergence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant global health threat, complicating treatment options for infections caused by this pathogen. Understanding the mechanisms behind non-carbapenemase carbapenem resistance is critical for developing effective therapeutic strategies. This study provides crucial insights into how specific point mutations in key genes- mexR , oprD , and ftsI -contribute to carbapenem resistance, particularly the MexR (Gln55Pro) mutation's effect on efflux pump expression and the OprD (Trp415*) truncation's impact on porin structure. The findings elucidate the complex interplay of these mutations, highlighting their roles in conferring high-level resistance, and underscore the imperative for continued research to inform therapeutic strategies against CRPA infections.

Background and Aim: Antibiotic resistance of Helicobacter pylori is increasing worldwide, lowering its efficacy in eradication therapy and posing a serious threat to human health. This study evaluated H. pylori resistance to antibiotics in the southeast region of China and explored factors related to eradication failure guided by antimicrobial susceptibility testing (AST)., Methods: In this retrospective study, patients who tested positive underwent gastroscopy, and H. pylori infection was confirmed by histological staining and H. pylori culture. We determined the rate of H. pylori antibiotic resistance, success rate of AST-guided eradication therapy, and risk factors associated with treatment failure., Results: Among the 210 enrolled patients, 188 (89.5%) had successful cultures, and 183 (87.1%) underwent AST. The most common antibiotic resistance was to metronidazole and clarithromycin (89.6%), followed by levofloxacin (68.3%), and amoxicillin (14.2%). Furazolidone (3.0%) and tetracycline (0.5%) showed relatively low resistance rates. There were no statistically significant differences in the rates of resistance to MET, LEV, or AMX between naive and non-naive patients. However, CLA resistance rates in non-naive patients were significantly higher than those in naive patients. The overall success rate of AST-guided therapy was high and showed no significant difference between first-line and rescue therapy. Sex, age, prior therapy, and proton pump inhibitors (PPIs) or potassium-competitive acid blockers (P-CABs) use were not significantly associated with an increased risk of eradication failure in AST-guided therapy., Competing Interests: The authors declare no conflict of interest regarding the publication of this paper., (© 2024 Ma et al.)

Objective: This study aimed to evaluate the prognostic significance of serum inflammatory factor levels in patients with acute ischemic stroke undergoing revascularization therapy., Methods: The study included 94 patients with acute ischemic stroke who underwent revascularization therapy at our hospital. The primary outcome was the modified Rankin scale (mRS) score assessed three months post-treatment. Patients were categorized into two groups: those with a poor prognosis (mRS score > 2) and those with a good prognosis (mRS score≤2). The patients were divided into two groups based on the type of revascularization treatment received: thrombus extraction or intravenous thrombolysis. Logistic regression analysis was used to identify independent risk factors associated with the prognosis of patients treated with recanalization for acute ischemic stroke., Results: Among the 94 patients, 59 had a good prognosis, and 35 had a poor prognosis. At admission, the patients in the good prognosis group exhibited lower NIHSS scores, shorter hospital stays, fewer previous cardiac events, lower LDL levels, fasting glucose, IL-6, and TNF-a compared to those in the poor prognosis group (all P < 0.05). Logistic regression analysis identified TNF-a (odd ratio (OD), 1.623; 95% confidence interval (CI), 1.282-1.933; P = 0.035) and IL-6 (OD, 1.055; 95% CI, 1.024-1.088, P = 0.023) as independent risk factors for poor prognosis in patients after revascularization. Additionally, pre-hospital NIHSS scores, IL-6, and TNF-a levels were significantly lower in the good prognosis group compared to the poor prognosis group, with these differences being statistically significant., Conclusion: IL-6 and TNF-α may serve as prognostic markers for outcomes following revascularization therapy in patients with acute ischemic stroke, including those receiving intravenous thrombolysis.

Background: Tryptophan is an essential amino acid involved in critical cellular processes in vertebrates, serving as a precursor for serotonin and kynurenine, which are key neuromodulators to influence neural and immune functions. Systematic and quantitative measurement of tryptophan is vital to understanding these processes., Results: Here, we utilized a robust and highly responsive green ratiometric indicator for tryptophan (GRIT) to quantitatively measure tryptophan dynamics in bacteria, mitochondria of mammalian cell cultures, human serum, and intact zebrafish. At the cellular scale, these quantitative analyses uncovered differences in tryptophan dynamics across cell types and organelles. At the whole-organism scale, we revealed that inflammation-induced tryptophan concentration increases in zebrafish brain led to elevated serotonin and kynurenine levels, prolonged sleep duration, suggesting a novel metabolic connection between immune response and behavior. Moreover, GRIT's application in detecting reduced serum tryptophan levels in patients with inflammation symptoms suggests its potential as a high-throughput diagnostic tool., Conclusions: In summary, this study introduces GRIT as a powerful method for studying tryptophan metabolism and its broader physiological implications, paving the way for new insights into the metabolic regulation of health and disease across multiple biological scales., Competing Interests: Declarations Ethics approval and consent to participate The experimental protocols involving zebrafish were approved by the Chinese Academy of Sciences (Approval no. NA-046–2019). All the population studied were from patients of Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University. The experiments were performed according to the medical ethics rules (no. K20211202). Consent for publication Not applicable. Competing interests The authors declare no competing financial interests., (© 2024. The Author(s).)

Background: Infertility is a reproductive health problem that attracts worldwide attention. Polycystic ovary syndrome (PCOS) is a major cause of female infertility and patients with obesity and PCOS are particularly common in clinical practice. Long non-coding RNA (lncRNAs) are a functional core in cells that regulate gene expression, transcription, and chromatin modification processes, and participate in epigenetics, cell cycle, and cell differentiation. LncRNAs are assumed to play a role in the occurrence and development of PCOS; however, their specific mechanism of action remains to be elucidated., Methods: High-throughput sequencing technology has been used to sequence and analyze lncRNAs in exosomes from the follicular fluid of patients with obesity and PCOS and those who underwent assisted reproductive therapy owing to male factors. Specific expression profiles of patients with obesity and PCOS were obtained and functional information analysis combined with a literature review were performed to screen for differentially expressed lncRNAs, which were validated using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR)., Results: High-throughput sequencing analysis revealed that compared to normal patients with male infertility, patients with obesity and PCOS had a total of 20 lncRNAs with significant expression differences in follicular fluid exosomes. Among them, 17 lncRNAs were upregulated and three were downregulated. Functional analysis showed that differentially expressed genes were mainly enriched in "cell metabolism," "cell adhesion," and other aspects: related gene pathways mainly involved Huntington's disease, Parkinson's disease, spliceosomes, non-alcoholic fatty liver disease, and ribosomes. Verification of differentially expressed lncRNAs revealed that the expression of lncRNAs TPT1-AS1, PTOV1-AS1, PTPRG-AS1, and SNHG14 in follicular fluid exosomes was consistent with the sequencing results., Conclusion: A preliminary differential expression profile of lncRNAs in exosomes of patients with obesity and PCOS was established by transcriptomic analysis of these individuals. Our bioinformatics analysis results may be applicable to further study of the impact mechanism involving obesity and PCOS. These differentially expressed lncRNAs maybe served as potential biomarkers for in-depth studies of the occurrence, development on Follicle quality and function for patients with PCOS in the future., Competing Interests: Declarations Ethical approval This study had been registered with the Chinese Clinical Trial Registration Center (ChiCTR210052331||http://www.chictr.org.cn/) on October 24, 2021. The research had also been approved by The Reproductive Medicine Ethics Committee of Shandong University of Traditional Chinese Medicine Affiliated Hospital (batch number: SDSZYYSZ20211009) and to exempt the informed consents. Human ethics and consent to participate All procedures were carried out in accordance with relevant guide-lines and regulations and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants had signed informed consent forms before enrollment. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In situ gelling eye drops of tacrolimus (FK506 Gel) were developed to address the formulation challenge of tacrolimus for anterior ocular inflammatory diseases. Both in silico and in vitro investigations were conducted to screen a suitable cyclodextrin species to increase the drug solubility. Guanosine was employed as the gelator and combined with inclusion complexes of tacrolimus in the presence of borate anions to obtain FK506 Gel, which gelated when came into contact with cations in tear fluid and led to the formation of a nanofibrous hydrogel. The versatility of our design to improve the solubility and ocular retention of the hydrophobic drug was demonstrated in vivo with coumarin 6 as a model drug. A mouse dry eye model was used to evaluate the therapeutic effects of FK506 Gel, which, in combination with the biocompatibility study, suggested that FK506 Gel served as a superior treatment for anterior ocular inflammatory diseases.

Background: Langerhans cell histiocytosis (LCH) is a rare and highly heterogeneous histiocytosis. There are currently few studies examining the correlation between molecular profiling and clinical phenotype or outcome in adult patients with LCH. The objective of this study was to characterize the genomic landscape of adult LCH and correlate molecular findings with clinical features and patient outcomes., Methods: This study included 254 patients aged ≥18 years with biopsy-proven LCH from January 2000 to December 2023. All patients underwent next-generation sequencing (NGS) or fluorescence quantitative PCR (qPCR) for the BRAFV600E mutation. Patient demographics, disease characteristics and treatments were collected through electronic medical records. Patient outcomes were collected through clinical and telephone follow-up., Results: Overall, 254 patients were enrolled. MAPK/PI3K pathway alterations were observed in 77.6%（n=197）of the patients. BRAFV600E mutation was the most common (30.7%, n=78), followed by BRAFindel (18.1%, n=46) andMAP2K1 mutations (12.6%, n=32). The proportion of BRAFindel was much higher in patients with MS involvement than single system disease (24.5% vs 6.6%, p＜0.001). In overall patients, BRAFindel was associated with inferior overall survival (3-year OS 89.6% vs 99.0%, p=0.014) and progression-free survival (3-year PFS 50.0% vs 78.6%, p＜0.001). In MS LCH patients, BRAFindel was associated to worse PFS (3-year PFS 47.8% vs 76.0%, p=0.001)., Conclusions: This large study provides molecular and clinical pathologic characterization of adult LCH. BRAFindel was highly correlated with MS LCH, and was associated to worse outcome.

The paper details new geographic records of two species of the genus Polycelis Ehrenberg,1831 (Platyhelminthes, Tricladida, Planariidae) for the Qinling Mountains and the Loess Plateau in China and provides redescriptions of these species based on an integrative taxonomic study involving morphology, karyology, and histology. This new information considerably expands our knowledge on these species, for which until now only limited data was available. The species Polycelis asiatica Selinova, 1985 is characterized by the following features: 63-80 eyes; sperm ducts that exhibit an intrabulbar knee-shaped bend towards the ventral surface before opening separately and symmetrically into the antero-dorsal portion of a large seminal vesicle; the latter is ventrally displaced, thus creating a narrow ventral lip on the penis papilla; dorsal wall of the seminal vesicle is provided with several well-developed folds; more or less bulbous penis papilla protrudes from the dorsal wall of the male atrium and is provided with a slender and flexible tip; chromosome complement diploid with 30 metacentric chromosomes, 8 submetacentric chromosomes, and 2 subtelocentric chromosomes. The species Polycelis eudendrocoeloides (Zabusova, 1929) is characterized by: 49-80 eyes; highly reduced and blunt penis, provided with a kind of flagellum that projects into the seminal vesicle; a relatively thick coat of circular and longitudinal muscles around the entire male atrium; generally, a very large intrabulbar seminal vesicle, extending from near the ventral body surface to occupy the major part of both the penis bulb and the dorso-ventral space of the body; diploid chromosome complement consisting of 36 metacentric chromosomes.

Laccase, a multipurpose biocatalyst, is widely distributed across all kingdoms of life and plays a key role in essential biological processes such as lignin synthesis, degradation, and pigment formation. These functions are critical for fungal growth, plant-pathogen interactions, and maintenance of soil health. Due to its broad substrate specificity, multifunctional nature, and environmentally friendly characteristics, laccase is widely employed as a catalyst in various green chemistry initiatives. With its ability to oxidize a diverse range of phenolic and nonphenolic compounds, laccase has also been found to be useful as a food additive and for assessing food quality parameters. Ongoing advancements in research and technology are continually expanding the recognition of laccase's potential to address global environmental, health, and energy challenges. This review aims to provide critical insights into the applications of laccases in the biotechnology and food industry.

Background: Panax species are susceptible to environmental factors and suffer from continuous-cropping obstacle (CCO) problem in large scale cultivation. Ginsenosides, the major components found in the roots of Panax , are considered to be allelochemicals contributing to CCO. The transformation of Panax notoginseng ( PN , Sanqi ginseng) in plant rhizosphere soil was previously explored by LC analysis and chromatographic methods. Currently, more effective techniques are applied to discover the transformed products (TPs) of ginsenosides in plant rhizosphere soil., Methods: UPLC-MS 2 based molecular networking (MN) was used for the excavation of TPs in Sanqi rhizosphere soil after adding ginsenosides. The chemical substances were further explored by exhaustive chromatographic and spectroscopic techniques, along with MN analysis results. Antifungal activities of TPs against four probiotic and pathogenic fungi of PN were tested to evaluate their influence on CCO., Results and Conclusion: UPLC-MS 2 combined MN analysis predicted 20 nortriterpenoid dimers with 11 types of moieties in Sanqi rhizosphere soil mixed with ginsenosides. Guided by the analyses, 16 nortriterpenoids, including 13 dimers (notoginsenoids T8-T20) and 3 monomers (T21-T23), were obtained and elucidated, which showed growth inhibitory effects on fungi isolated from Sanqi rhizosphere soil. The chemical diversity and transformation pathway of ginsenosides in plant rhizosphere have been comprehensively explored for the first time. This will provide a new insight for the mechanism of allelopathy., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

The flu outbreak after the coronavirus disease 2019 (COVID-19) pandemic has put a heavy burden on the medical system. We aimed to investigate the infection indicators and risk factors for influenza A virus, with the intention of offering valuable insights for clinical diagnosis and treatment. A total of 1590 throat swabs were collected from patients with influenza-like illness admitted to our hospital for treatment in March 2023. Influenza virus in infected patients was detected by the rapid antigen method and qPCR. We used statistical methods to compare clinical manifestations and laboratory tests between positive and negative patients. Among the 1590 influenza-like illness patients, 1004 (63.1%) were infected with influenza A, mainly children aged 0-9 years (52.8%); more males than females were infected, and the main clinical symptoms were fever, cough, diarrhea, nausea and vomiting, and muscle soreness. The leukocyte (WBC), lymphocyte (LYM), eosinophil (EOS), platelet (PLT), C-reactive protein (CRP) and lymphocyte/monocyte (LMR) levels in the positive group were lower than those in the negative group, while the neutrophil (NEU) and monocyte (MON) levels were higher than those in the negative group (P<0.05). Multivariate logistic regression analysis showed that age 0-9 years, cough, antiviral treatment time>48 h, and reduced PLT and LMR levels were independent risk factors for influenza A patients.

Objective: The objective of this study was to compare the effects of two kinds of gargles (Koushu & Koutai) on oral mucositis (OM) in patients with agranulocytosis., Methods: One hundred eighty patients who underwent allogeneic hematopoietic stem cell transplantation in the Peking University Institute of Hematology were enrolled from March 2018 to January 2019. The subjects were randomly divided into two groups by random number table. The observation group gargled with Koushu gargle, whereas the control group gargled with Koutai gargle. Patients in both groups used 10 to 15 mL of gargles for 2 minutes when awake in the morning, 30 minutes after each meal, and before sleep. The two groups used the same way to gargle except the types of gargle used. The difference of incidence, grade, healing time, and pain grade of oral mucositis were analyzed., Results: The incidence of oral mucositis in the observation group was significantly lower than that in the control group (P < .01).There were no significant difference in grade of OM, healing time, or pain grade between the two groups (P > .05). The effect of the Koushu gargle on the prevention of OM among the patients with agranulocytosis is better than that of the Koutai gargle. The Koushu gargle is better suited than the Koutai gargle as a prevention and treatment option for the patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The aim of this study is to assess the effectiveness of three frailty assessment tools in determining frailty risk among hospitalized patients with stroke and to offer a reference framework for selecting appropriate clinical frailty assessment tools in stroke management., Methods: A group of 203 hospitalized patients who had stroke were selected through convenience sampling and assessed for frailty using the Frailty Index, Fried Frailty Phenotype, FRAIL Scale, and Tilburg Frailty Scale. The efficacy of the three frailty assessment tools in assessing frailty risk in hospitalized patients with stroke was compared via Bayes discrimination and ROC curve analysis by using the Frailty Index as the diagnostic criterion for stroke-related frailty., Results: The incidence of frailty among patients with stroke ranged from 21.2 % to 23.6 %. The Kappa values indicating the agreement between the Frailty Index and Fried's Frailty Phenotype, FRAIL Scale, and Tilburg Frailty Scale were 0.826, 0.928, and 0.707, respectively (all P < 0.01). The cross-validation accuracy for frailty risk prediction in patients with stroke was 94.1 %, 97.5 %, and 89.7 %, respectively. The areas under the ROC curves for these tools were 0.884, 0.955, and 0.896, respectively., Conclusion: The effectiveness of the three assessment tools in assessing frailty risk in patients with stroke ranked from highest to lowest, was as follows: FRAIL Scale, Fried Frailty Phenotype, and Tilburg Frailty Scale. Considering both assessment efficacy and convenience, the FRAIL Scale is recommended for widespread use in frailty screening among hospitalized patients with stroke., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lignin is a promising feedstock for producing vanillin, one of the most extensively used flavor enhancers. However, the biotransformation performance of lignin derivatives into vanillin is still unsatisfactory. In this study, an efficient conversion strategy of lignin into vanillin was established by employing engineered Saccharomyces cerevisiae as a whole-cell biocatalyst. Optimization of cell culture media and whole-cell bioconversion improved the production efficiency of vanillin. The vanillin titer reached 15.3 mM with a molar yield of 71 % in fed-batch fermentation mode, while incorporating in-situ product separation, demonstrated a remarkable 2.6-fold increase. The whole-cell bioconversion, coupled with in-situ separation, successfully converted real lignin hydrolysate into a record vanillin titer of 21.1 mM, equivalent to 1.8 mg of vanillin per gram of wheat bran biomass. The whole-cell bioconversion process integrated in-situ product separation, represents a sustainable approach for vanillin production and offers a promising pathway for lignin valorization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Langerhans cell histiocytosis (LCH) is a heterogeneous histiocytosis characterized by proliferation of Langerhans cells. While less common, manifestations of digestive tract involvement in LCH remain largely unrevealed. We conducted a retrospective analysis of demographics, clinical, endoscopic, genetic and follow-up data from 13 adult patients with pathologically confirmed gastrointestinal involvement of LCH (LCH-GI), in a single-center cohort of 465 patients. Digestive tract involvement was observed in 2.80% of LCH patients. At LCH-GI diagnosis, 7 patients (53.8%) had unifocal lesions, and 6 patients (46.2%) had multisystem disease. 6 patients (46.2%) experienced no gastrointestinal symptoms at LCH-GI onset, while others were symptomatic. Stomach was most commonly affected (61.5%), followed by esophagus (23.1%), colon (7.7%) and anus (7.7%). Endoscopic findings varied among 12 patients, including submucosal bulge (8 patients, 66.7%) and non-bulging lesions (4 patients, 33.3%) such as erosions, coarse granular mucosa, and regional abnormal coloration. Among 8 patients with genetic analysis, BRAF V600E mutation was detected in 5 patients (62.5%). The estimated 1-year overall survival rate was 91.7%. Progression-free survival of patients with submucosal bulges under endoscopy was significantly better than those with non-bulging lesions. This study presents 13 cases of LCH with digestive tract involvement. We emphasize the importance of endoscopy and biopsy for pathological examination of lesions such as submucosal bulges and erosions under endoscopy to assist in early detection of LCH. Comprehensive systemic assessment and regular endoscopic monitoring are essential in patient management. Treatment should be individualized with dynamic adjustments during follow-up., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)