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Aspartame is the most common artificial sweetener and a famous sweet-taste receptor agonist. Macrophages are essential in the antibacterial system to maintain the stability of the intestinal environment. Recently, the sweet taste receptor has been found in macrophages. However, the effects of aspartame on macrophage phagocytosis in the gastrointestinal tract are little known. The current study sought to assess the influence of aspartame intake on the scavenging activity of mice to low-dose Escherichia coli infection and related mechanisms. Firstly, no inflammatory response or pathological injury was observed in the intestines of mice after oral administration of aspartame (25-100 mg/kg, i.g.) for 2 weeks. Subsequently, aspartame intake was found to enhance the scavenging activity of mice to low-dose E. coli infection. Similarly, aspartame dose-dependent strengthened the ability of RAW264.7 cells to phagocytose GFP-E.coli J96. Further mechanism evaluation reflected that aspartame could enhance macrophage phagocytosis, migration, and rearrangement via PLCβ-2/Ca 2+ /PKCβ/Rho A/ROCK1 pathway caused by sweet taste receptor activation. In conclusion, the present study, for the first time, demonstrated that aspartame could enhance the scavenging activity of mice to low-dose E. coli infection via strengthening macrophage phagocytic function through activating sweet taste receptor. It is then suggested that aspartame may affect the antibacterial activity of human gastrointestinal macrophages, and further studies need to validate these effects., (© 2024 Federation of American Societies for Experimental Biology.)

Primary osteoporosis, manifesting as decreased bone mass and increased bone fragility, is a "silent disease" that is often ignored until a bone breaks. Accordingly, it is urgent to develop reliable biomarkers and novel therapeutic strategies for osteoporosis treatment. Here, we identified REGγ as a potential biomarker of osteoporotic populations through proteomics analysis. Next, we demonstrated that REGγ deficiency increased osteoclast activity and triggered bone mass loss in REGγ knockout (KO) and bone marrow-derive macrophage (BMM)-conditional REGγ KO mice. However, the osteoclast activity decreased in BMM-conditional REGγ overexpression mice. Mechanistically, we defined that REGγ-20S proteasome directly degraded TRAF6 to inhibit bone absorption in a ubiquitin-independent pathway. More importantly, BMM-conditional Traf6 KO with REGγ KO mice could "rescue" the osteoporosis phenotypes. Based on NIP30 (a REGγ "inhibitor") dephosphorylation by CKII inhibition activated the ubiquitin-independent degradation of TRAF6, we selected TTP22, an inhibitor of CKII, and defined that TTP22 could alleviate osteoporosis in vitro and in vivo. Overall, our study reveals a unique function of NIP30/REGγ/TRAF6 axis in osteoporosis and provides a potential therapeutic drug TTP22 for osteoporosis., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Despite continued efforts to manage and control Tuberculosis (TB) in China, it remains a major health concern. Bone tuberculosis (Bone-TB), a common form of extrapulmonary tuberculosis, still adds considerably to the global TB case load. Diagnosing Bone-TB is often difficult as its symptoms can be similar to other bone or joint diseases, which leads to delayed detection and treatment. Currently, comprehensive reports on the epidemiological aspects of Bone-TB in China are scarce., Methods: This retrospective study analyzed demographic and clinical data from 2,191 patients diagnosed with Bone-TB in Southwest China between January 2011 and September 2023.This study fully reveals the characteristics of Bone-TB in Southwest China., Results: The overall trend of bone tuberculosis was a slow rise. Among 2191 patients, males, farmers, aged 42-68 years, and people with HIV and diabetes are the priority groups for the prevention and treatment of Bone-TB. The majority of the infected spines (1556/2191) were located in the thoracic vertebra (759/2191) and lumbar vertebra (715/2191). Forty-nine (2.24%) patients had drug-resistant TB (DR-TB). Forty-five (2.05%) died during the treatment. The total and actual hospitalization. Costs amounted to $3,837.10 and $1,914.35 (p < 0.01). Patients with DR-TB incurred the highest costs, amounting to $4,968.37. Cervical TB, with a prevalence of 5 patients (6.10%), exhibited the highest rates of catastrophic expenditures., Conclusions: From 2011 to 2023, the yearly occurrence of Bone-TB in southwestern China exhibited a rising pattern, marked by notable distinctions in terms of gender, age, and regional variations, indicating localized clustering characteristics., Competing Interests: Declarations Ethics Approval and Consent to Participate As per the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University and the Fourth People’s Hospital of Nanning, written informed consent from each patient was deemed unnecessary for this study due to the removal of all sensitive patient information prior to analysis. The study adhered to the principles of the Declaration of Helsinki and received approval from the Ethics Committee of the Fourth People’s Hospital of Nanning and the First Affiliated Hospital of Guangxi Medical University (Approval number: 2023-36-01, NO.2022-KY-E-152). Consent for Publication Not applicable. Competing Interests The authors declare no competing interests., (© 2024. The Author(s).)

The cell membrane remodeling mediated by cyclopropane fatty acid synthase (CfaS) plays a crucial role in microbial physiological processes resisting various environmental stressors, including acid. Herein, we found a relatively high proportion (24.8%-28.3%) of cyclopropane fatty acid (CFA) Cy-19:0 in the cell membrane of a newly isolated extreme acidophile, Acidithiobacillus caldus CCTCC AB 2019256, under extreme acid stress. Overexpression of the CfaS encoding gene cfaS2 in Escherichia coli conferred enhanced acid resistance. GC-MS analysis revealed a 3.52-fold increase in the relative proportion of Cy-19:0 in the cell membrane of the overexpression strain compared to the control. Correspondingly, membrane fluidity, permeability and cell surface hydrophobicity were reduced to varying degrees. Additionally, HPLC analysis indicated that the overexpression strain had 1.54-, 1.42-, 1.85-, 1.20- and 1.05-fold higher levels of intracellular glutamic acid, arginine, aspartic acid, methionine and alanine, respectively, compared to the control. Overall, our findings shed light on the role of CfaS derived from extreme acidophile in bacterial defense against environmental acid stress, potentially facilitating its application in the design and development of industrial microbial chassis cells for organic acid production., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors., (© 2024. The Author(s), under exclusive licence to Springer Nature Japan KK.)

The construction industry, as a major global energy consumer and carbon emitter, plays a crucial role in achieving global sustainability. A key strategy for the green transformation of this industry-without compromising development-involves fostering green technology innovation. Nevertheless, existing studies exhibit a notable gap in identifying and evaluating potential green technology innovation opportunities within the construction field, leading to a scarcity of decision-making information for governments and innovation entities during the research and development stage. Recognizing this, our study proposes a two-stage technology opportunity prediction approach based on interpretable machine learning from the perspective of technology convergence. Diverging from previous methods, it not only predicts the probability of technology opportunity occurrence but also forecasts the technical impact of convergence opportunities. By analysing 600,442 patent documents in the green and construction fields, we identify 305 high-potential technology convergence opportunities. Our results reveal that technologies such as carbon capture and storage, pollution alarms, solar energy, forestry techniques, wind energy, energy-saving methods, and waste materials for water treatment have significant potential for convergence with construction technologies. Additionally, we analyse the influencing factors behind these convergence innovations, finding that technical similarity and proximity play crucial roles. These findings provide robust decision support for governments and industry stakeholders in formulating scientifically grounded green technology innovation strategies, thereby accelerating the green transformation of the construction industry and contributing to the goal of sustainable development., Competing Interests: Declaration of competing interest Declarations of 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.)

Colon cancer is one of the leading causes of cancer-related mortality worldwide. Current treatments, including surgery, chemotherapy, and radiation therapy, often have limited efficacy due to tumor heterogeneity and resistance mechanisms. Therefore, there is a critical need for novel therapeutic strategies that can enhance the immune response against colon cancer cells while promoting their efficient clearance. In this study, we investigated the anti-tumor effects of Ro 90-7501, a specific small molecule, in colon cancer cell lines (HCT8 and SW480) and in vivo models. MTS, EdU, Scratch Wound and Transwell assays were performed to detect the cell proliferation and metastasis. Additionally, flow cytometry and immunofluorescence staining were used to analyze changes in apoptosis and necrosis. Furthermore, we examined its ability to induce immunogenic cell death (ICD) and promote retinoic acid-inducible gene I (RIG-I)-mediated autophagy. The expression levels of key molecules involved in ICD and autophagy were assessed using Western blot analysis, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Our findings demonstrated that Ro 90-7501 significantly suppressed colon cancer cell proliferation and metastasis, inducing apoptosis and necrosis. Mechanistically, Ro 90-7501 triggered ICD by upregulating the exposure of calreticulin (CRT) on the cell surface and increasing the release of high mobility group box 1 (HMGB1) and extracellular ATP levels. Concurrently, it promoted RIG-I-mediated autophagy via the MAVS-TRAF6 signaling axis, evidenced by increased expression of autophagy-related genes, such as microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 proteins, coupled with a reduction in P62 protein. Additionally, Ro 90-7501 treatment activated the RIG-I-MAVS-TRAF6 signaling axis in colon cancer cells. Furthermore, Ro 90-7501 enhanced the secretion of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα), thereby activating the immune response. In conclusion, Ro 90-7501 exhibits potent anti-tumor activity against colon cancer by inducing ICD and promoting RIG-I-mediated autophagy. These results suggest that Ro 90-7501 may serve as a promising therapeutic candidate for colon cancer treatment by enhancing both intrinsic cellular processes and adaptive immune responses. Further studies are warranted to elucidate the detailed mechanisms underlying these effects and to evaluate its therapeutic potential in clinical settings., 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.)

Septic Cardiomyopathy (SCM) is a syndrome of acute cardiac dysfunction in septic patients, unrelated to cardiac ischemia. Multiomics studies including transcriptomics and proteomics have provided new insights into the mechanisms of SCM. In here, a rat model of SCM was established by intraperitoneal injection of lipopolysaccharide (LPS). Biomarkers of SCM were characterized via a multi-omics analysis. The differentially expressed (DE) mRNAs predominantly appeared in pathways linked to the immune response, inflammatory response, and the complement and coagulation cascades, while DE proteins were mainly enriched in pathways associated with the complement and coagulation cascades. On this basis, the integrated analysis was performed between transcriptome and proteome. The potential biomarkers were further verified by RT-qPCR and WB. The current proteotranscriptomic research has furnished a valuable dataset and fresh perspectives that will enhance our comprehension of the development of SCM. This, in turn, is expected to expedite the formulation of novel approaches for the prevention and management of SCM in patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Natural silk nanofibers (SNF) are attractive conductive substrates due to their high aspect ratio, outstanding mechanical strength, excellent biocompatibility, and controllable degradability. However, the inherently non-conductivity severely restricts the potential sensor application of SNF-based aerogels. In this work, the conductive nanofibrous aerogels with low-density achieved through freeze-drying by dispersing carbon nanotubes (CNT) into SNF suspension. The addition of CNT significantly increases the conductivity with improved mechanical properties of composite aerogels. SEM results reveal that the distinct hierarchical structure comprising micropores and nanofibrous networks within the pores is formed when CNT content reached 30%. Furthermore, increased cell viability suggested the excellent biocompatibility of SNF-CNT-based conductive aerogel for tissue-engineering applications. Subsequently, the elastic water-borne polyurethane (WPU) is incorporated to SNF-CNT system to construct aerogel with good sensing properties. The introduction of WPU demonstrates enhanced compressive performances and an exceptionally high elastic recovery ratio of 99.8%, thereby exhibiting a stable and lossless strain-sensing signal output at 5% strain. This study provides a feasible choice and strategy for exploring the potential application of SNF in functional aerogels., (© 2024 Wiley‐VCH GmbH.)

Isoindolones constitute a dominant structural class in synthetic and medicinal chemistry. In this research, an electrochemical reaction involving 2-alkynylbenzamides, inorganic sulfites, and alcohols was first established to provide sulfonyl ester-substituted 3-hydroxyisoindolinone derivatives in moderate to good yields with excellent functional group tolerance. When bulky aryl-substituted 2-alkynylbenzamides are utilized as substrates, sulfonyl ester-substituted 3-alkylideneisoindolinones can be selectively generated with good chemoselectivity. Alkoxysulfonyl radicals derived from the anodic oxidation of inorganic sulfite with alcohols are involved in this transformation.

The healthy benefits of seaweed have increased its market demand in recent times. Quality control is crucial for seaweed to ensure the customers' interest and the sustainable development of seaweed farming industry. This study developed a quality control method for seaweed Sargassum fusiforme, rapid and simple, using near-infrared spectroscopy (NIR) and chemometrics for the prediction of antioxidant capacity of S. fusiforme from different growth stages, S. fusiforme was distinguished according to growth stage by partial least squares-discriminant analysis (PLS-DA) and particle swarm optimization-support vector machine (PSO-SVM). The antioxidant properties including 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity, and ferric reducing antioxidant power (FRAP) were quantified using competitive adaptive reweighted sampling (CARS)-PLS model. Based on the spectra data preprocessed by multiplicative scatter and standard normal variate methods, the PSO-SVM models can accurately identify the growth stage of all S. fusiforme samples. The CARS-PLS models exhibited good performance in predicting the antioxidant capacity of S. fusiforme, with coefficient of determination (R P 2 for FRAP, respectively. The quality and market price of S. fusiforme should increase in the order of maturation < growth < seedling regarding the antioxidant property. The overall results indicated that the NIR spectroscopy accompanied by chemometrics can assist for the quality control of S. fusiforme in a more rapid and simple manner. This study also provided a customer-oriented concept of seaweed quality grading based on deep insight into the antioxidant capability of S. fusiforme at different growth stages, which is highly valuable for precise quality control and standardization of seaweed market.-1 for FRAP, respectively. The quality and market price of S. fusiforme should increase in the order of maturation < growth < seedling regarding the antioxidant property. The overall results indicated that the NIR spectroscopy accompanied by chemometrics can assist for the quality control of S. fusiforme in a more rapid and simple manner. This study also provided a customer-oriented concept of seaweed quality grading based on deep insight into the antioxidant capability of S. fusiforme at different growth stages, which is highly valuable for precise quality control and standardization of seaweed market., 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.)

Industrial wastewater containing high levels of fluoride and phosphate poses significant environmental challenges and results in the waste of non-renewable resources. This study investigates the use of La(OH) 3 as a precipitating agent to selectively remove and separate fluoride from phosphate in such wastewater. The findings indicate that fluoride removal efficiency is highly dependent on the pH level and La(OH) 3 dosage. Using Response Surface Methodology, the optimal conditions for fluoride precipitation were identified as a pH range of 1.0 to 2.5, a reaction time of 60-80 min, a La/3F molar ratio of 2.0, and reaction temperature of 25 °C. Under these parameters, the fluoride removal efficiency exceeded 96.9 %, while phosphate removal remained around 7.2 %. Further Density Functional Theory calculations and characterization confirmed La(OH) 3 has a strong affinity for fluoride than phosphate under acidic conditions, leading to the formation of a LaF 3 precipitate without forming LaPO 4 , effectively separating fluoride from phosphate. These results demonstrate an efficient strategy for treating wastewater with high fluoride and phosphate content, enabling the selective precipitation and recovery of these elements for sustainable management., 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 B.V.)

Studying regulation of protein function at a systems level necessitates an understanding of the interplay among diverse post-translational modifications (PTMs). A variety of proteomics sample processing workflows are currently used to study specific PTMs but rarely characterize multiple types of PTMs from the same sample inputs. Method incompatibilities and laborious sample preparation steps complicate large-scale physiological investigations and can lead to variations in results. The single-pot, solid-phase-enhanced sample preparation (SP3) method for sample cleanup is compatible with different lysis buffers and amenable to automation, making it attractive for high-throughput multi-PTM profiling. Herein, we describe an integrative SP3 workflow for multiplexed quantification of protein abundance, cysteine thiol oxidation, phosphorylation, and acetylation. The broad applicability of this approach is demonstrated using cell and tissue samples, and its utility for studying interacting regulatory networks is highlighted in a time-course experiment of cytokine-treated β-cells. We observed a swift response in global regulation of protein abundances consistent with rapid activation of JAK-STAT and NF-κB signaling pathways. Regulators of these pathways as well as proteins involved in their target processes displayed multi-PTM dynamics indicative of a complex cellular response stages: acute, adaptation, and chronic (prolonged stress). PARP14, a negative regulator of JAK-STAT, had multiple co-localized PTMs that may be involved in intraprotein regulatory crosstalk. Our workflow provides a high-throughput platform that can profile multi-PTMomes from the same sample set, which is valuable in unraveling the functional roles of PTMs and their co-regulation., Competing Interests: Conflicts of interest none, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: SHR4640, a highly selective URAT1 inhibitor, was evaluated to investigate its inhibitory effects on CYP2C8 and CYP3A4 in vivo clinical trial. This study assessed the pharmacokinetic (PK) impact of SHR4640 when co-administered with the CYP2C8 probe substrate repaglinide and the CYP3A4 probe substrate midazolam., Research Design and Methods: In this single-center, randomized, double-blind, placebo-controlled study, participants were randomly allocated in a 1:1:1 ratio to SHR4640 Group A, SHR4640 Group B, and placebo group and received oral repaglinide, midazolam, SHR4640 or placebo at specific times. The primary endpoints included the main PK parameters of repaglinide and midazolam, both alone and in combination with SHR4640 (AUC 0-inf , AUC 0-t , and C max )., Results: The increase in the area under the concentration-time curve (AUC) for repaglinide, when co-administered with SHR4640, was less than 1.25-fold, while the AUC for midazolam exhibited a slight increase of 46%., Conclusions: SHR4640 exerts a weak inhibitory effect on the AUC of CYP enzyme probe substrates and has minimal potential for drug-drug interactions and presents a favorable safety profile., Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT06196580 (Name: PK Effects of SHR4640 on Repaglinide and Midazolam, and the Impact of SHR4640 on QT Interval).

Covalent organic frameworks (COFs) have emerged as a distinguished class of porous materials. Owing to their ability to be constructed through covalent bonds involving light elements, such as hydrogen, boron, carbon, nitrogen, and oxygen, COFs offer greater stability and lower cytotoxicity than metal organic frameworks do, addressing critical limitations in in vivo applications. Their unique attributes, such as high surface area, customizable pore sizes, and versatile surface functionalities, make them ideal for various biomedical applications. This review aims to provide an overview of the recent advancements in modern COFs for biomedical uses. First, a variety of methods for the synthesis of COFs are outlined, which ensures their suitability for medical use. Next, we delve into innovative biomedical applications, emphasizing their role in disease diagnostics and therapies. Finally, challenges, such as clinical translation, biocompatibility, and controlled drug release, are critically discussed, providing comprehensive insight into the potential of COFs in revolutionizing biomedical technologies. Overall, this review offers a comprehensive overview of COFs' capabilities and future prospects in enhancing biomedical technologies., (© 2024 Wiley‐VCH GmbH.)

Background: Pain is a relatively common complication after hook-wire puncture localization. However, the problem of pain occurrence following this localization procedure has not been sufficiently examined. In this prospective study, we aimed to investigate the incidence and risk factors associated with acute pain after preoperative CT-guided hook-wire puncture localization of pulmonary nodules., Methods: Clinical data were collected prospectively from patients with small pulmonary nodules who underwent preoperative CT-guided hook-wire puncture localization between May 2022 and May 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients were divided into two groups on the basis of the presence or absence of moderate-to-severe pain following the localization process. Univariate logistic analysis was conducted to analyse the clinical data of the two groups. Subsequently, the significant variables (P < 0.1) from the univariate analysis were subjected to multivariate logistic analysis, followed by the establishment of regression equations to determine the significant risk factors related to moderate-to-severe pain after hook-wire puncture localization., Results: A total of 281 patients with small pulmonary nodules undergoing preoperative CT-guided hook-wire puncture localization were finally included, with a mean age of 54.86 years (SD = 12.1 years) and female predominance (67.6%). In the resting state, 53% of the patients reported moderate-to-severe pain. Univariate analysis revealed that age (P = 0.085), the depth of localization needle insertion into the lung (P = 0.024) and the location of the chest wall puncture (P = 0.07) were associated with moderate-to-severe pain occurrence after hook-wire puncture localization (P < 0.1). Furthermore, multivariate logistic regression analysis demonstrated that the depth of localization needle insertion into the lung (OR = 0.953, 95% CI: 0.914-0.992, P = 0.02) and the location of the chest wall puncture (lateral chest wall vs. anterior chest wall: OR = 2.101, 95% CI: 1.166-3.784, P = 0.013; posterior chest wall vs. anterior chest wall: OR = 1.163, 95% CI: 0.895-2.971, P = 0.11) were independent predictors of moderate-to-severe pain incidence following CT-guided hook-wire puncture localization (P < 0.05)., Conclusion: Moderate-to-severe pain is prevalent in patients with pulmonary nodules who undergo preoperative CT-guided hook-wire puncture localization. The depth of needle insertion into the lung and the location of the chest wall puncture are significant predictors of moderate-to-severe pain onset., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Medical Ethics Committee of the Affiliated Hospital of Xuzhou Medical University (Approval No. XYFY2022-KL097-01) and complied with the principles of the Declaration of Helsinki and relevant ethical requirements. All patients or patients’ relatives participating in this study signed an informed consent form. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Laparoscopic surgery is a popular alternative for resection of colorectal neoplasms. Carbon dioxide pneumoperitoneum and Trendelenburg positioning in procedure can significantly increase airway pressure, when endotracheal tube cuff pressure is not monitored. This prospective observational study aimed to evaluate indicators, changes and its correlation factors of endotracheal tube cuff pressure during laparoscopic resection of colorectal neoplasms., Methods: 122 patients scheduled for laparoscopic resection of colorectal neoplasms under propofol/remifentanil total intravenous anesthesia with orotracheal intubation were included. Tracheal tube cuff pressure was monitored continuously by calibrated pressure transducers. The ability of several predictors to predict out-of-range tracheal tube cuff pressure at different time points and its correlation factors were assessed., Results: ROC analysis showed that waist-to-hip ratio has the highest AUC for predicting out-of-range tracheal cuff pressure (AUC: 0.86 [95% CI: 0.77-0.95]); Tracheal tube cuff pressure provided by palpation was 41.0 (29.0-53.3) cmH 2 0. Cuff pressure was 33.7 ± 2.9 cmH 2 0 at 15 min and comparable at 30 and 45 min after insufflation, all values were significantly higher than 25 cmH 2 0 (p < 0.001). Multiple linear regression showed tracheal tube cuff pressure was associated with peak airway pressure (p < 0.001)., Conclusions: Patients with normal BMI undergoing laparoscopic resection of colorectal neoplasms require continuous monitoring and timely adjustments of tracheal tube cuff pressure. Compared with BMI, waist-to-hip ratio is a better predictor of out-of-range tracheal tube cuff pressure., Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR2100054089, Date: 08/12/2021., Competing Interests: Declarations Ethics approval and consent to participate The protocol was approved by the Research Ethics Committee of Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University (Ethical Application Reference: 2022DZKY-024-01 Nanjing, China) on 18 March 2022. All methods were performed in accordance with relevant guidelines and regulations and with CONSORT recommendations. Before participation, all the patients and / or their legal guardians provided written informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A critical issue hindering the potential applications of semiconductor mixed-halide perovskites is the phase segregation effect, wherein localized regions enriched with one type of halide anions would be formed upon continuous photogeneration of the excited-state charge carriers. These unexpected phases are capable of remixing again in the dark under the entropic driving force, the process of which is now being exclusively studied after the mixed-halide perovskites have arrived at the final stage of complete phase segregation. Here, we show that after the removal of laser excitation from a solid film of the mixed-halide perovskite nanocrystals (NCs) with partial phase segregation, the iodide- and bromide-rich regions can continuously grow in the dark for a prolonged time period of several minutes. We propose that this dark phase segregation is sustained by the local electric fields from the surface-trapped charge carriers, whose slow dissipation out of the mixed-halide perovskite NCs causes a delayed occurrence of the reversal phase remixing process.

Background: Puerarin (Pue) is an isoflavone compound with significant therapeutic effect on cardiovascular diseases, but its poor water solubility and low oral bioavailability limit clinical application., Methods: In this study, Pue was prepared into PLGA nanoparticles (Pue-PLGA NPs) by emulsion solvent volatilization method. The morphology, particle size, Zeta potential, X-ray diffraction (XRD), and fourier transform infrared (FTIR) of the NPs were characterized. Additionally, their stability and in vitro release were evaluated. SD rats were orally administered wtih Pue and Pue-PLGA NPs, and a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to determine the concentration of blood samples and to investigate the pharmacokinetic behaviour of Pue and Pue-PLGA NPs in rats., Results: The NPs were observed by transmission electron microscopy (TEM) as regular spheroids and uniformly dispersed. The average particle size of the NPs was (167.1±5.26）nm, the Zeta potential was (-29.88±2.46)mV, the encapsulation rate was (83.12 %±4.73 %) and the drug loading capacity was (7.75 %±1.81 %). The results of in vitro release showed that the drug was released slowly and continuously from the NPs, reaching the release platform in 24 h, and the cumulative release amount was (88.55±2.86) %. The pharmacokinetic results showed that the AUC 0-24 , AUC 0-∞ , C max , T max , t 1/2 , MRT 0-24 and MRT 0-∞ of Pue-PLGA NPs were 2.196, 1.978, 1.327, 1.5, 1.385, 3.915 and 3.140 times of Pue, respectively. The relative bioavailability was (197.82±25.28) %., Conclusion: These results indicated that the prepared nanoparticles had small particle size, high encapsulation rate, drug loading capacity and good slow-release effect, and could significantly improve the oral bioavailability of Pue in rats., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study investigated compost quality and gaseous emissions during the algal sludge composting. The experiment explored the feasibility of low initial carbon to nitrogen (C/N) ratio composting by using different volume ratios of algal sludge and spent mushroom substrates (1:1, 1:2, 1:3, and 1:4, corresponding to C/N ratios of 9.5, 12.3, 14.6, 16.0, respectively). The results showed that increasing the proportion of algal sludge in the initial material led to a longer maturation time and higher nitrogen losses but also enhanced the mineralization of organic nitrogen (converted to NH 4 + and NO 3 - ) and reduced carbon losses. The addition of carbon-rich bulking agents within a certain range improved the diversity and interactions of bacterial communities during algal sludge composting. In conclusion, considering the nitrogen and carbon lost, retained, and made available across the four treatments, treatment 3 (C/N = 14.6) appears to be the optimal choice for low C/N composting., 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 Ltd.)

Previous survey studies have consistently shown a strong link between social anxiety and intolerance for uncertainty. However, this association lacks empirical validation from laboratory investigations. To bridge this gap, we conducted a study utilizing the ultimatum game task to assign distinct social connotations (egoistic, altruistic, and uncertain) to three initially neutral faces. Subsequently, we utilized the Approach-Avoidance Task (AAT) paradigm to evaluate participants' approach-avoidance tendencies towards the faces with varying social meanings. Additionally, we collected data on participants' levels of social anxiety and trait anxiety. Our results indicate that both social anxiety and trait anxiety levels impact individuals' avoidance behaviors when faced with socially uncertain cues. This suggests that individuals with higher levels of social anxiety may demonstrate increased sensitivity to uncertainty in social contexts, leading to avoidance behaviors. Crucially, our findings directly underscore the heightened avoidance tendencies of non-clinical individuals with social anxiety towards socially uncertain stimuli, thereby providing new empirical support for research on anxiety disorders related to uncertainty., Competing Interests: Declaration of Competing Interest The corresponding author, on behalf of all authors, declares the absence of any conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Gliomas represent a highly aggressive class of tumors located in the brain. Despite the availability of multiple treatment modalities, the prognosis for patients diagnosed with glioma remains unfavorable. Therefore, further exploration of new biomarkers is crucial to enhance the prognostic assessment of glioma and to investigate more effective treatment options. In this research, we utilized multiple machine learning techniques to assess the significance of genes related to angiogenesis and epithelial-mesenchymal transition (EMT) in the context of prognosis and treatment for glioma patients. The random forest algorithm highlighted the significance of CALU, and further analysis indicated that the effect of CALU on glioma progression may be regulated by MYC. Different machine learning approaches were employed in our investigation to uncover crucial genes associated with angiogenesis and EMT in glioma. Our findings verify the connection between these genes and the prognosis of patients with glioma, as well as the results of immunotherapeutic interventions. Notably, through experimental verification, we identified CALU as a new prognostic marker for glioma, and inhibiting the expression of CALU can impede the progression of glioma., Competing Interests: Declarations Ethics approval and consent to participate N/A. Conflict of interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

The mitochondrial malic enzyme 2 (ME2), which is frequently elevated during carcinogenesis and may be a target for cancer therapy, catalyzes the conversion of malate to pyruvate. The processes controlling ME2 activity, however, remain largely unclear. In this work, we show that human hepatocellular carcinoma (HCC) tissues contain high levels of ME2 and that the methylation of ME2 stimulates the growth and migration of HCC cells. Furthermore, we observed that ME2 interacts with protein arginine methyltransferase 1 (PRMT1) and that ME2 enzymatic activity is activated by mutation of ME2 at lysine 67. Mitochondrial respiration was markedly increased by activated ME2, which promoted cell division and carcinogenesis. Furthermore, a negative prognosis for patients was strongly linked with the expression levels of PRMT1 and ME2 R67K in HCC tissues. These findings imply that hepatocellular carcinoma growth is aided by PRMT1-mediated ME2 methylation, that is an essential signaling event that cancer cells need to continue mitochondrial respiration., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate The study was approved by the Human Research Ethics Committee of Guizhou Medical University. All procedures involving humans were in accordance with the ethical standards of the national responsible committee on human experimentation and with the Helsinki Declaration of 1964 and later versions. Informed consent was obtained from all patients. All animal studies were approved by the Guizhou Medical University Committee on Ethics of Animal Experiments (IRB). All animal experiments complied with the ARRIVE guidelines and were carried out in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments, or the National Research Council’s Guide for the Care and Use of Laboratory Animals. Consent for publication All authors have agreed to publish this manuscript., (© 2024. The Author(s).)

Due to the uncertain differentiation of neural stem cells (NSCs), replenishing lost neurons by endogenous neural differentiation to repair spinal cord injury (SCI) remains challenging. The electrical stimulation-induced drug release is a promising approach for the localized and controlled release of drugs to regulate the differentiation of NSCs into neurons. Here, we developed Zn-PDA@BT nanoparticles acted as Trojan Horse to enter cells through endocytosis for Zn 2+ -controlled release therapy by the potentials generated by the piezoelectric effect. Due to the presence of polydopamine (PDA), under ultrasound stimulation, the electrical signal derived from the piezoelectric effect of barium titanate nanoparticles can be attracted to the surface of Trojan Horse nanoparticles to facilitate the controlled release of Zn 2+ . And Zn 2+ bonded with PDA can increase the intracellular Zn 2+ concentration within mouse-derived NSCs (mNSCs) to regulate the differentiation of mNSCs, which could enhance excitatory neuronal differentiation and inhibit astrocyte differentiation of mNSCs by activating the TGF-β and p53 pathways. More importantly, this Trojan Horse therapy allowed mNSCs to differentiate into mature neurons in 5 days, while the natural differentiation process took 10 days. Moreover, the transplantation of mNSC-ingested Zn-PDA@BT nanoparticles effectively replenished lost neurons at the damaged site and promoted function recovery after SCI in vivo, demonstrating the great potential of electrical stimulation-induced Zn 2+ release for SCI repair.

Purpose: We performed a systematic review and meta-analysis to assess the current evidence on the effectiveness of botulinum toxin A (BTX-A) intradetrusor injections in paediatric NB patients who are resistant to antimuscarinic treatments., Methods: A study was carried out on PubMed, Medline, and Embase with the search terms: ('neurogenic bladder' OR 'myelomeningocele') AND 'toxin' AND ('children' OR 'paediatric'). The PICOS framework guided the search strategy and selection of studies in line with the PRISMA guidelines. Research involving original data that examined BTX-A in paediatric patients with NB was included. Studies were independently chosen and data were extracted by two reviewers., Results: Nineteen studies (one randomized controlled trial, six prospective studies, and 12 retrospective studies) that investigated the clinical application of BTX-A injections in children with NB were identified. None of the studies compared BTX-A to a placebo, and most lacked a control group. Results showed that maximal cystometric capacity increased by an average of 97.7 mL (34.1-162% increase) (95% confidence interval [CI] 59.6 to 135.8), while maximal detrusor pressure decreased by 25.2 cm H 2 O (95% CI -39.7 to -10.7). Bladder compliance improved by 5.3 mL/cm H 2 O (95% CI 2.9 to 7.8). After treatment, the average incontinence resolution rate among patients was 73.4%. Urinary tract infections were reported by 77 patients (13.6%)., Conclusions: BTX-A administered intradetrusorally enhances cystometric capacity, compliance, and maximum neurogenic detrusor overactivity in paediatric patients suffering from neurogenic bladder. Nonetheless, this conclusion lacks support from studies with a high level of evidence., (© 2024 Royal Australasian College of Surgeons.)

Fuxin is located in the atmospheric channel around Bohai Bay, and its geographical location is very special. Few existing studies have investigated the pollution characteristics and health risk assessment of heavy metals in atmospheric PM 2.5 during the four seasons in Fuxin, so a total of 180 PM 2.5 samples were collected from four sampling sites in Fuxin from December 2021 to November 2022. The seasonal distribution characteristics of V, Cr, Mn, Co, Ni, Cu, Zn, Pb, As, Sb, Cd and Ba were analysed via inductively coupled plasma-mass spectrometry (ICP‒MS), and the source of the heavy metals was analysed via the enrichment factor (EF) and principal component analysis (PCA). A health risk model was used to assess the health risk of respiratory exposure in men, women and children in Fuxin. The results revealed that the annual average mass order of heavy metals in Fuxin PM 2.5 was Zn (0.2947 μg·m -3 ) > Pb (0.0664 μg·m -3 ) > As (0.0225 μg·m -3 ) > Ba (0.0205 μg·m -3 ) > Mn (0.0187 μg·m -3 ) > Cu (0.0140 μg·m -3 ) > Cr (0.0095 μg·m -3 ) > V (0.0067 μg·m -3 ) > Ni (0.0061 μg·m -3 ) > Sb (0.0024 μg·m -3 ) > Cd (0.0019 μg·m -3 ) > Co (0.0007 μg·m -3 ). The annual average concentration of As was 3.75 times the GB3095-2012 (China) secondary standard limit, and the concentration of hazard quotient (HQ) in PM 2.5 was lower than 1, but the concentration of incremental lifetime cancer risk (ILCR) in As was higher than the cancer risk threshold (10 -4 ). These findings indicate a certain risk of cancer in the urban population of Fuxin. Therefore, it is necessary to control the emissions created from coal burning to minimize the health risks to the people of Fuxin., Competing Interests: Declarations Conflict of interests The authors have no relevant financial or nonfinancial interests to disclose. Ethics approval No ethical approval is needed. Consent to participate Informed consent was obtained from all individual participants included in the study. Consent to publish Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

The effectiveness of rehabilitation is contingent upon the motor recovery process which typically involves long-term motor skill re-acquisition. Given that the learning process can be modulated by task difficulty, elucidating the underlying neural mechanism is essential for optimizing rehabilitation prescription to suit different patient conditions. This study aimed to investigate the impact of task difficulty on cortical response during force-control training via electroencephalography (EEG). An 8-day visuomotor force-tracking training experiment was conducted. Healthy right-handed participants (N=33) were recruited and randomly assigned to 3 groups, and each group was tasked with a different level of difficulty. The task difficulty was manipulated by variation in force-production complexity and execution sequence assignments, with real-time visual feedback provided to participants for self-output adjustment. Behavioral performance was quantitatively assessed using a pre-defined score metric related to performance accuracy. The EEG signals were collected, and corresponding event-related desynchronization (ERD) and relative functional connectivity (FC) during the task execution were analyzed within the alpha- (8-13Hz) and beta- (15-30Hz) bands. A post-training experiment was also performed to evaluate the near-transfer capability of learning. Results showed all the behavioral performances improved during practice, while higher task difficulty level was affiliated with better post-training near-transfer ability. The dynamic neural response to training could be mediated by changes in difficulty level, where increased task complexity corresponded with the heightened activities in the beta-band priorly within the right dorsolateral prefrontal area. Additionally, stronger alpha-band functional connectivity was observed to be predominantly associated with the left motor area (LMA) during challenging tasks, and the intensification in connectivity persisted selectively post-training which appeared to be acritical factor for skill transfer performance improvement. These findings illustrated the dynamic neural mechanism through which task difficulty affects behavioral performance during long-term motor training with accurate force-control purpose. The selectively strengthened functional connectivity may contribute to facilitating new task execution after training interventions. Therefore, beneficial neural modulation can be expected to be feasible by well-designed task difficulty strategies for effective motor rehabilitation., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

In response to the challenges faced by clinicians treating bone defects caused by various factors, various bone repair materials have been investigated, but the efficiency of bone healing still needs to be improved due to the acting of scaffolds only in a single stage of bone tissue regeneration. We investigated the potential of a novel 3D scaffold to support different stages of bone tissue regeneration, including initial inflammation, proliferation, and remodeling. Eu (0, 0.5, 2, 3.5, 5, and 6.5%) was added to calcium polyphosphate to obtain 3D porous network-doped Eu calcium polyphosphate (EuCPP) scaffolds with ideal mechanical strength and pore size. Both in vitro and in vivo experiments proved that Eu 3+ released from 5% EuCPP scaffolds could significantly promote the migration and proliferation of bone marrow stromal cells which effectively promote angiogenesis; 5% EuCPP could significantly upregulate the ratio of OPG/RANKL in MC3T3-E1 and promote the secretion of osteogenic-related growth factors (ALP and OPN) from MC3T3-E1, indicating the potential of the scaffold to inhibit bone resorption and promote bone formation. In conclusion, 5% EuCPP possesses the biological properties of pro-angiogenesis, anti-inflammation, pro-osteogenesis, and inhibiting bone resorption, which may provide a sustained positive effect throughout the process of bone tissue repair.

A mouthguard electrochemical sensor for salivary glucose detection based on platinum metal hydrogel is proposed in this work. Conventional enzyme-based electrochemical glucose sensors are fraught with issues such as high cost, oxygen dependency, intricate immobilization procedures, and susceptibility to variations in temperature, pH, and so on. The detection of glucose in saliva, as a non-invasive sensing approach, presents a more convenient solution for diabetes monitoring. This study employs Pt metal hydrogel as the electrocatalytic material for glucose, with its microstructure characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. The sensor's electrochemical properties, sensing performance, anti-interference capability, and stability were assessed through methods including cyclic voltammetry (CV), chronoamperometry, and electrochemical impedance spectroscopy (EIS). Under neutral pH phosphate buffer (PB) solution in the laboratory setting, the sensor demonstrated an outstanding linear range (0-40 mM) and a low detection limit (0.119 mM). Implemented in a wearable mouthguard format, this electrochemical sensor enables the detection of glucose in physiological environments, specifically saliva, exhibiting favorable detection characteristics: a linear range of 0.58-3.08 mM and a detection limit of 0.082 mM. This innovation thus offers a practical and efficacious tool for the non-invasive monitoring of glucose levels relevant to diabetes management., 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.)

Coal mines are significant anthropogenic sources of methane emissions, detectable and traceable from high spatial resolution satellites. Nevertheless, estimating local or regional-scale coal mine methane emission intensities based on high-resolution satellite observations remains challenging. In this study, we devise a novel interpolation algorithm based on high-resolution satellite observations (including Gaofen5-01A/02, Ziyuan-1 02D, PRISMA, GHGSat-C1 to C5, EnMAP, and EMIT) and conduct assessments of annual mean coal mine methane emissions in Shanxi Province, China, one of the world's largest coal-producing regions, spanning the period 2019 to 2023 across various scales: point-source, local, and regional. We use high-resolution satellite observations to perform interpolation-based estimations of methane emissions from three typical coal-mining areas. This approach, known as IPLT SO (Interpolation based on Satellite Observations), provides spatially explicit maps of methane emission intensities in these areas, thereby providing a novel local-scale coal mine methane emission inventory derived from high-resolution top-down observations. For regional-scale estimation and mapping, we utilize high-resolution satellite data to complement and substitute facility-level emission inventories for interpolation (IPLT SO+GCMT , Interpolation based on Satellite Observations and Global Coal Mine Tracker). We evaluate our IPLT SO and IPLT SO+GCMT estimation with emission inventories, top-down methane emission estimates from TROPOMI observations, and TROPOMI's methane concentration enhancements. The results suggest a notable right-skewed distribution of methane emission flux rates from coal mine point sources. Our IPLT SO+GCMT estimates the annual average coal mine methane emission in Shanxi Province from 2019 to 2023 at 8.9 ± 0.5 Tg/yr, marginally surpassing top-down inversion results from TROPOMI (8.5 ± 0.6 Tg/yr in 2019 and 8.6 ± 0.6 Tg/yr in 2020). Furthermore, the spatial patterns of methane emission intensity delineated by IPLT SO+GCMT and IPLT SO closely mirror those observed in TROPOMI's methane enhancements. Our comparative assessment underscores the superior performance and substantial potential of the developed interpolation algorithm based on high-resolution satellite observations for multi-scale estimation of coal mine methane emissions., 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 in vitro production of animal-derived foods via cellular agriculture is emerging as a key solution to global food security challenges. Here, the potential for fiber-based scaffolds, including silk and cotton, in the cultivation of muscle cells for tissue formation was pursued. Mechanical properties and cytocompatibility with the mouse myoblast cell line C2C12 and immortalized bovine muscle satellite cells (iBSCs) were assessed, as well as pre-digestion options for the materials due to their resilience within the human digestive track. The fibers supported cell adhesion, proliferation, and guided muscle cell orientation, facilitating myotube formation per differentiation. A progressive increase in biomass was also documented. Interestingly, iBSC proliferation was enhanced with coatings of recombinant proteins while C2C12 cells showed minimal response. Thus, both cotton and silk yarns were suitable as fiber-based scaffolds towards cell supportive goals, suggesting an alternative path toward structured protein-rich foods via this initial stage of textile engineering for food. Biomass prediction models were generated, enabling forecasts of cell growth and maturation across various scaffold conditions and cell types. This capability enhances the precision of the cultivation process towards an engineering approach, building on the inherent benefits of hierarchical muscle tissue structure, but here via textile engineering with these initial muscle-coated edible fibers. Further, the approach offers to reduce costs by optimizing cultivation time and media needs. These approaches are part of a foundation for future scalable and sustainable cultivated meat production. STATEMENT OF SIGNIFICANCE: This research investigates the use of one-dimensional fiber-based scaffolds for cultivated meat production, contributing to advancements in cellular agriculture. It introduces a method to measure changes in biomass and scaffold degradation throughout the cultivation process. Additionally, our development of biomass prediction models improves the precision and predictability of cultivated meat production. This research not only aids in scaling up cultivated meats but also enhances the use of textile engineering techniques in tissue engineering, paving the way for producing complex, three-dimensional meat structures more sustainably., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Rationale: Hormone receptor-positive, HER2-negative advanced breast cancer complicated by pulmonary lymphangitic carcinomatosis (PLC) poses significant therapeutic challenges due to the lack of standardized treatment protocols. Despite various therapeutic interventions and supportive care, prognosis remains dismal., Patient Concerns: Herein, a 48-year-old Chinese woman presented with a persistent cough, unresponsive to anti-infective treatment for 1 month. A computed tomography (CT) scan revealed lymphatic vessel infiltration and a diffuse nodular pattern, suggestive of PLC., Diagnoses: Hormone receptor-positive, HER2-negative advanced breast cancer complicated by PLC., Interventions: The patient was treated with a regimen comprising low-dose apatinib, capecitabine, and albumin-bound paclitaxel., Outcomes: The patient achieved a partial response, with a progression-free survival exceeding beyond ten months. Symptoms of dyspnea and dry cough significantly improved, alongside a notable reduction in lymphangitic carcinomatosis., Lessons: This case highlights the potential antitumor activity of apatinib in breast cancer patients with presenting with PLC. While further studies are necessary, this therapeutic approach could represent a viable option for managing breast cancer in the context of a visceral crisis. The case also emphasizes the importance of individualized treatment strategies and further research to substantiate these promising findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 195 T2DM patients were defined as Control or DPN group. Clinical parameters were compared, and the association between HbA1c (or UACR) and DPN was analyzed. Risk factors for DPN were observed, and the diagnostic values of HbA1c and UACR were assessed., Results: Compared with 104 participants without DPN, 91 individuals with DPN exhibited higher HbA1c and UACR levels. In all patients, increased HbA1c and UACR were identified as risk factors for DPN in individuals with T2DM. Moreover, increased HbA1c was a risk factor for DPN in volunteers without DN, whereas elevated UACR was determined as a risk factor for DPN in participants with DN. The cut-off point for HbA1c (7.65%) in patients without DN had a sensitivity of 86.0% and specificity of 44.6%, while the cut-off point for UACR (196.081 mg/g) in patients with DN had a sensitivity of 52.9% and specificity of 76.2%., Conclusion: Elevated HbA1c and UACR levels are risk factors for DPN and may serve as potential biomarkers for DPN in T2DM patients., (© 2024. The Author(s).)

Background: Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome that predisposes patients to seizures. We aimed to estimate the prevalence, clinical characteristics and outcomes of seizures in NF1 patients, and analyze prognostic factors of seizures., Methods: Systematic searches were conducted in the PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, and grey literature databases from inception to April 2024. We identified observational studies that included NF1 patients with seizures. Clinical characteristics of seizures were summarized and meta-analyses of prevalence and outcomes were conducted. We assessed publication bias using funnel plots and conducted sensitivity analysis to assess stability and reliability. Individual patient data were analyzed to evaluate prognostic factors., Results: Fourteen studies were identified from 1021 records. A total of 337 patients with seizures from 4946 NF1 patients were included. Meta-analysis indicated the overall prevalence of seizures in NF1 patients was 8.1 % (95 % CI= 5.9-10.3 %). The first seizure usually occurs in childhood, with a median age range of 3.5-12.0 years. Focal seizures (54.2 %) and generalized tonic-clonic seizures (16.8 %) were the most common types. The seizure freedom rate was 68.5 % (95 % CI= 57.5-79.5 %), mostly with one or two antiseizure medications. Cortical malformation/hippocampus sclerosis emerged as an independent risk factor for persistent seizures (OR=5.19, 95 %CI=1.27-21.18, P=0.02)., Conclusion: Though NF1 patients face a higher risk of seizures than the general population, the majority achieve seizure freedom. Patients with cortical malformation or hippocampus sclerosis were at a higher risk of persistent seizures., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Using chemical fungicides is the main strategy for controlling potato late blight (PLB), a devastating pre- and postharvest disease caused by Phytophthora infestans , resulting in environmental pollution and health risks. It is of great importance to develop a biofungicide from microorganisms. Through isolating potato rhizosphere microorganisms, CQUSh011 was found to have antioomycete activity with strong inhibition on vegetative growth and virulence of P. infestans . Morphological and molecular identification indicated that CQUSh011 belongs to Streptomyces rapamycinicus . Based on genome, metabolome, and HPLC quantification, rapamycin and salicylic acid were found to be the two active metabolites against P. infestans . Continuous field trials showed that CQUSh011 has sustainable control efficiency against PLB, and the efficiency was better when combined with Infinito, along with an increased endophytic microbial community and biodiversity in potato roots. The results demonstrated the potential of CQUSh011 as a biofungicide against PLB and provided an alternative strategy for reducing the application of chemical fungicides.

Elucidating the intrinsic relationship between disease and mitochondrial viscosity is crucial for early diagnosis. However, current mitochondrial viscosity fluorescent probes are highly dependent on mitochondrial membrane potential (MMP) and are sensitive to other mitochondrial microenvironment parameters. To address these issues, a mitochondria-targeting MMP-independent and viscosity exclusive near-infrared (NIR) fluorescent probe, ACR-DMA, was developed. ACR-DMA consists of thiophene acetonitrile as the skeleton and viscosity-sensitive unit, a pyridinium cation for the mitochondria-targeting group, and a benzyl bromide subunit for mitochondrial immobilization. It is very sensitive to viscosity and shows significant "turn-on" fluorescence behavior at 710 nm with a more than 150-fold fluorescence intensity increase. Furthermore, ACR-DMA can be firmly immobilized in mitochondria and can monitor viscosity changes induced by nystain, monensin, and lipopolysaccharide. Additionally, it was successfully used to visualize mitochondrial viscosity changes resulting from tumors, inflammation, and drug-induced acute kidney injury, revealing the relationship between viscosity and disease both in vitro and in vivo . ACR-DMA is expected to be a promising candidate for diagnosing mitochondrial viscosity-related diseases.

Sulfur dioxide (SO 2 ) is a common environmental pollutant with significant hazards. However, sensors for SO 2 real-time monitoring at room temperature often face problems such as a poor response and sluggish recovery. In this work, a fuel cell-type gas sensor based on nitrogen-doped carbon nanotube (CNT) aerogels loaded with Cu particle electrode material and COF/Nafion composite electrolyte was developed, which exhibited excellent SO 2 sensitivity and fast response/recovery. The aerogel scaffold provided a high specific surface area and high electrical conductivity, and Cu particles provided good catalytic activity to SO 2 . In addition, N doping further enhanced the SO 2 capture capability and conductivity of the electrode material. For electrolyte construction, covalent organic framework (COF) nanosheets were synthesized by a bottom-up approach and blended with Nafion to prepare the COF/Nafion membrane; the composite membrane showed higher proton conductivity. Owing to these advantages, the fuel cell-type sensor exhibited an outstanding response of -3008.5 nA to 50 ppm of SO 2 with a rapid response time (35 s) and recovery time (77 s). Moreover, the rigid nanochannels of COF nanosheets improved the water retention properties of the electrolyte; this will help to simplify the structure of fuel cell-type sensors and provide a significant stimulus for their miniaturization. Based on the great sensing performance, a fuel cell-type SO 2 sensor is integrated into a portable detector and evaluated in the context of dynamic environmental monitoring. The results show that the fuel cell-type sensor with the carefully designed electrode and electrolyte will have great potential in environmental monitoring and safety assurance.

Although phytoremediation is more economical when compared with traditional physical and chemical soil remediation methods, it remains very expensive when considering the substantial area of the contaminated field. If the quantity of harvested residues can be reduced after each phytoremediation cycle, the practicability and commercial implementation of this environment friendly method can be improved. In this study, cadmium excretion on the leaf surface of Festuca arundinacea was evaluated under various blue and red light conditions. The results indicated that the percentage of decaying and deceased leaves increased by 8.5%, 31.1%, 59.7%, and 35.9% at a blue light ratio of 10%, 50%, 75%, and 100%, respectively, when compared with the control. The highest cadmium concentration was found in decaying and deceased leaves under 75% blue light treatment. Light treatments also altered the excreted cadmium amount on different leaf types. Under all treatments including the control, significantly more cadmium can be washed off from emerging and mature leaves than from decaying and deceased leaves, owing to the detoxification mechanism of the plant (p < 0.05). The differences in cadmium excretion on senescent and dead leaves under all treatments were not statistically significant, but the mass of cadmium excretion on young leaves under 75% and 100% blue light irradiation were significantly higher than that under other treatments (p < 0.05). Herein, a novel phytoremediation method involving the harvesting decaying and deceased leaves and washing emerging and mature leaves was proposed to decrease the costs of plant residue disposal., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Cancer is a multifaceted disease influenced by both intrinsic cellular traits and extrinsic factors, with the tumor microenvironment (TME) being crucial for cancer progression. To satisfy their high proliferation and aggressiveness, cancer cells always plunder large amounts of nutrients and release various signals to their surroundings, forming a dynamic TME with special metabolic, immune, microbial and physical characteristics. Due to the neglect of interactions between tumor cells and the TME, traditional cancer therapies often struggle with challenges such as drug resistance, low efficacy, and recurrence. Importantly, the development of gene editing technologies, particularly the CRISPR-Cas system, offers promising new strategies for cancer treatment. Combined with nanomaterial strategies, CRISPR-Cas technology exhibits precision, affordability, and user-friendliness with reduced side effects, which holds great promise for profoundly altering the TME at the genetic level, potentially leading to lasting anticancer outcomes. This review will delve into how CRISPR-Cas can be leveraged to manipulate the TME, examining its potential as a transformative anticancer therapy., (© 2024 Wiley-VCH GmbH.)

Background: Hepatocellular carcinoma (HCC) recurs after liver transplantation (LT) in ~17% of patients. We aimed to retrospectively compare the outcomes of patients treated with different tyrosine kinase inhibitors (TKIs) for recurrent HCC post-LT., Methods: Patients with recurrent HCC post-LT between 2006 and 2019 were included. The impact of sorafenib and lenvatinib treatment for recurrent disease was assessed using survival analysis with an a priori multivariable Cox regression (alpha-fetoprotein [AFP] at recurrence, recurrence lesion diameter, single-site versus multisite metastases)., Results: Seven hundred fifty-four patients underwent LT for HCC, of whom 120 (15.9%) developed recurrence. Of these patients, 56 received TKIs: sorafenib (n = 42) or lenvatinib (n = 14). The median age at LT was 60.8 y (interquartile range, 54.0-66.2); 52 (93%) were men and 26 (46%) were within Milan criteria at listing. Baseline characteristics at recurrence were comparable between the 2 groups, including largest tumor diameter (P = 0.15), receipt of local therapies before TKI (P = 0.33), and single-site recurrence (P = 0.75), and time from interventional treatment to start of TKI (P = 0.44). The AFP at recurrence was higher in the sorafenib group (95.0 versus 3.0 µg/L, P < 0.001). The median overall survival (OS) after initiation of TKI treatment was longer in the lenvatinib group (15.0 mo [95% confidence interval [CI], 11.5-31.5] versus 7.8 mo [95% CI, 4.0-15.4]; P = 0.02) with a 2.3-fold a priori adjusted effect on OS (adjusted hazard ratio 2.32 [95% CI, 1.03-5.20], P = 0.04)., Conclusions: Our findings suggest lenvatinib is a valuable treatment option for patients with HCC recurrence after LT., Competing Interests: S.P. received honoraria for talks from AstraZeneca and Amgen, as well as fees for scientific advisory boards from Taiho and Eisai. A.V. had been directly paid honoraria and has been paid consulting or advisory roles for AstraZeneca, BeiGene, Boehringer Mannheim, BMS, BTG, EISAI, GSK, Incyte, Ipsen, MSD, Hoffmann-La Roche, Servier, Sirtex, and Taiho. R.C.G. disclosed serving as a consultant for Incyte and Tempus and receiving grant/research support from Pfizer. J.J.K. received grants and personal fees from Roche and AstraZeneca and grants from Ibsen and Merck outside the submitted work. G.S. discloses consultancy for AstraZeneca, Roche, Novartis, Integra, and HepaRegeniX; received financial compensation for talks for Roche, AstraZeneca, Chiesi, and Integra; received a grant from Roche; and has research collaborations with AstraZeneca, Natera, Roche, Stryker, and HeparegeniX. G.M.O. received grants from Roche and AstraZeneca; consulting fees from AstraZeneca, Servier, and Incyte; payment for lectures from Roche; and support for attending meetings from MSD and Roche. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic refractory wounds have become a serious threat to human health and are characterized by prolonged inflammation, recurrent bacterial infections, and elevated ROS levels. However, current therapeutic strategies usually target a unilateral healing function and are unable to tackle the complexity and sensitivity of chronic refractory wound healing. This study fabricated a biomimetic nanozyme based on rhein (Cu-rhein NSs), which effectively mimics the activity of superoxide dismutase (SOD) for scavenging various free radicals. Additionally, zinc oxide microspheres (ZnO MSs) were prepared to enhance the antibacterial activity and mechanical properties of the modified hydrogel. Cu-rhein NSs and ZnO MSs were comodified onto an extracellular matrix-mimetic dual-network smart hydrogel constructed from oxidized sodium alginate, gelatin, and borax via dynamic borate and Schiff base bonds. The smart hydrogel presented the good biocompatibility and targeted the unique acidic microenvironment with high oxidative stress of chronic refractory wounds, intelligently releasing bionic nanozymes to effectively eliminate bacteria, reduce inflammatory responses, and scavenge multiple free radicals for reducing ROS. In vivo experiments on the rat model based on diabetic infection showed that the smart hydrogel could effectively eliminate bacteria, promote vascular regeneration and collagen deposition, reduce inflammatory response, and accelerate the healing of diabetic-infected wounds (almost complete healing within 14 days). The advantages of an intelligent, biomimetic tissue regeneration cascade management strategy against diabetic infected wound healing are highlighted.

Timely and accurate on-site detection of ochratoxin A (OTA) is extremely important for global public health. In this study, a fluorescence/colorimetric biosensor based on Ti 3 C 2 nano-materials (Ti 3 C 2 -NMS) and a machine-learning (ML) based fluorescence/colorimetric intelligent learning system for detection of OTA concentration (COTA) were developed. The sensor was fabricated by functionalizing Ti 3 C 2 -NMS prepared by physical-exfoliation assisted metal-ion-induction using ssDNA. The Ti 3 C 2 -NMS exhibited good fluorescence quenching characteristics (FQC) and peroxidase-like activity (PLA). More surprisingly, the functionalization of Ti 3 C 2 -NMS by ssDNA further enhanced the FQC and PLA of the material, which could be used for dual-mode detection of OTA. When different COTA existed, ssDNA competitively bound to OTA, resulting in regular changes in fluorescence and colorimetric signals of the sensor, which realized the accurate and sensitive biosensing detection of OTA in two modalities. Based on a series of fluorescent/colorimetric RGB datasets collected by a self-developed application, a dual-channel ML model had been developed. This model can be integrated into mobile phones, clouds, and PCs to achieve intelligent sensing detection of OTA with the assistance of fully connected artificial neural networks. The method constructed had high specificity, low cost, and fast responsiveness, with a LOD as low as 1.58 pg mL -1 , indicating excellent potential for application and promotion., 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 B.V.)

Richter transformation is still a serious risk in the era of innovative therapies, despite the fact that targeted therapy with Bruton's tyrosine kinase inhibitor has significantly improved the prognosis for chronic lymphocytic leukemia (CLL). We report a rare case of a 61-year-old male patient's CLL transforming into a synchronous clonal related plasmablastic lymphoma (PBL) after receiving ibrutinib. During COVID-19, the patient stopped taking ibrutinib, which caused the illness to worsen. Histology revealed that PBL was present in the right supraclavicular mass and that CLL had penetrated the bone marrow. Three cycles of CHP (cyclophosphamide, doxorubicin, and prednisone) were administered together with venetoclax and brentuximab vedotin. After receiving BCMA CAR-T cell treatment, the patient was in complete remission. For PBL transformation, a condition with a worse prognosis and few therapy choices, our results suggest the use of BCMA CAR-T and novel target agents., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Perovskite solar cells (PSCs) have emerged as a leading photovoltaic technology due to their high efficiency and low cost. Even though they have developed rapidly since their inception, with efficiencies of over 26%, inverted PSCs face challenges such as nonradiative recombination and ion migration. Surface treatment, especially the utilization of organic compounds, has improved efficiency and stability by optimizing the perovskite-charge transport layer interface. Herein, we report a facile and effective strategy by introducing 2,2'-bipyridyl to modify the surface of perovskite, achieving a power conversion efficiency of 24.43% with increasing open-circuit voltage and fill factor and good repeatability on multiple devices. We reveal that the 2,2'-bipyridyl molecule can chelate lead ions on the surface of perovskite, effectively suppressing nonradiative recombination. Furthermore, this modification can induce surficial n-doping to refine the energy level alignment, thereby minimizing charge transport losses. Additionally, the device maintained over 92% of the initial efficiency after 1000 h of operation at the maximum power point under continuous illumination. This surface chelation and defect passivation strategy employing 2,2'-bipyridyl offers a promising avenue for exploring the details of potential long-term degradation mechanisms and the development of commercially viable high-performance p-i-n PSCs.

Solar-driven CO2-to-methanol conversion provides an intriguing route for both solar energy storage and CO2 mitigation. For scalable applications, near-unity methanol selectivity is highly desirable to reduce the energy and cost endowed by low-value byproducts and complex separation processes, but so far has not been achieved. Here we demonstrate a molecule/nanocarbon hybrid catalyst composed of carbon nanotube-supported molecularly dispersed cobalt phthalocyanine (CoPc/CNT), which synergistically integrates high photothermal conversion capability for affording an optimal reaction temperature with homogeneous and intrinsically-efficient active sites, to achieve a catalytic activity of 2.4 mmol gcat-1 h-1 and selectivity of ~99% in direct photothermal CO2 hydrogenation to methanol reaction. Both theoretical calculations and operando characterizations consistently confirm that the unique electronic structure of CoPc and appropriate reaction temperature cooperatively enable a thermodynamic favorable reaction pathway for highly selective methanol production. This work represents an important milestone towards the development of advanced photothermal catalysts for scalable and cost-effective CO2 hydrogenation., (© 2024 Wiley‐VCH GmbH.)

Background: Porcine epidemic diarrhea virus (PEDV) infection and transmission pose a serious threat to the global swine industry. The search for a new host factor with anti-PEDV effect may be an effective potential target for the development of novel antiviral drugs. Interferon-induced transmembrane proteins (IFITMs) play a crucial role in the innate immune response triggered by viral infection, and it has been suggested that IFITMs can block the early stages of viral replication, but the mechanism of action is currently unclear. The current study sheds light on the role of IFITM1 in PEDV infection. Specifically, overexpression of IFITM1 suppresses PEDV proliferation in IPEC-J2 cells, while knockdown of IFITM1 has the opposite effect. Collectively, these findings underscore IFITM1's inhibitory role in PEDV infection, with critical implications for the residues and structural motifs within its CTD., Results: The study demonstrates that IFITM1, an interferon-induced transmembrane protein, plays a critical role in the antiviral response against Porcine Epidemic Diarrhea Virus (PEDV). Notably: Overexpression of IFITM1 suppresses PEDV proliferation.IFITM1 co-localizes with PEDV virions in the cytoplasm surrounding the nucleus.Immunocolloidal gold electron microscopy reveals IFITM proteins embedded on the surface of PEDV virions.IFITM1 directly interacts with the N protein of PEDV.C-terminal domain mutations in IFITM1 compromise its inhibitory function against PEDV, with specific amino acid residues playing a pronounced role.These findings enhance our understanding of innate immunity and antiviral defense mechanisms, with potential implications for therapeutic strategies against PEDV infection., Conclusions: The study establishes IFITM1 as a key player in the antiviral response against PEDV. Its inhibitory function, co-localization with virions, and interaction with the N protein provide valuable insights. Notably, the CTD mutations of IFITM1 have a fundamental impact on its modulatory action. These findings contribute to our understanding of innate immunity and antiviral defense mechanisms, with potential implications for therapeutic strategies against PEDV infection., (© 2024. The Author(s).)

To explore the efficacy of domestic single-hole robotic surgery system in the treatment of pediatric urological diseases. A prospective review of clinical data of children who underwent laparoscopic surgery in the Department of Urology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, was conducted from July to November 2023. All surgeries were performed using the sharp single-port serpentine arm robotic surgery system, with an umbilical access route. All surgeries are performed by the same chief physician. Operative time, intraoperative blood loss, incision size, and postoperative complications were recorded. A total of 12 patients were included, consisting of 8 males and 4 females, aged 8.0-17.0 (13.5±2.7) years. The procedures included 5 pyeloplasties (1 case of bilateral pyeloplasty), with a unilateral operative time [ M ( Q 1 , Q 3 ) ]of 180 (145, 200) minutes and a blood loss of 5 (5, 10) ml. Oral mucosa ureteroplasty was performed in 1 patient, taking 3 hours and 52 minutes with a blood loss of 10 ml. Renal cyst decortication was conducted in 1 case in 85 minutes with a blood loss of 20 ml. High ligation of the spermatic vein was conducted in 3 patients, with an average operative time of 97 minutes and no intraoperative blood loss. Bilateral gonadectomy was completed in 80 minutes with a blood loss of 5 ml. Ovarian cystectomy (1 case) was performed in 69 minutes with a blood loss of 5 ml. All surgeries were successfully completed without conversion to open surgery. Except for the oral mucosa ureteroplasty, which required an additional 5 mm auxiliary port, all procedures were performed through a 3 cm umbilical incision. Among the patients who underwent pyeloplasty, 1 case of urinary leak was identified and successfully treated conservatively with adequate drainage over 25 days. Re-stenosis was experienced by 1 patient with a long segment ureteral stricture postoperatively, while no Clavien-Dindo grade≥2 complications were observed in other patients. All umbilical wounds were concealed, and satisfactory postoperative appearances were noted. The domestic single-hole robotic surgery system is effective in treating pediatric urological diseases.

Alzheimer's disease (AD) is a prevalent and debilitating brain disorder that worsens progressively with age, characterized by cognitive decline and memory impairment. The accumulation of amyloid-beta (Aβ) leading to amyloid plaques and hyperphosphorylation of Tau, resulting in intracellular neurofibrillary tangles (NFTs), are primary pathological features of AD. Despite significant research investment and effort, therapies targeting Aβ and NFTs have proven limited in efficacy for treating or slowing AD progression. Consequently, there is a growing interest in non-invasive therapeutic strategies for AD prevention. Exercise, a low-cost and non-invasive intervention, has demonstrated promising neuroprotective potential in AD prevention. Astrocytes, among the most abundant glial cells in the brain, play essential roles in various physiological processes and are implicated in AD initiation and progression. Exercise delays pathological progression and mitigates cognitive dysfunction in AD by modulating astrocyte morphological and phenotypic changes and fostering crosstalk with other glial cells. This review aims to consolidate the current understanding of how exercise influences astrocyte dynamics in AD, with a focus on elucidating the molecular and cellular mechanisms underlying astrocyte remodeling. The review begins with an overview of the neuropathological changes observed in AD, followed by an examination of astrocyte dysfunction as a feature of the disease. Lastly, the review explores the potential therapeutic implications of exercise-induced astrocyte remodeling in the context of AD., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)