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Objective: We intended to investigate the relationships between visual sensory impairment (VSI) or auditory sensory impairment (ASI) and brain pathological changes associated with cognitive decline in older adults., Methods: We primarily tried to examine whether each sensory impairment is related to Alzheimer's disease (AD) pathology, specifically beta-amyloid (Aβ) deposition, through both cross-sectional and longitudinal approaches in cognitively unimpaired older adults. Self-report questionnaires on vision and hearing status were administered at the baseline. Neuroimaging scans including brain [ 11 C] Pittsburgh Compound B PET and MRI, as well as clinical assessments, were performed at baseline and 2-year follow-up., Results: Cross-sectional analyses showed that the VSI-positive group had significantly higher Aβ deposition than the VSI-negative group, whereas there was no significant association between ASI positivity and Aβ deposition. Longitudinal analyses revealed that VSI positivity at baseline was significantly associated with increased Aβ deposition over 2 years (β = 0.153, p = 0.025), although ASI positivity was not (β = 0.045, p = 0.518). VSI positivity at baseline was also significantly associated with greater atrophic changes in AD-related brain regions over the 2-year follow-up period (β = -0.207, p = 0.005), whereas ASI positivity was not (β = 0.024, p = 0.753). Neither VSI nor ASI positivity was related to cerebrovascular injury, as measured based on the white matter hyperintensity volume., Conclusion: The findings suggest that VSI is probably related to AD-specific pathological changes, which possibly mediate the reported relationship between VSI and cognitive decline. In contrast, ASI appears not associated with AD pathologies but may contribute to cognitive decline via other mechanisms.

This research delves into the Maillard reaction (MR) in high-solid gelatin-saccharide mixtures consisting of 8% and 72% of allulose, fructose, or fructo-oligosaccharides, which were subjected to varied duration (0-60min) of thermal processing prior to gelation. Physicochemical properties of the gels, including color, chemical composition, protein crosslinking, mechanical strength, in-vitro digestibility and antioxidant activities, were characterized. At pH ∼5.5 and intermediate water activities (0.6-0.7), fast browning was observed through sugar degradation and sugar-amine interactions, which were intensified by prolonged heating. The MR reactivity of saccharides followed: AL > FRU > FOS. Characteristic products (MRPs, e.g., α-dicarbonyls, 5-hydroxymethylfurfural, and advanced glycation end products) were identified, with the spectra of MRPs varying significantly between monosaccharides and oligosaccharides. The MR-induced protein glycation and crosslinking exhibited certain negative impacts on the gel strength and in-vitro protein digestibility. Furthermore, all gelatin-saccharide mixtures exhibited augmented antioxidant properties, with the gelatin-AL mixtures displaying the highest free radical scavenging rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ruican Wang reports financial support was provided by National Natural Science Foundation of China. Wenwen Pang reports financial support was provided by Science and Technology Program of Tianjin, China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cnidii Fructus (CF) is a herbal medicine with pharmacological activities such as antitumor, antiviral, antiallergic, antipruritic effects, and so on., Objective: In this study, an ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC- MS/MS) method was prepared and verified to measure the concentrations of seven analytes (bergapten, xanthotoxol, xanthotoxin, imperatorin, osthole, isopimpinellin, isoimperatorin) in HepG2 cells., Methods: The separation of seven analytes was performed on an ACQUITY UPLC® BEH C18 column (2.1×100 mm, 1.7 μm) with a gradient mobile phase system of 0.1% formic acid/water and acetonitrile., Results: The CV of analytes was within 7.77%, and the bias was in the range of -5.43%-3.84%. The matrix effects of analytes ranged from 92.95% to 104.58%, and the extraction recoveries ranged from 76.45% to 104.69%. The relative standard deviation of stability results was less than 8.21%, indicating that seven analytes were stable., Conclusion: The method was successfully applied to the determination of the content of seven analytes of CF extracts by UPLC-MS/MS, and the results will provide a reference for the cellular pharmacokinetics of CF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Intrinsic capacity(IC), self-rated health (SRH), and hand grip strength (HGS) reflect the health status from different aspects. This study aimed to investigate the relationship between IC, SRH, SRH combined with HGS and all-cause mortality among Chinese older adults living in communities., Methods: This study used data from the 2011 (baseline), 2013, 2015, 2018, and 2020 waves of the China Health and Retirement Longitudinal Study (CHARLS). We evaluated IC, SRH, and HGS using questionnaires. We assessed baseline levels of IC, SRH, and SRH combined HGS. Using the COX proportional hazards model, we investigated the associations between baseline IC, SRH, and SRH combined HGS and all-cause mortality. We used receiver operating characteristic curves (ROC) curves to compare the predictive effects of IC, SRH, and SRH combined HGS on all-cause mortality among Chinese older adults living in communities., Results: At baseline (2011), the study included a total of 4095 participants. The multifactorial Cox regression analysis results showed that older adults had a much higher risk of death from any cause compared to those who said they were in good health and had a normal hand grip strength, those who said they were in fair health and had a low hand grip strength [HR = 3.959, 95 % CI (2.892-5.421)], those who said they were in bad health and had a normal hand grip strength [HR = 3.150, 95 % CI (2.392-4.148)], and those who said they were in bad health and had a low hand grip strength [HR = 4.189, 95 % CI (3.123-5.618)]. The study looked at older adults who lived in the community. The area under the ROC curves (AUC) for IC and SRH combined HGS to predict death from any cause was 0.726 [95 % CI (0.708-0.744)] and 0.704 [95 % CI (0.683-0.725)], respectively., Conclusion: Combining SRH and HGS improves older adults' health management by more accurately predicting the risk of all-cause mortality., Competing Interests: Declaration of competing interest 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The hippocampus atrophies with age and is implicated in neurodegenerative disorders including Alzheimer's disease (AD). We examined the interplay between age and apolipoprotein E ( APOE ) genotype on total hippocampal volume., Methods: Using neuroimaging data from 37,463 UK Biobank participants, we applied linear regression to quantify the association of age and APOE with hippocampal volume and identified the age when volumes of ε2/ε3, ε3/ε4, and ε4/ε4 carriers significantly deviated from ε3/ε3 using generalized additive modeling., Results: Total hippocampal volume declined with age, with significant differences by APOE genotype emerging after age 60. ε3/ε4 and ε4/ε4 carriers displayed reduced volumes from ages 69 and 61, respectively, while ε2/ε3 showed delayed decline starting at the age of 76., Discussion: The association of APOE and hippocampal volume is age-dependent, with differences in volumes of ε4/ε4 carriers detected as early as age 61. This work underscores the importance of APOE genotype in determining when to begin screening for AD., Highlights: Apolipoprotein E ( APOE ) genotype shows an age-dependent association with total hippocampal volume.No association between APOE and total hippocampal volume was detected before age 60.Accelerated decline was observed in ε4/ε4 carriers at age 61 and ε3/ε4 at age 69.Delayed decline was evident in ε2/ε3 carriers starting at age 76., Competing Interests: L.J.B. is listed as an inventor on Issued U.S. Patent 8,080,371, “Markers for Addiction,” which covers the use of certain single nucleotide polymorphisms in determining the diagnosis, prognosis, and treatment of addiction. All other authors reported no biomedical financial interests or potential conflicts of interest. Author disclosures are available in the supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Uracil-DNA glycosylase (UDG), an enzyme for repairing uracil-containing DNA damage, is crucial for maintaining genomic stability. Simple and fast quantification of UDG activity is essential for biological assay and clinical diagnosis, since its aberrant level is associated with DNA damage and various diseases. Herein, we developed a fully integrated "sample in-signal out" distance-based paper analytical device (dPAD) for visual quantification of UDG using a flow-controlled uracil-rich DNA hydrogel (URDH). The uracil base sites contained in the DNA hydrogel are mis-incorporated with dUTP by rolling circle amplification (RCA), which simplifies the preparation process of the functionalized hydrogel. In the presence of UDG, the uracil in URDH can be recognized and removed to induce the permeability change of URDH, resulting in the visible distance signal along the paper channel. Using dPAD, as low as 6.4 × 10 -4 U/mL of UDG (within 80 min) is visually identified without any instruments and complicated operations. This integrated dPAD is advantageous for its simplicity, cost effectiveness, and ease of use. We envision that it has the great potential for point-of-care testing (POCT) in DNA damage testing, personalized healthcare assessment, and biomedical applications., 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.)

Objective: In this study, we performed RNA sequencing (RNA-seq) on the abdominal aorta tissue of New Zealand rabbits and investigated the potential association of lncRNA TCONS_02443383 with the development of AS through bioinformatics analysis of the sequencing data. The obtained results were further validated using quantitative real-time polymerase chain reaction (qRT-PCR)., Method: We induced an AS model in New Zealand rabbits by causing balloon injury to the abdominal aorta vascular wall and administering a high-fat diet. We then upregulated the expression level of the lncRNA TCONS_02443383 by injecting lentiviral plasmids through the ear vein. RNA sequencing (RNA-seq) was performed on the abdominal aorta tissues. We conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) analyses., Result: The overexpression of the lncRNA TCONS_02443383 led to an upregulation of peroxisome proliferator-activated receptor (PPAR) signaling pathways as well as genes related to cell adhesion., Conclusion: The overexpression of the lncRNA TCONS_02443383 can inhibit the occurrence and development of AS by upregulating peroxisome proliferator-activated receptor (PPAR) signaling pathways and genes related to cell adhesion., 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 coexistence of pesticides and plastic film residues in agricultural soils poses a significant threat to soil organisms due to their potential long-term contamination and combined toxic effects. Specifically, earthworms are at risk of simultaneously ingesting residual pesticides and microplastics, yet the impact of this combined exposure on their intestinal health and function remains poorly understood. In this study, earthworm (Eisenia fetida) were single and combined exposed to three particle sizes (10 μm, 500 μm, and 2 mm) of polyethylene microplastics (PE MPs) and imidacloprid (IMI) for 28 days, respectively. Our findings underscore that compared to single exposures, the combined exposure inflicted more profound injuries on intestinal tissues and elicited a heightened activation of intestinal digestive enzymes. Furthermore, the combined exposure significantly perturbed the relative abundance of several pivotal metabolic-associated gut microbiota, fostering an enrichment of pathogenic species. Metabolomics analysis showed combined exposure increased differential metabolites, disrupting amino acid, fatty acid, and carbohydrate metabolism in earthworm intestines, potentially hindering nutrient absorption and causing toxic metabolite accumulation. An integrated omics analysis implies that combined exposures have the potential to disrupt the relative abundance of crucial gut microbiota in earthworms, thereby altering their intestinal metabolism and subsequently impacting intestinal health and functionality. Overall, the results reveal that combined exposure of IMI and PE MPs exacerbate the negative effects on earthworm gut health, and this study holds significant implications for the holistic understanding of the combined toxic effects of microplastics and pesticide on soil 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. Published by Elsevier Ltd.)

Rapid and accurate diagnosis of tuberculosis (TB) is of great significance to control the spread of this devastating infectious disease. In this work, a sensitive and low-cost point-of-care testing (POCT) detection platform for TB was developed based on recombinase polymerase amplification (RPA)-catalytic hairpin assembly (CHA)-assisted dual signal amplification strategy. This platform could achieve homogeneous fluorescent and visual diagnosis of TB by using CdTe quantum dots (QDs) signal reporter. In the presence of target DNA (IS1081 gene fragment), RPA amplicons blocked by short oligonucleotide strands could trigger CHA signal amplification, leading to the Ag + releasing from C-Ag + -C structure and the fluorescence quenching of CdTe QDs by the released Ag + . Furthermore, the detection performance of CdTe QDs modified by 3-mercaptopropionic acid (MPA) or thiomalic acid (TMA) (MPA-capped QDs and TMA-capped QDs) was systematically compared. Experimental results demonstrated that TMA-capped QDs exhibited better detection sensitivity due to their stronger interaction with Ag + . The limits of detection (LODs) of fluorescence and visual analysis were as low as 0.13 amol L -1 and 0.33 amol L -1 . This method was successfully applied to the clinical sputum samples from 36 TB patients and 20 healthy individuals, and its quantitative results were highly consistent with those obtained by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). The proposed approach has the advantages of high sensitivity and specificity, simple operation and low cost, and is expected to be applied in clinical TB screening and diagnosis., 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.)

In recent years, the academic community has shown significant interest in per- or polyfluoroalkyl compounds (PFAS) due to their challenging degradation and potential health risks. Photocatalysis has been investigated for PFAS decomposition due to its environmentally friendly nature. In this study, BiOI with abundant iodine vacancies was synthesized through solvothermal and calcination methods (referred to as BiOI 1-x ), and was used for PFAS degradation with a low power UV light source. Compared to pure BiOI, BIOI 1-x showed higher photocatalytic activity towards PFOA (perfluorooctanoic acid). Within 5 h under 5 W LED light irradiation, the degradation rate of PFOA reached 51.9 % with BiOI 1-x calcined at 440 °C (No significant degradation of PFAS was observed with pure BiOI). Capture experiments, electron paramagnetic resonance spectroscopy, and electrochemical experiments revealed that the main active species in the system were photogenerated holes, followed by hydroxyl radicals. Furthermore, the presence of iodine vacancies significantly improved the efficiency of charge carrier separation and enhanced the photocatalytic performance. Finally, a hypothetical degradation pathway for PFOA in this system was suggested. This study achieved efficient degradation of PFAS under low power LED light (5 W), emphasizing its significant practical importance in terms of energy conservation., 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.)

Japanese spotted fever (JSF) is a neglected and potentially fatal infectious disease. Delays in diagnosis and treatment of JSF are important causes of poor prognosis. We report a case of JSF in a 75-year-old farmer who, following autumn field work in Sichuan, China, presented with an atypical triad of clinical symptoms: high fever, petechial rash, and notably no eschar. Without appropriate diagnosis and treatment, she developed septic shock and acute respiratory distress syndrome. The diagnosis of JSF was confirmed by the identification of Rickettsia japonica by metagenomic next-generation sequencing (mNGS) of the blood. After one week of treatment with doxycycline, the patient's clinical symptoms subsided without any complaints of discomfort., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

The rigid solid-solid contact at the interface between the solid electrolyte and electrodes in full-solid-state lithium-ion batteries (ASSBs) presents a considerable challenge to lithium ion transport. To address this, we propose using Li-concentrated succinonitrile (Li-SN45) as an efficient bilateral interface modifier in ASSBs. This material boasts exceptional ionic conductivity of 3.38 mS cm -1 and excellent corrosion resistance to the Li metal anode. The assembled ASSBs using layered cathodes and Li metal demonstrate outstanding discharge capacity (170 mAh g -1 @ 20 mA g -1 ) and superior long-term cycling performance (97% capacity retention after 100 cycles). MALDI-TOF results suggest the formation of a crystalline structure in Li-SN45, which facilitates smooth "anion-free" Li + hopping paths assisted by the oxygen atoms, as revealed by the solved crystal structure. Our findings enriched the understanding of Li transport dynamics in electrolytes of ASSBs, paving the way to designing superior next-generation ASSBs with fast Li transport.

Hematopoietic progenitor kinase 1 (HPK1, MAP4K1), a serine/threonine (SER/THR) kinase, has been identified as a negative immune regulator of T-cell receptor signaling. Deprivation of the HPK1 function suppresses tumor growth, providing an attractive strategy for cancer immunotherapy. Herein, we present a novel PROTAC-based HPK1 degrader compound DD205-291 with high selectivity and potency. DD205-291 showed a dose-dependent inhibition of SLP-76 phosphorylation and an induction of IL-2 and IFN-γ. Compared with other inhibitors, DD205-291 exhibited good efficacy and a favorable safety profile in the MC38 model. Specifically, oral administration of DD205-291 at 0.5 mg/kg in combination with anti-PD1 resulted in significant suppression with a TGI value of 91.0%. Furthermore, DD205-291 exhibited a low risk of cardiotoxicity and a wide safety window. This research effort demonstrates that DD205-291 is a promising preclinical candidate (PCC) for potential mono- and comboimmunotherapy of cancer.

The introduction of three-way catalytic converter (TWC) to meet stringent vehicular NO x emission standards worldwide has led to an unintended consequence of vehicle-derived ammonia (NH 3 ) emission, which might degrade air quality and affect human health, especially in urban areas. The nitrogen stable isotope composition of NH 3 (δ 15 N-NH 3 ) may be a useful tool to trace NH 3 sources, but the isotopic signature of vehicle-emitted NH 3 is lacking. Here we report the δ 15 N-NH 3 measured from tailpipe exhausts collected directly from 19 different vehicles equipped with TWC using "grab" sample technique optimized to avoid isotopic fractionation. We found a large of range of NH 3 concentration (from 1 to 37 ppm, x̄ ± 1σ = 10 ± 8 ppm) and δ 15 N value (from -38.1 ‰ to 49.0 ‰, x̄ ± 1σ = 1.2 ± 20.9 ‰) for our samples (n = 57). Our results indicate a correlation between δ 15 N-NH 3 and NH 3 concentrations (i.e. δ 15 N-NH 3 (‰) = 16.9(± 2.2)In(NH 3 concentration; ppm) - 31.7(± 4.7) (R 2  = 0.53, P < 0.01) that is associated with the catalyst temperature, which is generally agree with the results of theoretical calculation. After consideration of the vehicle emission evolution, dominant driving condition and tunnel δ 15 N-NH 3 variation, a representative δ 15 N-NH 3 value (mean min max ) of vehicle source is identified as 0.8000 -2.2000 5.2000 , which is distinct from (larger than) other NH 3 volatilization-related emission sources. Using our newly measured δ 15 N values and Bayesian mixing model, we approximate the overall contribution of vehicles to ambient NH 3 before, during, and after an international event in Beijing was 14.1 %, 7.9 %, and 21.5 %, respectively, which agree well with the course of traffic restriction. Collectively, our findings demonstrate the importance of using vehicle-emitted δ 15 N-NH 3 to quantify vehicular NH 3 contribution in urban atmospheres., (Copyright © 2024. Published by Elsevier B.V.)

This randomized, prospective, multicenter (12 centers in China) phase III trial (Chinese Clinical Trial Registry #ChiCTR2000041170) compared drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with apatinib and DEB-TACE monotherapy for patients with unresectable hepatocellular carcinoma (uHCC). Progression-free survival (PFS) was the primary endpoint. Overall survival (OS), mRECIST-based objective response rates (ORR) and disease control rates (DCR), and treatment-related adverse events (TRAEs) were secondary endpoints. Totally 243 cases were randomized, with 122 and 121 in the DEB-TACE + apatinib and DEB-TACE groups, respectively. Cases administered DEB-TACE + apatinib displayed markedly improved median PFS (7.1 months [95%CI 6.6-8.3] vs. 5.2 months [95%CI 5.0-5.9]) and OS (23.3 months [95%CI 20.7-29.6] vs. 18.9 months [95%CI 17.9-20.1] compared with those treated with DEB-TACE (both p < 0.001). Additionally, patients administered DEB-TACE + apatinib had elevated ORR (56.6% vs. 38.8%) and DCR (89.3% vs. 80.2%) versus the DEB-TACE group (both p < 0.001). Majority of TRAEs were mild and manageable. Regarding DEB-TACE-related TRAEs, the rates of hepatic artery thinning and spasms were elevated during the second DEB-TACE in cases administered DEB-TACE + apatinib vs. DEB-TACE. The commonest apatinib-related TRAEs in the DEB-TACE + apatinib group included hypertension, hand-foot syndrome, fatigue, and diarrhea. In conclusion, DEB-TACE plus apatinib demonstrates superior PFS versus DEB-TACE monotherapy in uHCC cases, maintaining a favorable safety profile with similar occurrences of AEs., Competing Interests: Competing interests The authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. Ethics The study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (SS-2020-017) and followed the Declaration of Helsinki. Before enrollment, all participants provided informed consent. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2000041170)., (© 2024. The Author(s).)

Background: Hospitalization provides a key opportunity to address tobacco use. Few studies have examined cessation treatment in hospitals in low- and middle-income countries (LMIC). We aimed to measure tobacco abstinence among individuals discharged from a Mumbai hospital after the implementation of cessation counseling compared to abstinence among those discharged pre-implementation., Methods: Pre-post intervention study in the Prince Aly Khan Hospital, Mumbai pre- (11/2015-10/2016) and post-implementation (02/2018-02/2020) of LifeFirst counseling. LifeFirst is multi-session (up to six sessions) counseling extending from hospitalization up to six months post-discharge. Primary analyses compare self-reported 6-month continuous abstinence among hospitalized individuals post-implementation (intervention) with pre-implementation (comparator) using an intent-to-treat approach that includes all participants offered LifeFirst post-implementation in the intervention group. Secondary analyses compare those who received ≥ 1 LifeFirst session with the pre-implementation group., Results: We enrolled n = 437 individuals pre-implementation (8.7% dual use, 57.7% smokeless tobacco, 33.6% smoking) and n = 561 post-implementation (8.6% dual use, 64.3% smokeless tobacco, 27.1% smoking). Post-implementation, 490 patients (87.3%) accepted ≥ 1 counseling session. Continuous abstinence 6-months post-discharge was higher post-implementation (post: 41.6% vs. pre: 20.0%; adjusted odds ratio [aOR]: 2.86, 95% confidence interval [CI] 1.94-4.21). Those who received LifeFirst had higher odds of continuous abstinence compared to pre-implementation (aOR: 2.95, 95% CI 1.98-4.40)., Conclusion: Post-discharge abstinence was more common after implementation of a multi-session tobacco counseling program for hospitalized patients compared to abstinence among patients hospitalized before implementation. These findings represent observational evidence of a promising association between post-discharge abstinence and a hospital-based tobacco cessation program implemented within routine practice in an LMIC setting., Competing Interests: GK has a family financial interest in Dimagi Inc. She was not involved in selection of the data collection platform. GK has received research grants from the National Comprehensive Cancer Network with funding from Astra Zeneca. HG is an employee of the Narotam Sekhsaria Foundation. All other authors declare that they have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2024 Gupte 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.)

Fluorescent unnatural amino acids give biochemists, biophysicists, and bioengineers new ways to probe the properties of proteins and peptides. Here, the synthesis of acridon-2-ylalanine (Acd) is optimized for large-scale production to enable ribosomal incorporation through genetic code expansion (GCE), and fluorenylmethoxycarbonyl (Fmoc)-protected Acd is prepared for solid-phase peptide synthesis (SPPS). We demonstrate the utility of Acd in several applications: first, Acd quenching by Tyr is used in the design of fluorescent protease sensors made by SPPS. Second, we demonstrate Acd incorporation into a lanthanide-binding peptide that is generated either by GCE or by SPPS and demonstrate the utility of Acd for sensitizing the emission of Eu 3+ . Finally, Acd is inserted into the intrinsically disordered protein, α-synuclein, using GCE and used to study ion binding and aggregation.

Quantification is essential in the research and development of polysaccharides. However, achieving simplicity and specificity in polysaccharide quantification remains a challenging task. Enzyme-linked immunosorbent assay (ELISA) based on antibodies provides a straightforward and specific quantification strategy. Nevertheless, acquiring antibodies for polysaccharides is complicated. Carbohydrate-binding modules (CBMs), which can be efficiently obtained, exhibit the capability to specifically recognize and bind carbohydrates. In this study, we verified the feasibility of a CBM-based ELISA for the quantification of hyaluronic acid (HA) by replacing an antibody with a CBM. The CBM-based ELISA, which employed a HA-specific CBM, exhibited a linear detection range spanning from 10 to 100 μg/mL. Both intra-assay and inter-assay coefficients of variation remained below 15 % and recoveries ranged from 96.26 % to 98.22 %, indicating favorable precision and accuracy. The method exhibited specificity exclusively to HA, suggesting its reliance on CBM binding specificity. The effectiveness of the method in analyzing commercial products was confirmed. Additionally, a comparison with the carbazole assay revealed a highly significant correlation (r = 0.994). By integrating CBMs with ELISA, the study presented a novel and easily implementable solution for simple and specific quantification of HA., 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.)

Background: With existing researches identifying an increased rate of long-term conditions (LTCs) among Inflammatory Bowel Disease (IBD) patients, yet there is a lack of exploration into the patterns of comorbidity and prognostic rates for IBD patients with multiple morbidities., Methods: The study included 8,305 participants who self-reported having IBD, comprising ulcerative colitis (UC) and Crohn's disease (CD). Latent class analysis (LCA) was utilized to create optimal categories of LTC combinations for UC and CD patients with additional long-term conditions. Using Cox proportional hazards models, we compared the all-cause mortality rates over a 16-year follow-up among UC and CD patients within different LTC categories, both without LTCs and with the addition of one LTC, the probability of major adverse cardiovascular events (MACE), and the rates of IBD-related surgeries., Results: A total of 5,617 participants reported having two or more LTCs, with the LCA method identifying three prevalence categories among CD patients, and four prevalence categories among UC patients. The highest mortality rate among CD patients was found in category 3: (HR 1.789, 95% CI (1.439-2.224)), and the highest rates of MACE were also in category 3: (HR 11.432, 95% CI (9.332-14.005)), with hypertension being the distinguishing characteristic of this category, and the highest rates of IBD-related surgeries being associated with pain in category 1: (HR 1.217, 95% CI (0.983-1.506)). Among UC patients, the highest mortality rate was in category 3: (HR 2.221, 95% CI (1.837-2.684)), with the highest MACE rates found in category 3: (HR 6.422, 95% CI (5.659-7.288)), and the highest rates of IBD-related surgeries being associated with pain, also in category 3: (HR 1.218, 95% CI (1.041-1.425))., Conclusion: The rates of adverse health outcomes in IBD patients is closely associated with multimorbidity patterns, underscoring the need to fully consider multimorbidity patterns in the assessment, management, and treatment strategies for IBD., Competing Interests: Declarations Ethics approval and consent to participate The UK Biobank received ethical approval from the North West Multi-center Research Ethics Committee, Manchester, U.K. (REC reference for UK Biobank 11/NW/0382), and all participants provided written informed consent. Consent for publication Not Applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Ulcerative colitis (UC), an inflammatory bowel disease, seriously affects people's quality of life. Diet-derived active peptides and Lactobacillus plantarum have shown promise for mitigating symptoms of UC. This investigation explored the combined effects of α-lactalbumin (α-LA) hydrolysate, which boasts a high antioxidant capacity, and L. plantarum 69-2 (L69-2) on a colitis mouse model. The results showed that α-LA hydrolysate with a molecular weight <3 kDa obtained with neutral protease had excellent antioxidant activity and potential to enhance probiotic proliferation. Furthermore, the synergistic application of α-LA hydrolysate and L69-2 could alleviate the adverse impact of colon inflammation by reducing oxidative stress and regulating immune disorders. It maintains the intestinal epithelial barrier, thereby reducing immune system over-activation, promoting the colonization of beneficial bacteria, and regulating intestinal immune responses. Simultaneously, it remodels the structure of the disrupted intestinal flora. The increase in the richness and diversity of the flora leads to the production of beneficial metabolites, which in turn inhibits the activation of the TLR4/NF-κB inflammatory pathway. This study provides a novel perspective on milk-derived peptide synergism with probiotics in alleviating UC.

Addressing the mounting challenge of ammonia nitrogen pollution in aquatic ecosystems necessitates the selective oxidation of ammonia nitrogen to nitrogen gas, a pivotal aspect of eco-friendly nitrogen removal processes. Ultrasound cavitation, renowned for its capacity to generate reactive oxygen species (ROS), has garnered considerable attention in environmental remediation. This study reveals a highly synergistic mechanism in ultrasound coupled stirring (US-ST), establishing optimal coupling conditions through sound field monitoring and quantification of ROS. In comparison to ultrasound treatment alone (US), the sound pressure amplitude significantly increased from ±18 to ±30 kPa in US-ST, markedly reducing the cavitation nucleation threshold and augmenting the steady-state concentration of hydroxyl radicals (HO • ) by 13-fold. Further, with appropriate charge transfer conditions enabled by the acoustoelectric characteristics of the passive film on stirring paddles, the concentrations of superoxide ( • O 2 - ) and singlet oxygen ( 1 O 2 ) elevated to 9.54 × 10 -10 M and 8.43 × 10 -13 M, respectively. Under the regulation of 500 rpm stirring vortex, a maximum sonochemical efficiency of 6.5 × 10 5 mg J -1 was achieved. In the context of domestic wastewater, ammonia nitrogen degradation was achieved through the oxidation and thermal dissociation effects of US-ST. The concentration decreased from 27.5 to 3.4 mg/L after 2 h, with an impressive N 2 selectivity of 96.8%. This study elucidates the targeted conversion mechanism of ammonia nitrogen in US-ST, introducing an emerging water treatment technology propelled by mechanical energy.

The task of image fusion for optical images and SAR images is to integrate valuable information from source images. Recently, owing to powerful generation, diffusion models, e.g., diffusion denoising probabilistic model and score-based diffusion model, are flourished in image processing, and there are some effective attempts in image fusion by scholars' progressive explorations. However, the diffusion models for image fusion suffer from inevitable SAR speckle that seriously shelters from effective information in the same location of optical image. Besides, these methods integrate pixel-level features without information for high-level tasks, e.g., target detection and image classification, which leads fused images are insufficient and their application accuracies are low, for high-level tasks. To tackle these hurdles, we propose the semantic information guided diffusion posterior sampling for image fusion. Firstly, we employ the SAR-BM3D as preprocessing to despeckle. Then, the sampling model is established with fidelity, regularization and semantic information guidance term. The first two terms are obtained by the variational diffusion method via variational inference and first-order stochastic optimization. The last term is served by cross entropy loss between annotation and classification result from FLCNet we design. Finally, the experiments validate the feasibility and superiority of the proposed method on WHU-OPT-SAR dataset and DDHRNet dataset., (© 2024. The Author(s).)

To strengthen the control of pollution sources and promote soil pollution management of agricultural land, this study constructed a comprehensive source apportionment framework, which significantly improved the reliability of potential source analysis compared with the traditional single model. The spatial distribution pattern of agricultural soil heavy metals (SHMs) content in Lintong, a typical river valley city in China, was determined and the degree of contamination was evaluated. A scientific source apportionment methodological framework was constructed through correlation analysis methods together with multiple source apportionment receptor models. Finally, the Monte Carlo simulation method was used to derive the results of the human health risk assessment (HHRA). The results revealed the following: (1) Agricultural soils were moderately and mildly polluted, accounting for 28.8 % and 71.2 % of the total number of sampling points, respectively. (2) The overall correlation of heavy metals (HMs) was strong according to the coupling analysis of the SHMs, in which a strong correlation (0.8-1) was reached among Cu, Ni, Pb, Cr and Zn, indicating that these HMs were most likely homologous or composite. (3) Multimodel analysis of the SHMs sources revealed that the first and second principal components were agricultural (41.36 %) and industrial (19.69 %) sources, respectively, and the remaining principal components were road traffic, natural factors, and atmospheric deposition or surface runoff, respectively. (4) The average comprehensive noncarcinogenic health risk indices for adults and children were 4.2259E-02 and 1.4194E-01, respectively, which were within the slight risk range, indicating that the risk caused by SHMs to the human body can be almost negligible. This study adopted a mixed method to reveal the risk of SHMs pollution and its sources, which provides some reference and technical support for traceability analysis, zoning control, and health risk studies of regional pollutants and is helpful for formulating scientific management measures and targeting control policies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kang Hou reports financial support was provided by Shaanxi Province Department of Science and Technology. Kang Hou reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they 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.)

Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) is a globally devastating pest and has evolved with varying levels of resistance to a broader spectrum of insecticides. CarEs are major enzymes involved in insecticide detoxification and metabolic resistance. Four CarE genes were identified and cloned from H. armigera , and the expression pattern analyses indicated that they were predominantly expressed in the detoxifying tissues and larval feeding periods. The insecticide inductive assays further suggested that these CarE genes with expressions were significantly upregulated after beta -cypermethrin, lambda -cyhalothrin, malathion, and chlorpyrifos exposures. The purified recombinant proteins of both CarE016B and CarE016C by bacterial expression exhibited significantly higher catalytic efficiency toward α-naphthyl acetate and also showed relatively stronger binding with both β-cypermethrin and λ-cyhalothrin compared to the CarE006C and CarE015A. In vitro metabolism assay with HPLC suggests that CarE016B and CarE016C have the ability to metabolize β-cypermethrin, λ-cyhalothrin, and malathion with varying hydrolase activities. GC-MS/MS analysis identified 3-phenoxybenzaldehyde (3-PBAld) as the metabolite of both β-cypermethrin and λ-cyhalothrin. Homology modeling and molecular docking analyses further indicate that these three types of insecticides could be anchored into the active pocket of both CarEs. Collectively, these results demonstrate that both CarE016B and CarE016C play a critical role in the detoxification of pyrethroid and organophosphate insecticides in H. armigera . This study provides the foundations for a comprehensive understanding of the role of the CarEs family in insecticide detoxification and resistance in H. armigera .

Recently, understanding the complex relationship between the mechanical properties and material characteristics of desulfurized rubber asphalt has received significant research attention. In this study, the rheological properties of rubber asphalt prepared by three kinds of desulfurized rubber powder are analyzed, and the mechanical response of rubber asphalt mixture is predicted using various mathematical models. Firstly, the rheological properties of desulfurized rubber asphalt are assessed through multiple stress creep recovery test, linear amplitude scanning test, and low-temperature creep test. The results indicate that the high-temperature performance index of desulfurized rubber asphalt is highly sensitive to the degree of desulfurization. As the degree of desulfurization of the rubber powder increases, the fatigue damage rate of asphalt gradually decreases, leading to an increase in the fatigue life. Notably, the difference between the m-critical temperature and stiffness-critical temperature (ΔTc) for only ML40MA does not exceed the threshold value, indicating that it has the best low-temperature cracking resistance. Additionally, the swelling capacity of desulfurized rubber powder in asphalt is better than that of ordinary rubber powder. Finally, the comprehensive performance of desulfurized rubber asphalt is characterized based on the gray correlation method. The gray correlation coefficient of ML60MA is 0.78, which is higher than that of ML40MA and ML80MA, indicating its best overall performance., (© 2024. The Author(s).)

Objective: To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Design: This population-based cohort study was conducted using a nationwide healthcare claims database (2014-2022) of Korea. We included individuals with MASLD (aged ≥40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimated HRs with 95% CIs., Results: After 1:1 propensity score matching, we included 22 550 patients who initiated SGLT-2i and GLP-1RA (median age=57 years, 60% male), and 191 628 patients who initiated SGLT-2i and TZD (median age=57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.93, 95% CI 0.76 to 1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR 0.77, 95% CI 0.72 to 0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR 0.87 (95% CI 0.80-0.94); female: HR 0.62 (95% CI 0.55-0.69))., Conclusions: In this nationwide cohort study, SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, while demonstrating similar effectiveness to GLP-1RA., Competing Interests: Competing interests: J-YS received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, and pharmaceutical companies, including LG Chem, UCB, SK bioscience and Pfizer, outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Russian wildrye (RWR, Psathyrostachys juncea ) is an outcrossing perennial grass that plays a crucial role in foragaing and rangeland restoration due to its tiller producing capabilities, nevertheless, a genetic map has yet to be constructed due to a shortage of efficient and reliable molecular markers. This also limits the identification, localization, and cloning of economically important traits related to tiller density during breeding., Methods: Therefore, this study aimed to create a F 1 mapping population with 147 individual lines and their two parents, which were selected based on varying tiller densities. We then used this mapping population to conduct specific-locus amplified fragment sequencing (SLAF-seq) to generate SLAF markers and discover single nucleotide polymorphisms (SNPs)., Results: Initially, we generated a total of 1,438.38 million pair-end reads with an average sequencing depth of 84.92 in the maternal line, 79.34 in the parental line, and 27.05 in each F 1 individual line, respectively. Following the filtering of low-depth SLAF tags, a total of 558,344 high-quality SLAFs were identified. A total of 1,519,903 SNP markers were obtained, and 62,424 polymorphic SNPs were discovered. From these, 4,644 polymorphic SNPs were selected and used for the construction of a genetic map encompassing seven linkage groups. The genetic map spanned 1,416.60 cM with an average distance of 0.31 cM between adjacent markers. Comparative analysis between the seven linkage groups of RWR SLAF tag and the whole-genome sequences in barley ( Hordeum vulgare L.) revealed homology values ranging from 17.5% to 34.6%, and the collinearity between the RWR linkage groups and the barley homology groups ranged from 0.6787 to 0.9234, with an average value of 0.8158. Additionally, 143 significant quantitative trait locus (QTLs) with Logarithm of Odds (LOD) value greater than 2.5 for five tiller related traits were detected using three consecutive years of phenotypic trait data from the F1 population, further verifying the map's reliability., Competing Interests: The authors declare that they have no competing interests., (© 2024 Ma et al.)

Spinal cord injury (SCI) is a debilitating condition of the central nervous system (CNS) that leads to severe impairments in sensory and motor functions. Previous studies have pointed out that patient age is a critical factor influencing SCI prognosis. However, the role of microglia in age-related differences in SCI outcomes remains unclear. The current study aims to identify specific microglial subtypes and investigate their responses and functional differences in SCI recovery across different age groups. Single-cell RNA sequencing (scRNA-seq) data were obtained from the Gene Expression Omnibus (GEO) database, integrating multiple datasets to identify microglial subtypes. We performed pseudotime trajectory analysis and cell-cell communication analysis to understand microglial differentiation and interactions. Finally, immunofluorescence staining of mouse model samples was conducted to validate our bioinformatics findings. Microglia were classified into four subtypes: Homeostatic, Proliferating, Inflammatory A, and Inflammatory B. The Young SCI group exhibited a higher proportion of Homeostatic microglia and Inflammatory microglia A, whereas the old SCI group had more Inflammatory Microglia B but lacked Homeostatic Microglia. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that markers for homeostasis microglia were enriched in immune modulation pathways. While makers for Inflammatory Microglia were enriched in immune response pathways. Specifically, markers for Inflammatory microglia B were enriched in pathways associated with overactive immune response. Pseudotime analysis indicated that microglia in young mice predominantly differentiated into Inflammatory Microglia A and Homeostatic Microglia, whereas in old mice, they tended to only differentiate into Inflammatory Microglia B. CellChat analysis showed increased pro-inflammatory signaling generated by Inflammatory Microglia B, exclusively in the old group. Our study demonstrates significant differences in microglial subtypes and functions between different age groups following SCI. These findings provide novel insights into the development of age-related therapeutic strategies and microglia-targeted biological treatments for SCI., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Microfluidic-based nucleic acid testing (NAT) has been proven as an alternative approach for in-situ and rapid NA detection. However, these on-chip methods still require complex peripherals, which contradict the purpose of point-of-care (POC) applications. One of the major challenges is the integration of NA purification and amplification in a miniaturized setup with high mass and heat transfer efficiency. Here, we propose a hand-held in-situ nucleic acid detection device featuring a dual-functional GHz acoustofluidic resonator. The device is designed to utilize GHz acoustic streaming and acoustothermal effects to address both liquid mixing and heating issues, ensuring uniform reaction conditions and consistent thermal management in the microfluidic channel. By replacing traditional magnetic beads with polystyrene beads as matrix for solid-phase microextraction, the redundant washing and elution steps are eliminated, thereby simplifying the NA extraction process. The mixing and heating functions can be seamlessly switched by adjusting the applied power, thereby enhancing NA processing without the need for additional peripherals. The developed hand-held NAT apparatus achieved a detection limit of 10³ copies per milliliter in complex plasma samples within 35 min. Our method simplifies workflows, improves NA retention, and is suitable for processing complex biological samples, making it ideal for POC and in-field testing applications., Competing Interests: Declaration of competing interest The authors declare that there are no competing financial or non-financial interests related to the work described in this manuscript. We confirm that the work presented in this manuscript is original, and no part of it has been published or submitted for publication elsewhere. All authors have contributed to the manuscript and have approved the final version for submission., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Trehalase (Treh) is crucial for ovarian development as it directly regulates the energy supply by hydrolyzing trehalose into glucose. Juvenile hormone (JH) is also essential for ovarian development, but how it affects Treh2 activity remains unclear. This study, which employed Helicoverpa armigera as a model, showed that HaTreh2 transcription and enzymatic activity peaks coincided with the peak of JH titers (the 2 and 3 days after emergence). Compared to the dsGFP control, knockdown of HaTreh2 transcription severely impaired ovarian development. LC-MS/MS and site mutation experiments demonstrated that JH triggered the serine 345 phosphorylation of HaTreh2 via the GPCR-cAMP-PKA pathway, thereby activating its enzymatic activity. Additionally, HaTreh2 is directly bound with trehalose transporter (HaTreT) under JH induction, thus controlling intracellular trehalose and glucose contents as well as the transcription of HaTreT. TreT controls the amount of trehalose, which serves as a substrate for Treh1, entering the cell. Treh2, on the other hand, uses extracellular trehalose as substrate, and the hydrolysis product glucose is further transported into the cell. Here, HaTreh2 regulated the substrate that HaTreh1 can act upon in the cell by directly binding with HaTreT during ovarian development when JH is induced. Therefore, JH systematically regulated trehalose metabolism during ovarian development through regulating the activity of HaTreh2. This study sheds light on the coordinated interplay between JH pathway and sugar metabolism in ovarian development., (© 2024 Royal Entomological Society.)

Lemon yellow (LY) is an azo dye which is widely used as food colorant. The continuous consumption can result in the safety concerns for both human and environmental health. This study describes a new sulphur quantum dot (SQD) based fluorescent sensor, which was facilely prepared with oxidized-glutathione (GSSG) as passivator at mild condition of 75 °C. The obtained sulphur quantum dots (GSSG-SQDs) have a relative quantum yield of 0.25, which is 2-5 times that of most SQDs. GSSG-SQDs were used as a sensor for lemon yellow in the concentration range of 0.10-70 μM and the limit of detection of 60 nM. The application was verified with the real sensing of lemon yellow in the soft drinking and tap water, having the standard recovery from 92.5 % to 105 %. Given the great luminescence and photostability, GSSG-SQDs were used as a filler for the preparation of luminescent films and hydrogels as a promising material for a wide range of applications such as information encryption and bioengineering., 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.)

Objectives: To evaluate evidence of Malassezia overgrowth following successful topical antibacterial monotherapy of refractory canine bacterial otitis using semi-quantitative cultures., Materials and Methods: Twenty-nine dogs with bacterial otitis were treated topically with either fluoro-quinolone [0.5% enrofloxacin (18 dogs, 19 treatment events, 25 ears) or 0.1% marbofloxacin (1 ear), with 0.1% dexamethasone] ("FQ") SID, or 143 mg/mL piperacillin/18 mg/mL tazobactam ("PT") BID (11 dogs, 14 treatment events, 19 ears) for 8 to 36 days (mean 20 days). At visits 1 (V1) and 2 (V2), ear swab tips were washed in PBS + Triton X-100 and serial dilutions spread-plated onto blood, MacConkey (37°C, 48 hours) and modified Dixon's agar (32°C, 14 days) to generate semiquantitative counts. Microbes were identified by phenotype and MALDI-TOF., Results: Prior to treatment, Pseudomonas aeruginosa was isolated alone or in combination with other bacteria in 14 FQ-treated ears and 18 PT-treated ears; the next most frequent bacteria were Streptococcus canis (8 FQ, 2 PT) and Staphylococcus pseudintermedius (8 FQ, 1 PT). The proportions of dogs' ears (excluding cross-over treatments and contra-lateral affected ears) from which bacteria were isolated were significantly reduced by treatment with both FQ (V1, 13/15; V2, 5/15) and PT (V1, 14/14; V2, 2/14). The proportions of dogs' ears from which yeasts (Malassezia pachydermatis, Candida spp.) were isolated were significantly increased by treatment in dogs treated with PT (V1, 1/14; V2, 14/14) but not FQ (V1, 3/15; V2, 6/15)., Clinical Significance: Otitis cases that receive potent antibacterial monotherapy must be monitored for yeast overgrowth., (© 2024 The Author(s). Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Dipeptidyl peptidase 4 (DPP-4) is a promising biomarker for cancer and metabolic diseases. We demonstrate the design of novel fluorescent DPP-4 probes based on the protease's native substrates using a thioamide as a quencher for measuring in vitro kinetics, inhibition with sitagliptin, and DPP-4 activity in saliva samples.

Antibiotic resistance poses a significant public health threat worldwide. The rise in antibiotic resistance and the sharp decline in effective antibiotics necessitate the development of innovative antibacterial agents. Based on the central symmetric structure of glycine-serine-glycine, combined with tryptophan and arginine, we designed a range of antimicrobial peptides (AMPs) that exhibited broad-spectrum antibacterial activity. Notably, AMP W 5 demonstrated a rapid and effective sterilization against methicillin-resistant Staphylococcus aureus (MRSA), displaying both a minimum inhibitory concentration and a minimum bactericidal concentration of 8 µM. Mechanistic studies revealed that AMP W 5 killed bacterial cells by disrupting the cytoplasmic membrane integrity, triggering leakage of cell contents. AMP W 5 also exhibited excellent biocompatibility in both in vitro and in vivo safety evaluations. AMP W 5 treatment significantly reduced skin bacterial load in our murine skin infection model. In conclusion, we designed a novel centrosymmetric AMP representing a promising medical alternative to conventional antibiotics for treating MRSA infections., Importance: Increasing antibiotic resistance and the paucity of effective antibiotics necessitate innovative antibacterial agents. Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing bacterial infections with high incidence and mortality rates, showing increasing resistance to clinical drugs. Antimicrobial peptides (AMPs) exhibit significant potential as alternatives to traditional antibiotics. This study designed a novel series of AMPs, characterized by a glycine-serine-glycine-centered symmetrical structure, and our results indicated that AMP W5 exhibited a rapid and effective bactericidal effect against MRSA. AMP W5 also demonstrated excellent biocompatibility and a bactericidal mechanism that disrupted membrane integrity, leading to leakage of cellular contents. The notable reduction in skin bacterial load observed in mouse models reinforced the clinical applicability of AMP W5. This study provides a promising solution for addressing the increasing threat of antibiotic-resistant bacteria and heralds new prospects for clinical applications., Competing Interests: The authors declare no conflict of interest.

The objective of the study was to ascertain an optimal Helicobacter pylori diagnostic strategy using population-level laboratory data comparing the performance of serology against urea breath test (UBT). H. pylori diagnostic test results for serology and UBT from two laboratories over a 12-year period (2006-20017) were extracted, linked, and analyzed. A subset of this population underwent both methods of testing within days of each other, enabling a direct comparison of the two methods. The average prevalence of H. pylor i positivity was 21.3% by serology and 17.5% by UBT. There were 2,612 individuals who had serology performed first, followed by UBT within 14 days. For this subset, the sensitivity of serology compared with UBT was 96.5% with a specificity of 79.2%. The negative predictive value for serology was 98.4%. Contrary to various recent clinical guidelines, the data show that serology still has utility as a sensitive enough test to be used as an initial H. pylori screening test in a lower prevalence population. Negative serology can be used with confidence to rule out active infection, whereas a positive serology could be followed up with a UBT or a similar performing test such as stool antigen to differentiate active from past infection. For population-based diagnostic recommendations, such a strategy may be ideal since serology generally costs less than UBT and may be combined with a blood draw being done for other diagnostic tests. Continuing to offer serology increases options for patients and may provide economic benefits for single-payer health care systems or health maintenance organizations., Importance: This study compares the performance of serology with urea breath test in the diagnosis of Helicobacter pylori in a population-level data set and mimics a head-to-head direct comparison as the study population had both tests performed within 2 weeks of each other. This provides new information supporting the use of serology in a diagnostic algorithm. There are several instances where serology could be preferable to patients to rule out disease, despite some guidelines suggesting serology should not be used., Competing Interests: The authors declare no conflict of interest.

Metabolic syndrome (MetS) is a cluster of conditions that increase the risk of cardiovascular disease and diabetes. This study aimed to investigate the association between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and MetS in a large, nationally representative US population. We analyzed data from 28,178 participants in the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Logistic regression models were used to evaluate the association between NPAR and MetS. Restricted cubic spline (RCS) models were employed to assess the dose-response relationship. Mediation analyses were conducted to explore potential mediating effects of serum uric acid and triglyceride-glucose (TyG) index. After adjusting for confounders, participants in the highest NPAR quartile had a 14% higher risk of MetS compared to those in the lowest quartile (OR 1.14, 95%CI 1.03-1.27, P = 0.010). RCS models revealed a monotonic increasing trend between NPAR and MetS risk (P for overall association = 0.002). Mediation analyses showed that serum uric acid and TyG index mediated 14.93% and 29.45% of the total effect of NPAR on MetS, respectively. Subgroup analyses indicated that the positive association between NPAR and MetS was more pronounced in Mexican Americans, individuals aged 20-65 years, those with lower income, males, current smokers, and moderate drinkers. Higher NPAR is associated with increased risk of MetS in the US adult population. This association is partially mediated by serum uric acid and TyG index. These findings suggest that NPAR may serve as a novel biomarker for MetS risk assessment and provide insights into potential mechanisms linking inflammation and metabolic disorders., (© 2024. The Author(s).)

This study compared the changes of bacterial necromass carbon (BNC) in composting of three distinct organic wastes [sewage sludge (SW), kitchen waste (KW), and pig manure (PM)] and their relationship with bacterial communities and humus formation. Results revealed that BNC content significantly differed across treatments, with KW exhibiting the highest level at 13 mg/g, followed by PM, where BNC changed between 8 % and 444 % of microbial biomass. Humification index and degree of polymerization indicated that PM had higher humification potential. Network analysis showed that key bacterial phyla contributing to BNC included Firmicutes in KW and Proteobacteria and Gemmatimonadota in SW and PM. Structural equation modeling demonstrated that BNC promoted the formation of humic acid in KW, while core bacteria facilitated the conversion of fulvic acid to humic acid in PM. These findings underscored the crucial role of bacterial necromass in enhancing humification and highlighted the distinct humification processes in 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 Elsevier Ltd. All rights reserved.)

Objective: Androgen insensitivity syndrome (AIS) due to androgen receptor (AR) mutations create a spectrum of clinical presentations based on residual AR function with the mildest impairment creating mild AIS (MAIS) whose undefined molecular mechanism and subtle clinical features leave it little understood and underdiagnosed., Design: in silico modelling and in vitro androgen bioassay of the mutated AR to identify its structural and physiological mechanism. Describing clinical features and responses to high dose testosterone treatment of three cases of MAIS cases across a six-generation family pedigree., Methods: Structural and dynamic in silico molecular modelling and in vitro yeast-based androgen bioassays of the mutant AR. Three cases of MAIS with consistent (gynecomastia, micropenis) and variable (infertility) clinical features across generations and effects of high dose testosterone treatment., Results: The missense AR exon 8 mutation (nucleotide aga > gga, p.R872G arginine to glycine), known to cause increases ligand dissociation rate from mutant AR in binding assays, modelling shows the mutation weakens the closure energy of the "lid" of the ligand binding pocket allowing for easier ligand dissociation from binding site but with unimpaired in vitro androgen bioactivity. High dose testosterone treatment for 3 years in one young man caused increased virilisation and height growth but was ineffective for micropenis. Genetic counselling allowed effective prediction of MAIS risks in progeny for a carrier and non-carrier sisters., Conclusions: The differential diagnosis and clinical management of MAIS is reviewed. The novel molecular mechanism of an AR ligand binding domain mutation in MAIS may be present in other case of MAIS.

Introduction: Danwei communities are a testament to China's socialist urban development, characterized by the self-sufficiency, strong social networks, and institutional management. In the historical context of urban development in China, many old communities have evolved from former housing areas of Danwei. After more than 40 years of use, the buildings, and environments in the old Danwei communities remain in disrepair, dirty, disorderly and poor condition. Many functions have failed that negatively affect the quality of life and health of residents. After Covid-19, improving the mental health of residents has become a major goal of public policies in various countries., Methods: To explore the residents' mental health in the micro-renewal, this study carried out a survey regarding residents' evaluation on the micro-renewal and their mental health in two renewed Danwei communities in Hengyang, China. More than 800 respondents joined the interview, among them, 634 samples are effective for analysis. Entropy-TOPSIS is applied to analyze the weights of various indicators of micro-renewal. And multinominal logit model is used to examine the relationship between the personal factors, satisfaction on various items of micro-renewal and mental health., Results and Discussion: The findings indicates that the mental health level of residents living in Danwei community is affected by micro-renewal. The socio-demographic characteristics and behavior factors can influence on the possibility of being in different levels of mental health. The satisfaction on the components of micro-renewal and improvements after micro-renewal is also determiner of residents' mental health level. In addition, the heterogeneity is address in mental health., 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 Chen, Shi, Wang, Sun, Lin, Chang, Yan, Peng and Feng.)

The gastrointestinal bacterial microbiota is essential for maintaining the health of dairy cows and ensuring their production potential, and it may also help explain the breed-related phenotypic differences. Therefore, investigating the differences in gastrointestinal bacterial microbiota between breeds is critical for deciphering the mechanisms behind these differences and exploring the potential for improving milk production by regulating the gastrointestinal bacterial microbiota. This study holistically examined the differences between rumen and hindgut bacterial microbiota in a large cohort of two breeds of dairy cows, comprising 184 Jersey cows and 165 Holstein cows. Significant distinctions were identified between the rumen and hindgut bacterial microbiota of dairy cows, with these differences being consistent across breeds. A total of 20 breed-differentiated microorganisms, comprising 14 rumen microorganisms and 6 hindgut microorganisms, were screened, which may be the primary drivers of the observed differences in lactation performance between Jersey and Holstein cows. The present study revealed the spatial heterogeneity of the gastrointestinal bacterial microbiota of Jersey and Holstein cows and identified microbial biomarkers of different breeds. These findings enhance our understanding of the differences in the gastrointestinal bacterial microbiota between Jersey and Holstein cows and may provide useful information for optimizing the composition of the intestinal bacterial microbiota of the two breeds of dairy cows.

Mitochondrial dynamics and mitophagy are intimately linked physiological processes that are essential for cardiac homeostasis. Here we show that cardiac Krüppel-like factor 9 (Klf9) is dysregulated in human and rodent cardiomyopathy. Both global and cardiac-specific Klf9-deficient mice displayed hypertrophic cardiomyopathy. Klf9 knockout led to mitochondrial disarray and fragmentation, impairing mitochondrial respiratory function in cardiomyocytes. Furthermore, cardiac Klf9 deficiency inhibited mitophagy, thereby causing accumulation of dysfunctional mitochondria and acceleration of heart failure in response to angiotensin II treatment. In contrast, cardiac-specific Klf9 transgene improved cardiac systolic function. Mechanistically, Klf9 knockout decreased the expression of PGC-1α and its target genes involved in mitochondrial energy metabolism. Moreover, Klf9 controlled the expression of Mfn2, thereby regulating mitochondrial dynamics and mitophagy. Finally, adeno-associated virus-mediated Mfn2 rescue in Klf9-CKO hearts improved cardiac mitochondrial and systolic function. Thus, Klf9 integrates cardiac energy metabolism, mitochondrial dynamics and mitophagy. Modulating Klf9 activity may have therapeutic potential in the treatment of heart failure., Competing Interests: Competing interests All authors declare no competing interests. There are no conflicts of interest in the submission of this manuscript, which was approved by all authors for publication. We also confirm that this work is original. It has not been published elsewhere and is not currently under consideration for publication elsewhere., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The metabolism research of bioactive phenolic acids  widely found in natural products is of great significance for elucidating pharmacologic mechanisms and screening lead compounds. However, it is time-consuming and vulnerable to interference to conduct the traditional metabolism approach by applying organisms or biomaterials. Herein, a bionic technology was established by combining online electrochemistry-mass spectrometry (EC-MS) with offline electrochemistry-liquid chromatography-mass spectrometry (EC-LC-MS) to investigate the oxidative transformation and metabolic processes of the active phenolic acids (including salvianolic acid A, caffeic acid, 3, 5-O-dicaffeoylquinic acid, ferulic acid, salvianic acid A, and protocatechuic acid). Phase I metabolism of the phenolic acids were simulated by applying a three-electrode controlled potential electrochemical reactor with a boron-doped diamond electrode, with glutathione mixed into the oxidative products simultaneously for obtaining the phase II metabolites. Finally, structural characterization of the simulated metabolites of the phenolic acids was achieved successfully, including hydroxylation, methylation, demethylation, decarboxylation, etc. It was revealed that the simulated metabolism process based on an electrochemical system was effective in yielding a wide variety of metabolites for these compounds, which was also compared with the metabolism results applying rat liver microsomes. Consequently, this bionic technology is expected to be a powerful tool to investigate the material basis for the efficacy of active ingredients of natural products., (© 2024 Wiley‐VCH GmbH.)

Study Objectives: Sleep deprivation (SD) is prevalent in our increasingly round-the-clock society. Optimal countermeasures such as ample recovery sleep are often unfeasible, and brief naps, while helpful, do not fully restore cognitive performance following SD. Thus, we propose that targeted interventions, such as repetitive transcranial magnetic stimulation (rTMS), may enhance cognitive performance recovery post-SD., Methods: We recruited 50 participants for two SD experiments. In the first experiment, participants performed a psychomotor vigilance task (PVT) under three conditions: normal sleep (resting wakefulness), after 24 h of SD, and following a subsequent 30-min nap. We analyzed dynamic changes in PVT outcomes and cerebral responses across conditions to identify the optimal stimulation target. Experiment 2 adopted the same protocol except that, after the nap, 10-Hz, sham-controlled, individualized rTMS was administrated. Then, an analysis of variance was conducted to investigate the ability of stimulation to improve the PVT reaction times., Results: Through task-related functional magnetic resonance imaging, we identified cerebral responses within the right middle frontal gyrus (MFG) as the optimal stimulation target. Subsequent application of individualized 10-Hz rTMS over the right MFG attenuated SD-induced deterioration of vigilance., Conclusion: Our findings suggest that combining a brief nap with individualized rTMS can significantly aid the recovery of vigilance following SD. This approach, through modulating neural activity within functional brain networks, is a promising strategy to counteract the cognitive effects of SD., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important RNA virus that has caused huge economic losses to swine industry in the whole world. Ubiquitin specific protease 8 (USP8), a pivotal regulator of protein degradation, intricately contributes to orchestrating the delicate balance of various biological processes through its deubiquitinating activity. However, the role of USP8 in antiviral immune response to PRRSV remains elusive. In the study, by means of overexpressing USP8, we identified that USP8 suppressed the replication of PRRSV, while reducing USP8 expression using siRNA significantly led to the promotion of PRRSV replication. And USP8 facilitates the production of IFN-β and some IFN-stimulated genes (ISGs) during PRRSV infection. Mechanistically, USP8 promoted mitochondrial antiviral signaling protein (MAVS)-mediated IFN-β signaling. Moreover, USP8 interacted with MAVS and exerted anti-PRRSV effects in a MAVS-dependent manner. This study highlights the importance of USP8 in regulating PRRSV replication, which may enhance our comprehension of its role in innate immunity and its impact on viral replication., 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.)

This study examines the factors influencing COVID-19 vaccination intentions among Chinese residents over the age of 60, with a focus on the mediating roles of Health Beliefs and Cues to Vaccination Action in the relationship between vaccine knowledge and vaccination intentions. We conducted a cross-sectional online survey involving 1,305 participants from Southwest China. Multiple logistic regression analysis identified potential determinants of vaccination intention, including socioeconomic characteristics, knowledge, health beliefs, and cues to vaccination action. Furthermore, mediation analysis using the causal mediation analysis method explored the mediating effects within the knowledge-to-intention pathway. Vaccination intention and its related factors: among the 1212 elderly people included in the study, 92.9% expressed willingness to receive the COVID-19 vaccine. Main factors influencing their vaccination willingness included Residency (urban vs. rural, OR = 0.47, p < 0.01), Age (75 + vs. others, OR = 0.41, p < 0.05), Marital status (OR = 0.36, p < 0.01), Occupation ( business/service vs. others, OR = 0.33, p < 0.05), Awareness of vaccine effectiveness (OR = 1.23, p < 0.01), Cues to vaccination action (OR = 1.31, p < 0.01) and COVID-19 related knowledge (OR = 1.06, p < 0.01). The analysis revealed two significant mediators-Health Beliefs and Cues to Vaccination Action. These mediators (p<0.05 for both natural indirect effect and natural direct effect) acted along two key pathways: (1) From Knowledge of COVID-19 to Health Beliefs to Vaccination Intention: Natural Direct Effects (NDE) ranged from 0.012 to 0.016, with Natural Indirect Effects (NIE) from 0.001 to 0.003, indicating that mediators accounted for 4% to 18% of the total effect. (2) From Knowledge of COVID-19 to Cues of Vaccination Action to Vaccination Intention: NDE ranged from 0.012 to 0.016 and NIE from 0.002 to 0.003, with mediators accounting for 9% to 20% of the effect. The intention to vaccinate against COVID-19 among older adults varies significantly based on socioeconomic and health belief factors. The study identifies health beliefs and cues to action not only as direct contributors but also as crucial mediators in the pathway from knowledge to vaccination intention among older individuals. These findings can extend our understanding of the impact of sociodemographic factors and health beliefs on the COVID-19 vaccination willingness among older adults., (© 2024. The Author(s).)

Purpose: To examine the discrepancy in breast density assessments by radiologists, LIBRA software, and AI algorithm and their association with breast cancer risk., Methods: Among 74,610 Korean women aged ≥ 34 years, who underwent screening mammography, density estimates obtained from both LIBRA and the AI algorithm were compared to radiologists using BI-RADS density categories (A-D, designating C and D as dense breasts). The breast cancer risks were compared according to concordant or discordant dense breasts identified by radiologists, LIBRA, and AI. Cox-proportional hazards models were used to determine adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)]., Results: During a median follow-up of 9.9 years, 479 breast cancer cases developed. Compared to the reference non-dense breast group, the aHRs (95% CIs) for breast cancer were 2.37 (1.68-3.36) for radiologist-classified dense breasts, 1.30 (1.05-1.62) for LIBRA, and 2.55 (1.84-3.56) for AI. For different combinations of breast density assessment, aHRs (95% CI) for breast cancer were 2.40 (1.69-3.41) for radiologist-dense/LIBRA-non-dense, 11.99 (1.64-87.62) for radiologist-non-dense/LIBRA-dense, and 2.99 (1.99-4.50) for both dense breasts, compared to concordant non-dense breasts. Similar trends were observed with radiologists/AI classification: the aHRs (95% CI) were 1.79 (1.02-3.12) for radiologist-dense/AI-non-dense, 2.43 (1.24-4.78) for radiologist-non-dense/AI-dense, and 3.23 (2.15-4.86) for both dense breasts., Conclusion: The risk of breast cancer was highest in concordant dense breasts. Discordant dense breast cases also had a significantly higher risk of breast cancer, especially when identified as dense by either AI or LIBRA, but not radiologists, compared to concordant non-dense breast cases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The "shell biorefinery," which valorizes the shell waste chitin into fine chemicals, has developed rapidly in recent years. Herein, we present a novel base-free heteropolyacid-catalyzed oxidation method for the transformation of chitin biomass into organic acid. After a series of optimization experiments, a 5.93 % yield of formic acid and 25.09 % yield of acetic acid were achieved in the presence of 0.5 equivalent of Mo-V-P heteropolyacids (H 4 PMo 11 VO 40 ·2H 2 O) and air at 180 °C under hydrothermal conditions for 4 h. Meanwhile, we have demonstrated that the Keggin-type heteropolyacid catalysts are capable of efficiently converting microcrystalline chitin into organic acids. The synthesized heteropolyacids are well characterized with FT-IR, XRD, ICP-AES, and TGA. The possible reaction pathway was speculated accordingly. This method offers several advantages, including readily available raw materials, simple operation, and relatively higher yield., Competing Interests: Declaration of competing interest Hongjun Zang reports financial support was provided by Tianjin science and technology commission (No. 18JCYBJC87200). Hongjun Zang reports a relationship with Tianjin science and technology commission that includes: funding grants. If there are other authors, they 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/aims: Non-alcoholic fatty liver disease (NAFLD), now the most common chronic liver worldwide, has become a significant public health concern. This study aims to analyze the evolving epidemiology of NAFLD in South Korea., Methods: We utilized claim data from the Korean National Health Insurance Service from 2010 to 2022 to analyze NAFLD's incidence, prevalence, and progression., Results: From 2010 to 2022, the incidence and prevalence rates of NAFLD each increased from 1.87% to 4.47% and from 10.49% to 17.13%, respectively. The differences in prevalence rates between urban and rural areas were minimal in 2012 and 2022, yet both areas showed significant increases in the prevalence of NAFLD over the decade. The NAFLD group had a higher prevalence of comorbidities compared to the control group, and the most common comorbid condition was hypertension. Moreover, the ten-year incidence rates of malignancy, heart disease, and stroke in the NAFLD group were 13.42%, 15.72%, and 8.36%, respectively, which were significantly higher than those in the control group. The incidence rates of cirrhosis and hepatocellular carcinoma in NAFLD over 10 years were 2.22% and 0.77%, respectively. The total medical costs of NAFLD patients more than doubled over ten years and were all significantly higher than those of the control group., Conclusion: A significant increase in NAFLD prevalence and its impact on healthcare utilization was observed in South Korea. With NAFLD leading to serious liver diseases and increased healthcare costs, integrated care strategies that include both medical treatment and lifestyle modifications are essential.