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Rationale: Ethylene oxide (EO) sterilization is commonly employed for the sterilization of medical devices and has a very high market share. However, EO and its metabolite ethylene chlorohydrin (ECH) are toxic to humans. In compliance with the classification and residue limits of medical devices defined by ISO 10993-7, our study established two extraction methods for the testing of EO and ECH., Methods: The first method involves simulated-use extraction using water as the extraction solvent. While the second, exhaustive extraction, directly extracts sample through headspace sampling analysis. Gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode was utilized, requiring only 16 min. Then, the developed method was applied to assess 10 commercially available medical devices sterilized by EO., Results: In simulated-use extraction, calibration curves were evaluated in the range of 1-100 and 5-500 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 85.0% to 95.2% and from 94.8% to 102.4%. In exhaustive extraction, calibration curves spanned 0.5-50 and 2-200 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 101.6% to 102.1% for EO and from 98.1% to 102.2% for ECH. After analysis of the 10 commercially available medical devices, two cotton swabs were found to have ECH of 35.1 and 28.4 μg per device, and four medical devices were found to have EO with concentration below the limit of quantification. Meanwhile, we found that the EO internal standard (propylene oxide) recommended by ISO 10993-7 had interference problems with other similar substances and was not suitable as an internal standard for EO., Conclusions: This study offers a sensitive and straightforward analytical approach to EO and ECH residues in a variety of medical devices. In addition, the results show that the EO or ECH content of these types of medical devices in our study falls below the regulatory limits, therefore instilling confidence among consumers regarding their safe use., (© 2024 John Wiley & Sons Ltd.)

Water is essential to the formation of intracontinental granites, but its origin remains elusive. Here we address this scientific problem by analyzing D/H isotopes of apatites, hydrous minerals in Jurassic and Early Cretaceous granites and basalts from eastern North China Craton, where water was previously interpreted as derived from subducting slab. Results reveal extremely low δD values in pristine Early Cretaceous granitic (-203‰ to -127‰) and basaltic (-197‰ to -107‰) apatites, contrasting with relatively high δD values (-137‰ to -47‰) in Jurassic granites. Given the depth-dependent D/H isotopic fractionation during slab dehydration and high-water contents in coeval primitive mafic magmas, the Early Cretaceous magma water is attributed to the stagnant slab within the mantle transition zone. Secular change in the depth of water aligns with steepening of subducting Paleo-Pacific plate from Jurassic to Early Cretaceous, demonstrating the potential of apatite H isotopes in tracing water origin in granites and basalts., (© 2024. The Author(s).)

Background: Reducing exposure to risk factors and screening represent 2 major approaches to gastric cancer (GC) prevention, but public knowledge GC risk factors and screening behaviour remain unknown. We aimed to investigate public awareness of GC risk factors, adherence to screening, and barriers hindering screening practices in China., Methods: This community-based household survey was conducted within Shijiazhuang, China, and 1490 residents were recruited through a multistage stratified cluster random sampling approach. A self-administered questionnaire was completed which consisted of three sections: demographics, awareness of GC risk factors, and personal screening behaviours. Factors associated with knowledge of risk factors and screening behaviours were evaluated using binary logistic regression analysis., Results: The mean risk factor awareness score of 12 (7, 15) revealed insufficient knowledge in 51.1% of participants. Dietary lifestyle factors were better understood than physical activity and weight-related factors. Marital status (OR 1.967; 95% CI 1.415 to 2.734), higher income (OR 1.197; 95% CI 1.010 to 1.418), and a history of upper gastrointestinal problems (OR 0.048; 95% CI 1.002 to 1.311) were associated with higher awareness. Merely 21.5% underwent GC screening, with higher rates linked to older age (OR 1.642; 95% CI 1.418 to 1.902), higher education (OR 1.398; 95% CI 1.176 to 1.662), a history of upper gastrointestinal problems (OR 3.842; 95% CI 2.833 to 5.209), and moderate (OR 2.077; 95% CI 1.352 to 3.191) and high (OR 2.529; 95% CI 1.311 to 4.878) perceived GC risk. Notably, participants commonly refused gastroscopy due to the absence of symptoms or signs., Conclusions: In Shijiazhuang, more than half of participants demonstrated inadequate knowledge of GC risk factors, and screening participation rates were remarkably low. This emphasizes the need for targeted interventions to enhance GC awareness and significantly improve screening rates., Competing Interests: The authors have declared that no competing interest exsist., (Copyright: © 2024 Wang 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.)

Meat quality (MQ) is unstable during cold chain logistics (CCL). Different technologies have been developed to enhance MQ during the CCL process, while most of them cannot cover all the links of the cold chain because of complex environment (especially transportation and distribution), compatibility issues, and their single effect. Electric fields (EFs) have been explored as a novel treatment for different food processing. The effects and potential advantages of EFs for biological cryopreservation have been reported in many publications and some commercial applications in CCL have been realized. However, there is still a lack of a systematic review on the effects of EFs on their quality attributes in meat and its applications in CCL. In this review, the potential mechanisms of EFs on meat physicochemical properties (heat and mass transfer and ice formation and melting) and MQ attributes during different CCL links (freezing, thawing, and refrigeration processes) were summarized. The current applications and limitations of EFs for cryopreserving meat were also discussed. Although high intensity EFs have some detrimental effects on the quality attributes in meat due to electroporation and electro-breakdown effect, EFs present good applicability opportunities in most CCL scenes that have been realized in some commercial applications. Future studies should focus on the biochemical reactions of meat to the different EFs parameters, and break the limitations on equipment, so as to make EFs techniques closer to usability in the production environment and realize cost-effective large-scale application of EFs on CCL., 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.)

Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors., (© 2024. The Author(s).)

Rationale: This article reports a case of coronavirus disease (COVID-19)-associated autoimmune encephalitis (AE) and reviews the relevant literature to investigate the clinical manifestations, auxiliary inspection, diagnosis and treatment, and prognosis of AE associated with COVID-19., Patient Concerns: A 68-year-old female with fatigue developed altered consciousness after 2 days of fever, thereafter testing positive for COVID-19. The protein levels in the lumbar puncture cerebrospinal fluid were elevated, and cranial magnetic resonance imaging (MRI) scan indicated T2-weighted hyperintensity in the temporal lobe., Diagnoses: The patient was diagnosed with COVID-19-associated AE., Interventions: After admission, the patient received pulse steroid therapy with methylprednisolone. Additionally, gastric protection, blood glucose control, nutritional support, and other treatments were administered., Outcomes: The symptoms were significantly relieved by steroid pulse therapy. At the 3-month follow-up, the patient had recovered completely without any obvious discomfort., Lessons: The possibility of AE should be considered if neurological symptoms occur a few days after infection with COVID-19, with early diagnosis and immediate steroid pulse therapy resulting in better outcomes., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

PERK/CHOP pathway-mediated excessive endoplasmic reticulum (ER) stress is closely linked to aging-related cognitive impairment (ARCD). Zerumbone (ZB), a naturally occurring sesquiterpene molecule obtained from dietary bitter ginger, has garnered significant interest due to its diverse range of biological properties. It is unclear, though, if ZB can reduce ARCD by preventing ER stress that is dependent on the PERK/CHOP pathway. Here, the PERK-CHOP ER stress pathway was the main focus of an evaluation of the effects and mechanisms of ZB for attenuating ARCD in D-galactose (D-gal)-induced aging mice and SH-SY5Y cells. According to our findings, ZB not only greatly decreased neuronal impairment both in vitro and in vivo , but also significantly alleviated learning and memory failure in vivo . ZB significantly reduced the activation of the PERK/CHOP pathway and neuronal apoptosis in vitro and in vivo , exhibiting the down-regulation of GRP78, p-PREK/PERK, and CHOP expression levels, in addition to suppressing oxidative damage (MDA drop and SOD rise). Comparable outcomes were noted in SH-SY5Y cells subjected to severe ER stress caused by TM. On the other hand, 4-PBA, an ER stress inhibitor, considerably reversed these modifications. Remarkably, CCT020312 (a PERK activator) dramatically overrode the inhibitory effects of ZB on the PERK/CHOP pathway and neuronal death in D-gal-induced SH-SY5Y cells. In contrast, GSK2606414 (a PERK inhibitor) significantly increased these effects of ZB. In summary, our results suggested that ZB prevented D-gal-induced cognitive deficits by blocking the PERK/CHOP-dependent ER stress pathway and apoptosis, suggesting that ZB might be a natural sesquiterpene molecule that relieves ARCD.

To explore the changes in water status and protein characteristics of Tibetan pork (TP) under modified atmosphere packaging (MAP) with different oxygen concentrations compared to Duroc×Landrace×Yorkshire pork (DLY), the water holding capacity (WHC), water distribution, protein oxidation, and conformation of both types were determined. Results indicate that under MAP, TP pork and DLY pork exhibited higher water retention and lower protein oxidation compared to air packaging. However, with increased oxygen concentration in the MAP, protein oxidation intensified, leading to reduced WHC in the pork. Compared to DLY pork, TP pork in different packaging conditions maintained the integrity of protein secondary and tertiary structures, reducing protein cross-linking aggregation. The lower content of P 3 in the two-dimensional relaxation spectra, shorter T 1 and T 2 relaxation times, and higher proton density suggest better water retention properties in Tibetan pork. These findings support the development of long-distance preservation and transportation technologies for TP pork., Competing Interests: 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., (© 2024 The Authors.)

Krüppel-like factors (KLFs) are a family of basic transcription factors with three conserved Cys2/His2 zinc finger domains located in their C-terminal regions. It is acknowledged that KLFs exert complicated effects on cell proliferation, differentiation, survival, and responses to stimuli. Dysregulation of KLFs is associated with a range of diseases including cardiovascular disorders, metabolic diseases, autoimmune conditions, cancer, and neurodegenerative diseases. Their multidimensional roles in modulating critical pathways underscore the significance in both physiological and pathological contexts. Recent research also emphasizes their crucial involvement and complex interplay in the skeletal system. Despite the substantial progress in understanding KLFs and their roles in various cellular processes, several research gaps remain. Here, we elucidated the multifaceted capabilities of KLFs on body health and diseases via various compliable signaling pathways. The associations between KLFs and cellular energy metabolism and epigenetic modification during bone reconstruction have also been summarized. This review helps us better understand the coupling effects and their pivotal functions in multiple systems and detailed mechanisms of bone remodeling and develop potential therapeutic strategies for the clinical treatment of pathological diseases by targeting the KLF family., Competing Interests: 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., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Background: Poor glucose control might deteriorate the impaired pulmonary function, which can ultimately lead to mortality. However, few studies have examined the effect modification of glucose control on the association between pulmonary function and mortality. This study aimed to examine the association of pulmonary function with mortality and determine the effect modification of glycemic level on the association of pulmonary function with mortality in persons with type 2 diabetes (T2DM)., Methods: A retrospective cohort study included 3846 persons with T2DM with pulmonary function testing in Taiwan during 2002-2020. Expiratory volume in 1 s (FEV1) was measured as pulmonary function. Cox proportional hazards models were used and the effect modification of pulmonary function parameters and glucose control was assessed by their product terms., Results: There were 733 deaths during an average follow-up of 7.83 years. Significant associations of FEV1 and mortality were found (hazards ratio [HR] for FEV1 Z-scores of <0 to -1, <-1 to -2 and <-2: 1.47 [1.20, 1.80], 2.48 [1.95, 3.14] and 3.07 [1.74, 5.44] compared with participants with Z-score ≥0, respectively. All p for trend<0.001). Significant effect modifications were found and the association between FEV1 and mortality was stronger in persons with good glycemic control compared with poor glycemic control (FEV1-FPG effect modification, P = 0.01; FEV1-HbA1c effect modification, P = 0.03)., Conclusion: Pulmonary function, measured by FEV1, is significantly associated with mortality in persons with T2DM. Significant effect modification of glucose control on the association between pulmonary function parameters and mortality was found., 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.)

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) gene editing has attracted extensive attentions in various fields, however, its clinical application is hindered by the lack of effective and safe delivery system. Herein, we reported a cationic micelle nanoparticle composed of cholesterol-modified branched small molecular PEI (PEI-CHO) and biodegradable PEG-b-polycarbonate block copolymer (PEG-PC), denoted as PEG-PC/PEI-CHO/pCas9, for the CRISPR/Cas9 delivery to realize genomic editing in cancer. Specifically, PEI-CHO condensed pCas9 into nanocomplexes, which were further encapsulated into PEG-PC nanoparticles (PEG-PC/PEI-CHO/pCas9). PEG-PC/PEI-CHO/pCas9 had a PEG shell, protecting DNA from degradation by nucleases. Enhanced cellular uptake of PEG-PC/PEI-CHO/pCas9 nanoparticles was observed as compared to that mediated by Lipo2k/pCas9 nanoparticles, thus leading to significantly elevated transfection efficiency after escaping from endosomes via the proton sponge effect of PEI. In addition, the presence of PEG shell greatly improved biocompatibility, and significantly enhanced the in vivo tumor retention of pCas9 compared to PEI-CHO/pCas9. Notably, apparent downregulation of GFP expression could be achieved both in vitro and in vivo by using PEG-PC/PEI-CHO/pCas9-sgGFP nanoparticles. Furthermore, PEG-PC/PEI-CHO/pCas9-sgMcl1 induced effective apoptosis and tumor suppression in a HeLa tumor xenograft mouse model by downregulating Mcl1 expression. This work may provide an alternative paradigm for the efficient and safe genome editing in cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Dementia poses a growing global mental health impact, with variations in prevalence by gender, possibly influenced by reproductive factors. Ectopic pregnancy (EP), known for its association with cardiovascular diseases and depression, which are also predictors of dementia, prompted an exploration of their interplay., Methods: Using Taiwan's National Health Insurance Research Database, this nationwide cohort study examined 53,096 individuals to investigate the link between EP and dementia. Covariates included age, insured premiums, comorbidity by Charlson Comorbidity Index revised by excluding dementia, level of care, and residence. Surgical approaches, number of EP episodes, and dementia subtypes were considered in outcomes analysis using Cox regression., Results: Among 13,274 women diagnosed with EP, 791 developed dementia over a 15-year follow-up, particularly vascular dementia. Adjusting for the covariates, the adjusted sub-distribution Hazard Ratio (asHR) with competing risks was 1.644 (95% CI, 1.394-2.053; p < 0.001). For patients with more than one episode, it was even higher (asHR=1.670 [95% CI, 1.419-2.092; p < 0.001]). Post-ectopic depression, prevalent in 62.2% within four weeks, was associated with a greater dementia risk compared to those without (asHR=1.702 [95% CI, 1.444-2.125; p<0.001] vs. asHR=1.551 [95%CI, 1.310-1.937; p<0.001]). Antidepressant treatments showed a partial protective effect, reducing the increased risk by 14.7%., Conclusion: An EP history is linked to an earlier onset and a higher risk of overall dementia, VaD in particular, in a dose dependent manner, regardless of surgical intervention and stroke. Post-ectopic depression exacerbates dementia risk, while antidepressants offer partial protection. These findings underscore the potential benefit of screening and treating depression in women following EPs., 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 Yao, Chung, Chien, Li, Lee, Huang, Yang and Tzeng.)

Purpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS)., Patients and Methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect., Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL., Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chen et al.)

Objectives: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD)., Methods: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes., Results: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay ( P <0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group ( P >0.05)., Conclusions: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

Aims: To explore the effectiveness of continuous home wound care on patients with diabetic foot ulcers (DFUs)., Design: A non-randomized parallel controlled non-inferiority trial., Methods: Patients with Wagner grade I-III DFUs hospitalized in two distant campuses of the same hospital were included. All patients received infection treatment and wound bed preparation during hospitalization; after discharge, patients in one of the campuses received routine outpatient wound care, and those treated in the other received continuous home wound care. The per-protocol analysis was performed to compare ulcer healing indicators, knowledge, health belief, self-management behaviour and medical expenses of the two groups., Results: Between October 2021 and December 2022, 116 patients were enrolled in the study; 107 completed. The home care was not inferior in terms of ulcer healing rate and demonstrated significant enhancements in the understanding of warning signs, health belief and self-management behaviour. Additionally, the home care saved 220.38 yuan (24.32 UK pounds) in direct medical expenses for each additional one square centimetre of ulcer healing., Conclusion: The continuous home wound care enhanced self-management behaviour of the patients and saved their medical expenses while not compromising ulcer healing., Impact: This is to date the first study to conduct continuous home wound care practice for patients with DFUs and confirmed its safety and non-inferiority in ulcer healing, and supported its superiority in improving self-management behaviour and saving medical expenses., Reporting Method: We have adhered to the transparent reporting of evaluations with nonrandomized designs statements and the corresponding checklist was followed., Patient or Public Contribution: The patients and their primary caregivers were involved in intervention design, we received input from them about the factors that facilitate and hinder patient self-management behaviours to develop intervention strategies., (© 2023 John Wiley & Sons Ltd.)

Purpose: This study aimed to investigate the in vitro tolerance to decentration of biaspheric intraocular lens (IOLs) with refractive phase-ring extended depth-of-focus (EDOF) and diffractive trifocal designs., Methods: This experimental study was carried out at the Department of Optics and Optometry and Vision Science, University of Valencia, Spain. The modulation transfer function (MTF) of the ETLIO130C EDOF and the TFLIO130C trifocal IOLs (AST Products Inc., Billerica, MA, USA) were determined at different levels of decentration for a given wavelength and pupil diameter using the PMTF optical bench (Lambda-X Ophthalmics, Nivelles, Belgium). The modulation transfer function (MTF) curves, the through-focus MTF curves, and the Strehl ratios were measured at 3-mm pupil aperture for 0.25-, 0.50- and 0.75-mm decentration., Results: The optical design of the trifocal TFLIO130C IOL is robust to small decentrations, with virtually no change in MTF response for 0.25 mm decentration. For greater decentration levels, the MTF response is slightly reduced with increasing decentration. The ETLIO130C EDOF design is robust to decentration, as the MTF response is only minimally affected when increasing the decentration up to 0.75 mm., Conclusions: MTF responses are slightly reduced with greater levels of decentration, but the range of focus provided by both trifocal and EDOF designs are preserved. The effects for average levels of decentration reported in the literature are minimum for both IOL designs., (© 2024. The Author(s).)

In order to explore the application prospects of static magnetic field (SMF) combined with supercooling in meat preservation, this study proposed a novel method of supercooling assisted by a stationary magnetic field (SMF + supercooling) for the preservation of chilled pork, evaluating its cooling rate and quality changes (e.g., water holding capacity, color, pH, and TVB-N), as well as the evolution trend of the microbiota. The results showed that SMF + supercooling significantly (P < 0.05) improved the cooling rate of pork. Compared to chilling and supercooling, SMF + supercooling significantly delayed the increase of TVB-N and TVC on the 12th day of storage (P < 0.05). SMF + supercooling treatment achieves the maintenance of pork water-holding capacity by inhibiting water migration, reducing drip loss, cooking loss, and centrifugal loss of pork. The 16S rDNA bacteria flora analysis demonstrated that SMF + supercooling treatment reduced the relative abundance of spoilage bacteria such as Acinetobacter, Streptococcus, and Pseudomonas, delaying the deterioration of pork quality caused by microbial growth. The SMF + supercooling treatment can be considered a novel refrigeration preservation method that delays the deterioration of pork quality and extends its shelf life., 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.)

With the continuous advancement of wearable technology and advanced medical monitoring, there is an increasing demand for electronic devices that can adapt to complex environments and have high perceptual sensitivity. Here, a novel artificial injury perception device based on an Ag/HfO x /ITO/PET flexible memristor is designed to address the limitations of current technologies in multimodal perception and environmental adaptability. The memristor exhibits excellent resistive switching (RS) performance and mechanical flexibility under different bending angles (BAs), temperatures, humid environment, and repetitive folding conditions. Further, the device demonstrates the multimodal perception and conversion capabilities toward voltage, mechanical, and thermal stimuli through current response tests under different conditions, enabling not only the simulation of artificial injury perception but also holds promise for monitoring and controlling the movement of robotic arms. Moreover, the logical operation capability of the memristor-based reconfigurable logic (MRL) gates is also demonstrated, proving the device has great potential applications with sensing, storage, and memory functions. Overall, this study not only provides a direction for the development of the next-generation flexible multimodal sensors, but also has significant implications for technological advancements in many fields such as robotic arms, electronic skin (e-skin), and medical monitoring., (© 2024 Wiley‐VCH GmbH.)

Background: The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks., Methods: We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019-2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI)., Results: Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97-3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09-2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees., Conclusions: Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications., (© 2024. The Author(s).)

Background: The main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis., Methods: A total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves., Results: Cardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96-16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds., Conclusions: In patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis., (© 2024. The Author(s).)

Background: Multidrug resistance (MDR) limits successful cancer chemotherapy. P-glycoprotein (P-gp), BCRP and MRP1 are the key triggers of MDR. Unfortunately, no MDR modulator was approved by FDA to date. Here, we will investigate the effect of BI-2865, a pan-KRAS inhibitor, on reversing MDR induced by P-gp, BCRP and MRP1 in vitro and in vivo, and its reversal mechanisms will be explored., Methods: The cytotoxicity of BI-2865 and its MDR removal effect in vitro were tested by MTT assays, and the corresponding reversal function in vivo was assessed through the P-gp mediated KBv200 xenografts in mice. BI-2865 induced alterations of drug discharge and reservation in cells were estimated by experiments of Flow cytometry with fluorescent doxorubicin, and the chemo-drug accumulation in xenografts' tumor were analyzed through LC-MS. Mechanisms of BI-2865 inhibiting P-gp substrate's efflux were analyzed through the vanadate-sensitive ATPase assay, [ 125 I]-IAAP-photolabeling assay and computer molecular docking. The effects of BI-2865 on P-gp expression and KRAS-downstream signaling were detected via Western blotting, Flow cytometry and/or qRT-PCR. Subcellular localization of P-gp was visualized by Immunofluorescence., Results: We found BI-2865 notably fortified response of P-gp-driven MDR cancer cells to the administration of chemo-drugs including paclitaxel, vincristine and doxorubicin, while such an effect was not observed in their parental sensitive cells and BCRP or MRP1-driven MDR cells. Importantly, the mice vivo combination study has verified that BI-2865 effectively improved the anti-tumor action of paclitaxel without toxic injury. In mechanism, BI-2865 prompted doxorubicin accumulating in carcinoma cells by directly blocking the efflux function of P-gp, which more specifically, was achieved by BI-2865 competitively binding to the drug-binding sites of P-gp. What's more, at the effective MDR reversal concentrations, BI-2865 neither varied the expression and location of P-gp nor reduced its downstream AKT or ERK1/2 signaling activity., Conclusions: This study uncovered a new application of BI-2865 as a MDR modulator, which might be used to effectively, safely and specifically improve chemotherapeutic efficacy in the clinical P-gp mediated MDR refractory cancers., (© 2024. The Author(s).)

Nanoagrochemicals present promising solutions for augmenting conventional agriculture, while insufficient utilization of nanobiointerfacial interactions hinders their field application. This work investigates the multiscale physiochemical interactions between nanoagrochemicals and rice ( Oryza sativa L.) leaves and devises a strategy for elevating targeting efficiency of nanoagrochemicals and stress resilience of rice. We identified multiple deposition behaviors of nanoagrochemicals on hierarchically structured leaves and demonstrated the crucial role of leaf microarchitectures. A transition from the Cassie-Baxter to the Wenzel state significantly changed the deposition behavior from superlattice assembly, ring-shaped aggregation to uniform monolayer deposition. By fine-tuning the formulation properties, we achieved a 415.9-fold surge in retention efficiency, and enhanced the sustainability of nanoagrochemicals by minimizing loss during long-term application. This biointerface design significantly relieved the growth inhibition of Cd(II) pollutant on rice plants with a 95.2% increase in biomass after foliar application of SiO 2 nanoagrochemicals. Our research elucidates the intricate interplay between leaf structural attributes, nanobiointerface design, and biological responses of plants, fostering field application of nanoagrochemicals.

This present study investigated how heat treatment affects the mechanical properties of 3D-printed black carbon fiber HTPLA by manipulating two parameters: heating temperature and holding time. The mechanical properties of 3D-printed black carbon fiber HTPLA components are crucial for assessing their structural integrity and performance. The shrinkage and dimensional accuracy of the 3D-printed parts were also explored using a vernier caliper. The microstructure of both heat-treated and non-heat-treated HTPLA black carbon fiber 3D-printed parts was examined using scanning electron microscopy. Samples were prepared, printed, heat-treated, and mechanically tested, and their microstructure was observed and recorded. The results showed that heat treatment improved the material's strength, hardness, and crystallinity, leading to better mechanical properties. However, statistical analysis indicates no clear evidence that the two factors, optimum heating temperature and holding time, affect the mechanical properties of heat-treated printed parts. Nonetheless, further study suggests that these factors might be important in optimizing the heat treatment process., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:NOR AIMAN SUKINDAR reports administrative support, article publishing charges, and writing assistance were provided by Rabdan Academy. Ahmad Shah Hizam Md Yasir reports a relationship with Rabdan Academy that includes: employment. 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., (© 2024 The Authors.)

Exposure to indoor dust is of concern since dust may be contaminated by various toxic chemicals and people spend considerable time indoors. Factors impacting human exposure risks to contaminants in indoor dust may differ from those affecting the loadings of contaminants, but the dominant factors have not yet been well clarified. In this study, the occurrence, human exposure, and related influencing factors of several classes of legacy and emerging contaminants in residential dust across Beijing were investigated, including per- and polyfluoroalkyl substances (PFASs) and three types of flame retardants (FRs), i.e., organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), and novel halogenated FRs (NHFRs). OPEs (median: 3847 ng/g) were the most abundant group, followed by PBDEs (1046 ng/g) and NHFRs (520 ng/g). PFASs (14.3 ng/g) were one to two orders of magnitude lower than FRs. The estimated daily intakes of these contaminants were relatively higher for toddlers than other age groups, with oral ingestion being the main exposure pathway compared with dermal contact. Higher human exposure risks were found in new buildings or newly finished homes due to the elevated intake of emerging contaminants (such as OPEs). Furthermore, higher risks were also found in homes with wooden floors, which were mainly associated with higher levels of PFASs, chloroalkyl and alkyl OPEs, compared with tile floors. Citizens in the urban area also showed higher exposure risks than those in the suburban area. The quantity of household appliances and finishing styles (simple or luxurious) showed an insignificant impact on overall human exposure risks despite their significant effect on the levels of some of the dust contaminants. Results in this study are of importance in understanding human exposure to the co-existence of multiple contaminants in indoor dust., 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.)

This research investigated the relationship between volume energy density and the microstructure, density, and mechanical properties of the Ti-5Al-5Mo-3V-1Cr-1Fe alloy fabricated via the SLM process. The results indicate that an increase in volume energy density can promote a transition from a columnar to an equiaxed grain structure and suppress the anisotropy of mechanical properties. Specifically, at a volume energy density of 83.33 J/mm 3 , the average aspect ratio of β grains reached 0.77, accompanied by the formation of numerous nano-precipitated phases. Furthermore, the relative density of the alloy initially increased and then decreased as the volume energy density increased. At a volume energy density of 83.33 J/mm 3 , the relative density reached 99.6%. It is noteworthy that an increase in volume energy density increases the β grain size. Consequently, with a volume energy density of 83.33 J/mm 3 , the alloy exhibited an average grain size of 63.92 μm, demonstrating optimal performance with a yield strength of 1003.06 MPa and an elongation of 18.16%. This is mainly attributable to the fact that an increase in volume energy density enhances thermal convection within the molten pool, leading to alterations in molten pool morphology and a reduction in temperature gradients within the alloy. The reduction in temperature gradients promotes equiaxed grain transformation and grain refinement by increasing constitutive supercooling at the leading edge of the solid-liquid interface. The evolution of molten pool morphology mainly inhibits columnar grain growth and refines grain by changing the grain growth direction. This study provided a straightforward method for inhibiting anisotropy and enhancing mechanical properties.

Objectives: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China., Methods: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed., Results: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis., Conclusions: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Aims: Alcohol drinking is associated with central obesity, hypertension, and hyperlipidemia, which further causes metabolic syndrome (MetS). However, prior epidemiological studies on such associations lack experimental evidence for a causal relationship. This study aims to explore the causal relationship between drinking behavior and MetS in Taiwan population by using Mendelian randomization (MR) analysis., Methods: A cross-sectional study was conducted using the Taiwan Biobank database, which comprised 50 640 Han Chinese who were 30-70 years old without cancer from 2008 to 2020. In MR analysis, we constructed weighted and unweighted genetic risk scores by calculating SNP alleles significantly associated with alcohol drinking. We calculated odds ratios and 95% confidence interval (CI) by using a two-stage regression model., Results: A total of 50 640 participants were included with a mean age of 49.5 years (SD: 1.67 years), 36.6% were men. The adjusted odds ratio (aOR) of MetS per 5% increase in the likelihood of genetic predisposition to drink based on weighted genetic risk score with adjustment was 1.11 (95% CI: 1.10, 1.12, P < .001). Analysis was also conducted by grouping the likelihood of genetic predisposition to drink based on quartiles with multivariate adjustment. Using Q1 as the reference group, the aORs of MetS for Q2, Q3, and Q4 were 1.19 (1.12, 1.27, p < .001), 1.31 (1.23, 1.40, p < .001), and 1.87 (1.75, 2.00, p < .001), respectively, for the weighted genetic risk score., Conclusions: This study shows a modest relationship between drinking behavior and MetS by using MR analysis., (© The Author(s) 2024. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In recent years, the transformer-based language models have achieved remarkable success in the field of extractive text summarization. However, there are still some limitations in this kind of research. First, the transformer language model usually regards the text as a linear sequence, ignoring the inherent hierarchical structure information of the text. Second, for long text data, traditional extractive models often focus on global topic information, which poses challenges in how they capturing and integrating local contextual information within topic segments. To address these issues, we propose a long text extractive summarization model that employs a local topic information extraction module and a text hierarchical extraction module to capture the local topic information and document's hierarchical structure information of the original text. Our approach enhances the ability to determine whether a sentence belongs to the summary. In this experiment, ROUGE score is used as the experimental evaluation index, and evaluates the model on three large public datasets. Through experimental validation, the model demonstrates superior performance in terms of ROUGE-1, ROUGE-2, and ROUGE-L scores compared to current mainstream summarization models, affirming the effectiveness of incorporating local topic information and document hierarchical structure into the model., (© 2024. The Author(s).)

Bioinspired tactile devices can effectively mimic and reproduce the functions of the human tactile system, presenting significant potential in the field of next-generation wearable electronics. In particular, memristor-based bionic tactile devices have attracted considerable attention due to their exceptional characteristics of high flexibility, low power consumption, and adaptability. These devices provide advanced wearability and high-precision tactile sensing capabilities, thus emerging as an important research area within bioinspired electronics. This paper delves into the integration of memristors with other sensing and controlling systems and offers a comprehensive analysis of the recent research advancements in memristor-based bionic tactile devices. These advancements incorporate artificial nociceptors and flexible electronic skin (e-skin) into the category of bio-inspired sensors equipped with capabilities for sensing, processing, and responding to stimuli, which are expected to catalyze revolutionary changes in human-computer interaction. Finally, this review discusses the challenges faced by memristor-based bionic tactile devices in terms of material selection, structural design, and sensor signal processing for the development of artificial intelligence. Additionally, it also outlines future research directions and application prospects of these devices, while proposing feasible solutions to address the identified challenges., (© 2023 Wiley‐VCH GmbH.)

Background: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC., Patients and Methods: R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan-Meier curves were plotted for outcomes estimation., Results: A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB ( p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB ( p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS., Conclusions: Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment.

The effect of low-voltage electrostatic field (LVEF) assisted -9 °C (LVEF-9) and -12 °C (LVEF-12) frozen, non-LVEF-assisted -9 °C (NLVEF-9) and -12 °C (NLVEF-12) frozen, and conventional frozen (CF-18, -18 °C) storage on the muscle microstructure and the oxidative denaturation of the lamb protein during the subsequent frozen storage process after finishing initial freezing was investigated. Compared with NLVEF-9, LVEF-9, and NLVEF-12, LVEF-12 maintained the better integrity of muscle microstructure, demonstrated by smaller holes, more complete Z-line and M-line, and no significant difference with CF-18 (P > 0.05). Furthermore, LVEF-12 effectively inhibited protein oxidative denaturation as shown by the lower carbonyl content, surface hydrophobicity, and higher total/active sulfhydryl groups and Ca 2+ -ATPase activity. Moreover, LVEF-12 effectively maintained the integrity of the secondary and tertiary structure of proteins, reduced cross-linking aggregation of proteins, and sustained better functional properties, as shown by higher α-helix content, fluorescence intensity, protein solubility, and lower R-value, disulfide bonds., 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 © 2023 Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) is a common degenerative joint disease that can cause severe pain, motor dysfunction, and even disability. A growing body of research indicates that gut microbiota and their associated metabolites are key players in maintaining bone health and in the progression of OA. Short-chain fatty acids (SCFAs) are a series of active metabolites that widely participate in bone homeostasis. Gold nanoparticles (GNPs) with outstanding anti-bacterial and anti-inflammatory properties, have been demonstrated to ameliorate excessive bone loss during the progression of osteoporosis (OP) and rheumatoid arthritis (RA). However, the protective effects of GNPs on OA progression are not clear. Here, we observed that GNPs significantly alleviated anterior cruciate ligament transection (ACLT)-induced OA in a gut microbiota-dependent manner. 16S rDNA gene sequencing showed that GNPs changed gut microbial diversity and structure, which manifested as an increase in the abundance of Akkermansia and Lactobacillus. Additionally, GNPs increased levels of SCFAs (such as butyric acid), which could have improved bone destruction by reducing the inflammatory response. Notably, GNPs modulated the dynamic balance of M1/M2 macrophages, and increased the serum levels of anti-inflammatory cytokines such as IL-10. To sum up, our study indicated that GNPs exhibited anti-osteoarthritis effects via modulating the interaction of "microbiota-gut-joint" axis, which might provide promising therapeutic strategies for OA., (© 2024. The Author(s).)

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Cheng, Jian, Xiang, Xu, Wang, Yang, Lin and Zheng.)

Circulating tumor cells (CTCs) are precursors of distant metastasis in a subset of cancer patients. A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis. It remains elusive how CTCs evade immune surveillance and elimination by immune cells. In this study, we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle (EVs)-derived CD45 (termed as CD45 + CTCs) that resisted T cell attack. A higher percentage of CD45 + CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients. Moreover, CD45 + tumor cells orchestrated an immunosuppressive milieu and CD45 + CTCs exhibited remarkably stronger metastatic potential than CD45 - CTCs in vivo. Mechanistically, CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells, thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response. Together, these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis, providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis., (© 2024. The Author(s).)

Osteoporosis (OP) is a severe global health issue that has significant implications for productivity and human lifespan. Gut microbiota dysbiosis has been demonstrated to be closely associated with OP progression. Melatonin (MLT) is an important endogenous hormone that modulates bone metabolism, maintains bone homeostasis, and improves OP progression. Multiple studies indicated that MLT participates in the regulation of intestinal microbiota and gut barrier function. However, the promising effects of gut microbiota-derived MLT in OP remain unclear. Here, we found that OP resulted in intestinal tryptophan disorder and decreased the production of gut microbiota-derived MLT, while administration with MLT could mitigate OP-related clinical symptoms and reverse gut microbiota dysbiosis, including the diversity of intestinal microbiota, the relative abundance of many probiotics such as Allobaculum and Parasutterella, and metabolic function of intestinal flora such as amino acid metabolism, nucleotide metabolism, and energy metabolism. Notably, MLT significantly increased the production of short-chain fatty acids and decreased trimethylamine N-oxide-related metabolites. Importantly, MLT could modulate the dynamic balance of M1/M2 macrophages, reduce the serum levels of pro-inflammatory cytokines, and restore gut-barrier function. Taken together, our results highlighted the important roles of gut microbially derived MLT in OP progression via the "gut-bone" axis associated with SCFA metabolism, which may provide novel insight into the development of MLT as a promising drug for treating OP., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Neutrophils are important innate immune cells with plasticity, heterogenicity, and functional ambivalency. While bone marrow is often regarded as the primary source of neutrophil production, the roles of extramedullary production in regulating neutrophil plasticity and heterogenicity in autoimmune diseases remain poorly understood. Here, we report that the lack of wingless-type MMTV integration site family member 5 (WNT5) unleashes anti-inflammatory protection against colitis in mice, accompanied by reduced colonic CD8 + T cell activation and enhanced splenic extramedullary myelopoiesis. In addition, colitis upregulates WNT5 expression in splenic stromal cells. The ablation of WNT5 leads to increased splenic production of hematopoietic niche factors, as well as elevated numbers of splenic neutrophils with heightened CD8 + T cell suppressive capability, in part due to elevated CD101 expression and attenuated pro-inflammatory activities. Thus, our study reveals a mechanism by which neutrophil plasticity and heterogenicity are regulated in colitis through WNT5 and highlights the role of splenic neutrophil production in shaping inflammatory outcomes., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through C sp 3 -H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert -butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.

Background: The SelectSecure™ 3830 lead is an innovative, lumenless, and thin active fixed lead with a nonretractable screw-in tip and a diameter of 4.1 Fr, making it the thinnest pacing lead available. Its high anti-extrusion properties and durability have shown favorable outcomes in cardiac pacing, especially in pediatric patients. The superfine design and easy implantation of the lead have rendered it a preferred choice in children, particularly in cases of congenital heart disease., Case Presentation: This case series presents two infant patients who underwent transvenous endocardial pacing using the SelectSecure™ 3830 lead, along with a comprehensive literature review on the topic. The study followed the patients for 5 years and 3 years, respectively, and observed stable pacing parameters, indicating a positive therapeutic outcome and safety. This article discusses the optimal age and body shape for transvenous lead implantation in infants and highlights the advantages and disadvantages of endocardial and epicardial pacing approaches. Although endocardial pacing offers several benefits such as minimal trauma, short hospital stay, and longer battery life, it may not be suitable for intracardiac shunts, and venous occlusion remains a concern. On the other hand, epicardial pacing may be considered for children with challenging endocardial access but comes with higher risk of lead failure and coronary artery compression. This study emphasizes the importance of careful follow-up in pediatric patients with pacing, as lead failure can occur in young patients owing to growth and development, leading to syncope and battery depletion. The article also underscores the significance of selecting the appropriate pacing location to minimize the impact of cardiac function, with right ventricular septal pacing emerging as a preferable option., Conclusions: The SelectSecure™ 3830 lead presents a promising solution for transvenous endocardial pacing in pediatric patients with high degree atrioventricular block and bradycardia, ensuring safe and effective pacing as they grow and develop., (© 2024. The Author(s).)

Cancer immunotherapy, exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy, is revolutionizing cancer therapy. They induce long-term tumor regression and overall survival benefit in many types of cancer. With the advances in our knowledge about the tumor immune microenvironment, remarkable progress has been made in the development of small-molecule drugs for immunotherapy. Small molecules targeting PRR-associated pathways, immune checkpoints, oncogenic signaling, metabolic pathways, cytokine/chemokine signaling, and immune-related kinases have been extensively investigated. Monotherapy of small-molecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance. Here, we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations., (© 2024 The Authors.)

Modern X-ray free-electron lasers (XFELs) can generate pulses with durations ranging from femtoseconds to attoseconds. The numerical evaluation of ultra-short XFEL pulses through beamline systems is a critical process of beamline system design. However, the bandwidth of such ultra-short XFEL pulses is often non-negligible, and the propagation cannot be simply approximated using the central wavelength, especially in dispersive beamline systems. We developed a numerical model which is called Fourier optics based Ultrashort x-Ray pulse propagatION tool (FURION). This model can not only be used to simulate dispersive beamline systems but also to evaluate non-dispersive beamline systems. The FURION model utilizes Fresnel integral and angular spectrum integral to perform ultra-short XFEL pulse propagation in free space. We also present the method for XFEL pulse propagation through different types of dispersive gratings, which are commonly used in soft X-ray beamline systems. By using FURION, a start-to-end simulation of the FEL-1 beamline system at Shenzhen superconducting soft X-ray free electron laser (S 3 FEL) is carried out. This model can also be used to evaluate gratings-based spectrometers, beam splitters, pulse compressors, and pulse stretchers. This work provides valuable insights into the start-to-end simulation of X-ray beamline systems.

Biodegradable guanidinium-functionalized polycarbonates kill cancer cells via membrane translocation without causing resistance after repeated use, but the exact molecular targets of the polycarbonates are unknown. Here, we investigate the protein targets of the polycarbonates through affinity-based protein profiling and report myeloid-derived growth factor (MYDGF) as the main protein target. Direct binding of the polycarbonates to MYDGF protein is validated through biolayer interferometry. MYDGF is overexpressed in a range of cancer cells, and knockdown of MYDGF is shown to reduce cell proliferation in cancer cells. Through morphological profiling, we also identify similarities in phenotypic effects of the functionalized polycarbonates with topoisomerase I inhibitors, MDM2 inhibitors, and phosphatidylinositol 3kinase inhibitors against cancer cells, suggesting a common mechanism through the PIK3/AKT pathway leading to apoptosis. These findings present the first macromolecular compound targeting MYDGF and may serve as an example for MYDGF modulation as a potential new target for macromolecular chemotherapeutic development.

Introduction: Maintaining physical and cognitive function among older adults is important. These functional states are affected by mitochondria through various mechanisms, such as cellular energy production and oxidative stress control. Owing to its involvement in the relations among the brain, cognition, and physical function, mitochondrial function may be affected by mitochondrial DNA (mtDNA) haplogroups. This study explored the effect of mtDNA haplogroups and brain microstructure on physical and cognitive functions among community-dwelling older adults., Methods: This study was a community-based cross-sectional research. A total of 128 subjects aged 65 years and older without dementia completed several assessments, including mtDNA sequencing, physical and cognitive function tests, and magnetic resonance imaging (MRI) scans. Cognitive function and impairment were assessed by the MMSE and AD8 questionnaires. mtDNA haplogroups were classified by HaploGrep 2 software, and white matter microstructural integrity was scanned by 3T MRI., Results: The mean age of the subjects was 77.3 years. After the adjustment for covariates, the mtDNA haplogroup D carriers showed significantly lower mini-mental state examination (MMSE) scores than other carriers (p = 0.047). Further considering the brain microstructure, the mtDNA haplogroup D (p = 0.002) and white matter volumes in the left precuneus corrected for total intracranial volumes (p = 0.014) were found to be independently influencing factors of the MMSE scores., Conclusions: The mtDNA haplogroup D and white matter microstructure regulated the cognitive function among community-dwelling older adults. The findings provide new insights into the research gap. Scientists must further venture into this field., 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 © 2023. Published by Elsevier B.V.)

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library. We successfully identified LGOd1 as a novel anticancer agent with a characteristic levoglucosenone (LGO) scaffold. The mechanistic studies revealed that LGOd1 treatment leads to HCC cell death by interfering with cellular copper homeostasis, which is similar to a recently reported copper-dependent cell death named cuproptosis. While the prototypical cuproptosis is brought on by copper ionophore-induced copper overload, mechanistic studies indicated that LGOd1 does not act as a copper ionophore, but most likely by interacting with the copper chaperone protein CCS, thus LGOd1 represents a potentially new class of compounds with unique cuproptosis-inducing property. In summary, our findings highlight the critical role of bioavailable copper in the regulation of cell death and represent a novel route of cuproptosis induction., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Bone acts as a self-healing organ, which undergoes continuous regeneration process that is tightly regulated by the cooperation of osteoclasts with the capability of bone resorption and osteoblasts with the capability of bone formation. Generally, bone marrow derived mesenchymal stem cells (BMSCs) differentiated to final osteoblasts have been considered as critical role in bone remodeling. In this regard, several transcription factors (TFs) whose binding sites are initially hidden deep within accessible chromatin that participate in modulating osteoblast differentiation and bone matrix mineralization. Then, it is necessary to explore further the dynamic changes about the epigenetic transcription machinery during osteoblastogenesis. Here, we performed the chromatin accessibility and transcriptomic landscape of osteoblast differentiation and mineralization by using transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-Seq). Our data found that global chromatin accessibility during osteoblastogenesis was extensively improved. Above this, it is shown that key target genes including Col6a3, Serpina3n, Ms4a4d, Lyz2, Phf11b and Grin3a were enriched in differential loci RNA-seq and ATAC-Seq peaks with continuous changed tendency during osteoblasts differentiation and mineralization. In addition, Analysis of Motif Enrichment (AME) was used to elucidate TFs which modulated these target genes. In this study, it was shown for the first time that these important TFs including MEF2A, PRRX1, Shox2 and HOXB13 could alter promoter accessibility of target genes during osteoblastogenesis. This helps us understand how TF binding motif accessibility influences osteoblast differentiation. In addition, it also suggests that modulating the chromatin accessibility of osteogenesis could be developed as the promising strategies to regulate bone regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Dajianzhong decoction (DJZ) is a classical famous formula for treating yang-deficiency-syndrome in traditional Chinese medicine and recorded in Jin-Kui-Yao-Lue in Dynasty of Dong Han. Cognitive aging can present similar features of mitochondrial energy deficits to the clinical features of Yang deficiency. However, there is poor understanding of the effects of DJZ treatment on mitophagy in cognitive aging., Aim of the Study: The aims of this work were to decipher the effectiveness and mechanism of DJZ against cognitive aging, focusing on mitophagy., Materials and Methods: YFP-Parkin HeLa cells, D-galactose (D-gal) -induced mice (500 mg/kg for 35 d, s. c.) and SH-SY5Y cells (80 mg/ml for 6 h) were established. Firstly, the formation of YFP-Parkin puncta (a well-known mitophagy marker) in YFP-Parkin HeLa cells was employed to discover the mitophagy induction of DJZ. Moreover, the genes and proteins related to PINK1/Parkin pathway and mitochondrial functions were evaluated after treatment with DJZ in vivo (3.5 g/kg or 1.75 g/kg, i. g, 35 d) and in vitro (0.2, 2 and 20 μg/ml, 12 h). Furthermore, the effectiveness of DJZ (3.5 g/kg or 1.75 g/kg, i. g) for alleviating cognitive aging and nerve damage was measured in D-gal mice. Finally, siPINK1 was applied to reverse validation of DJZ in vitro., Results: The formation of YFP-Parkin puncta in YFP-Parkin HeLa cells was markedly induced by DJZ in a dose-dependent manner. The immunofluorescence intensity of Parkin and the protein expression of Parkin in mitochondrial membrane in D-gal mice were significantly increased after treatment of DJZ. The inhibition of PINK1/Parkin pathway in D-gal-induced mice and SH-SY5Y cells was significantly activated by DJZ. Simultaneously, the impairment of mitochondrial functions induced by D-gal were markedly reversed by DJZ. In addition, DJZ significantly ameliorated the neuropathological injury and cognitive declines in D-gal mice. Finally, after PINK1 was knocked down by siPINK1 in vitro, the neuroprotective effects of DJZ and the Parkin enhancement effect of DJZ were markedly reversed., Conclusion: Our findings firstly showed DJZ could relieve cognitive aging through facilitating PINK1/Parkin-mediated mitophagy to protect against mitochondrial functions, indicating DJZ may be regarded as a promising intervention in cognitive aging., 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 © 2023 Elsevier B.V. All rights reserved.)

Low-voltage electrostatic fields (LVEF) are recognized as a new technology that can improve the quality of frozen meat. To determine the extent to which LVEF assistance affects the quality of frozen pork for long-term storage, pork was frozen and stored at -18 and -38 °C for up to 5 months. Water-holding capacity, muscle microstructure, and protein properties were investigated after up to 5 months of frozen storage with and without LVEF assistance. In comparison to traditional -18 and -38 °C frozen storage, LVEF treatment inhibited water migration during frozen storage and thawing. As a result, thawing losses were reduced by 15.97% (-18 °C) and 3.38% (-38 °C) in LVEF-assisted compared to conventional freezing methods. LVEF helped to maintain the muscle fiber microstructure and reduce muscle protein denaturation by miniaturizing ice crystal formation by freezing. As a result of this study, LVEF is more suitable for freezing or short-term frozen storage, while a lower temperature plays a more significant role in long-term frozen storage.

A visible-light-promoted research protocol for constructing dihydropyrido[1,2- a ]indolone skeletons is herein described proceeding through a cascade cyclization mediated by trifluoromethyl radicals. This method allows the efficient synthesis of various indole derivatives without the need of photocatalysts or transition-metal catalysts. Mechanism experiments indicate that the process involves a radical chain process initiated by the homolysis of Umemoto's reagent. This straightforward method enables a rapid access to heterocycles containing a trifluoromethyl group., (Copyright © 2024, Yang et al.)

Memristors, promising nanoelectronic devices with in-memory resistive switching behavior that is assembled with a physically integrated core processing unit (CPU) and memory unit and even possesses highly possible multistate electrical behavior, could avoid the von Neumann bottleneck of traditional computing devices and show a highly efficient ability of parallel computation and high information storage. These advantages position them as potential candidates for future data-centric computing requirements and add remarkable vigor to the research of next-generation artificial intelligence (AI) systems, particularly those that involve brain-like intelligence applications. This work provides an overview of the evolution of memristor-based devices, from their initial use in creating artificial synapses and neural networks to their application in developing advanced AI systems and brain-like chips. It offers a broad perspective of the key device primitives enabling their special applications from the view of materials, nanostructure, and mechanism models. We highlight these demonstrations of memristor-based nanoelectronic devices that have potential for use in the field of brain-like AI, point out the existing challenges of memristor-based nanodevices toward brain-like chips, and propose the guiding principle and promising outlook for future device promotion and system optimization in the biomedical AI field.