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Vesicle-associated membrane protein (VAMP)-associated proteins (VAPs) are highly conserved endoplasmic reticulum (ER)-resident proteins that establish ER contacts with multiple membrane compartments in many eukaryotes. However, VAP-mediated membrane-tethering mechanisms remain ambiguous. Here, focusing on fission yeast ER-plasma membrane (PM) contact formation, using systematic interactome analyses and quantitative microscopy, we predict a non-VAP-protein direct binding-based ER-PM coupling. We further reveal that VAP-anionic phospholipid interactions may underlie ER-PM association and define the pH-responsive nature of VAP-tethered membrane contacts. Such conserved interactions with anionic phospholipids are generally defective in amyotrophic lateral sclerosis-associated human VAPB mutant. Moreover, we identify a conserved FFAT-like motif locating at the autoinhibitory hotspot of the essential PM proton pump Pma1. This modulatory VAP-Pma1 interaction appears crucial for pH homeostasis. We thus propose an ingenious strategy for maintaining intracellular pH by coupling Pma1 modulation with pH-sensory ER-PM contacts via VAP-mediated interactions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Motivation: High-throughput time-lapse imaging is a fundamental tool for efficient living cell profiling at single-cell resolution. Label-free phase-contrast video microscopy enables noninvasive, nontoxic, and long-term imaging. The tradeoff between speed and throughput, however, implies that despite the state-of-the-art autofocusing algorithms, out-of-focus cells are unavoidable due to the migratory nature of immune cells (velocities >10 μm/min). Here, we propose PostFocus to (i) identify out-of-focus images within time-lapse sequences with a classifier, and (ii) deploy a de-noising diffusion probabilistic model to yield reliable in-focus images., Results: De-noising diffusion probabilistic model outperformed deep discriminative models with a superior performance on the whole image and around cell boundaries. In addition, PostFocus improves the accuracy of image analysis (cell and contact detection) and the yield of usable videos., Availability and Implementation: Open-source code and sample data are available at: https://github.com/kwu14victor/PostFocus., (© The Author(s) 2024. Published by Oxford University Press.)

In cancer treatment, radiation therapy (RT) induces direct tumor cell death due to DNA damage, but it also enhances the deaths of radiosensitive immune cells and is followed by local relapse and up-regulation of immune checkpoint ligand PD-L1. Since the binding between PD-1 and PD-L1 curtails anti-tumor immunities, combining RT and PD-L1 inhibitor, anti-PD-L1, is a potential method to improve the treatment efficacy by RT. Some experiments support this hypothesis by showing that the combination of ionizing irradiation (IR) and anti-PD-L1 improves tumor reduction comparing to the monotherapy of IR or anti-PD-L1. In this work, we create a simplified ODE model to study the order of tumor growths under treatments of IR and anti-PD-L1. Our synergy analysis indicates that both IR and anti-PD-L1 improve the tumor reduction of each other, when IR and anti-PD-L1 are given simultaneously. When giving IR and anti-PD-L1 separately, a high dosage of IR should be given first to efficiently reduce tumor load and then followed by anti-PD-L1 with strong efficacy to maintain the tumor reduction and slow down the relapse. Increasing the duration of anti-PD-L1 improves the tumor reduction, but it cannot prolong the duration that tumor relapses to the level of the control case. Under some simplification, we also prove that the model has an unstable tumor free equilibrium and a locally asymptotically stable tumor persistent equilibrium. Our bifurcation diagram reveals a transition from tumor elimination to tumor persistence, as the tumor growth rate increases. In the tumor persistent case, both anti-PD-L1 and IR can reduce tumor amount in the long term., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The treatment of brain tumors in pregnant patients poses challenges, as the out-of-field dose exposure to the fetus can potentially be harmful. A pregnant patient with prior radiation treatment was presented with a brain tumor at our clinic. This work reports on our pre-treatment study that compared fetal dose exposure between intensity-modulated proton therapy (IMPT) using pencil beam scanning (PBS) and conventional photon 3D conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT), and the subsequent pregnant patient's radiation treatment., Materials and Methods: Pre-treatment measurements of clinical plans, 3DCRT, VMAT, and IMPT, were conducted on a phantom. Measurements were performed using a device capable of neutron detections, closely following AAPM guidelines, TG158. For photon measurements, fetus shielding was utilized. On patient treatment days, which was determined to be proton treatment, shielding was used only during daily imaging for patient setup. Additionally, an in vivo measurement was conducted on the patient., Results: Measurements showed that IMPT delivered the lowest fetal dose, considering both photon and neutron out-of-field doses to the fetus, even when shielding was implemented for photon measurements. Additionally, the proton plans demonstrated superior treatment for the mother, a reirradiation case., Conclusion: The patient was treated with proton therapy, and the baby was subsequently delivered at full term with no complications. This case study supports previous clinical findings and advocates for the expanded use of proton therapy in this patient population., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Given the urgent climate change and food security challenges, upcycled food products are crucial for sustainable food production and waste management. This study investigates Taiwanese consumer behavior towards upcycled foods using the value-attitude-behavior (VAB) theory, focusing on "product knowledge", "green perceived quality", and "price sensitivity". Of the 335 distributed surveys, 320 valid responses (95.5% effectiveness) were analyzed. The results indicated that eco-conscious values strongly influenced consumer attitudes and anticipated guilt (β = 0.647, p < 0.001; β = 0.691, p < 0.001), shaping behavioral intentions (β = 0.290, p < 0.001). Attitudes significantly correlated with intentions, validating the VAB framework. However, anticipated guilt showed a minimal impact (β = 0.029, p = 0.629), revealing complex consumer emotions. Green perceived quality and product knowledge were the key decision-making factors (β = 0.193, p < 0.001; β = 0.146, p < 0.001). Surprisingly, price sensitivity positively influences intentions (β = 0.764, p < 0.001), suggesting the consumer prioritization of quality and environmental values over price. These insights inform strategies for businesses to enhance consumer engagement and sustainability alignment, advancing progress towards Sustainable Development Goals (SDGs).

Mycobacterium tuberculosis (Mtb), the tuberculosis-causing agent, exhibits diverse genetic lineages, with known links to virulence. While genomic and transcriptomic variations between modern and ancient Mtb lineages have been explored, the role of small non-coding RNA (sRNA) in post-translational gene regulation remains largely uncharted. In this study, Mtb Lineage 1 (L1) Sabahan strains (n = 3) underwent sRNA sequencing, revealing 351 sRNAs, including 23 known sRNAs and 328 novel ones identified using ANNOgesic. Thirteen sRNAs were selected based on the best average cut-off value of 300, with RT-qPCR revealing significant expression differences for sRNA 1 (p = 0.0132) and sRNA 29 (p = 0.0012) between Mtb L1 and other lineages (L2 and L4, n = 3) (p > 0.05). Further characterization using RACE (rapid amplification of cDNA ends), followed by target prediction with TargetRNA3 unveils that sRNA 1 (55 base pairs) targets Rv0506, Rv0697, and Rv3590c, and sRNA 29 (86 base pairs) targets Rv33859c, Rv3345c, Rv0755c, Rv0107c, Rv1817, Rv2950c, Rv1181, Rv3610c, and Rv3296. Functional characterization with Mycobrowser reveals these targets involved in regulating intermediary metabolism and respiration, cell wall and cell processes, lipid metabolism, information pathways, and PE/PPE. In summary, two novel sRNAs, sRNA 1 and sRNA 29, exhibited differential expression between L1 and other lineages, with predicted roles in essential Mtb functions. These findings offer insights into Mtb regulatory mechanisms, holding promise for the development of improved tuberculosis treatment strategies in the future., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The HEART score, the T-MACS model and the GRACE score support early decision-making for acute chest pain, which could be complemented by CT coronary angiography (CTCA). However, their performance has not been directly compared., Methods: In this secondary analysis of a multicentre randomised controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, C-statistics and performance metrics (using the predefined cut-offs) of clinical decision aids and CTCA, alone and then in combination, for the index hospital diagnosis of acute coronary syndrome and for 30-day coronary revascularisation were assessed in those who underwent CTCA and had complete data., Results: Among 699 patients, 358 (51%) had an index hospital diagnosis of acute coronary syndrome, for which the C-statistic was higher for CTCA (0.80), followed by the T-MACS model (0.78), the HEART score (0.74) and the GRACE score (0.60). The negative predictive value was higher for the absence of coronary artery disease on CTCA (0.90) or a T-MACS estimate of <0.05 (0.83) than a HEART score of <4 (0.81) and a GRACE score of <109 (0.55). For 30-day coronary revascularisation, CTCA had the greatest C-statistic (0.80) with a negative predictive value of 0.96 and 0.92 in the absence of coronary artery disease and obstructive coronary artery disease, respectively. The combination of the T-MACS estimates and the CTCA findings was most discriminative for the index hospital diagnosis of acute coronary syndrome (C-statistic, 0.88) and predictive of 30-day coronary revascularisation (C-statistic, 0.85). No patients with a T-MACS estimate of <0.05 and normal coronary arteries had acute coronary syndrome during index hospitalisation or underwent coronary revascularisation within 30 days., Conclusions: In intermediate-risk patients with suspected acute coronary syndrome, the T-MACS model combined with CTCA improved discrimination of the index hospital diagnosis of acute coronary syndrome and prediction of 30-day coronary revascularisation., Trial Registration Number: NCT02284191., Competing Interests: Competing interests: KO reports research grants from the British Heart Foundation, the Jon Moulton Charity Trust and University of Edinburgh. RFS reports research grants from AstraZeneca and Cytosorbents; consulting fees and/or honoraria from Alfasigma, AstraZeneca, Chiesi, Cytosorbents, Daiichi-Sankyo, Idorsia, Novartis, Novo Nordisk, Pfizer, PhaseBio and Tabuk. NC reports research grants from Beckman Coulter, Boston Scientific, HeartFlow and Haemonetics; consulting fees and/or honoraria from Abbott, Boston Scientific and Edwards Lifesciences; travel sponsorship from Abbott, Biosensors and Edwards Lifesciences. AK reports honoraria from the TomTec Imaging Systems. CR reports honoraria from GE HealthCare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Vascular damage is one of the significant complications of diabetes mellitus (DM). Central to this damage is endothelial damage, especially under high-glucose conditions, which promotes inflammation via the NF-κB signaling pathway. Inflammatory processes in endothelial cells directly contribute to endothelial dysfunction, such as promoting inflammatory cytokine release and activation of adhesion molecules. Vitexin, a compound found in many medicinal plants, shows promise in countering oxidative stress in diabetic contexts and modulating blood glucose. However, its effect on high-glucose-induced endothelial cell activation has not yet been studied. This research explores vitexin's potential role in this process, focusing on its influence on the NF-κB pathway in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with 30 mM glucose (high glucose, HG) with or without vitexin treatment for 24 h. Western blotting assay was conducted for the NF-κB pathway and p-p38. Adhesion molecules (ICAM-1, VCAM-1, E-selectin, and MCP-1) were studied using flow cytometry, while pro-inflammatory cytokines were investigated using ELISA. Monocyte adhesion and vascular permeability tests were conducted to confirm the protective effect of vitexin under HG exposure. This study confirms vitexin's capacity to suppress p38 MAPK and NF-κB activation under HG conditions, reducing HG-elevated adhesion molecules and pro-inflammatory cytokine secretion. Additionally, vitexin mitigates HG-stimulated vascular permeability and monocyte adhesion. In conclusion, this study shows the therapeutic potential of vitexin against hyperglycemia-related vascular complications via p38 MAPK/NF-κB inhibition., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objective: Adverse and benevolent childhood experiences (ACEs and BCEs) impact health across the lifespan. No known study has investigated these associations across different health domains using a representative adult sample. This study examined the associations between adult physical, mental, and behavioral health with ACEs and BCEs based on two ACEs conceptualizations., Method: A cross-sectional population-based survey was conducted in Hong Kong. Thirteen ACEs were measured and conceptualized as cumulative ACE scores and ACE patterns. Self-reports of BCEs; 10 physical health problems; current mental health; posttraumatic stress; history of diagnosed mental illness; suicidal thought and suicide attempt; and engagement in three health risk behaviors (smoking, illicit substance misuse, binge drinking) were also included. A series of regression analyses were conducted to examine the association between childhood experiences and health., Results: In a random sample of 1,070 Hong Kong adults ( M age = 41.78 years; 53.93% female; mean ACEs = 1.64), 649 (60.65%) reported at least one ACE. Four ACE patterns were identified ( Low ACEs, Household Instability, Household Violence, and High ACEs ). Higher ACE scores associated with poorer health in a dose-response fashion. Two ACE patterns shared similar average ACE scores but differentially linked with outcomes across health domains. High BCEs negatively associated with mental and behavioral health problems., Conclusions: Public health responses to ACEs should consider both the accumulation and co-occurrence of ACE exposure. Schools, neighborhoods, and the wider community should take an active role in helping children and families create more positive experiences as a universal prevention strategy to safeguard population health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: To compare the surgical outcomes of the inverted internal limiting membrane (ILM) flap technique and ILM insertion for macular hole (MH) without retinal detachment in eyes with extremely high myopia., Methods: In this retrospective study, we analyzed 22 eyes with an axial length ≥ 30.0 mm that had underwent MH surgery between April 2015 and August 2021. The surgical procedures involved either an inverted ILM flap or ILM insertion. The outcomes were compared between the two techniques. Closure of the MH was confirmed by optical coherence tomography (OCT). The best-corrected visual acuity (BCVA) was measured before and after surgery. Associated complications were documented., Results: The median of axial length was 30.64 mm (range, 30.0-34.42). The MH closed in 100% (22/22) eyes and did not recur with a median follow-up of 12.5 months. For the inverted ILM flap technique, the median BCVA improved significantly from 0.80 logarithm of the minimum angle of resolution (logMAR) (range, 0.40-2.00) before surgery to 0.70 logMAR (range, 0.09-1.52) after surgery (p = 0.002). In addition, the median of final BCVA was better for the inverted ILM flap than ILM insertion (0.7 logMAR V.S. 1.00 logMAR; p = 0.016)., Conclusions: In eyes with extremely high myopia, despite comparable effects on MH closure for both ILM insertion and the inverted ILM flap, the later technique achieved significantly better visual outcomes., (© 2024. The Author(s).)

Adopting noble metals on non-noble metals is an effective strategy to balance the cost and activity of electrocatalysts. Herein, a thorough analysis of the synergistic OER is conducted at the heterogeneous interface formed by Ir clusters and NiCo 2 O 4 based on DFT calculations. Specifically, the electrons spontaneously bring an e g occupancy of interfacial Ir close to unity after the absorbed O, providing more transferable electrons for the conversion of the absorbed O-intermediates. Besides, the diffuse distribution of electrons in the Ir 5 d orbital fills the antibonding orbital after O is absorbed, avoiding the desorption difficulties caused by the stronger Ir-O bonds. The electrons transfer from Ir to Co atoms at the heterogeneous interface and fill the Co 3 d band near the Fermi level, stimulating the interfacial Co to participate in the direct O-O coupling (DOOC) pathway. Experimentally, the ultrathin-modulated NiCo 2 O 4 nanosheets are used to support Ir clusters (Ir cluster -E-NiCo 2 O 4 ) by the electrodeposition method. The as-synthesized Ir cluster -E-NiCo 2 O 4 catalyst achieves a current density of 10 mA cm -2 at an ultralow overpotential of 238 mV and works steadily for 100 h under a high current of 100 mA cm -2 , benefiting from the efficient DOOC pathway during the OER.

Background/objectives: The study aimed to examine the physical fitness and activity levels of kindergarteners in Hong Kong during the coronavirus disease 2019 pandemic., Methods: A total of 2052 kindergarteners (48% girls; 32.9% Grade 1, 34% Grade 2, and 33.1% Grade 3) were recruited from July 2020 to November 2021. Participants completed the physical fitness tests, including body composition, flexibility, lower-limb muscle strength, upper-limb muscle strength, lower-limb muscle endurance, and agility. Children's physical activity and overall well-being were examined using parental proxy reports. Parents also reported their physical activity and parental support to children's physical activity engagement, as well as their perception of children's kindergarten physical activity environment. Fitness differences by age and gender were analyzed using one-way ANOVA and ANCOVA measuring effect size with partial eta-squared. Additionally, correlations assessed the relationship between children's fitness and parents' proxy reports., Results: The results of the physical fitness tests were higher than those in previous studies conducted by the Physical Fitness Association of Hong Kong in 2015-2018. Gender-based differences were observed in most tests for children aged 4 years and older, with boys showing higher scores in the standing long jump, shot put, and balance tests, while girls had higher scores in the sit-and-reach test. Parents' proxy questionnaire answers indicated that children's continuous jump test performances were significantly related to their frequency of physical activity per week (r = 0.19, p < 0.001), and that children's health was significantly and positively correlated with their fitness level (r = 0.179, p < 0.009). Inadequate school physical activity was associated with poor upper-limb strength (r = 0.078, p < 0.005). Moreover, a high level of parental support for their children's participation in physical activity was correlated with a high level of parental participation in vigorous-intensity physical activities (r = 0.167, p < 0.005)., Conclusion: The physical fitness of children in Hong Kong was less affected by the epidemic. Parents' healthy behaviors and support were related to children's participation in PA. Efforts to improve children's physical fitness and motor development should include parent education and physical activity involvement., 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 Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

We examined associations between prenatal tobacco exposure (with and without cannabis exposure) and children's performance on laboratory measures of sustained attention, attentional set shifting, and working memory in middle childhood (9-12 years of child age). Participants were recruited in the first trimester of pregnancy and oversampled for prenatal tobacco exposure; with a smaller sample (n = 133; n = 34 non-substance exposed, n = 37 exposed to tobacco only, n = 62 co-exposed) invited (oversampled for co-exposure) to participate in the middle-childhood assessment (M age = 10.6, SD = 0.77; 68% Black, 20% Hispanic). Results for sustained attention indicated lower attention (percent hits) at the first epoch for tobacco only exposed compared to non-exposed and co-exposed; a trend (p = .07) towards increases in impulsive responding across time (a total of 8 epochs) for tobacco exposed (with and without cannabis) compared to non-exposed children; and a significant association between higher number of cigarettes in the first trimester and greater increases in impulsive responding across epochs. However, children prenatally exposed to tobacco (with and without cannabis) demonstrated greater short-term memory compared to children not prenatally exposed, and this difference was driven by higher scores for children prenatally co-exposed to tobacco and cannabis compared to those who were non-exposed. Overall, results suggest that prenatal tobacco exposure, especially in the first trimester, may increase risk for impulsive responding on tasks requiring sustained attention, and that co-use of cannabis did not exacerbate these associations. The higher short-term memory scores among children who were co-exposed compared to non-exposed are perplexing and need replication, particularly in studies with larger sample sizes and samples exposed only to cannabis to examine this more closely., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Antibiotics are routinely added to ornamental fish tanks for treating bacterial infection or as a prophylactic measure. However, the overuse or subtherapeutical application of antibiotics could potentially facilitate the selection of antibiotic resistance in bacteria, yet no studies have investigated antibiotic use in the retail ornamental fish sector and its impact on microbial communities. The present study analyzed the concentrations of twenty antibiotics in the carriage water (which also originates from fish tanks in retail shops) collected monthly from ten local ornamental fish shops over a duration of three months. The antibiotic concentrations were correlated with the sequenced microbial community composition, and the risk of resistance selection in bacteria was assessed. Results revealed that the detected concentrations of tetracyclines were the highest among samples, followed by fluoroquinolones and macrolides. The concentrations of oxytetracycline (44.3 to 2,262,064.2 ng L -1 ) detected across three months demonstrated a high risk for resistance selection at most of the sampled shops. Zoonotic pathogens (species of Rhodococcus , Legionella , and Citrobacter ) were positively correlated with the concentrations of oxytetracycline, tetracycline, chlortetracycline, and enrofloxacin. This suggests that antibiotic use in retail shops may increase the likelihood of selecting for zoonotic pathogens. These findings shed light on the potential for ornamental fish retail shops to create a favorable environment for the selection of pathogens with antibiotics, thereby highlighting the urgent need for enhanced antibiotic stewardship within the industry.

Background: Memory and attention are important for daily functioning, and their function deteriorates due to aging. However, fruit and vegetable consumption are one of the protective factors against deterioration in memory and attention. This systematic review of randomized controlled trials (RCTs) aims to identify the effects of fruit and vegetable consumption on memory and attention., Methods: We conducted a systematic search in EBSCOhost, ProQuest, PubMed, Embase, and Web of Science from inception up to 06/09/2022. The inclusion criteria were peer-reviewed articles, fruit and vegetable intake measured using randomized controlled trials, and the outcome measures that showed the results of memory and attention scores. Two researchers independently extracted articles that met the selection criteria and evaluated the quality of each study., Results: There were 70 articles identified from the databases, of which 13 articles met the inclusion criteria and were included in this systematic review. There were 493 participants in total. The results show that consumption of fruit and vegetable intake improved memory and attention in longitudinal studies (10 to 12 weeks). Children showed improvement in immediate recall after supplementation with blueberries. Older adults required a higher dose of fruit and vegetable intake consumption to achieve significant improvement compared with children and younger adults. Furthermore, the effect of fruits and vegetables on memory showed better immediate memory recall than delayed recall., Conclusion: This systematic review showed that there is an improvement in memory and attention with fruit and vegetable intake consumption. Hence, awareness of fruit and vegetable intake consumption is important to maintain cognitive health., (© 2024. The Author(s).)

Background: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes., Objectives: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction., Methods: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18 F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction., Results: Increased 18 F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; P interaction  = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions., Conclusions: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction., Competing Interests: Funding Support and Author Disclosures The PRE(18)FFIR study was funded by the Wellcome Trust (WT103782AIA). The funder played no roles in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and any decisions to submit the manuscript for publication. The University of Edinburgh and the National Health Service Lothian Health Board were cosponsors. Dr Rudd is part-supported by the National Institute for Health and Care Research Cambridge Biomedical Research Centre, the British Heart Foundation, the Higher Education Funding Council for England, the Engineering and Physical Sciences Research Council, and the Wellcome Trust. Dr Piotr is supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health (R35HL161195). Dr Mills is supported by the British Heart Foundation (CH/F/21/90010, RE/18/5/34216, and RG/20/10/34966). Dr van Beek is supported by the Scottish Imaging Network. Dr Williams is supported by the British Heart Foundation (FS/ICRF/20/26002). Dr Dweck is supported by the British Heart Foundation (FS/SCRF/21/32010). Dr Newby is supported by the British Heart Foundation (CH/09/002, RE/18/5/34216, and RG/F/22/110093). Dr Moss is a current employee of AstraZeneca. Dr Williams has given talks for Canon Medical Systems, Novartis, and Siemens Healthineers. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The present study aimed to report the prevalence of ICD-11 posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) in the general adult Hong Kong population, and examine the validity of the Chinese International Trauma Questionnaire (ITQ). This descriptive cross-sectional population-based telephone survey included a representative sample of 1070 non-institutionalized permanent Hong Kong residents ages 18-64 years. Participants provided responses to the Chinese version of the ITQ, and measures of adverse childhood experiences (ACEs), depression, anxiety, and stress. Based on the diagnostic algorithm of the ITQ, 5.9% of the sample screened positive for either CPTSD or PTSD, with CPTSD (4.2%) being more common that PTSD (1.7%). Results of the confirmatory factor analysis indicated the first-order correlated 6-factor model to be the best fitting solution. Symptom cluster summed scores were all positively and significantly correlated with all criterion variables. This investigation established the prevalence rates of ICD-11 PTSD and CPTSD using a general adult population sample in Hong Kong. The Chinese ITQ demonstrated sound factorial validity and concurrent validity. Future research can further characterize ICD-11 PTSD and CPTSD in subgroups using the Chinese ITQ., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP., 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: Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation., Aim: To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism., Methods: Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H 2 O 2 and treated with the metabolites to evaluate ROS and SIRT1 expression., Results: HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, β-leucine (β-Leu) and traumatic acid, were also found to attenuate H 2 O 2 -induced oxidative stress in NCM460 cells by up-regulating SIRT1., Conclusion: HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Adolescents are experiencing an unprecedented cyber-saturated environment where the disclosure of private information should be approached with caution. This study aims to investigate the effects of school environment, including student support, teacher support, and opportunities for autonomy, on students' disclosure of private information and their experiences with cyberbullying., Methods: In September 2022, a total of 1,716 students (mean age = 14.60, SD = 1.35) from three regular and vocational schools in China participated in the survey., Results: The results showed that 35.6% of the participants had experienced victimization by cyberbullying, and 12.6% had perpetrated cyberbullying. Vocational school students reported significantly higher rates of cyberbullying and lower levels of perceived school climate than students from regular school. Student support in the school environment was found to negatively affect both cyberbullying perpetration and victimization, with this impact appearing to be stronger in regular schools as compared to vocational schools. Opportunities for autonomy and the disclosure of private information were positively correlated with experiences of cyberbullying., Discussion: This study introduces a novel perspective that perceived school climate influences adolescents' disclosure of private information and their involvement in cyberbullying. The findings could provide implications for future research and practices aimed at child protection in cyberspace., 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, Tang, Zhu and Chan.)

Background: Although abundant evidence has confirmed cyberbullying as a global online risk, little is known about the coping strategies employed by victims and those who experiencing bullying. A validated scale for coping with cyberbullying could inform evidence-based social services and enable comparative studies of this phenomenon among victims from different backgrounds. This study aims to validate the Coping Strategies for Victims of Cyberbullying (CSVC) scale among Chinese adolescents and to compare its effectiveness between victims and bully-victims (individuals with dual roles)., Methods: A 25-item CSVC scale was translated and adapted for cultural relevance in the Chinese context. A sample of 1,716 adolescents, aged 13-18 years, from two middle schools and one high school in China, was recruited. Both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted., Results: The EFA revealed that the Chinese version of the CSVC scale had satisfactory validity. The CFA demonstrated a good fit for the eight-factor model in assessing different coping strategies for cyberbullying. Differences in the selection of coping strategies were observed between the general adolescent population and sexual and gender minorities., Conclusions: Future intervention studies may use this validated scale to educate adolescents, both those affected by cyberbullying and those who are not, to learn a broader range of coping strategies and to choose more effective ones., (© 2024. The Author(s).)

Solid-state batteries based on lithium metal anodes, solid electrolytes, and composite cathodes constitute a promising battery concept for achieving high energy density. Charge carrier transport within the cells is governed by solid-solid contacts, emphasizing the importance of well-designed interfaces. A key parameter for enhancing the interfacial contacts among electrode active materials and electrolytes comprises externally applied pressure onto the cell stack, particularly in the case of ceramic electrolytes. Reports exploring the impact of external pressure on polymer-based cells are, however, scarce due to overall better wetting behavior. In this work, the consequences of externally applied pressure in view of key performance indicators, including cell longevity, rate capability, and limiting current density in single-layer pouch-type NMC622||Li cells, are evaluated employing cross-linked poly(ethylene oxide), xPEO, and cross-linked cyclodextrin grafted poly(caprolactone), xGCD-PCL. Notably, externally applied pressure substantially changes the cell's electrochemical cycling performance, strongly depending on the mechanical properties of the considered polymers. Higher external pressure potentially enhances electrode-electrolyte interfaces, thereby boosting the rate capability of pouch-type cells, despite the fact that the cell longevity may be reduced upon plastic deformation of the polymer electrolytes when passing beyond intrinsic thresholds of compressive stress. For the softer xGCD-PCL membrane, cycling of cells is only feasible in the absence of external pressure, whereas in the case of xPEO, a trade-off between enhanced rate capability and minimal membrane deformation is achieved at cell pressures of ≤0.43 MPa, which is considerably lower and more practical compared to cells employing ceramic electrolytes with ≥5 MPa external pressure.

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon antibody-mediated disease of the central nervous system. Its classic presentation includes long segments of spinal cord inflammation, optic neuritis with or without intractable vomiting, and hiccups. Here, we described a case of a 39-year-old woman with an atypical presentation of vertigo, which was finally diagnosed as NMOSD by a positive serum aquaporin-4 antibody., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The early myocardial response of hypertension is an elevation of angiotensin-II (Ang-II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT-R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti-inflammatory and anti-oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang-II-induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang-II 1 μM for 24 h to induce cellular damage. We found that EA protected against Ang-II-increased cell surface area and pro-hypertrophic gene expression in H9c2. EA reduced Ang-II-caused AT-R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang-II-enhanced p38 and extracellular-signal-regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang-II stimulation also reversed NF-κB activity and iNOS expression. This study shows that EA protects against Ang-II-induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang-II-induced myocardial hypertrophy., (© 2024 Wiley Periodicals LLC.)

Background: Management of tibial pilon fracture in elderly patients with psychiatric illness remains challenging for orthopedic doctors because of patients' poor bone quality and inability for self-care. This study aimed to ascertain the viability and reliability of primary arthrodesis by using retrograde hindfoot nail for these difficult cases., Methods: We retrospectively reviewed eight elderly consecutive patients (age older than 65 years) with tibial pilon fractures and psychiatric illness from January of 2012 to December of 2019 in our institute. Primary tibiotalocalcaneal arthrodesis with retrograde hindfoot nail was used as a definitive procedure. The bone union time, wound complication rate, ankle alignment, necessity for narcotic agents, and ambulation status were evaluated., Results: The average length of follow-up was 22.25 months (range, 15-36 months). Additional bone grafting surgery was performed for one patient because of fusion-site nonunion 6 months postoperatively. Another patient required debridement and removal of posterior calcaneal screw because of implant prominence and local infection. Osseous union with angular deformity less than 10° was achieved in all patients finally. The average bone union time was 6.6 months (range, 4-12 months). In terms of walking ability, six patients were capable of outdoor ambulation (classes 2 and 3). Two patients required oral pain medication at the final visit., Conclusions: The current study involved only a small number of patients, and two of the eight cases encountered undesired complications (one local infection and one bone nonunion); however, we believe that our method may serve as a valuable alternative for the treatment of tibial pilon fractures in elderly patients with psychiatric illness, considering the specificity of this fragile population.

Background: Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI) are available., Methods: We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months (interquartile range: 26-73 months) follow-up period were compared between patients with the low prealbumin level (< 170 mg/L) and those with the high prealbumin level (≥ 170 mg/L)., Results: A total of 114 patients (4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class III (9.9% vs. 4.4%, P = 0.034), cardiovascular death (8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events (19.2% vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level (< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events (odds ratio = 1.918, 95% CI: 1.250-2.942, P = 0.003). The cut-off value of prealbumin level for predicting in-hospital death was 170 mg/L (area under the curve = 0.703, 95% CI: 0.651-0.754, P < 0.001; sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level (170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results., Conclusions: Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardiovascular mortality in STEMI patients., (© 2024 JGC All rights reserved; www.jgc301.com.)

Spinal tuberculosis, also referred to as Pott's disease, presents a significant risk of severe paralysis if not promptly detected and treated, owing to complications such as spinal cord compression and deformity. This article presents the genetic analysis of a Mycobacterium tuberculosis STB-T1A strain, isolated from the spine of a 29-year-old female diagnosed with spinal tuberculosis. Genomic DNA was extracted from pure culture and subjected to sequencing using the Illumina NovaSeq 6000 sequencing system. The genome of the M. tuberculosis STB-T1A strain spans 4,367,616 base pairs with a G+C content of 65.56 % and 4174 protein-coding genes. Comparative genomic analysis, conducted via single nucleotide polymorphism (SNP)-based phylogenetic analysis using the Maximum Likelihood method, revealed that the strain falls within the Indo-Oceanic lineage (Lineage 1). It clusters with the M. tuberculosis 43-16836 strain, which was isolated from the cerebrospinal fluid of a patient with tuberculous meningitis in Thailand. The complete genome sequence has been deposited at the National Center for Biotechnology Information (NCBI) GenBank database with the accession number JBBMVZ000000000., (© 2024 The Author(s).)

Abstract Background/purpose: Computer aided implant surgery has been widely adopted in modern implant dentistry. However, absence of reliable anatomic landmarks for superimposing digital data sets for patients with terminal dentition or complete edentulism remained challenging. Utilization of additional fiducial markers intraorally as the reference points for the improvement of accuracy became crucial in implant digital workflow. Nevertheless, the choice of the material for fiducial markers should present the least radiographic artifacts under cone beam computed tomography (CBCT) for better accuracy. The aim of this in vitro study was to investigate the volume of radiographic artifacts generated through different materials under the image of CBCT., Materials and Methods: Fifteen dental materials were selected and configured into cubic shape. All the materials were scanned initially with the laboratory scanner as the control groups. The samples were scanned by CBCT machine as test groups and the volume of artifact generated under CBCT images were compared and analyzed using 3D modeling software., Results: Eleven out of fifteen materials could be recognized under CBCT images. Volumetric analysis reported that statistically significant differences among the materials could be noted, and the flowable composite resin presented the least volumetric difference. Lithium disilicate glass-ceramic, flowable composite resin, and gutta-percha presented the least deformation and maintained their cubic shapes., Conclusion: The results of the present study may imply that flowable composite resin compared to all ceramic materials, amalgam and gutta-percha may be a preferable choice when utilized as fiducial markers under CBCT images., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The impact of hepatic resection type on long-term oncological prognosis of patients with early-stage hepatocellular carcinoma (HCC) has not been systematically investigated. We sought to determine risk factors, recurrence patterns, and survival outcomes after anatomical resection (AR) versus non-anatomical resection (NAR) for early-stage HCC., Methods: From a prospectively collected multicenter database, consecutive patients undergoing curative hepatectomy for early-stage HCC were identified. Recurrence patterns, overall survival (OS), recurrence-free survival (RFS), and risk factors were investigated in patients undergoing AR versus NAR using propensity score matching (PSM), subgroup analysis, and COX regression analysis., Results: A total of 3585 patients with early-stage HCC were enrolled, including 1287 and 2298 in the AR and NAR groups, respectively. After PSM, the OS and RFS of patients in the AR group were 58.8% and 42.7%, which were higher than those in the NAR group (52.2% and 30.6%, both p < 0.01). The benefits of AR were consistent across most subgroup analyses of OS and RFS. Multivariable COX regression analysis showed that AR was independently associated with better OS and RFS. Notably, although recurrence patterns were comparable, the risk factors for recurrence were not identical for AR versus NAR. Microvascular invasion and narrow resection margin were only associated with a higher recurrence rate after NAR., Conclusions: This study demonstrated that AR decreases the risk of tumor recurrence and improves OS and RFS in patients with early-stage HCC. AR should be adopted as long as such a surgical maneuver is feasible for initial treatment of early-stage HCC., (© 2023. Asian Pacific Association for the Study of the Liver.)

Objective: Research has documented the associations of child maltreatment with a range of physical health problems, but little is known about the physical growth patterns of children who experience maltreatment in early childhood. This study aimed to examine the association between various discipline approaches and physical growth in preschool-aged children., Methods: In the first year of preschool, parents of 661 Chinese preschool-aged children completed a questionnaire with items pertaining to the frequency of using physical maltreatment, psychological aggression, neglect, and nonviolent discipline toward the child. Children's weight and height were assessed annually using direct assessment in the first and two subsequent years. Longitudinal analyses were performed using multiple regression models., Results: More frequent neglect and psychological aggression during the first year of preschool were associated with a higher likelihood of a decreased BMI z score in subsequent years. Conversely, increased experience of physical maltreatment in the first year was associated with an increased likelihood of having overweight or obesity in the third year., Conclusions: Results indicate that early maltreatment experience can impact physical growth. This highlights the importance of preventing abusive parenting and encouraging healthy habits in young children who have experienced maltreatment to decrease their future risk for weight problems., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii , A. acaulis , and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii , 30 phyla and 504 genera for A. acaulis , as well as 39 phyla and 533 genera for A. ernestii . Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium , Afipia , and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha , Pseudogymnoascus , and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures ( p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.

Background: Systemic inflammatory indicators are important in the prognoses of various diseases. Such indicators, including the neutrophil-to-lymphocyte ratio (NLR), can be meaningful in predicting the clinical outcome in patients diagnosed with idiopathic membranous nephropathy (IMN)., Materials and Methods: 112 IMN patients diagnosed by renal biopsy were recruited retrospectively. The endpoint was defined as a combination of partial and complete remission. Statistical analysis determined the independent factors associated with clinical remission and the predictive utility of NLR., Results: Within the 12-month follow-up period, 72 patients achieved clinical remission after treatment. Univariate analysis identified significant differences in serum albumin, estimated glomerular filtration rate (eGFR), proteinuria, neutrophil count, and NLR between the remission group and the non-remission group (all p < 0.05). Cox proportional hazards indicated that elevated eGFR (HR 1.022, 95% CI (1.009 - 1.035), p = 0.001), lower NLR (HR 0.345, 95% CI (0.237 - 0.501), p = 0.0001), and decreased proteinuria (HR 0.826, 95% CI (0.693 - 0.984), p = 0.032) were protective elements for remission. With an optimal cut-off value of 2.61, the pre-treatment NLR had an excellent ability to identify the remission (area under the curve (AUC), 0.785). Participants were separated into low- and high-NLR groups by using 2.61. Kaplan-Meier survival curves revealed significantly higher remission rates in the lower group (p < 0.0001)., Conclusion: The NLR is an effective indicator for predicting clinical remission in patients with IMN.

Six pairs of enantiomeric dilignans, (+)/(-)-magdiligols A-F, have been isolated from an ethanolic extract of the barks of Magnolia officinalis var. biloba. Their chemical structures were elucidated by extensive spectroscopic analyses, NMR calculation with DP4+ analysis, and the electronic circular dichroism spectra calculation. (+)/(-)-1-3 possessed a dihydrobenzopyran ring, while a propyl chain of 1 was linked via ether bond. (+)/(-)-Magdiligols D and E ((+)/(-)-4 and 5) were dilignans possessing a furan ring. (+)-Magdiligol B ((+)/(-)-2), (+)/(-)-magdiligol C ((+)/(-)-3), and racemes 2, 3, and 5 showed potential hepatoprotective effects against APAP-induced HepG2 cell damage, increased the cell viability from 65.4% to 72.7, 78.7.76.6, 73.9, 77.9 and 73.2%, via decreasing the level of the live enzymes ALH and LDH consistently. (+)/(-)-Magdiligols B-D ((+)/(-)-2-4) and (+)/(-)-magdiligol F ((+)/(-)-6) exhibited significant antioxidative activity. (+)/(-)-Magdiligols B-C ((+)/(-)-2 and 3), (-)-magdiligol D ((-)-4), and (+)-magdiligol E ((+)-5) displayed significant PTP1B inhibitory activity with IC 50 values 1.41-3.42 μM. (+)/(-)-Magdiligol B ((+)/(-)-2), and its raceme (2) demonstrated α-glucosidase inhibitory activity with the IC 50 values 1.47, 2.88 and 1.85 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The early language environment, especially high-quality, contingent parent-child language interactions, is crucial for a child's language development and later academic success. In this secondary analysis study, 89 parent-child dyads were randomly assigned to either the Music Together® (music) or play date (control) classes. Children were 9- to 15-month old at baseline, primarily white (86.7%) and female (52%). Measures of conversational turns (CTs) and parental verbal quality were coded from parent-child free play episodes at baseline, mid-intervention (month 6), and post-intervention (month 12). Results show that participants in the music group had a significantly greater increase in CT measures and quality of parent verbalization post-intervention. Music enrichment programs may be a strategy to enhance parent-child language interactions during early childhood., (© 2023 The Authors. Child Development © 2023 Society for Research in Child Development.)

Previously, we found that the levels of soluble amyloid precursor protein α (sAPPα) are regulated, in part, by acetylcholinesterase (AChE) in human A549 (p53 wild-type) and H1299 (p53-null) NSCLC cell lines. In this study, we found regulation of sAPPα levels in the media by leptin, a widely recognized obesity-associated adipokine that has recently been shown to play a possible role in cancer signaling. Increased levels of sAPPα, that were accompanied by lower Aβ40/42 levels in the media of A549 and H1299 cells, were detected upon cell incubation with leptin. Conversely, knockdown of leptin or its receptor led to reduced levels of sAPPα and increased levels of Aβ40/42 in the media of A549 and H1299 cells, suggesting that leptin likely shifts APP processing toward the non-amyloidogenic pathway. A549 cell treatment with leptin increased acetylcholine levels and blocked the activities of AChE and p53. Treatment with leptin resulted in increased activation of PKC, ERK1/2, PI3K, and the levels of sAPPα, effects that were reversed by treatment with kinase inhibitors and/or upon addition of AChE to A549 and H1299 cell media. Cell viability increased by treatment of A549 and H1299 cells with leptin and decreased upon co-treatment with AChE and/or inhibitors targeting PKC, ERK1/2, and PI3K. This study is significant as it provides evidence for a likely carcinogenic role of leptin in NSCLC cells via upregulation of sAPPα levels in the media, and highlights the importance of targeting leptin as a potential therapeutic strategy for NSCLC treatment., (© 2024. The Author(s).)

Background: Diabetic nephropathy (DN) and atherosclerosis (AS) are prevalent and severe complications associated with diabetes, exhibiting lesions in the basement membrane, an essential component found within the glomerulus, tubules, and arteries. These lesions contribute significantly to the progression of both diseases, however, the precise underlying mechanisms, as well as any potential shared pathogenic processes between them, remain elusive., Methods: Our study analyzed transcriptomic profiles from DN and AS patients, sourced from the Gene Expression Omnibus database. A combination of integrated bioinformatics approaches and machine learning models were deployed to identify crucial genes connected to basement membrane lesions in both conditions. The role of integrin subunit alpha M (ITGAM) was further explored using immune infiltration analysis and genetic correlation studies. Single-cell sequencing analysis was employed to delineate the expression of ITGAM across different cell types within DN and AS tissues., Results: Our analyses identified ITGAM as a key gene involved in basement membrane alterations and revealed its primary expression within macrophages in both DN and AS. ITGAM was significantly correlated with tissue immune infiltration within these diseases. Furthermore, the expression of genes encoding core components of the basement membrane was influenced by the expression level of ITGAM., Conclusion: Our findings suggest that macrophages may contribute to basement membrane lesions in DN and AS through the action of ITGAM. Moreover, therapeutic strategies that target ITGAM may offer potential avenues to mitigate basement membrane lesions in these two diabetes-related complications., (© 2024. The Author(s).)

Interleukin-27 (IL-27) is known to play opposing roles in immunology. The present paper considers, specifically, the role IL-27 plays in cancer immunotherapy when combined with immune checkpoint inhibitor anti-PD-1. We first develop a mathematical model for this combination therapy, by a system of Partial Differential Equations, and show agreement with experimental results in mice injected with melanoma cells. We then proceed to simulate tumor volume with IL-27 injection at a variable dose F and anti-PD-1 at a variable dose g. We show that in some range of "small" values of g, as f increases tumor volume decreases as long as fc (g) and increases in a range where f>F c (g), where F c (g) is a monotone increasing function of g. This demonstrates that IL-27 can be both anti-cancer and pro-cancer, depending on the ranges of both anti-PD-1 and IL-27., Competing Interests: Declaration of competing interest There is no interest of conflict., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Evidence supports the effectiveness of serious games in health education, but little is known about their effects on the psychosocial well-being of children in the general population., Objective: This study aimed to investigate the potential of a mobile game-based safety education program in improving children's safety and psychosocial outcomes., Methods: Safe City is a mobile roleplaying game specifically designed to educate children in Hong Kong about safety. This randomized controlled trial included 340 children in grades 4 through 6. Intervention arm participants (n=170) were instructed to play the Safe City mobile game for 4 weeks, whereas control arm participants (n=170) received a safety booklet. All participants completed a survey on safety knowledge and behaviors and psychosocial problems at baseline (T1), 1 month postintervention (T2), and 3 months postintervention (T3). Cumulative game scores and mini-game performance were analyzed as a proxy for the extent of exposure to the game. Outcome data were analyzed using 2-sample 2-tailed t tests to compare mean change from T1 to T2 and to T3 for intervention versus control arm participants. The association of game use with outcome changes postintervention was analyzed using generalized additive models., Results: No significant differences were found in mean changes between the intervention and control arms. However, use analyses showed that higher game scores were associated with improvements in safe behavior (P=.03) and internalizing problems (P=.01) at T3. Matching and Spot the Danger mini-game performance significantly predicted improvements in safety knowledge at T2 and T3., Conclusions: Analysis of use has shown that playing the Safe City mobile game can result in significant improvements in safety knowledge and reductions in unsafe behavior and internalizing problems. These findings provide evidence for the positive impact of serious games on psychological and social well-being, highlighting the potential of technology-driven interventions to assist children in learning about safety and preventing injuries., Trial Registration: ClinicalTrials.org NCT04096196; https://clinicaltrials.gov/show/NCT04096196., International Registered Report Identifier (irrid): RR2-10.2196/17756., (©Rosa S Wong, Keith T S Tung, Frederick K W Ho, Wilfred H S Wong, Chun Bong Chow, Ko Ling Chan, King Wa Fu, Patrick Ip. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.02.2024.)

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Chimeric antigen receptor (CAR) T cell show promise in cancer treatments, but their mechanism of action is not well understood. Decoding the mechanisms used by individual T cells can help improve the efficacy of T cells while also identifying mechanisms of T cell failure leading to tumor escape. Here, we used a suite of assays including dynamic single-cell imaging of cell-cell interactions, dynamic imaging of fluorescent reporters to directly track cytotoxin activity in tumor cells, and scRNA-seq on patient infusion products to investigate the cytotoxic mechanisms used by individual CAR T cells in killing tumor cells. We show that surprisingly, overexpression of the Granzyme B (GZMB) inhibitor, protease inhibitor-9 (PI9), does not alter the cytotoxicity mediated by CD19-specific CAR T cells against either the leukemic cell line, NALM6; or the ovarian cancer cell line, SkOV3-CD19. We designed and validated reporters to directly assay T cell delivered GZMB activity in tumor cells and confirmed that while PI9 overexpression inhibits GZMB activity at the molecular level, this is not sufficient to impact the kinetics or magnitude of killing mediated by the CAR T cells. Altering cytotoxicity mediated by CAR T cells required combined inhibition of multiple pathways that are tumor cell specific: (a) B-cell lines like NALM6, Raji and Daudi were sensitive to combined GZMB and granzyme A (GZMA) inhibition; whereas (b) solid tumor targets like SkOV3-CD19 and A375-CD19 (melanoma) were sensitive to combined GZMB and Fas ligand inhibition. We realized the translational relevance of these findings by examining the scRNA-seq profiles of Tisa-cel and Axi-cel infusion products and show a significant correlation between GZMB and GZMA expression at the single-cell level in a T cell subset-dependent manner. Our findings highlight the importance of the redundancy in killing mechanisms of CAR T cells and how this redundancy is important for efficacious T cells., (© 2024. The Author(s).)

Diabetic nephropathy (DN) is characterized by chronic low-grade renal inflammatory responses, which greatly contribute to disease progression. Abnormal glucose metabolism disrupts renal lipid metabolism, leading to lipid accumulation, nephrotoxicity, and subsequent aseptic renal interstitial inflammation. In this study, we investigated the mechanisms underlying the renal inflammation in diabetes, driven by glucose-lipid metabolic rearrangement with a focus on the role of acetyl-CoA synthetase 2 (ACSS2) in lipid accumulation and renal tubular injury. Diabetic models were established in mice by the injection of streptozotocin and in human renal tubular epithelial HK-2 cells cultured under a high glucose (HG, 30 mmol/L) condition. We showed that the expression levels of ACSS2 were significantly increased in renal tubular epithelial cells (RTECs) from the diabetic mice and human diabetic kidney biopsy samples, and ACSS2 was co-localized with the pro-inflammatory cytokine IL-1β in RTECs. Diabetic ACSS2-deficient mice exhibited reduced renal tubular injury and inflammatory responses. Similarly, ACSS2 knockdown or inhibition of ACSS2 by ACSS2i (10 µmol/L) in HK-2 cells significantly ameliorated HG-induced inflammation, mitochondrial stress, and fatty acid synthesis. Molecular docking revealed that ACSS2 interacted with Sirtuin 1 (SIRT1). In HG-treated HK-2 cells, we demonstrated that ACSS2 suppressed SIRT1 expression and activated fatty acid synthesis by modulating SIRT1-carbohydrate responsive element binding protein (ChREBP) activity, leading to mitochondrial oxidative stress and inflammation. We conclude that ACSS2 promotes mitochondrial oxidative stress and renal tubular inflammation in DN by regulating the SIRT1-ChREBP pathway. This highlights the potential therapeutic value of pharmacological inhibition of ACSS2 for alleviating renal inflammation and dysregulation of fatty acid metabolic homeostasis in DN. Metabolic inflammation in the renal region, driven by lipid metabolism disorder, is a key factor in renal injury in diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is abundantly expressed in renal tubular epithelial cells (RTECs) and highly upregulated in diabetic kidneys. Deleting ACSS2 reduces renal fatty acid accumulation and markers of renal tubular injury in diabetic mice. We demonstrate that ACSS2 deletion inhibits ChREBP-mediated fatty acid lipogenesis, mitochondrial oxidative stress, and inflammatory response in RTECs, which play a major role in the progression of diabetic renal tubular injury in the kidney. These findings support the potential use of ACSS2 inhibitors in treating patients with DN., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: A recently hypothesized cause of cell death called disulfidptosis has been linked to the expansion, emigration, and vascular rebuilding of cancer cells. Cancer can be treated by targeting the pathways that trigger cell death., Aim: To discover the long non-coding RNA of the disulfidaptosis-related lncRNAs (DRLs), prognosis clinical survival, and treat patients with colorectal cancer with medications., Methods: Initially, we queried the Cancer Genome Atlas database to collect transcriptome, clinical, and genetic mutation data for colorectal cancer (CRC). Training and testing sets for CRC patient transcriptome data were generated randomly. Key long non-coding RNAs (lncRNAs) related to DRLs were then identified and evaluated using a least absolute shrinkage and selection operator procedure, as well as univariate and multivariate Cox regression models. A prognostic model was then created after risk scoring. Also, Immune infiltration analysis, immune checkpoint analysis, and medication susceptibility analysis were used to investigate the causes of the different prognoses between high and low risk groups. Finally, we validated the differential expression and biomarker potential of risk-predictive lncRNAs through induction using both NCM460 and HT-29 cell lines, as well as a disulfidptosis model., Results: In this work, eight significant lncRNAs linked to disulfidptosis were found. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of differentially expressed genes between high- and low-risk groups from the prognostic model showed a close relationship with the immune response as well as significant enrichment in neutrophil extracellular trap formation and the IL-17 signaling pathway. Furthermore, significant immune cell variations between the high-risk and low-risk groups were seen, as well as a higher incidence of immunological escape risk in the high-risk group. Finally, Epirubicin, bortezomib, teniposide, and BMS-754807 were shown to have the lowest sensitivity among the four immunotherapy drugs., Conclusion: Our findings emphasizes the role of disulfidptosis in regulating tumor development, therapeutic response, and patient survival in CRC patients. For the clinical treatment of CRC, these important LncRNAs could serve as viable therapeutic targets., Competing Interests: Conflict-of-interest statement: All the authors declare that the study was carried out without any commercial or financial relationships which could be considered a potential conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Previous research has well-documented that family functioning is an important predictor of individuals' physical and mental health. However, relatively little research has explored family functioning at the family and population levels, such as changes in family functioning across years and whether predictors of family functioning differ across different family structures. Understanding of the changes in family functioning across years and factors promoting family functioning will inform the development of preventive measures to enhance family health and resilience. Objectives of the study were: (1) to examine the changes in family functioning across a 6-year study period and (2) to study protective factors associated with family functioning and the extent to which the factors are the same or different across different family structures., Method: The study involved secondary data analysis of the biannual Family Survey carried out by the Family Council, an advisory body to the Hong Kong government. A series of ANOVA and regression analyses were conducted using data of four population-based cross-sectional household surveys conducted in Hong Kong in 2011, 2013, 2015, and 2017., Results: There were some fluctuations in overall family functioning scores across the study period, but no significant difference was found between the scores in 2011 and 2017. Different predictors of family functioning were found for different family types, and frequent family communication was a common protective factor for most family types, including never married, married/cohabiting with children, and married/cohabiting with no children., Conclusion: The study is among the first to examine changes in family functioning at the population level. Monitoring and addressing family functioning may help tackle various social problems and future public health crises. Interventions to promote family functioning should address both common and different protective factors of different family types., (© 2024. The Author(s).)

The genus Tripterygium was of great medicinal value and attracted much attention on the taxonomic study using morphological and molecular methods. In this study, we assembled 12 chloroplast genomes of Tripterygium to reveal interspecific difference and intraspecific variation. The sequence length (156,692-157,061 bp) and structure of Tripterygium were conserved. Comparative analyses presented abundant variable regions for further study. Meanwhile, we determined the ndhB gene under positive selection through adaptive evolution analysis. And the phylogenetic analyses based on 15 chloroplast genomes supported the monophyly of Tripterygium hypoglaucum and the potential sister relationship between Tripterygium wilfordii and Tripterygium regelii . Molecular dating analysis indicated that the divergence time within Tripterygium was approximately 5.99 Ma (95% HPD = 3.11-8.68 Ma). The results in our study provided new insights into the taxonomy, evolution process, and phylogenetic construction of Tripterygium using complete plastid genomes., 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 Xu, Zhang, Fang, Wang, Jin, Wei and Ma.)

Background: Microvascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique., Methods: Twelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function., Results: With the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = - 0.353, P = 0.022), LV remodeling index (r = - 0.312, P = 0.033), fasting blood glucose (r = - 0.313, P = 0.043), and HbA1c (r = - 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration., Conclusions: Myocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling., (© 2024. The Author(s).)