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Background: Ischemic left ventricular (LV) aneurysm is associated with LV thrombus and subsequent embolic events. However, there is currently no evidence-based recommendation for anticoagulation in these patients., Objective: To determine the characteristics of LV aneurysms associated with a high risk of thrombus formation., Methods: This retrospective study included all hospitalized patients with ischemic LV aneurysm who underwent cardiac magnetic resonance (CMR) from September 2015 to June 2023. Baseline characteristics and CMR parameters were compared between patients with and without LV thrombus. Factors associated with LV thrombus were identified using univariable and multivariable logistic regression analyses., Results: Among the 317 patients included in this study, 88 (27.8%) had LV thrombus. Patients with LV thrombus demonstrated a higher prevalence of heart failure, lower left ventricular ejection fraction, and greater volume, mass, and global extent of late gadolinium enhancement (LGE). They also exhibited distinct LV aneurysm characteristics, such as a larger maximum transverse dimension (maximum width), a wider aneurysm neck, and a higher aneurysm shape index (ratio of maximum length to neck width). Multivariable logistic regression analyses identified aneurysm neck width (OR 1.33 per 5 mm, 95% CI 1.00-1.77, P = 0.047), shape index (OR 1.63 per 20%, 95% CI 1.23-2.16, P = 0.001), and LGE global extent > 50% (OR 6.58, 95% CI 3.04-14.27, P < 0.001) as significant predictors of LV thrombus., Conclusions: A wider aneurysm neck, a higher aneurysm shape index, and LGE global extent > 50% are associated with LV thrombus in patients with ischemic LV aneurysm., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: The anti-tumor effects of Traditional Chinese Medicine has been recognized in regulating the tumor microenvironment. Jianpi Jiedu Recipe (JPJDR) is clinically effective in enhancing the chemotherapy efficacy in Colorectal Cancer (CRC) treatment and significantly improved the quality of life of CRC patients. However, its therapeutic mechanism remains to be investigated., Material and Methods: The active compounds of each herb in JPJDR were obtained from the HIT2.0 and HERB databases supported by evidence in literature. Single-cell RNA sequencing data of CRC were obtained from published studies (PMID: 32451460, 32103181, and 32561858). Pathway enrichment was analyzed using the reactome database, and gene correlation analysis was performed using the corrplot R software package. Gene expression regulated by JPJDR was verified by RT-qPCR., Results: Ye Pu Tao Teng, Ba Yue Zha, Huang Qi, Bai Zhu, Yi Yi Ren and Dang Shen contained 4,7, 18, 26,3 and 30 compounds, respectively, and they target to 38, 7, 262, 309, 50, 54 genes, respectively. JPJDR is involved in a range of immune-related biological processes, including cytokine signaling, cell proliferation, apoptosis and cellular senescence. JPJDR regulates various cell types in the CRC microenvironment, including malignant CRC cells, immune cells (including CD4+ T cell, CD8+ T cell, B cell, plasma cell, mast cell, and myeloid cell), and stromal cells (including fibroblast, pericyte, enteric glial cell, and endothelial cell). We confirmed that JPJDR significantly downregulated the expression of HMGB1 and MT2A in CRC., Conclusions: JPJDR regulates a range of cell types in the CRC microenvironment, including malignant CRC, immune cells and stromal cells. Downregulation of HMGB1 and MT2A might be the important mediators for JPJDR to modulate the CRC microenvironment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Herein, we synthesized fly ash aggregates (FAAs) through a hydrothermal synthesis process utilizing fly ash, quicklime, and cement under saturated steam conditions at 180 °C. We systematically investigated the influence and mechanisms governing the physical and mechanical properties of autoclaved FAAs by incrementally replacing cement with quicklime in 5% equal mass intervals. Our results revealed that the substitution of cement with quicklime yielded lightweight aggregates (LWAs) exhibiting water absorption ranging from 1.33% to 22.88% after 1 h and 1.67% to 26.22% after 24 h, loose bulk densities between 847 kg/m 3 and 1043 kg/m 3 , apparent densities spanning from 1484 kg/m 3 to 1880 kg/m 3 , and cylinder compressive strengths varying from 11.9 MPa to 18.5 MPa. Notably, as the proportion of quicklime substitution for cement increased, there was a corresponding augmentation in water consumption during granulation, resulting in an elevated water-cement ratio ranging from 27.5% to 51.39%. This led to an enhancement in the water absorption of the FAAs, accompanied by a decrement in cylinder compressive strength and overall density. The hydration products, including tobermorite and calcium silicate hydrate, contributed to the creation of a dense microstructure within the FAAs. However, with higher quantities of quicklime replacing cement, the content of hydration products increased while the proportion of unreacted fly ash particles decreased significantly. The resultant weakening micro-aggregate effect emerged as a pivotal factor contributing to the observed decrement in the strength of these FAAs. The findings of this research are anticipated to provide significant theoretical insights and technical support for the selection of calcareous materials in the resource-recycling process of fly ash.

Background: Frailty is an independent risk factor for cardiovascular events. It is uncertain whether frailty modifies the efficacy of intensive blood pressure (BP) control among participants with type 2 diabetes mellitus(T2DM)., Methods: The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD BP) trial, a two-by-two factorial trial, examined the effects of systolic BP (<120 vs <140 mm Hg) and glycaemic control on cardiovascular events in T2DM. We constructed a frailty index using the Rockwood cumulative deficit approach. Cox proportional hazard models were used to estimate the effectiveness of intensive BP treatment according to frailty status. The primary composite outcome was non-fatal myocardial infarction, non-fatal stroke or death from cardiovascular causes., Results: There were 4733 participants (mean age: 62.7 years; 39.9% frailty). The mean average number of antihypertensive medications was higher in frail patients compared with non-frail patients in both the standard (2.2 vs 1.7) and intensive (3.1 vs 2.7) treatment groups. In the standard glycaemic arm, intensive BP treatment reduced the risk of the primary outcome (HR 0.75, 95% CI 0.58 to 0.97) regardless of frailty status (p value for interaction=0.86). The benefits of intensive BP intervention were consistent across the spectrum of the frailty index (p value for interaction=0.96) in the standard glycaemic arm. However, no benefits of intensive BP treatment (HR 1.08, 95% CI 0.82 to 1.43) were observed in the intensive glycaemic arm., Conclusions: In the ACCORD BP study, the benefit of intensive BP treatment was consistent regardless of frailty in the setting of standard glycaemic control. Frailty should not be a barrier to intensive BP control in patients with T2DM treated with guideline-recommended standard glycaemic control., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: We aim to determine the effectiveness of a community-based, health instructor led, multifaceted family intervention, as compared with usual care, on blood pressure (BP) management among Chinese rural residents, with or without hypertension., Methods/design: The Healthy Family Program is a cluster randomized controlled trial being undertaken in 80 villages (each with approximately 100 residents) with a target to enroll a total of 8000 older adults (aged 40-80 years). Villages were randomly assigned in a 1:1 ratio to either an intervention group to receive multifaceted strategies or a control group to continue with usual standard of care. The main components of the multifaceted intervention strategies include: 1) Establishing a BP management team led by family health instructors, with team members including family leaders and village doctors, and 2) Implementing an intervention that focused on six areas: education for a healthy lifestyle, free provision of sodium substitute, weight management, physical exercise, BP monitoring, and appropriate antihypertensive treatment for individuals with hypertension. The primary outcome is change in systolic BP from baseline to 6 months in all participants, reported as the absolute difference between intervention and control groups. After the 6-month intervention, support from the study coordination center and the distribution of low-sodium salt will be withdrawn, and all participants will be followed up until 12 months. As of December 31, 2024, 24 villages in the intervention group have completed the 6-month intervention., Conclusion: The Healthy Family Program will provide critically important data on the effectiveness of a novel BP management strategy in rural China., Trial Registration: The study is registered at ClinicalTrials.gov (NCT06427096)., (Copyright © 2025. Published by Elsevier Inc.)

The further commercialization of layer-structured Ni-rich LiNi 0.83 Co 0.11 Mn 0.06 O 2 (NCM83) cathode for high-energy lithium-ion batteries (LIBs) has been challenged by severe capacity decay and thermal instability owing to the microcracks and harmful phase transitions. Herein, Ti 4+ -doped NCM83 cathode materials are rationally designed via a simple and low-cost in-situ modification method to improve the crystal structure and electrode-electrolyte interface stability by inhibiting irreversible polarizations and harmful phase transitions of the NCM83 cathode materials due to Ti 4+ -doped forms stronger metal-O bonds and a stable bulk structural. In addition, the optimal doping amount of the composite cathode material is also determined through the results of physical characterization and electrochemical performance testing. The optimized Ti 4+ -doped NCM83 cathode material presents wider Li + ions diffusion channels (c = 14.1687 Å), lower Li + /Ni 2+ mixing degree (2.68 %), and compact bulk structure. The cell assembled with the optimized Ti 4+ -doped NCM83 cathode material exhibits remarkable capacity retention ratio of 95.4 % after 100cycles at 2.0C and room temperature, and outstanding reversible discharge specific capacity of 148.2 mAh g -1 at 5.0C. Even under elevated temperature of 60 °C, it delivers excellent capacity retention ratio of 92.2 % after 100cycles at 2.0C, which is significantly superior to the 47.9 % of the unmodified cathode material. Thus, the in-situ Ti 4+ -doped strategy presents superior advantages in enhancing the structural stability of Ni-rich cathode materials for LIBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chemotherapy-induced alopecia (CIA) represents one of the most common side effects of cancer treatment. Currently, scalp cooling systems are utilized to treat CIA, but their safety and effectiveness remain limited. The objective of this study was to investigate the effect of fucoidan on CIA and to elucidate the possible mechanism of fucoidan in treating CIA. The results showed that when the dosage of fucoidan was 100 mg/kg·d, it could effectively alleviate CIA induced by cyclophosphamide and promote hair recovery. Altering the dosage affected the therapeutic effect. A lower dosage (50 mg/kg·d) could not effectively prevent the hair from falling off, and the regrown hair was sparse, while an increased dosage led to slow hair growth, although the hair regrown was thick and black. It was also found that with the increase in dosage, key CIA proteins P53 and Fas were down-regulated. However, the cyclin was decreased when the dose was too high. In addition, fucoidan proved beneficial to cyclophosphamide treatment, which further inhibited tumor growth, aggravated tumor necrosis, and reduced the side effects of cyclophosphamide, especially at high doses. These results demonstrate that fucoidan has a therapeutic effect on CIA and does not compromise the effect of chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

To date, less attention has been paid to λ-carrageenases and their enzymatic hydrolysates than to κ- and ι-carrageenases and their hydrolysates. In this study, a Gram-negative strain Polaribacter sp. NJDZ03 was isolated from the surface of an Antarctic macroalga, Desmarestia sp., and a novel λ-carrageenase gene car3193 was isolated from it. The car3193 gene was 2832 bp long, and encoded an enzyme consisting of 943 amino acids. Although Car3193 had the typical PQQ structure at the N-terminal, its predicted active sites, Arg93 and Asn361, differed from those of other reported λ-carrageenases. The optimum temperature and pH of recombinant Car3193 towards λ-carrageenan were 50 °C and 7.0, respectively. The degradation products of λ-carrageenan produced by Car3193 were λ-neocarrabiose-, λ-neocarratetraose-, and λ-neocarraoctose-saccharides. Two products of enzymatic hydrolysis, λ-COs-1 (degree of polymerization 2; DP2) and λ-CO S- 2 (DP8), showed excellent anti-inflammatory activity towards lipopolysaccharide-induced RAW264.7 macrophages. Treatment with λ-COs-1 (DP2) and λ-CO S- 2 (DP8) significantly inhibited the secretion of the pro-inflammatory factors TNF-α, IL-6, IL-1β, and NO by RAW264.7 macrophages, and stimulated the secretion of the anti-inflammatory factors TGF-β1 and IL-10. The anti-inflammatory activity of λ-COs-1 was stronger than that of λ-CO S -2, and λ-COs-1 had a dose-dependent bioactive effect, whereas λ-CO S -2 did not. Further analyses showed that these carrageenan oligomers stimulated an anti-inflammatory response by inhibiting the NF-κB signaling pathway. Car3193 has potential applications in industry because of its high activity and strong stability, and its ability to generate bioactive products., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined., Methods: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study., Conclusions: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF., Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04347330)., Competing Interests: Conflict of interest The principal Investigators of CRAFT study have no disclosures of financial and other competing interests. CSA reports receiving funding from the Medical Research Council (MRC) and Medical Research Foundation (MRF) of the UK, and the National Health and Medical Research (NHMRC) of Australia, and Penumbra and Takeda. AP is the nonremunerated Chair of the Board of George Medicines, a commercial spin-out of The George Institute that is aiming to bring a novel fixed-dose antihypertensive combination to market, and reports receiving funding from NHMRC., (Copyright © 2024. Published by Elsevier Inc.)

Background: Conduction disturbances play an important role in the occurrence and development of heart failure (HF). Studies suggest autoantibodies may attack the conduction system. However, whether autoantibodies are associated with conduction disturbances in patients with HF is unclear., Objective: The purpose of this study was to assess whether anti-SSA, anti-Ro/Sjögren syndrome-related antigen A antibodies known for congenital atrioventricular block (AVB), is associated with conduction disturbances in patients with HF., Methods: This retrospective observational study used data from patients with HF who were admitted to Beijing Anzhen Hospital between January 2018 and June 2022. Patients who were tested for anti-SSA and had undergone electrocardiographic examination during hospitalization were included. Conduction disturbances, including AVB, bundle branch block (BBB), and intraventricular conduction delay, were confirmed by a cardiologist blinded to anti-SSA status. Univariate and multivariable logistic regression analyses were performed to assess the association between anti-SSA and conduction disturbances., Results: A total of 766 patients were included in this study, of whom 70 (9.1%) were anti-SSA positive. Subjects who were anti-SSA positive showed a higher prevalence of AVB (20% vs 10.6%) and BBB (27.3 % vs 10.9 %), including both left BBB and right BBB (all P <.05). After adjusting for known risk factors, anti-SSA was independently associated with AVB (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.18-5.43; P = .03) and BBB (OR 3.15; 95% CI 1.68-5.89; P <.001)., Conclusion: Anti-SSA is independently associated with AVB and BBB in patients with HF. Further study of the role of autoantibodies in the development of conduction abnormalities in patients with HF to generate possible targeted treatments is required., (Copyright © 2024. Published by Elsevier Inc.)

Background: Influenza vaccination confers broad benefits in the elderly and certain high-risk populations, but its effectiveness in patients with acute heart failure (HF) is uncertain. Rates of influenza vaccination are low in China due to poor awareness, cultural misunderstandings, and cost., Aims: To determine the effectiveness of influenza vaccination in patients with acute HF admitted to hospitals in China., Methods: The second Population Assessment of Influenza and Disease Activity (PANDA II) study is a two-arm, parallel-group, county-level hospital-based, cluster randomized controlled trial to determine the benefits and risks of full access to routine free influenza vaccination before hospital discharge, compared to routine limited use of influenza vaccination, on the primary endpoint of death or hospital readmission. Consecutive hospitalized patients at each site are enrolled to a target of 50 participants in each autumn-winter influenza outbreak period (October to March) over 3 consecutive years to reach the required sample size. Patients are centrally followed up at 1, 3, 6, and 12 months after hospital discharge (or death if earlier). Site numbers varied across year according to predicted influenza activity and logistical reasons., Conclusions: This study offers a unique chance to clarify uncertainties surrounding the effectiveness of influenza vaccination in patients with HF and to lay the groundwork for future prevention strategies., Trial Registration: This trial was registered with the acronym PANDA II (Population Assessment of Influenza and Disease Activity) at ChiCTR.org.cn (ChiCTR2100053264). Registered on 17 November 2021., Competing Interests: Declarations. Ethics approval and consent to participate {24}: This trial received approval from the Clinical Research Ethics Committee at Beijing Anzhen Hospital (Research Ethics Review (2021) No.18). Prior to participation, all subjects and/or their legal guardian(s) will provide informed consent. The study will be conducted in accordance with the protocol, applicable regulatory requirements, and the ethical principles of the Declaration of Helsinki as adopted by the 18th World Medical Assembly in Helsinki, Finland, in 1964 and subsequent versions. Consent for publication {32}: Not applicable. Competing interests {28}: The PANDA II main trial is an academic study conceived and conducted by cardiovascular interventionalists in academic research institutions. Study logistics, handling of data, and statistical assessments will be financed by the HHRC, Beijing, China. The steering committee will apply for grants from public funds and from the manufacturer of the influenza vaccine used in the study. Possible external sponsors will have no influence on the conduct of the study. The authors declare that they have no other competing interests., (© 2024. The Author(s).)

Objectives: Recent studies have increasingly demonstrated that a multiplatform water environment combined with lard gavage is an effective method for establishing a mouse model of diarrhea. However, the interactions between intestinal microorganisms and diarrhea, as well as the relationships among energy metabolism, fluid balance, and gastrointestinal function in this model, remain poorly understood., Methods: Building on previous research, this study aimed to optimiz and replicate a multiplatform water environment combined with a lard gavage model. Male Kunming mice, free of specific pathogens, were randomly divided into four groups: a normal control group (ZC), a standing group (ZL), a standing combined with lard group (ZLZ), and a standing combined with internal and external wet conditions group (ZLZS). The mice in the ZL, ZLZ, and ZLZS groups were subjected to 4 hours of daily standing in a custom-designed multiplatform water environment. Starting on day 8, mice in the ZLZ and ZLZS groups were gavaged with lard (0.4 mL per session, twice daily) for 7 consecutive days, while those in the ZLZS group were additionally exposed to a wet litter environment (50 g/100 mL). The ZC and ZL groups received equal volumes of sterile water via gavage. The microbiota in the small intestine, as well as serum levels of cAMP, cGMP, VIP, Gas, and D-xylose, were analyzed., Results: Compared with the ZLZ group, the ZLZS group showed significantly lower serum levels of cAMP/cGMP ( p <0.01) and Gas ( p <0.01). D-xylose levels were lower in the ZL, ZLZ, and ZLZS groups compared to the ZC group, while VIP levels were significantly higher in the ZL and ZLZS groups ( p <0.01). Moverover, Corynebacterium , Empedobacter , and Pseudochrobactrum were identified as characteristic bacterial genera in the ZLZS group. The mechanism by which the small intestinal microbiota induces diarrhea was linked to the biosynthesis of secondary bile acids., Conclusion: A multiplatform water environment combined with lard gavage can effectively induce diarrhea, and the addition of an external wet environment exacerbates this condition by affecting small intestinal contents microbiota and other functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Yu, Xie, Guo, Wu, Tian, Wang, Zhou and Cai.)

Osteoarthritis (OA) is a prevalent articular disorder characterized by joint degeneration and persistent pain; it imposes a significant burden on both individuals and society. While OA has traditionally been viewed as a localized peripheral disorder, recent preclinical and clinical studies have revealed the crucial interconnections between the bone and the brain, highlighting the systemic nature of OA. The neuronal pathway, molecular signaling, circadian rhythms, and genetic underpinnings within the bone-brain axis play vital roles in the complex interplay that contributes to OA initiation and progression. This review explores emerging evidence of the crosstalk between the bone and brain in OA progression, and discusses the potential contributions of the bone-brain axis to the development of effective interventions for managing OA., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Standardized and reliable medical photographs are crucial for preoperative and postoperative comparisons and academic communication in the medical field. There is limited research on photographic techniques in patients with cleft lip. Deformities of the lip and nose in patients with cleft lip are not only associated with morphological abnormalities but also with abnormalities of muscle function., Methods: Considering the morphology and function of the lips and nose in cleft lip patients, the study captured the deformity of cleft lip patients in 6 positions: frontal view, 45 degrees left-right tilted side view, 90 degrees left-right tilted side view, and basal view, and in 5 facial expressions: tightly closed lips, slightly open mouth, smiling, teeth bared, and pout., Results: In 6 different positions and 5 different expressions, we took pictures of lip and nasal deformities covering most of the common deformities in patients with cleft lip, such as white lip scarring, interruption of continuity of vermillion border, lip prolapse, asymmetric corners of the mouth, collapsed ala nasi, loss of the nasal base and deviated nasal septum., Conclusions: This paper suggests a set of effective, easy-to-follow, and precise photographic protocols to assist cleft lip surgeons in capturing suitable and informative, high-quality 2D digital photographs., Level of Evidence: Level-V., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

As a crucial sink of metal-containing nanoparticles (MNPs), road dust can record their spatiotemporal variations in urban environments. In this study, taking Shanghai as a representative megacity in China, a total of 272 dust samples were collected in the winter and summer of 2013 and 2021/2022 to understand the spatiotemporal variations and driving factors of MNPs. The number concentrations of Fe-, Ti-, and Zn-containing NPs were 3.8 × 10 6 - 8.4 × 10 8 , 2.3 × 10 6 -1.4 × 10 8 , and 6.0 × 10 5 -2.3 × 10 8 particles/mg, respectively, according to single particle (sp)ICP-MS analysis. These MNPs showed significantly higher number concentrations in summer than in winter. Hotspots of Fe-containing NPs were more concentrated in industrial and traffic areas, Zn-containing NPs were mainly distributed in the central urban areas, while Ti-containing NPs were abundant in areas receiving high rainfall. The structural equation model results indicates that substantial rainfall in summer can help remove MNPs from atmospheric PM 2.5 into dust, while in winter industrial and traffic activities were the primary contributors for MNPs. Moreover, the contribution of traffic emissions to MNPs has surpassed industrial one over the last decade, highlighting the urgency to control traffic-sourced MNPs, especially those from non-exhaust emissions by electric vehicles., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yi Yang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA-PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important., Purpose: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA-PAI patients without PH., Study Type: Retrospective., Population: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non-PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex- and age-matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography., Field Strength/sequence: 3 T/Cine imaging sequence with a steady-state free precession readout., Assessment: Cardiac MRI-derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA-PAI patients with and without PH., Statistical Tests: Student's t test, one-way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P-value of <0.05 was considered statistically significant., Results: Although the TA-PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non-PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non-PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA-PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non-PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non-PH 14.8 ± 3.9%) than those without PH., Data Conclusion: Right ventricular dysfunction was detected in the TA-PAI patients without PH. MR-feature tracking may be an effective method for detecting early cardiac damage in the TA-PAI patients without PH., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 3., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Light chain cardiac amyloidosis (AL-CA) is associated with a high incidence of mortality. Big endothelin-1 (ET-1), the precursor of endothelial-vasoconstrictive ET-1, is closely related to the concentration of bioactive ET-1. Association between big ET-1 and prognosis of AL-CA has not yet been documented. The purpose of this study was to evaluate the prognostic value of big ET-1 for poor outcomes in moderate to severe AL-CA., Methods: Big ET-1 levels were determined on admission in patients with newly diagnosed AL-CA with modified Mayo 2004 stage II or III. Primary outcome was all-cause mortality. The secondary outcomes included death from cardiac cause and the composite of the primary outcome or hospitalisations due to worsening heart failure., Results: Overall, 141 patients were retrospectively included (57 stage II, 34 stage IIIa, 50 stage IIIb). During a median follow-up time of 25.7 months, 84 (59.6%) patients died. Patients with big ET-1 levels of ≤0.88 pmol/L had longer survival than those with >0.88 pmol/L (median survival time: 34.1 months vs 15.3 months, log-rank p<0.001), which was also observed in the validation cohort (log-rank p=0.026). Higher big ET-1 levels were predictive for all-cause mortality after multivariable adjustment (HR 1.91, 95% CI 1.05 to 3.49, p=0.035). Big ET-1 levels added an incremental prognostic value over modified Mayo 2004 stage (C-index: from 0.671 to 0.696, p=0.025; integrated discrimination improvement 0.168, p=0.047)., Conclusions: Big ET-1 is a strong and independent predictor of mortality in patients with moderate to severe AL-CA, which may indicate a possible role for risk stratification in patients with this disease., Competing Interests: Competing interests: NL declares fees from Alnylam and Pfizer unrelated to this article. AJF declares fees from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Imedos Systems, Medtronic, MSD, Mundipharma, Novartis, Novo Nordisk, Pierre Fabre, Pfizer, Roche, Schwabe Pharma, Vifor and Zoll, as well as grant support by Novartis, AstraZeneca and Berlin Heart unrelated to this article., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The main purpose of this study was to explore the mechanical properties of the anterior cruciate ligament and its attachments following reconstruction with the all-inside technique after anterior cruciate ligament injury., Methods: Knee joint computed tomography data were collected from healthy volunteers, and knee joint models were created using Mimics software. A normal knee joint model, an all-inside reconstructed anterior cruciate ligament model, and a traditional reconstructed anterior cruciate ligament model were established. A tensile force of 134 N and a bending moment of 5 N/m were applied at the anterior aspect of the proximal tibia in these three models. The knee joint was subjected to external rotation, internal rotation, varus, valgus, flexion, and extension under this bending moment. The magnitude and distribution of stress on the ligament or graft and the magnitude and distribution of stress on the graft attachments were observed under different loading conditions., Results: Under different external forces, the maximum stress on the ligament in the normal model fluctuated from 1.949 to 18.302 MPa, with an uncertain distribution of maximum stress. The maximum stress on the graft in the all-inside reconstructed anterior cruciate ligament model fluctuated from 0.705 to 3.465 MPa and was mainly distributed at the junction of the graft and the tibial footprint. In the traditional reconstructed anterior cruciate ligament model, the maximum stress on the graft fluctuated from 5.012 to 59.269 MPa and was primarily distributed at the junction of the interference screw and the graft. The concentration of stress on the loop and plate in the all-inside reconstructed anterior cruciate ligament model fluctuated from 70.461 to 346.363 MPa, with maximum stress distributed at the junction of the loop and the tibial surface. The maximum stress on the interference screw in the traditional reconstructed anterior cruciate ligament model fluctuated from 10.184 to 92.298 MPa, with maximum stress primarily distributed at the end of the interference screw., Conclusion: Under different external forces, the graft used in all-inside anterior cruciate ligament reconstruction is subjected to fewer external forces than that used in traditional anterior cruciate ligament reconstruction, which may indicate a relatively stable mechanical environment. The strength of the loop and plate can theoretically tolerate daily knee joint movements of patients without injury., 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, Xue, Li, Mu, Yao, Wang, Chen and Zhang.)

The Xuanfei Baidu (XFBD) prescription, a traditional Chinese medicine prescription, has demonstrated significant anti-inflammatory activities; however, the number of its reported constituents is limited, and its anti-inflammatory constituents are unclear. In this study, the constituents of XFBD granule, a granule dosage of XFBD prescription, were thoroughly examined in vitro and in vivo using liquid chromatography-quadruple-time-of-flight-mass spectrometry, and the anti-inflammatory constituents were screened. A total of 214 constituents were identified from the XFBD granule, 62 of which were confirmed via comparison with reference standards. After intragastric administration of XFBD granule, 63 and 28 constituents were absorbed into the rat sera and lungs in prototype form, respectively. XFBD granule and XFBD-containing serum were found to significantly reduce nitric oxide (NO) and interleukin-6 (IL-6) secretion in lipopolysaccharide-induced RAW264.7 cells. Five anti-inflammatory constituents (verbasoside, scutellarin, luteolin, apigenin, and pogostone) were found to reduce the concentration of NO and IL-6 in a dose-dependent manner. Moreover, the combination of these five constituents could significantly reduce NO secretion even when the concentration of each constituent was two to three orders of magnitude lower than their individual minimum effective concentrations. Overall, this study provides a valuable reference for the discovery of effective constituents from the XFBD granule., (© 2024 John Wiley & Sons Ltd.)

Aims: To predict the vagus nerve stimulation (VNS) efficacy for pediatric drug-resistant epilepsy (DRE) patients, we aim to identify preimplantation biomarkers through clinical features and electroencephalogram (EEG) signals and thus establish a predictive model from a multi-modal feature set with high prediction accuracy., Methods: Sixty-five pediatric DRE patients implanted with VNS were included and followed up. We explored the topological network and entropy features of preimplantation EEG signals to identify the biomarkers for VNS efficacy. A Support Vector Machine (SVM) integrated these biomarkers to distinguish the efficacy groups., Results: The proportion of VNS responders was 58.5% (38/65) at the last follow-up. In the analysis of parieto-occipital α band activity, higher synchronization level and nodal efficiency were found in responders. The central-frontal θ band activity showed significantly lower entropy in responders. The prediction model reached an accuracy of 81.5%, a precision of 80.1%, and an AUC (area under the receiver operating characteristic curve) of 0.838., Conclusion: Our results revealed that, compared to nonresponders, VNS responders had a more efficient α band brain network, especially in the parieto-occipital region, and less spectral complexity of θ brain activities in the central-frontal region. We established a predictive model integrating both preimplantation clinical and EEG features and exhibited great potential for discriminating the VNS responders. This study contributed to the understanding of the VNS mechanism and improved the performance of the current predictive model., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD., Methods: A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria., Results: A total of 5700 patients were included, with a mean age of 66.4 years old. During a median of 3.29 years follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria ( P  > 0.05)., Conclusion: This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups., Registration: URL: https://clinicaltrials.gov/ , Unique identifier: NCT01206062., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Individuals experience difficulty falling asleep in a new environment, termed the first night effect (FNE). However, the impact of the FNE on sleep-induced brain plasticity remains unclear. Here, using a within-subject design, we found that the FNE significantly reduces visual plasticity during sleep in young adults. Sleep-onset latency (SOL), an indicator of the FNE, was significantly longer during the first sleep session than the second session, confirming the FNE. We assessed performance gains in visual perceptual learning after sleep and increases in the excitatory-to-inhibitory neurotransmitter (E/I) ratio in early visual areas during sleep using magnetic resonance spectroscopy and polysomnography. These parameters were significantly smaller in sleep with the FNE than in sleep without the FNE; however, these parameters were not correlated with SOL. These results suggest that while the neural mechanisms of the FNE and brain plasticity are independent, sleep disturbances temporarily block the neurochemical process fundamental for brain plasticity., (© 2024. The Author(s).)

The pervasive use of information technologies (IT) has tremendously benefited our daily lives. However, unpredicted technical breakdowns and errors can lead to the experience of stress, which has been termed technostress. It remains poorly understood how people dynamically respond to unpredicted system runtime errors occurring while interacting with the IT systems on a behavioral and neuronal level. To elucidate the mechanisms underlying such processes, we conducted a functional magnetic resonance imaging (fMRI) study in which 15 young adults solved arithmetic problems of three difficulty levels (easy, medium and hard) while two types of system runtime errors (problem errors and feedback errors) occurred in an unexpected manner. The problem error condition consisted of apparently defective displays of the arithmetic problem and the feedback error condition involved erroneous feedback. We found that the problem errors positively influenced participants' problem-solving performance at the high difficulty level (i.e., hard tasks) at the initial stage of the session, while feedback errors disturbed their performance. These dynamic behavioral changes are mainly associated with brain activation changes in the posterior cingulate and the default mode network, including the posterior cingulate cortex, the mPFC, the retrosplenial cortex and the parahippocampal gyrus. Our study illustrates the regulatory role of the posterior cingulate in coping with unpredicted errors as well as with dynamic changes in the environment., (© 2024. The Author(s).)

Drought is one of the natural stresses that greatly impact plants. Castor bean (Ricinus communis L.) is an oil crop with high economic value. Drought is one of the factors limiting castor bean growth. The drought resistance mechanisms of castor bean have become a research focus. In this study, we used castor germinating embryos as experimental materials, and screened genes related to drought resistance through physiological measurements, proteomics and metabolomics joint analysis; castor drought-related genes were subjected to transient silencing expression analysis in castor leaves to validate their drought-resistant functions, and heterologous overexpression and backward complementary expression in Arabidopsis thaliana, and analysed the mechanism of the genes' response to the participation of Arabidopsis thaliana in drought-resistance.Three drought tolerance-related genes, RcECP 63, RcDDX 31 and RcA/HD1, were obtained by screening and analysis, and transient silencing of expression in castor leaves further verified that these three genes corresponded to drought stress, and heterologous overexpression and back-complementary expression of the three genes in Arabidopsis thaliana revealed that the function of these three genes in drought stress response.In this study, three drought tolerance related genes, RcECP 63, RcDDX 31 and RcA/HD1, were screened and analysed for gene function, which were found to be responsive to drought stress and to function in drought stress, laying the foundation for the study of drought tolerance mechanism in castor bean., (© 2024. The Author(s).)

It has remained unclear whether individuals with psychiatric disorders involving altered visual processing employ similar neuronal mechanisms during perceptual learning of a visual task. We investigated this question by training patients with body dysmorphic disorder, a psychiatric disorder characterized by distressing or impairing preoccupation with nonexistent or slight defects in one's physical appearance, and healthy controls on a visual detection task for human faces with low spatial frequency components. Brain activation during task performance was measured with functional magnetic resonance imaging before the beginning and after the end of behavioral training. Both groups of participants improved performance on the trained task to a similar extent. However, neuronal changes in the fusiform face area were substantially different between groups such that activation for low spatial frequency faces in the right fusiform face area increased after training in body dysmorphic disorder patients but decreased in controls. Moreover, functional connectivity between left and right fusiform face area decreased after training in patients but increased in controls. Our results indicate that neuronal mechanisms involved in perceptual learning of a face detection task differ fundamentally between body dysmorphic disorder patients and controls. Such different neuronal mechanisms in body dysmorphic disorder patients might reflect the brain's adaptations to altered functions imposed by the psychiatric disorder., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cell fate is precisely modulated by complex but well-tuned molecular signaling networks, whose spatial and temporal dysregulation commonly leads to hazardous diseases. Biomolecular condensates (BCs), as a newly emerging type of biophysical assemblies, decipher the molecular codes bridging molecular behaviors, signaling axes, and clinical prognosis. Particularly, physical traits of BCs play an important role; however, a panoramic view from this perspective toward clinical practices remains lacking. In this review, we describe the most typical five physical traits of BCs, and comprehensively summarize their roles in molecular signaling axes and corresponding major determinants. Moreover, establishing the recent observed contribution of condensate physics on clinical therapeutics, we illustrate next-generation medical strategies by targeting condensate physics. Finally, the challenges and opportunities for future medical development along with the rapid scientific and technological advances are highlighted.

Aims: Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in different patient populations. We aimed to compare the association of BMI, frailty, and clinical adverse events between a US cohort from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study and a Chinese cohort from the Heart Failure Registry of Patient Outcomes (HERO) study., Methods and Results: We used data of 1715 participants enrolled from America in the TOPCAT study and 1487 patients with HFpEF in the Chinese registry study, the HERO. We evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all-cause mortality, and HF hospitalization were analysed by Cox proportional hazards models. The patients' mean age was 72 ± 11 years for both study populations, with 50% and 46% female for the TOPCAT study and the HERO study, respectively. Patients in the TOPCAT study had a higher mean BMI (33.9 vs. 24 kg/m 2 ), with 72.3% vs. 52.9% defined as moderately to severely frail (frailty index > 0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [hazard ratio (HR) 1.84 (95% confidence interval: 1.46-2.32)], all-cause mortality [HR 1.73 (1.34-2.25)], and HF hospitalization [HR 1.83 (1.40-2.40)] in the TOPCAT study. The corresponding numbers in the HERO study were 1.26 (1.01-1.57), 2.21 (1.45-3.35), and 1.15 (0.81-1.37), respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies., Conclusions: BMI distribution and association between BMI and frailty risk were different between the two study populations. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment., Methods: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed., Results: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes., Conclusion: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes., (© 2023 The Association for the Publication of the Journal of Internal Medicine.)

China leads the world in freshwater pearl production, an industry in which the triangle sail mussel ( Sinohyriopsis cumingii ) plays a pivotal role. In this paper, we report a high-quality chromosome-level genome assembly of S. cumingii with a size of 2.90 Gb-the largest yet reported among bivalves-and 89.92% anchorage onto 19 linkage groups. The assembled genome has 37,696 protein-coding genes and 50.86% repeat elements. A comparative genomic analysis revealed expansions of 752 gene families, mostly associated with biomineralization, and 237 genes under strong positive selection. Notably, the fibrillin gene family exhibited gene family expansion and positive selection simultaneously, and it also exhibited multiple high expressions after mantle implantation by transcriptome analysis. Furthermore, RNA silencing and an in vitro calcium carbonate crystallization assay highlighted the pivotal role played by one fibrillin gene in calcium carbonate deposition and aragonite transformation. This study provides a valuable genomic resource and offers new insights into the mechanism of pearl biomineralization.

Background: To evaluate whether cancer modifies the effect of intensive blood pressure control on major cardiovascular outcomes., Methods: Using data of the SPRINT (Systolic Blood Pressure Intervention Trial), we compared the risk of the composite outcomes of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death in patients with and without a history of cancer. Using Cox proportional hazards regression, we tested interactions between history of cancer and intensive blood pressure control on major cardiovascular outcomes., Results: The study included a total of 9336 patients, with a mean age of 67.9±9.4 years, among whom 2066 (22.2%) were cancer survivors. Over a median follow-up of 3.2 years, 561 primary cardiovascular outcomes were observed. Cancer survivors had a similar risk of experiencing the primary outcome compared with patients without cancer after multivariable adjustment (adjusted hazard ratio, 0.94 [95% CI, 0.77-1.15]). Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, 0.51-0.97]) and patients without cancer (HR, 0.76 [95% CI, 0.63-0.93]; P for interaction 0.74)., Conclusions: In SPRINT study, intensive blood pressure treatment reduced the risk of major cardiovascular events in cancer survivors to a similar extent to that of patients without cancer. Cancer history not requiring active treatment in last 2 years should not be an obstacle to intensive treatment of hypertension. This post hoc analysis should be considered as hypothesis-generating and merit further clinical trial., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062., Competing Interests: Disclosures None.

Alginate lyase Aly448, a potential new member of the polysaccharide lyase (PL) 7 family, which was cloned and identified from the macroalgae-associated bacterial metagenomic library, showed bifunctionality. The molecular docking results revealed that Aly448 has two completely different binding sites for alginate (polyMG), poly-α-l-guluronic acid (polyG), and poly-β-d-mannuronic acid (polyM) substrates, respectively, which might be the molecular basis for the enzyme's bifunctionality. Truncational results confirmed that predicted key residues affected the bifunctionality of Aly448, but did not wholly explain. Besides, Aly448 presented excellent biochemical characteristics, such as higher thermal stability and pH tolerance. Degradation of polyMG, polyM, and polyG substrates by Aly448 produced tetrasaccharide (DP4), disaccharide (DP2), and galactose (DP1), which exhibited excellent antioxidant activity. These findings provide novel insights into the substrate recognition mechanism of bifunctional alginate lyases and pave a new path for the exploitation of natural antioxidant agents.

Methamphetamine abuse results in a host of social and medical issues. Methamphetamine use disorder (MUD) can hinder the brain and impair cognitive functions and mental health. Transcranial magnetic stimulation (TMS) is a non-invasive approach in the treatment of MUD. Recent studies have demonstrated encouraging and positive effects of TMS on the craving, affective symptoms, sleep quality, and cognitive functions in individuals with MUD. The regulation of specific brain activities through TMS has also been found to be a contributing factor to these positive outcomes. It is essential to employ more techniques, participants, and stimulation parameters and targets in the future., 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 Published by Elsevier Ltd.)

Soilborne diseases cause significant economic losses in agricultural production around the world. They are difficult to control because a host plant is invaded by multiple pathogens, and chemical control often does not work well. In this study, we isolated and identified an endophytic Streptomyces sp. NEAU-DD186 from moss, which showed broad-spectrum antifungal activity against 17 soilborne phytopathogenic fungi, with Bipolaris sorokiniana being the most prominent. The strain also exhibited strong antibacterial activity against soilborne phytopathogenic bacteria Ralstonia solanacearum . To evaluate its biocontrol potential, the strain was prepared into biofertilizer by solid-state fermentation. Response surface methodology was employed to optimize the fermentation conditions for maximizing spore production and revealed that the 1:1 ratio of vermicompost to wheat bran, a temperature of 28°C, and 50% water content with an inoculation amount of 15% represented the optimal parameters. Pot experiments showed that the application of biofertilizer with a spore concentration of 10 8 CFU/g soil could effectively suppress the occurrence of tomato bacterial wilt caused by R. solanacearum and wheat root rot caused by B. sorokiniana , and the biocontrol efficacy was 81.2 and 72.2%, respectively. Chemical analysis of strain NEAU-DD186 extracts using nuclear magnetic resonance spectrometry and mass analysis indicated that 25-O-malonylguanidylfungin A and 23-O-malonylguanidylfungin A were the main active constituents, which showed high activity against R. solanacearum (EC 50 of 2.46 and 2.58 µg ml -1 ) and B. sorokiniana (EC 50 of 3.92 and 3.95 µg ml -1 ). In conclusion, this study demonstrates that Streptomyces sp. NEAU-DD186 can be developed as biofertilizer to control soilborne diseases., Competing Interests: The author(s) declare no conflict of interest.

Aim: The purpose of this study was to comprehensively explore the ocular toxicity associated with chimeric antigen receptor (CAR) T-cell therapy. Materials & methods: Data were assembled from the US FDA's Adverse Event Reporting System (FAERS) database from 2017 to 2023. Information component and reporting odds ratio methods were used for signal detection in total/categorized CAR T-cell therapy. Results: A total of 17 positive signals (preferred term) were detected, yet none of them were documented in the product information. Some adverse events were with death outcomes and overlapped a lot with cytokine-release syndrome. Conclusion: The ocular adverse events associated with CAR-T cell therapy are noteworthy, and it is imperative to maintain increased alertness and institute early intervention strategies.

Osteosarcomas are malignant bone tumors that typically originate in the epiphyses of the long bones of the extremities in adolescents. Asiatic acid has been reported to possess anti‑inflammatory, neuroprotective, antidiabetic, antitumor and antimicrobial activities. The present study used a combination of network pharmacological prediction and in vitro experimental validation to explore the potential pharmacological mechanism of asiatic acid against osteosarcoma. A total of 78 potential asiatic acid targets in osteosarcoma were identified using databases. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the PI3K/AKT and MAPK signaling pathways are essential in the treatment of osteosarcoma with asiatic acid. Molecular docking revealed binding of asiatic acid to EGFR, Caspase‑3, ESR1, HSP90AA1, IL‑6 and SRC proteins. asiatic acid inhibited proliferation through G2/M cell cycle arrest in osteosarcoma cells. In addition, asiatic acid induced mitochondria‑dependent apoptosis as demonstrated by increases in Bax and VDAC1 expression, and a decrease in Bcl‑2 protein expression. The increased autophagosomes, increased LC3‑II/I ratios and decreased p62 expression in the treatment group indicated that asiatic acid triggered autophagy. In addition, asiatic acid decreased the levels of phosphorylated (p‑)PI3K/PI3K and p‑AKT/AKT, increased reactive oxygen species (ROS) and upregulated the levels of p‑ERK1/2/ERK1/2, p‑p38/p38 and p‑JNK/JNK in osteosarcoma cells. These results demonstrated that asiatic acid inhibited osteosarcoma cells proliferation by inhibiting PI3K/AKT and activating ROS/MAPK signaling pathways, suggesting asiatic acid is a potential agent against osteosarcoma.

Objective: Sacral nerve stimulation (SNS) is emerging as a novel treatment for irritable bowel syndrome (IBS). However, its effects are limited, and the underlying mechanisms remain largely unknown., Materials and Methods: In this study, rats were divided into three groups (n = 12 rats per group): 1) the SNS group; 2) the sham SNS group (the sham group for short); and 3) the control group. The SNS and sham groups were exposed to chronic and acute stress to establish an IBS model. Electrode implantation surgery was performed in rats with the IBS model. The SNS group received electrical stimulation for 30 minutes every day for seven days. Abdominal withdrawal reflex (AWR) was used to evaluate the effect of SNS on visceral sensitivity in diarrhea-predominant IBS (IBS-D) rats. The frequency domain of heart rate variability (HRV) was analyzed to assess the effect of SNS on regulating the autonomic function. The expression of transient receptor potential vanilloid 1 (TRPV1) in the colon, spinal cord, and hippocampus was detected by immunohistochemistry to explore the mechanism of SNS in IBS-D rats., Results: Compared with the sham group, AWR scores were significantly decreased under different gas volumes of stimulation of 0.4, 0.6, and 0.8 ml for rectal distention in the SNS group (all p < 0.05). However, there was no significant difference <1.0 ml between the two groups (p > 0.05). Compared with the sham group, the frequency domain indexes of HRV were significantly altered. Normalized low-frequency power and low frequency-to-high frequency ratio were significantly decreased, and normalized high-frequency power was significantly increased in the SNS group (all p < 0.05). Moreover, the expression of TRPV1 in the spinal cord and colon in the SNS group was significantly decreased compared with the sham group (both p < 0.05). These results suggested that chronic SNS not only improved the visceral sensitivity and autonomic dysfunction but also decreased the expression of TRPV1 in the spinal cord-gut tissue in IBS-D rats., Conclusion: Chronic SNS was found to have an inhibitory effect on visceral hypersensitivity in IBS-D rats, providing experimental evidence for its potential clinical application in IBS., Competing Interests: Conflict of interest The authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Individuals experience difficulty falling asleep in a new environment, termed the first night effect (FNE). However, the impact of the FNE on sleep-induced brain plasticity remains unclear. Here, using a within-subject design, we found that the FNE significantly reduces visual plasticity during sleep in young adults. Sleep-onset latency (SOL), an indicator of the FNE, was significantly longer during the first sleep session than the second session, confirming the FNE. We assessed performance gains in visual perceptual learning after sleep and increases in the excitatory-to-inhibitory neurotransmitter (E/I) ratio in early visual areas during sleep using magnetic resonance spectroscopy and polysomnography. These parameters were significantly smaller in sleep with the FNE than in sleep without the FNE; however, these parameters were not correlated with SOL. These results suggest that while the neural mechanisms of the FNE and brain plasticity are independent, sleep disturbances temporarily block the neurochemical process fundamental for brain plasticity.

It is generally believed that learning of a perceptual task involving low-level neuronal mechanisms is similar between individuals. However, it is unclear whether this assumption also applies to individuals with psychiatric disorders that are known to have altered brain activation during visual processing. We investigated this question in patients with body dysmorphic disorder (BDD), a psychiatric disorder characterized by distressing or impairing preoccupation with nonexistent or slight defects in one's physical appearance, and in healthy controls. Participants completed six training sessions on separate days on a visual detection task for human faces with low spatial frequency (LSF) components. Brain activation during task performance was measured with functional magnetic resonance imaging (fMRI) on separate days prior to and after training. The behavioral results showed that both groups of participants improved on the visual detection task to a similar extent through training. Despite this similarity in behavioral improvement, neuronal changes in the Fusiform Face Area (FFA), a core cortical region involved in face processing, with training were substantially different between groups. First, activation in the right FFA for LSF faces relative to High Spatial Frequency (HSF) faces that were used as an untrained control increased after training in BDD patients but decreased in controls. Second, resting state functional connectivity between left and right FFAs decreased after training in BDD patients but increased in controls. Contrary to the assumption that learning of a perceptual task is subserved by the same neuronal mechanisms across individuals, our results indicate that the neuronal mechanisms involved in learning of a face detection task differ fundamentally between patients with BDD and healthy individuals. The involvement of different neuronal mechanisms for learning of even simple perceptual tasks in patients with BDD might reflect the brain's adaptations to altered functions imposed by the psychiatric disorder., Competing Interests: Conflict of Interests: The authors declare no conflict of interest.

Both the midbrain systems, encompassing the ventral striatum (VS), and the cortical systems, including the dorsal anterior cingulate cortex (dACC), play roles in reinforcing and enhancing learning. However, the specific contributions of signals from these regions in learning remains unclear. To investigate this, we examined how VS and dACC are involved in visual perceptual learning (VPL) through an orientation discrimination task. In the primary experiment, subjects fasted for 5 hours before each of 14 days of training sessions and 3 days of test sessions. Subjects were rewarded with water for accurate trial responses. During the test sessions, BOLD signals were recorded from regions including VS and dACC. Although BOLD signals in both areas were associated with positive and negative RPEs, only those in dACC associated with negative RPE showed a significant correlation with performance improvement. Additionally, no significant correlation was observed between BOLD signals associated with RPEs in VS and dACC. These results suggest that although signals associated with positive and negative RPEs from both midbrain and cortical systems are readily accessible, only RPE signals in the prefrontal system, generated without linking to RPE signals in VS, are utilized for the enhancement of VPL.

Background: Systolic blood pressure (SBP) time in target range (TTR) indicates the mean value, exposure time, and variability in blood pressure over time. The prognostic value of SBP TTR for incident atrial fibrillation (AF) in patients with hypertension is unclear., Methods: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. SBP target ranges for intensive and standard arms were defined as 110 to 130 and 120 to 140 mm Hg, respectively. TTR was calculated by linear interpolation method using SBP from months 0 to 3. We used Cox proportional regression models to assess the association of SBP TTR with incident AF., Results: Among 7939 participants included in this analysis, 187 incident AF cases occurred during follow-up. After multivariable adjustment, a 10% increase in SBP TTR was independently associated with a 7% lower risk of incident AF (hazard ratio, 0.93 [95% CI, 0.88-0.97]; P =0.003). The restricted spline curve depicted a linear and inverse relationship between SBP TTR and incident AF. Sensitivity analyses generated consistent results when calculating TTR over a longer period or setting target range as 110 to 140 mm Hg for the whole population., Conclusions: Higher SBP TTR independently predicts a lower risk of incident AF. Efforts to attain SBP within 110 to 140 mm Hg over time may be an effective strategy to prevent AF., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01206062., Competing Interests: Disclosures C. Ma has received honoraria for presentations from AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, and Pfizer. J. Dong has received honoraria for presentations from Johnson & Johnson. All other authors declare no competing interests.

Osteoarthritis (OA) is a joint disease characterized by articular cartilage loss, which afflicts many people worldwide. Knowing the disease severity can improve the recovery rate of OA. Antibody array technology was utilized for protein expression profiling of synovial fluid from eight mild knee OA patients, eight severe knee OA patients and 16 healthy persons. Subsequently, 48 mild OA patients, 56 severe OA patients and 24 healthy controls were utilized for validation by ELISA. In the protein expression profiling, inducible costimulator (ICOS) levels were markedly higher in OA patients compared with those in the healthy population, and were significantly higher in severe OA than those in mild OA. Furthermore, ICOS levels were shown to be significantly correlated with WOMAC, MRI-MOAKS and MRI-UTE-T2* scores. The multivariate logistic regression analysis indicated that higher levels of ICOS could significantly increase the risk of severe OA. Synovial ICOS levels were positively correlated with the radiographic severity of OA. ICOS may represent a biomarker for predicting the OA severity and may be involved in the development and progression of knee OA., (© 2023 The Scandinavian Foundation for Immunology.)

The lesion core is the area with the most serious injury and vigorous repair. Existing nanocarriers are difficult to break through the targeted delivery to the lesion core for precise treatment in the intracellular and extracellular microenvironment. Herein, a cellular membrane-engineered nanovesicle (CMEV) with a hierarchical structure is constructed using the double emulsion-extrusion method by integrating a neutrophil membrane, functional antibody, and gelled drug-loaded core as a three-stage booster to target the lesion core and deliver catestatin (CST), a small therapeutic peptide, for ischemic cardiomyopathy therapy. By coating the neutrophil membrane outside the shell, CMEV is endowed with the function of neutrophil-like migration to achieve the first stage of tissue targeting. Based on the specific anchoring to injured myocardium, a myosin light chain 3 (MLC3) antibody is embedded to fulfill the second stage of CMEV accumulation in the lesion core. The gelled core containing CST-sodium alginate (NaAlg) with a pH-responsive shell is prepared by ionic cross-linking to accomplish the third stage of precise CST administration. Triggered by the microenvironment, NaAlg electrostatically adheres to the lesion core for sustained release, enhancing the efficacy of CST in improving cardiomyocyte apoptosis, excessive fibrosis, macrophage polarization, and angiogenesis. Thus, the "three-stage booster" nanovesicle significantly ameliorates cardiac function and adverse remodeling to treat ischemic cardiomyopathy., (© 2023 Wiley-VCH GmbH.)

Innovation has emerged as a crucial factor in the sustenance and growth of enterprises. Nonetheless, small and medium-sized enterprises (SMEs) confront numerous challenges in their pursuit of innovation, owing to constraints in capital, expertise, and knowledge resources. Drawing on the resource-based theory and the input-process-output (IPO) model, this study devises a mechanism model to assess the impact of knowledge heterogeneity and innovation performance on small and medium-sized manufacturing enterprises in Guizhou Province, China. The objective is to offer recommendations for the advancement and innovation of enterprises with relative knowledge resource deficiencies. A total of 324 valid questionnaires were gathered, and the acquired data were analyzed employing SPSS 23.0 and Amos 26.0. The findings reveal that knowledge heterogeneity exerts a significantly positive influence on innovation performance. Task conflict and relationship conflict serve as partial mediators in the effects of knowledge heterogeneity on innovation performance. By capitalizing on the heterogeneity of internal and external knowledge, enterprises can effectively enhance their innovation outcomes. Furthermore, the study demonstrates that knowledge sharing possesses a moderating effect on the impact of knowledge heterogeneity on task conflict, relationship conflict, and innovation performance. In a conducive sharing environment, the ultimate effect of knowledge heterogeneity on innovation is subject to alteration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gan 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.)

Blau syndrome (BS) is a rare genetic immune disease which commonly presents in childhood. Currently, the miss-rate of BS diagnosis is very high, and an effective clinical management of BS has not been well established. This case report depicts a 54-year-old male Chinese patient presenting with hand malformation, fever, skin rash and joint pain. His diagnosis was ultimately confirmed according to typical medical history and genetic analysis. This case report will further help clinicians to be aware of this rare clinical entity for correct diagnosis and proper treatment., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Soil-borne diseases cause significant economic losses in global agricultural production. These diseases are challenging to control due to the invasion of multiple pathogens into host plants, and traditional chemical control methods often yield unsatisfactory results. In this study, we isolated and identified an endophytic Streptomyces , designated as NEAU-ZSY13, from the leaf of Perilla frutescens . This isolate exhibited broad-spectrum antifungal activity against 17 soil-borne phytopathogenic fungi, with Bipolaris sorokiniana being the most prominent. Additionally, it displayed strong antibacterial activity against the soil-borne phytopathogenic bacterium Ralstonia solanacearum . To assess its biocontrol potential, the isolate was utilized to produce a biofertilizer through solid-state fermentation. The fermentation conditions were optimized using response surface methodology to maximize the spore production. The results revealed that more abundant spores were produced with a 1:2 ratio of vermicompost to wheat bran, 60% water content, 20% inoculation amount and 28°C. Subsequent pot experiments demonstrated that the application of the biofertilizer with a spore concentration of 10 8  CFU/g soil effectively suppressed the occurrence of tomato bacterial wilt caused by R. solanacearum and wheat root rot caused by B. sorokiniana , with biocontrol efficacies of 72.2 and 78.3%, respectively. Chemical analysis of NEAU-ZSY13 extracts, using nuclear magnetic resonance spectrometry and mass analysis, identified niphimycin C and niphimycin A as the primary active constituents. These compounds exhibited high activity against R. solanacearum (EC 50 of 3.6 and 2.4 μg mL -1 ) and B. sorokiniana (EC 50 of 3.9 and 3.4 μg mL -1 ). In conclusion, this study demonstrates the potential of Streptomyces sp. NEAU-ZSY13 as a biofertilizer for the control of soil-borne diseases., 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 © 2023 Wang, Gao, Yang, Du, Zeng, Bing, Xia, Shen and Liu.)

Background: Frailty is associated with an increased risk of all-cause death and cardiovascular events. However, it is uncertain whether frailty modifies the efficacy and safety of intensive blood pressure control., Methods: Data from SPRINT (Systolic Blood Pressure Intervention Trial) were used to construct a frailty index. Subgroup differences in intensive blood pressure control treatment effects and safety outcomes were measured on a relative and an absolute scale in patients with and without frailty (defined as a frailty index >0.21) using Cox proportional hazard models and generalized linear models, respectively. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death., Results: A total of 9306 patients (mean age, 67.9±9.4 years), 2560 (26.7%) of whom had frailty, were included in our study. Over a median follow-up of 3.22 years, 561 primary outcomes were observed. Patients with frailty had a significantly higher risk of primary outcome in both the intensive and standard blood pressure control arms (adjusted hazard ratio, 2.10 [95% CI, 1.59-2.77] and 1.85 [95% CI, 1.46-2.35], respectively). Intensive treatment effects on primary and secondary outcomes were not significantly different on a relative scale (except for cardiovascular death [hazard ratio in patients with and without frailty, 0.91 (95% CI, 0.52-1.60) versus 0.30 (95% CI, 0.16-0.59), respectively; P interaction =0.01]) or absolute scale. There was no significant interaction between frailty and risks for serious adverse events with intensive treatment., Conclusions: Frailty status was a marker of high cardiovascular risk. Patients with frailty benefit similarly to other patients from intensive blood pressure control without an increased risk of serious adverse events., Competing Interests: Disclosures None.

Although alveolar macrophages (AMs) play important roles in preventing and eliminating pulmonary infections, little is known about their regulation in healthy animals. Since exposure to LPS often renders cells hyporesponsive to subsequent LPS exposures ("tolerant"), we tested the hypothesis that LPS produced in the intestine reaches the lungs and stimulates AMs, rendering them tolerant. We found that resting AMs were more likely to be tolerant in mice lacking acyloxyacyl hydrolase (AOAH), the host lipase that degrades and inactivates LPS; isolated Aoah-/- AMs were less responsive to LPS stimulation and less phagocytic than were Aoah+/+ AMs. Upon innate stimulation in the airways, Aoah-/- mice had reduced epithelium- and macrophage-derived chemokine/cytokine production. Aoah-/- mice also developed greater and more prolonged loss of body weight and higher bacterial burdens after pulmonary challenge with Pseudomonas aeruginosa than did wildtype mice. We also found that bloodborne or intrarectally-administered LPS desensitized ("tolerized") AMs while antimicrobial drug treatment that reduced intestinal commensal Gram-negative bacterial abundance largely restored the innate responsiveness of Aoah-/- AMs. Confirming the role of LPS stimulation, the absence of TLR4 prevented Aoah-/- AM tolerance. We conclude that commensal LPSs may stimulate and desensitize (tolerize) alveolar macrophages in a TLR4-dependent manner and compromise pulmonary immunity. By inactivating LPS in the intestine, AOAH promotes antibacterial host defenses in the lung., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cheng 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.)

Uncertainties about the efficacy of influenza vaccination for populations with heart failure (HF) in preventing cardiovascular outcomes, as well as lack of effective vaccination strategies, may contribute to low vaccine coverage rate (VCR) in China and globally. We assessed the feasibility of a strategy to promote influenza vaccines in patients hospitalized with acute HF in China and to inform the design of a hybrid effectiveness-implementation cluster randomized trial to evaluate this strategy on mortality and hospital re-admission. We conducted a cluster randomized pilot trial involving 11 hospitals in Henan Province in China, with mixed-methods evaluation between December 2020 and April 2021. A process evaluation involved interviews with 51 key informants (patients, health professionals, policy makers). The intervention included education about influenza vaccination and availability of free vaccines administered prior to hospital discharge for HF patients, while usual care included attending community-based points of vaccination (PoV) for screening and vaccination. Implementation outcomes focused on reach, fidelity, adoption, and acceptability. Recruitment rates were assessed for trial feasibility. Effectiveness outcomes were influenza VCR, HF-specific rehospitalizations and mortality at 90 days. A total of 518 HF patients were recruited from 7 intervention and 4 usual care hospitals (mean of 45 participants per hospital per month). VCR was 89.9% (311/346, 86.1-92.8%) in the intervention group and 0.6% (1/172, 0.0-3.7%) in the control group. The process evaluation demonstrated reach to patients with lower socioeconomic and education status. There was good fidelity of the intervention components, with education and PoV set up processes being adapted to local hospital workflow and workforce capacity. Intervention was acceptable and adopted by patients and health professionals. However, outside of a trial setting, concerns were raised around vaccination reimbursement costs, workforce accountability and capacity. The intervention strategy appears feasible and acceptable for improving VCR in HF patients at county-level hospitals in China. Trial registration: This pilot trial is registered with the acronym PANDA II Pilot (Population Assessment of Influenza and Disease Activity) at ChiCTR.org.cn (ChiCTR2000039081)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu 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.)