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Dissolved organic carbon (DOC) components can be highly variable in aquatic ecosystems, and play a pivotal role in the global carbon cycles. To comprehend potential effects of nutrient enrichment on portion of DOC biodegradability (%BDOC), we conducted an extensive investigation on 26 urban lakes in a major metropolitan area in subtropical China in a small gradient of trophic levels from mesotrophic to light and middle eutrophic. In addition to field measurements on lake ambient conditions and laboratory analysis of DOC characteristics, we conducted a 28-day temperature-controlled incubation experiment, in which %BDOC of lake waters was determined. In the mesotrophic waters, %BDOC ranged from 0.6 to 41.4 % (11.2 ± 8.9 %). The %BDOC levels spanned from 5.2 to 20.2 % (10.7 ± 4.0 %) in the light eutrophic waters, and the %BDOC ranged from 2.7 to 35.0 % (13.7 ± 8.4 %) in the middle eutrophic waters. We found a significant change in DOC chemical composition across the study lakes characterized by shifting of trophic levels. Although the experiment found significant changes in the factors that can influence %BDOC, a significant difference was not observed in %BDOC among the three trophic levels. The %BDOC was primarily influenced by the inherent DOC concentration and aromaticity, with eutrophication leading to the varied driving factors of %BDOC in lake systems. We show that most of the lake water DOC was stable. The findings indicate the intricate interplay between biological metabolism and nutrient availability governing %BDOC dynamics in urban lake ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In recent studies, accumulating evidence has revealed a strong association between the inflammatory response and the prognosis of many tumors. There is a certain correlation of neutrophil-to-lymphocyte ratio (NLR) with the prognosis in gastric cancer (GC) patients undergoing neoadjuvant chemotherapy (NAC). However, the existing research results have remained controversial., Aim: To explore the relationship between NLR ratio and prognosis of GC patients receiving NAC., Methods: A thorough systematic search was performed in databases such as PubMed, Embase, Web of Science, and Cochrane Library, the search is available until February 29, 2024, and studies exploring the interaction of NLR with clinical outcomes were collected. Relevant studies meeting pre-defined inclusion and exclusion criteria were carefully chosen. The outcomes included progression-free survival (PFS), relapse-free survival, disease-free survival (DFS), and overall survival (OS). The hazard ratio (HR) and its corresponding 95% confidence interval (CI) were utilized for estimation., Results: Our analysis encompassed 852 patients and incorporated data from 12 cohort studies. The comprehensive analysis revealed a significant association of high NLR with reduced OS (HR = 1.76; 95%CI: 1.22-2.54, P = 0.003), relapse-free survival (HR = 3.73; 95%CI: 1.74-7.96, P = 0.0007), and PFS (HR = 2.32; 95%CI: 1.42-3.81, P = 0.0008) in patients. However, this correlation in disease-free survival was not significant. NLR demonstrated its crucial role in effectively predicting the OS of GC patients undergoing NAC at different detection times, ages, regions, and NLR thresholds., Conclusion: In GC patients receiving NAC, an elevated NLR is strongly associated with reduced OS and PFS. NLR has become an effective biomarker for patient prognosis evaluation, providing valuable insights for the treatment strategies of NAC in GC patients., 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.)

Background: Intermittent fasting (IF) holds promise for enhancing metabolic health. However, the optimum IF forms and their superiority over continuous energy restriction (CER) remain unclear due to disconnected findings., Methods: We systematically searched PubMed, Embase, and the Cochrane databases for meta-analyses of randomized controlled trials (RCTs) investigating the association between IF and metabolic health outcomes. Subsequently, we performed an umbrella review and network meta-analysis (NMA) to evaluate the efficacy of different forms of IF (time-restricted eating (TRE), alternate-day fasting (ADF), and 5:2 diet (regular eating for 5 days and energy restriction for 2 days per week)) compared to CER and usual diets on metabolic health outcomes. To assess the certainty of both direct and indirect estimates, we employed the Confidence in Network Meta-Analysis (CINeMA) approach. Additionally, we calculated the surface under the cumulative ranking curve (SUCRA) for each dietary strategy to determine their ranking in terms of metabolic health benefits., Results: Ten of the best and non-redundant meta-analysis studies, involving 153 original studies and 9846 participants, were included. When considering direct evidence only, all IF forms significantly reduced body weight compared to usual diets. In NMA incorporating indirect evidence, all IF regimens also significantly reduced body weight compared to usual diets. In the SUCRA of NMA, IF ranked higher than usual diets or CER in 85.4% and 56.1% of the outcomes, respectively. ADF had the highest overall ranking for improving metabolic health (ranked first: 64.3%, ranked second: 14.3%)., Conclusions: Overall, all IF forms demonstrate potentials to improve metabolic health, with ADF appearing to produce better outcomes across investigated outcomes. Further high-quality trials are warranted to confirm the (relative) efficacy of IF on metabolic health., Trial Registration: PROSPERO (record no: CRD42022302690)., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

( S )-Methoprene has been widely applied as a powerful biochemical pesticide to control disease vectors and other pestiferous arthropods of economic importance. As a juvenile hormone analogue, many products based on ( S )-methoprene are developed and commercialized in the USA, Europe, and elsewhere. However, the agricultural use of ( S )-methoprene and its analogues remains underexplored. Here, based on an intermediate derivatization strategy and structural modification, a series of enantiopure ( S )-methoprene derivatives were designed for their expected bioactivity against two crop-threatening pests. Six compounds showed more than 2-fold stronger inhibition of emergence against Plutella xylostella than ( S )-methoprene, among which one that was designated as B2 showed even superior activity to the conventional chemical pesticide and biopesticide with IE 50 of 0.02 mg/L. Nine compounds exhibited over 2-fold higher bioactivity against Aphis craccivora growth than ( S )-methoprene. The physicochemical property evaluation and toxicological test showed that the potent ( S )-methoprene derivatives were low toxic to the nontarget organism and the environment. Molecular docking studies further demonstrated that the high bioactivity of B2 may be partially attributed to its great affinity for binding to juvenile hormone receptors of P. xylostella . The current study suggests that B2 is a biochemical pesticide candidate with potency to be developed as a new agrochemical for lepidopteran control.

Riparian ecosystems are essential carbon dioxide (CO 2 ) sources, which considerably promotes climate warming. However, the other greenhouse gas fluxes (GHGs), such as methane (CH 4 ) and nitrous oxide (N 2 O), in the riparian ecosystems have not been well studied, and it remains unclear whether and how these GHG fluxes respond to extreme weather, fertilization and hydrological alterations associated with reservoir management. Here, we assessed the impacts of hydrological alterations (i.e., flooding frequency) and fertilization (nitrogen and/or phosphorus) induced by human activities (hydroengineering construction and agricultural activities) on GHG fluxes, and further investigated the underlying mechanisms in two contrasting years (normal vs. extreme rainfall years) in a reservoir riparian zone dominated by grasses. The significant combined effects of extreme rainfall events and human activities (hydrological alterations and fertilization) on the GHGs were observed. Continuous flooding reduced CO 2 emissions by 24% but increased CH 4 emissions by ∼4 times in a normal rainfall year. In addition, nitrogen fertilization promoted CO 2 emissions by 37%. However, these phenomena were not observed in the year with extreme rainfall events, which made the flooding levels homogeneous across the treatments. Furthermore, we found that CO 2 fluxes were driven by the soil moisture, nutrient content, aboveground biomass, and root carbon content, while CH 4 and N 2 O fluxes were merely driven by the soil properties (pH, moisture, and nutrient content). This study provides valuable insights into the crucial role of extreme rainfall events, hydrological alteration, and fertilization in regulating GHG fluxes in riparian ecosystems, as well as supports the integration of these changes in GHG emission models., 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.)

Diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus, is primarily characterized by damage to Schwann cells caused by oxidative stress under hyperglycemic conditions. Recently, we demonstrated the ability of coumarin-rich Ficus formosana Maxim. to alleviate DPN in ovariectomized diabetic mice. However, the underlying mechanisms remain unclear. In this study, we established an in vitro DPN model using RSC96 Schwann cells exposed to high glucose levels. Daphnetin, a natural coumarin found abundantly in Ficus formosana Maxim., was co-incubated with Schwann cells in a high-glucose medium to investigate its protective effects against DPN. The free radical scavenging capacity of daphnetin was evaluated, along with assessments of cell viability, apoptosis, H 2 O 2 levels, and the expression of proteins by the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutamate-cysteine ligase catalytic subunit (GCLC) pathway in RSC96 Schwann cells. The results showed that daphnetin was non-toxic within the tested concentration range of 6.25 μM to 50 μM in RSC96 Schwann cells. Moreover, daphnetin significantly improved cell viability, exhibited strong antioxidant activity, reduced H 2 O 2 levels, and regulated the Nrf2/GCLC pathway protein expressions in RSC96 cells cultured in high-glucose medium. Additionally, daphnetin influenced apoptosis-related proteins by decreasing the expression levels of Bax and Caspase 3, while increasing the Bcl-2 expression level in high-glucose-treated RSC96 cells. These findings suggest that daphnetin may alleviate oxidative stress induced by high glucose levels through activation of the Nrf2/GCLC pathway and inhibition of Schwann cell apoptosis, underscoring its potential as a therapeutic agent for DPN.

Background: Non-invasive measurement of liver stiffness (LS), traditionally performed in the supine position, has been established to assess liver fibrosis. However, fibrosis degree is not the sole determinant of LS, necessitating the identification of relevant confounders. One often-overlooked factor is body posture, and it remains unclear whether normal daily postures interfere with LS irrespective of fibrosis. A prospective two-group comparison study was conducted to investigate the relationship between posture and LS., Methods: Sixty-two adults participated, divided into two groups: patients with chronic liver disease and healthy controls. Both groups were assessed using transient elastography (TE) under the supine, seated, and standing postures. Randomization was applied to the order of the two upright postures. A two-way mixed ANOVA was conducted to assess the posture-dependence of LS and its variations between two groups., Results: Results showed that posture differentially affected LS depending on the presence of liver fibrosis. In 31 healthy individuals (baseline LS range: 3.5-6.8 kPa), a transition from the supine (5.0 ± 1.0 kPa) to seated (5.7 ± 1.4 kPa; p = 0.036) or standing (6.2 ± 1.7 kPa; p = 0.002) positions increased LS, indicating liver stiffening. Conversely, in 31 patients with varying fibrosis stages (baseline LS range: 8.8-38.2 kPa), posture decreased LS from the supine (15.9 ± 7.3 kPa) to seated (13.8 ± 6.2 kPa; p < 0.001) or standing (13.9 ± 6.2 kPa; p = 0.001) positions. No significant difference in LS was observed between the seated and standing positions in both groups (control group: 5.7 vs. 6.2 kPa, p = 0.305; patient group: 13.8 vs. 13.9 kPa, p = 1). Additionally, different postures did not elicit significant changes in the success rate (supine, 98.6 ± 4%; seated, 97.6 ± 6%; standing, 99.1 ± 3%; p = 0.258) and IQR/median value (supine, 25 ± 8%; seated, 29 ± 15%; standing, 29 ± 12%; p = 0.117), implying no impact on both measurement feasibility and reliability., Conclusions: We demonstrated, for the first time, the feasibility of utilizing upright postures as an alternative measurement protocol for TE. We further unravel a previously unrecognized role of transitioning between different postures to assist the diagnosis of cirrhosis. The findings suggested that daily physiological activity of postural changes suffices to alter LS. Therefore, body positioning should be standardized and carefully considered when interpreting LS., (© 2024. The Author(s).)

Simultaneous monitoring of key metabolites like dopamine, ascorbic acid, and uric acid is essential for early disease diagnosis and evaluating treatment. Electrochemical techniques are increasingly used for precise, point-of-care testing (POCT) of these metabolites. Herein, a sample pretreatment method called effervescent solid-phase extraction (ESPE) was proposed for efficient enrichment of trace analytes for electrochemical detection. In an ESPE process, effervescent tablets made of gold nanoparticle-decorated graphene oxide (Au/GO) were first self-dispersed in a test solution to promote the enrichment of analytes on the Au/GO adsorbents, followed by the addition of flocculant effervescent tablets to cause Au/GO sheets to form self-assembled aggregates, which then can be efficiently collected by the foam electrodes. The entire sample pretreatment process operates without external power and takes only 5 min. With the assistance of the ESPE method, our electrochemical sensors achieve an ultralow detection limit for dopamine, ascorbic acid, and uric acid of 80 pM, 1.8 nM, and 460 pM, respectively, which are two to three orders of magnitude lower than the results obtained by the drop casting technique. The enhancement mechanism of our approach is based on increasing the contact probability with analytes through dynamic dispersion of the Au/GO adsorbents, in contrast to the static diffusion mechanism relied on Brownian motion. We also show that combining the ESPE solution kit with a portable micro-electrochemical workstation can attain the same detection level as HPLC in real urine samples. The proposed ESPE approach holds great promise for POCT applications in 2D material-based biosensors., 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.)

The precise preparation of hierarchical micelles is a fundamental challenge in modern materials science and chemistry. Herein, poly(di-n-hexylfluorene)-block-poly(3-tetraethylene glycol thiophene) (poly(1 m -b-2 n )) diblock copolymers and polyfluorene-block-polythiophene-block-poly(phenyl isocyanide) triblock copolymers were synthesized using a one-pot process via the sequential addition of corresponding monomers using a Ni(II) complex as a single catalyst for living/controlled polymerization. The crystallization-driven self-assembly of amphiphilic conjugated poly(1 m -b-2 n ) led to the formation of nanofibers with controlled lengths and narrow dispersity. The block copolymers exhibited white, yellow, and red emissions in different self-assembly states. By using uniform poly(1 m -b-2 n ) nanofibers as seeds, introducing the polyfluorene-block-polythiophene-block-poly(phenyl isocyanide) triblock polymer as a unimer in the seed growth process, and adjusting the structure of the poly(phenyl isocyanide) block and the polarity of self-assembly solvent, A-B-A triblock micelles, multiarm branched micelles, and raft micelles were prepared., (© 2024 Wiley-VCH GmbH.)

Background: Atherosclerotic cardiovascular diseases remain the leading cause of mortality in diabetic patients, with endothelial cell (EC) dysfunction serving as the initiating step of atherosclerosis, which is exacerbated in diabetes. Krüppel-like factor 11 (KLF11), known for its missense mutations leading to the development of diabetes in humans, has also been identified as a novel protector of vascular homeostasis. However, its role in diabetic atherosclerosis remains unexplored., Methods: Diabetic atherosclerosis was induced in both EC-specific KLF11 transgenic and knockout mice in the Ldlr -/- background by feeding a diabetogenic diet with cholesterol (DDC). Single-cell RNA sequencing (scRNA-seq) was utilized to profile EC dysfunction in diabetic atherosclerosis. Additionally, gain- and loss-of-function experiments were conducted to investigate the role of KLF11 in hyperglycemia-induced endothelial cell dysfunction., Results: We found that endothelial KLF11 deficiency significantly accelerates atherogenesis under diabetic conditions, whereas KLF11 overexpression remarkably inhibits it. scRNA-seq profiling demonstrates that loss of KLF11 increases endothelial-to-mesenchymal transition (EndMT) during atherogenesis under diabetic conditions. Utilizing gain- and loss-of-function approaches, our in vitro study reveals that KLF11 significantly inhibits EC inflammatory activation and TXNIP-induced EC oxidative stress, as well as Notch1/Snail-mediated EndMT under high glucose exposure., Conclusion: Our study demonstrates that endothelial KLF11 is an endogenous protective factor against diabetic atherosclerosis. These findings indicate that manipulating KLF11 could be a promising approach for developing novel therapies for diabetes-related cardiovascular complications., (© 2024. The Author(s).)

Background and Purpose: This study aimed to investigate the association between iron content in grey matter (GM) nuclei and functional outcome in acute ischaemic stroke (AIS) patients utilizing quantitative susceptibility mapping., Methods: Forty AIS patients and 40 age-, sex- and education-matched healthy controls underwent quantitative susceptibility mapping to assess susceptibility values, which are positively correlated with iron content, in the caudate nucleus, putamen, globus pallidus, thalamus, red nucleus and substantia nigra. The nuclei on the contralateral side were measured in AIS patients to minimize confounding due to oedema or haemorrhage. Functional outcome was determined by the modified Rankin Scale (mRS) score at 3 months after stroke. Poor outcome was defined as mRS >2, whilst a good outcome was defined as ≤2., Results: Susceptibility values were significantly higher in most contralateral GM nuclei in AIS patients than in the corresponding left or right nuclei in healthy controls. AIS patients with poor outcome showed significantly lower susceptibility value than those with good outcome in the contralateral caudate nucleus, but no significant differences were observed in other GM nuclei. Binary logistic regression analysis revealed a significant association between the susceptibility value of the contralateral caudate nucleus and poor outcome after adjustment for confounders (adjusted odds ratio 0.692, 95% confidence interval 0.486-0.986, p = 0.042). Receiver operating characteristic curve analysis showed an acceptable ability of the susceptibility value of the contralateral caudate nucleus to predict poor outcome (area under the curve 0.740, p = 0.013)., Conclusions: Lower iron content in the contralateral caudate nucleus was associated with poor functional outcome in AIS patients., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Predicting individual prognosis is difficult despite various risk factor studies, due to the complex recovery involving peripheral nerve restoration and cerebral plasticity. This study uses fixel-based analysis (FBA) to better understand neural pathway alterations, hypothesizing that FBA can effectively link functional outcomes with diffusion metrics in the process of rehabilitation. The authors recruited 50 participants including 30 patients and 20 healthy controls into the study. All of them underwent assessment 3 months and 6 months after injury. Both whole-brain fixel-based analysis and tract of interest analysis were performed. The authors observed multiple regions including the superior corona radiata, posterior limb of the internal capsule, and cerebral peduncle displaying significant changes of FD (fiber density), FC (fiber-bundle cross-section), and FDC (fiber density and cross-section). Patients with unfavorable outcomes showed increased FD in the ipsilesional side and decreased FD in the contralesional side compared with patients with favorable outcomes. In addition, FD values of the contralesional side exhibited positive correlations with differences in FGS at 3 months and 6 months. Conversely, FD values in the ipsilesional side showed a negative correlation. Our findings suggest that FD metrics within the corticobulbar tract could serve as predictive biomarkers for symmetry outcomes. Thus, FBA holds promise for early estimation of behavioral outcomes in facial palsy, guiding more targeted interventions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Owing to the extensive use of antibiotics for treating infectious diseases in livestock and humans, the resulting residual antibiotics are a burden to the ecosystem and human health. Hence, for human health and ecological safety, it is critical to determine the residual antibiotics with accuracy and convenience. Graphene-based electrochemical sensors are an effective tool to detect residual antibiotics owing to their advantages, such as, high sensitivity, simplicity, and time efficiency. In this work, we comprehensively summarize the recent advances in graphene-based electrochemical sensors used for detecting antibiotics, including modifiers for electrode fabrication, theoretical elaboration of electrochemical sensing mechanisms, and practical applications of portable electrochemical platforms for the on-site monitoring of antibiotics. It is anticipated that the current review will be a valuable reference for comprehensively comprehending graphene-based electrochemical sensors and further promoting their applications in the fields of healthcare, environmental protection, and food safety.

To investigate the impact of Small Intestinal Bacterial Overgrowth (SIBO) on the efficacy of Fecal Microbiota Transplantation (FMT) in patients with chronic constipation, our research team included 218 patients with chronic constipation treated with FMT. Based on the results of the SIBO breath test, the patients were divided into two groups: the constipation with SIBO group (SIBO) and the constipation without SIBO group (non-SIBO). The efficacy of the two groups was evaluated using constipation-related scoring scales. At the same time, feces and small intestinal fluid samples were collected from both groups before and after FMT to compare the changes in the intestinal microbiota through 16S rRNA sequencing. In this study, it was found that the clinical efficacy of FMT in the SIBO group was superior to that in the non-SIBO group. After FMT treatment, both groups showed a significant increase in bowel frequency and improvement in stool characteristics. Abdominal symptoms, rectal symptoms, and defecation symptoms were significantly alleviated ( P < 0.05), and patients' quality of life was significantly enhanced ( P < 0.05). After FMT, except for the Constipation Assessment Scale scores, other scale scores showed significant differences between the two groups, the SIBO group scoring significantly better than the non-SIBO group ( P < 0.05). After FMT, there were minor changes in the colonic microbiota but more substantial changes in the small intestinal microbiota. At baseline, the SIBO group had a higher abundance of Veillonella , and lower abundances of Escherichia-Shigella and Acinetobacter compared to the non-SIBO group. Chronic constipation patients with SIBO have a better response to FMT than those without SIBO., Importance: Existing studies have rarely considered the impact of the small intestine's microbial state on the efficacy of fecal microbiota transplantation (FMT), nor have they extensively explored the effect of the small intestine's microbial state on the recovery of colonic motility. Therefore, this study investigates the influence of small intestinal bacterial overgrowth (SIBO) on the efficacy of FMT in treating constipation, specifically the impact of the microbial state of the small intestine on the restoration of colonic homeostasis, and consequently on the recovery of colonic motility., Competing Interests: The authors declare no conflict of interest.

Agroforestry system with high biodiversity augments ecosystem stability and minimizes its vulnerability to environmental disturbances and disease. Deciphering the underlying mechanisms of interspecies allelopathic interactions in disease suppression in agroforestry offer a sustainable strategy for plant disease management. Here, we utilized Panax ginseng cultivated under Pinus koraiensis forests, where the occurrences of Alternaria leaf spot are low, as a research model to investigate the role of allelochemicals in disease suppression. Our findings demonstrate that foliar application of leachates from the needles of P. koraiensis effectively enhanced the resistance of P. ginseng against Alternaria leaf spot. Through GC-MS analysis, we identified and quantified endo-borneol as a key compound in the leachates of P. koraiensis, and validated its capacity to prime resistance in its neighbor P. ginseng. We discovered that endo-borneol not only directly activates defense-related pathways of P. ginseng to induce resistance, but also indirectly recruits its rhizospheric beneficial microbiota by enhancing the secretion of ginsenosides, thereby triggering induced systemic resistance (ISR). Importantly, the higher concentrations of endo-borneol from 10 to 100 mg/L demonstrated a stronger capacity to induce plant resistance and enhance root secretion to recruit more microbiota compared with the lower concentrations from 0.01 to 1 mg/L. Moreover, endo-borneol exhibited antifungal activity against the growth of the pathogen Alternaria panax when its concentrations exceeding 10 mg/L. These results reveal the multifaceted functions of allelochemical endo-borneol in disease suppression in agroforestry system and highlight its potential as an environmental-friendly compound for sustainable agriculture., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims/introduction: This study aimed to identify low- and high-risk diabetes groups within prediabetes populations using data from the Taiwan Biobank (TWB) and UK Biobank (UKB) through a clustering-based Unsupervised Learning (UL) approach, to inform targeted type 2 diabetes (T2D) interventions., Materials and Methods: Data from TWB and UKB, comprising clinical and genetic information, were analyzed. Prediabetes was defined by glucose thresholds, and incident T2D was identified through follow-up data. K-means clustering was performed on prediabetes participants using significant features determined through logistic regression and LASSO. Cluster stability was assessed using mean Jaccard similarity, silhouette score, and the elbow method., Results: We identified two stable clusters representing high- and low-risk diabetes groups in both biobanks. The high-risk clusters showed higher diabetes incidence, with 15.7% in TWB and 13.0% in UKB, compared to 7.3% and 9.1% in the low-risk clusters, respectively. Notably, males were predominant in the high-risk groups, constituting 76.6% in TWB and 52.7% in UKB. In TWB, the high-risk group also exhibited significantly higher BMI, fasting glucose, and triglycerides, while UKB showed marginal significance in BMI and other metabolic indicators. Current smoking was significantly associated with increased diabetes risk in the TWB high-risk group (P < 0.001). Kaplan-Meier curves indicated significant differences in diabetes complication incidences between clusters., Conclusions: UL effectively identified risk-specific groups within prediabetes populations, with high-risk groups strongly associated male gender, higher BMI, smoking, and metabolic markers. Tailored preventive strategies, particularly for young males in Taiwan, are crucial to reducing T2D risk., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background and Purpose: DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR., Experimental Approach: A total of 300 consecutive ACS patients naive to P2Y 12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared., Key Results: Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT-678., Conclusion and Implications: These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by hepatic lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation. Here we show that AGXT is suppressed and LDHA is activated in livers from patients and mice with MASH, leading to oxalate overproduction. In turn, oxalate promotes steatosis in hepatocytes by inhibiting peroxisome proliferator-activated receptor-α (PPARα) transcription and fatty acid β-oxidation and induces monocyte chemotaxis via C-C motif chemokine ligand 2. In male mice with diet-induced MASH, targeting oxalate overproduction through hepatocyte-specific AGXT overexpression or pharmacological inhibition of LDHA potently lowers steatohepatitis and fibrosis by inducing PPARα-driven fatty acid β-oxidation and suppressing monocyte chemotaxis, nuclear factor-κB and transforming growth factor-β targets. These findings highlight hepatic oxalate overproduction as a target for the treatment of MASH., (© 2024. The Author(s).)

Background: The rising global elderly population increases the demand for caregiving, yet traditional methods may not fully assess the challenges faced by vital informal caregivers., Objective: To investigate the efficacy of Large Language Model (LLM) in detecting overburdened informal caregivers, benchmarking against rule-based and machine learning methods., Methods: 1,791 eligible informal caregivers from Southern Taiwan and utilized their textual case summary reports for the LLM. We also employed structured questionnaire results for machine learning models. Furthermore, we leveraged the visualization of the LLM's attention mechanisms to enhance our understanding of the model's interpretative capabilities., Results: The LLM achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of 0.84 and an Area Under the Precision-Recall Curve (AUPRC) of 0.70, marking an 8% and 14% improvement over traditional methods. The visualization of the attention mechanism accurately reflected the evaluations of human experts, concentrating on descriptions of high-burden descriptions and the relationships between caregivers and recipients., Conclusion: This research demonstrates the notable capability of LLM to accurately identify high-burden caregivers in Long-term Care (LTC) settings. Compared to traditional approaches, LLM offers an opportunity for the future of LTC research and policymaking., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Deformable image registration is an essential technique of medical image analysis, which plays important roles in several clinical applications. Existing deep learning-based registration methods have already achieved promising performance for the registrations with small deformations, while it is still challenging to deal with the large deformation registration due to the limits of the image intensity-similarity-based objective function., Purpose: To achieve the image registration with large-scale deformations, we proposed a multilevel network architecture FCNet to gradually refine the registration results based on semantic feature consistency constraint and flow normalization (FN) strategy., Methods: At each level of FCNet, the architecture is mainly composed to a FeaExtractor, a FN module, and a spatial transformation module. FeaExtractor consists of three parallel streams which are used to extract the individual features of fixed and moving images, as well as their joint features, respectively. Using these features, the initial deformation field is estimated, which passes through a FN module to refine the deformation field based on the difference map of deformation filed between two adjacent levels. This allows the FCNet to progressively improve the registration performance. Finally, a spatial transformation module is used to get the warped image based on the deformation field. Moreover, in addition to the image intensity-similarity-based objective function, a semantic-feature consistency constraint is also introduced, which can further promote the alignments by imposing the similarity between the fixed and warped image features. To validate the effectiveness of the proposed method, we compared our method with the state-of-the-art methods on three different datasets. In EMPIRE10 dataset, 20, 3, and 7 fixed and moving 3D computer tomography (CT) image pairs were used for training, validation, and testing respectively; in IXI dataset, atlas to individual image registration task was performed, with 3D MR images of 408, 58, and 115 individuals were used for training, validation, and testing respectively; in the in-house dataset, patient to atlas registration task was implemented, with the 3D MR images of 94, 3, and 15 individuals being training, validation, and testing sets, respectively., Results: The qualitative and quantitative comparison results demonstrated that the proposed method is beneficial for handling large deformation image registration problems, with the DSC and ASSD improved by at least 1.0% and 25.9% on EMPIRE10 dataset. The ablation experiments also verified the effectiveness of the proposed feature combination strategy, feature consistency constraint, and FN module., Conclusions: Our proposed FCNet enables multiscale registration from coarse to fine, surpassing existing SOTA registration methods and effectively handling long-range spatial relationships., (© 2024 American Association of Physicists in Medicine.)

Environmental warming and eutrophication pose significant challenges to shallow lake systems, where dissolved organic matter (DOM) serves as a diverse and intricate mixture of organic macromolecules, playing a pivotal role in aquatic ecosystems. Despite its complexity, comprehending the interplay between environmental changes and DOM composition alterations and their subsequent impacts on aqueous CO 2 partial pressure (pCO 2 ) is essential for a better understanding of carbon cycling. Yet, our current understanding in this realm remains limited. To address this gap, mesocosm systems were established to investigate how elevated water temperature and eutrophication, alongside changes in DOM composition, influence pCO 2 dynamics. Results indicate that while temperature and nutrient levels do not directly influence pCO 2 fluctuations, they indirectly affect aqueous pCO 2 through their modulation of DOM composition. Elevated temperature and nutrient concentrations notably enhance both the production and degradation of indigenous protein-like organic matter and increase the accumulation of humic-like organic compounds, with phosphorus released from sediment playing a particularly significant role. Furthermore, the degradation rate of protein-like organic matter significantly exceeds its accumulation rate. On the other hand, the impact of water eutrophication on DOM composition surpasses that of temporal temperature variations, with a 2∼4 °C temperature rise showing minimal effects on DOM composition. Notably, the degradation of protein-like organic matter markedly increases aqueous pCO 2 , while the rise in humic-like organic matter in water exerts minimal influence on pCO 2 concentrations. A comprehensive understanding of carbon cycling processes under environmental changes will facilitate effective management of lake ecosystems and the advancement of carbon mitigation technologies., 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.)

Genetic studies of blood pressure (BP) traits to date have been performed on conventional measures by brachial cuff sphygmomanometer for systolic BP (SBP) and diastolic BP, integrating several physiologic occurrences. Genetic associations with central SBP (cSBP) have not been well-studied. Genetic discovery studies of BP have been most often performed in European-ancestry samples. Here, we investigated genetic associations with cSBP in a Chinese population and functionally validated the impact of a novel associated coiled-coil domain containing 93 (CCDC93) gene on BP regulation. An exome-wide association study (EWAS) was performed using a mixed linear model of non-invasive cSBP and peripheral BP traits in a Han Chinese population (N = 5,954) from Beijing, China genotyped with a customized Illumina ExomeChip array. We identified four SNP-trait associations with three SNPs, including two novel associations (rs2165468-SBP and rs33975708-cSBP). rs33975708 is a coding variant in the CCDC93 gene, c.535C>T, p.Arg179Cys (MAF = 0.15%), and was associated with increased cSBP (β = 29.3 mmHg, P = 1.23x10-7). CRISPR/Cas9 genome editing was used to model the effect of Ccdc93 loss in mice. Homozygous Ccdc93 deletion was lethal prior to day 10.5 of embryonic development. Ccdc93+/- heterozygous mice were viable and morphologically normal, with 1.3-fold lower aortic Ccdc93 protein expression (P = 0.0041) and elevated SBP as compared to littermate Ccdc93+/+ controls (110±8 mmHg vs 125±10 mmHg, P = 0.016). Wire myography of Ccdc93+/- aortae showed impaired acetylcholine-induced relaxation and enhanced phenylephrine-induced contraction. RNA-Seq transcriptome analysis of Ccdc93+/- mouse thoracic aortae identified significantly enriched pathways altered in fatty acid metabolism and mitochondrial metabolism. Plasma free fatty acid levels were elevated in Ccdc93+/- mice (96±7mM vs 124±13mM, P = 0.0031) and aortic mitochondrial dysfunction was observed through aberrant Parkin and Nix protein expression. Together, our genetic and functional studies support a novel role of CCDC93 in the regulation of BP through its effects on vascular mitochondrial function and endothelial function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kumar 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.)

Objective. Respiratory motion, cardiac motion and inherently low signal-to-noise ratio (SNR) are major limitations of in vivo cardiac diffusion tensor imaging (DTI). We propose a novel enhancement method that uses unsupervised learning based invertible wavelet scattering (IWS) to improve the quality of in vivo cardiac DTI. Approach. Our method starts by extracting nearly transformation-invariant features from multiple cardiac diffusion-weighted (DW) image acquisitions using multi-scale wavelet scattering (WS). Then, the relationship between the WS coefficients and DW images is learned through a multi-scale encoder and a decoder network. Using the trained encoder, the deep features of WS coefficients of multiple DW image acquisitions are further extracted and then fused using an average rule. Finally, using the fused WS features and trained decoder, the enhanced DW images are derived. Main result. We evaluate the performance of the proposed method by comparing it with several methods on three in vivo cardiac DTI datasets in terms of SNR, contrast to noise ratio (CNR), fractional anisotropy (FA), mean diffusivity (MD) and helix angle (HA). Comparing against the best comparison method, SNR/CNR of diastolic, gastric peristalsis influenced, and end-systolic DW images were improved by 1%/16%, 5%/6%, and 56%/30%, respectively. The approach also yielded consistent FA and MD values and more coherent helical fiber structures than the comparison methods used in this work. Significance. The ablation results verify that using the transformation-invariant and noise-robust wavelet scattering features enables us to effectively explore the useful information from the limited data, providing a potential mean to alleviate the dependence of the fusion results on the number of repeated acquisitions, which is beneficial for dealing with the issues of noise and residual motion simultaneously and therefore improving the quality ofinvivocardiac DTI. Code can be found inhttps://github.com/strawberry1996/WS-MCNN., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Many patients with constipation also suffer from varying degrees of malnutrition, and the relationship between the two conditions is a vicious cycle. Surgery is the final step in the treatment of constipation, with a success rate of up to 95%. This study aims to investigate the effects of surgical treatment on the nutritional status of patients with chronic constipation and malnutrition., Methods: A total of 60 patients with chronic constipation and various degrees of malnutrition who underwent surgery in our department from January 2020 to March 2023 were included in this study. Biochemical tests including BMI, albumin, total protein, hemoglobin, cholesterol and lymphocyte count were conducted, as well as measurements of inflammatory markers such as Interleukin-6 (IL-6), Interleukin-8 (IL-8), and C-reactive protein (CRP). Additionally, multiple nutritional risk screening scales (NRS2002, MUST, NRI, and MNA) and the prognostic nutritional index (PNI) were used to assess the nutritional status of patients before surgery, as well as at 1 month, 3 months, and 6 months post-surgery. Finally, we analyzed the factors influencing postoperative recovery outcomes in patients., Results: Compared to pre-operation, the BMI of patients significantly increased at 1 month, 3 months, and 6 months after the operation, with statistically significant differences ( p  < 0.001). Multiple nutritional risk assessment tools (NRS2002, MUST, NRI, and MNA), as well as the prognostic nutritional index (NPI), indicated a reduction in nutritional risk and improvement in nutritional status at 1, 3, and 6 months post-surgery, compared to pre-surgery levels ( p  < 0.001). The levels of albumin, total protein, and hemoglobin in patients at 1, 3, and 6 months after the surgery were significantly higher than those before the surgery ( p  < 0.001). However, there was no significant change in the number of lymphocytes. Inflammatory markers such as IL-6, IL-8, and CRP exhibited a significant decrease after the surgery, reaching normal levels at 6 months post-surgery ( p  < 0.001). Low BMI, low PNI, and low cholesterol levels are independent risk factors for patient prognosis ( p  < 0.05)., Conclusion: Surgical treatment can enhance the nutritional status of constipation patients with malnutrition, which in turn promotes the restoration of intestinal motility. The patient's nutritional status will impact the postoperative recovery outcomes., 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 Wang, Tian, Li, Ye, Cui, Lin, Yang, Zhao, Li, Feng and Chen.)

Objective: To evaluate disparities in gene expression profiles between Ovarian Clear Cell Carcinoma (OCCC) and High-Grade Serous Ovarian Carcinoma (HGSOC)., Study Design: A descriptive study. Place and Duration of the Study: The Second People's Hospital of Jingdezhen, Jiangxi, China, between 31st December 2017 and December 2023., Methodology: Basic and clinical diagnostic information, along with genetic test reports, were compiled from all patients within the included groups. Differential gene expression between the two cohorts was scrutinised to elucidate its clinical significance., Results: Comparative analysis revealed nine differentially expressed genes in OCCC relative to HGSOC, with six exhibiting significant disparities (p <0.05). These genes are implicated in pivotal cellular processes including the cell cycle, apoptosis, DNA damage repair, and the PI3K pathway. Notably, aberrant expression patterns, such as overexpression of MET and downregulation of PTEN and SMARCA4, correlated with adverse prognosis and survival outcomes in selected patients., Conclusion: Distinctive gene expression profiles between OCCC and HGSOC underscore disparate tumorigenic mechanisms, thereby laying a foundation for the tailored therapeutic interventions. Further elucidation of the identified differentially expressed genes is warranted to delineate their role in OCCC pathogenesis and prognostic significance., Key Words: Ovarian clear cell carcinoma, High-grade serous ovarian cancer, Gene expression profiles, Homologous recombination repair.

The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems 1,2 . However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications 3,4 . Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine., (© 2024. The Author(s).)

To promote the generalization ability of breast tumor segmentation models, as well as to improve the segmentation performance for breast tumors with smaller size, low-contrast and irregular shape, we propose a progressive dual priori network (PDPNet) to segment breast tumors from dynamic enhanced magnetic resonance images (DCE-MRI) acquired at different centers. The PDPNet first cropped tumor regions with a coarse-segmentation based localization module, then the breast tumor mask was progressively refined by using the weak semantic priori and cross-scale correlation prior knowledge. To validate the effectiveness of PDPNet, we compared it with several state-of-the-art methods on multi-center datasets. The results showed that, comparing against the suboptimal method, the DSC and HD95 of PDPNet were improved at least by 5.13% and 7.58% respectively on multi-center test sets. In addition, through ablations, we demonstrated that the proposed localization module can decrease the influence of normal tissues and therefore improve the generalization ability of the model. The weak semantic priors allow focusing on tumor regions to avoid missing small tumors and low-contrast tumors. The cross-scale correlation priors are beneficial for promoting the shape-aware ability for irregular tumors. Thus integrating them in a unified framework improved the multi-center breast tumor segmentation performance.

In this study, an economic and controllable Marangoni self-assembly approach is designed to prepare the heterostructured nanocoatings (8-28 nm) consisting of alternately stacked mosaic nanosheets of hexagonal boron nitride (h-BN) and graphene. The resulting 2D nanocoatings exhibit a combination of advantageous properties, such as prevention of interfacial reactions, robust interfacial binding, a labyrinthine barrier effect, inhibition of galvanic corrosion, and alleviation of internal stress. The protective property of graphene/h-BN heterostructured nanocoatings is studied through potentiodynamic polarization curves and electrochemical impedance spectroscopy, with the theoretical support of first-principles calculations. The corrosion current density of ≈28 nm-thick graphene/h-BN multilayer coated stainless steel is 1.82 × 10 -8  A cm -2 , which decreases by an order of magnitude compared to that of an uncoated one, meanwhile, the corrosion potential increases from -0.192 to 0.023 V (increase: ≈0.215 V). The enhancement of anticorrosion performance of heterostructured nanocoatings can be attributed to the labyrinth barrier effect associated with highly ordered horizontal arrangement, effective coverage of metal substrates by mosaic multilayers, and suppressed galvanic corrosion effect by insulating BNNS monolayers. This study can shed much light on the effective solution of many stubborn issues confronted by the development of anticorrosive 2D nanocoatings., 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.)

Total organic carbon (TOC) is a crucial indicator of organic pollutants, widely used in environmental water quality monitoring and risk assessment. Conventional TOC detection methods often require high temperatures, complex equipment, and inefficient oxidation processes, limiting their field application due to time consumption, intricate operations, and limited sensitivity. Therefore, we developed a novel approach for TOC measurement using catalytic oxidation vapor generation coupled with miniaturized point discharge optical emission spectrometry (μPD-OES). This method employs urchin-like Co 3 O 4 microspheres to convert organic pollutants to carbon dioxide during persulfate catalytic oxidation, followed by collection and quantification via carbon atomic emission line (λ = 193.0 nm). Standard or sample solutions were acidified with phosphoric acid and purged with Ar before quantification. Under optimal conditions, the proposed method achieved a detection limit of 0.01 mg L -1 , offering precision (RSD, n = 11) better than 3.7 %. The feasibility of the system was tested using a certified reference material (GBW(E)082053) and environmental water samples, achieving satisfactory recoveries (98-102 %). This method provides high oxidation efficiency, sensitivity, and accuracy, while also reducing the demand for expensive and bulky instruments and minimizing energy consumption, making it suitable for rapid, sensitive field analysis of TOC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This review explores the emerging role of screen-printed electrodes (SPEs) in the detection of breast cancer biomarkers. We discuss the fundamental principles and fabrication techniques of SPEs, highlighting their adaptability and cost-effectiveness. The review examines various modification strategies, including nanomaterial incorporation, polymer coatings, and biomolecule immobilization, which enhance sensor performance. We analyze the application of SPEs in detecting protein, genetic, and metabolite biomarkers associated with breast cancer, presenting recent advancements and innovative approaches. The integration of SPEs with microfluidic systems and their potential in wearable devices for continuous monitoring are explored. While emphasizing the promising aspects of SPE-based biosensors, we also address current challenges in sensitivity, specificity, and real-world applicability. The review concludes by discussing future perspectives, including the potential for early screening and therapy monitoring, and the steps required for clinical implementation. This comprehensive overview aims to stimulate further research and development in SPE-based biosensors for improved breast cancer management.

When amino acids are plentiful in the diet, the liver upregulates most enzymes responsible for amino acid degradation. In particular, the activity of urea cycle enzymes increases in response to high-protein diets to facilitate the excretion of excess nitrogen. KLF15 has been established as a critical regulator of amino acid catabolism including ureagenesis and we have recently identified FoxO transcription factors as an important upstream regulator of KLF15 in the liver. Therefore, we explored the role of FoxOs in amino acid metabolism under high-protein diet. Our findings revealed that the concentrations of two urea cycle-related amino acids, arginine and ornithine, were significantly altered by FoxOs knockdown. Additionally, using KLF15 knockout mice and an in vivo Ad-luc analytical system, we confirmed that FoxOs directly regulate hepatic Ass1 expression under high-protein intake independently from KLF15. Moreover, ChIP analysis showed that the high-protein diet increased FoxOs DNA binding without altering the nuclear protein amount. Therefore, FoxOs play a direct role in regulating ureagenesis via a KLF15-independent pathway in response to high-protein intake., 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.)

Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear. Our study reveals that ANXA1 levels are elevated in the adipose tissue of individuals with obesity. Whole-body or adipocyte-specific ANXA1 deletion aggravates obesity and metabolic disorders. ANXA1 levels are higher in stromal vascular fractions (SVFs) than in mature adipocytes. Further investigation into the role of ANXA1 in SVFs reveals that ANXA1 overexpression induces lower numbers of mature adipocytes, while ANXA1-knockout SVFs exhibit the opposite effect. This suggests that ANXA1 plays an important role in adipogenesis. Mechanistically, ANXA1 competes with MYC binding protein 2 (MYCBP2) for interaction with PDZ and LIM domain 7 (PDLIM7). This exposes the MYCBP2-binding site, allowing it to bind more readily to the SMAD family member 4 (SMAD4) and promoting its ubiquitination and degradation. SMAD4 degradation downregulates peroxisome proliferator-activated receptor gamma (PPARγ) transcription and reduces adipogenesis. Treatment with Ac2-26, an active peptide derived from ANXA1, inhibits both adipogenesis and obesity through the mechanism. In conclusion, the molecular mechanism of ANXA1 inhibiting adipogenesis was first uncovered in our study, which is a potential target for obesity prevention and treatment., (© 2024. The Author(s).)

Background: Facial palsy, often resulting from trauma or iatrogenic treatments, leads to significant esthetic and functional impairment. Surgical interventions, such as masseteric-to-facial nerve transfer combined with static suspension, are frequently recommended to restore facial nerve function and symmetry., Methods: This study examines how Botulinum Toxin A (BoNT-A) treatment on the unaffected side affects facial symmetry and brain connectivity in patients with severe oral commissure droop from facial nerve damage. Patients were divided into two groups: one received BoNT-A injections on the unaffected side, and the other did not., Results: Our findings revealed that BoNT-A treatment not only improved facial symmetry but also induced significant modifications in brain functional network connectivity. These modifications extended beyond the sensorimotor network, involving high-level cognitive processes, and exhibited a significant correlation with the degree of facial asymmetry., Conclusions: These results provide valuable insights into the mechanisms underlying the positive effects of BoNT-A intervention on motor recovery and brain plasticity in facial palsy patients. Furthermore, the study emphasizes the importance of a multidisciplinary approach to facial palsy rehabilitation. Understanding these intricate interactions between facial symmetry restoration and brain network adaptations may pave the way for more effective treatments and improved quality of life for individuals dealing with facial palsy., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medications. This study integrated genetic, proteomic, and metabolomic data to identify causation between increased triglyceride (TG)-rich lipoproteins and AAA risk. Three hypertriglyceridemia mouse models were employed to test the hypothesis that increased plasma TG concentrations accelerate AAA development and rupture. In the angiotensin II-infusion AAA model, most Lpl -deficient mice with severely high plasma TG concentrations died of aortic rupture. Consistently, Apoa5 -deficient mice with moderately increased TG concentrations had accelerated AAA development, while human APOC3 transgenic mice with dramatically increased TG concentrations exhibited aortic dissection and rupture. Increased TG concentrations and palmitate inhibited lysyl oxidase maturation. Administration of antisense oligonucleotide targeting Angptl3 profoundly inhibited AAA progression in human APOC3 transgenic mice and Apoe -deficient mice. These results indicate that hypertriglyceridemia is a key contributor to AAA pathogenesis, highlighting the importance of triglyceride-rich lipoprotein management in treating AAA.

Oxalic acid (OA) is a predominant constituent in kidney stones, contributing to 70-80% of all cases. Rapid detection of OA is vital for the early diagnosis and treatment of kidney stone conditions. This work introduces a novel electrochemical sensing approach for OA, leveraging vanadium disulfide (VS 2 ) nanoflowers synthesized via hydrothermal synthesis. These VS 2 nanoflowers, known for their excellent electrocatalytic properties and large surface area, are used to modify glassy carbon electrodes for enhanced OA sensing. The proposed OA sensor exhibits high sensitivity and selectivity across a wide linear detection range of 0.2-20 μM, with an impressively low detection limit of 0.188 μM. The practicality of this sensor was validated through interference studies, offering a promising tool for the early diagnosis and monitoring of kidney stone diseases.

Human-induced disturbances such as dam construction and regulation have led to widespread alterations in hydrological processes and thus substantially influence plant characteristics in the hydro-fluctuation zones (HFZs). To reveal utilization of limited resources and mechanisms of inter-specific competition and species co-existence of plant communities based on niche breadth and overlap under the different HFZs of the Three Gorges Reservoir (TGR) in China, we conducted a field investigation with 368 quadrats on the effects of hydrological alterations on plant diversity and niche characteristics. The results showed anti-seasonal flooding precipitated the gradual disappearance of the original diverse niches, resulting in the reduction of plant species richness and functional diversity and more obvious competition among plant species with similar resource requirements. Annuals, perennials and shrubs accounted for 71.23%, 27.39% and 1.37%, respectively, suggesting that annuals and flood-tolerant riparian herbs were favored under such novel flooding conditions. A consistent increase in species number, Shannon-Wiener diversity index and Simpson dominance index with altitude was inconsistent with hump-shaped diversity-disturbance relationship of the intermediate disturbance hypothesis, while the opposite trend was observed for the Pielou evenness index. This species distribution pattern might be caused by several synergetic attributes (e.g., the submergence depth, plant tolerant capacity to flooding, life form, dispersal mode and inter-specific competition). Vegetation types shifted from xerophytes to mesophytes and eventually to hygrophytes with the increasing flooding time in the HFZs. Hydrological alterations proved to be the paramount driver of vegetation distribution in the different HFZs. The niche analysis provided the first insights on the mechanisms of resource utilization and inter-specific competition, of which annuals could germinate quickly after soil drainage to achieve the greatest competitive advantages and occupy a larger niche space than other plants. Vegetation was still in the early stage of primary succession in the novel riparian forests. Therefore, vegetation restoration strategies should be biased towards herbaceous plants, due to annuals with better environmental adaptability, supplemented by shrubs and small trees. To establish a complete reference system for vegetation restoration, natural vegetation monitory plots in the different succession stages should be established in the different HFZs of the TGR, and their environmental conditions, community structures and inter-specific relationships further analyzed., Competing Interests: The authors declare that they have no known competing financial, interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Purpose: Chronic obstructive pulmonary disease (COPD), characterized by airflow limitation and breathing difficulty, is usually caused by prolonged inhalation of toxic substances or long-term smoking habits. Some abnormal features of COPD can be observed using medical imaging methods, such as magnetic resonance imaging (MRI) and computed tomography (CT). This study aimed to conduct a multi-modal analysis of COPD, focusing on assessing respiratory diaphragm motion using MRI series in conjunction with low attenuation volume (LAV) data derived from CT images., Materials and Method: This study utilized MRI series from 10 normal subjects and 24 COPD patients, along with thoracic CT images from the same patients. Diaphragm profiles in the sagittal thoracic MRI series were extracted using field segmentation, and diaphragm motion trajectories were generated from estimated diaphragm displacements via registration. Re-sliced sagittal CT images were used to calculate regional LAVs for four distinct lung regions. The similarities among diaphragm motion trajectories at various positions were assessed, and their correlations with regional LAVs were analyzed., Results: Compared with the normal subjects, patients with COPD typically exhibited fewer similarities in diaphragm motion, as indicated by the mean normalized correlation coefficient of the vertical motion component (0.96 for normal subjects vs. 0.76 for severity COPD patients). This reduction was significantly correlated with the LAV% in the two lower lung regions with a regression coefficient of 0.81., Conclusion: Our proposed evaluation method may assist in the diagnosis and therapy planning for patients with COPD., (© 2024. The Author(s) under exclusive licence to Japan Radiological Society.)

Aortic aneurysms, particularly abdominal aortic aneurysms (AAAs), exhibit sex differences, with higher prevalence and severity in males than females, both in humans and experimental mouse models. In fact, male sex has been considered as the most potent nonmodifiable risk factor for AAA. Currently, there are no medications approved for the treatment of aortic aneurysms, despite the high lethality of ruptured aneurysms, which account for nearly 2% of all deaths. Moreover, the underlying molecular mechanisms mediating the sexual dimorphism of aortic aneurysms remain largely unknown. In this issue of the JCI, Mu et al. revealed a mechanism by which androgens, male sex hormones, exacerbate aortic aneurysms by suppressing programmed cell death protein 1 (PD-1) expression in T cells in an aldosterone and high salt-induced aortic aneurysm mouse model.

Cadmium (Cd) pollution has been a significant concern in heavy metal pollution, prompting plants to adopt various strategies to mitigate its damage. While the response of plants to Cd stress and the impact of exogenous melatonin has received considerable attention, there has been limited focus on the responses of closely related species to these factors. Consequently, our investigation aimed to explore the response of three different species of rape to Cd stress and examine the influence of exogenous melatonin in this scenario. The research findings revealed distinctive responses among the investigated rape species. B. campestris showed the resistance to Cd and exhibited lower Cd absorption and sustained its physiological activity under Cd stress. In contrast, B. juncea accumulated much Cd and increased the amount of anthocyanin to mitigate the Cd-damage. Furthermore, B. napus showed the tolerance to Cd and tended to accumulate Cd in vacuoles under Cd stress, thereby decreasing the Cd damage and leading to higher activity of antioxidant enzymes and photosynthesis. Moreover, the application of exogenous melatonin significantly elevated the melatonin level in plants and mitigated Cd toxicity by promoting the activity of antioxidant enzymes, reducing Cd absorption, enhancing the chelating capacity with Cd, decreasing Cd accumulation in organelles, and reducing its fluidity. Specifically, exogenous melatonin increased the F HAc content in B. campestris, elevated the phytochelatins (PCs) level in B. napus, and stimulated photosynthesis in B. juncea. In summary, the findings underscore the species-specific responses of the three species of rape to both Cd stress and exogenous melatonin, highlighting the potential for tailored mitigation strategies based on the unique characteristics of each species., 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.)

Kidneys from donors with prolonged warm and cold ischemia are prone to posttransplant T cell-mediated rejection (TCMR) due to ischemia-reperfusion injury (IRI). However, the precise mechanisms still remain obscure. Renal tubular epithelial cells (TECs) are the main target during IRI. Meanwhile, we have previously reported that murine double minute 2 (MDM2) actively participates in TEC homeostasis during IRI. In this study, we established a murine model of renal IRI and a cell model of hypoxia-reoxygenation by culturing immortalized rat renal proximal tubule cells (NRK-52E) in a hypoxic environment for different time points followed by 24 h of reoxygenation and incubating NRK-52E cells in a chemical anoxia-recovery environment. We found that during renal IRI MDM2 expression increased on the membrane of TECs and aggregated mainly on the basolateral side. This process was accompanied by a reduction of a transmembrane protein, programmed death ligand 1 (PD-L1), a coinhibitory second signal for T cells in TECs. Using mutant plasmids of MDM2 to anchor MDM2 on the cell membrane or nuclei, we found that the upregulation of membrane MDM2 could promote the ubiquitination of PD-L1 and lead to its ubiquitination-proteasome degradation. Finally, we set up a coculture system of TECs and CD4 + T cells in vitro; our results revealed that the immunogenicity of TECs was enhanced during IRI. In conclusion, our findings suggest that the increased immunogenicity of TECs during IRI may be related to ubiquitinated degradation of PD-L1 by increased MDM2 on the cell membrane, which consequently results in T-cell activation and TCMR. NEW & NOTEWORTHY Ischemic acute kidney injury (AKI) donors can effectively shorten the waiting time for kidney transplantation but increase immune rejection, especially T cell-mediated rejection (TCMR), the mechanism of which remains to be elucidated. Our study demonstrates that during ischemia-reperfusion injury (IRI), the translocation of tubular murine double minute 2 leads to basolateral programmed death ligand 1 degradation, which ultimately results in the occurrence of TCMR, which may provide a new therapeutic strategy for preventing AKI donor-associated TCMR.

Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease worldwide. Caspase 8 and FADD-like apoptosis regulator (CFLAR) has been identified as a potent factor in mitigating non-alcoholic steatohepatitis (NASH) by inhibiting the N-terminal dimerization of apoptosis signal-regulating kinase 1 (ASK1). While arginine methyltransferase 1 (PRMT1) was previously reported to be associated with increased hepatic glucose production, its involvement in hepatic lipid metabolism remains largely unexplored. The interaction between PRMT1 and CFLAR and the methylation of CFLAR were verified by Co-IP and immunoblotting assays. Recombinant adenoviruses were generated for overexpression or knockdown of PRMT1 in hepatocytes. The role of PRMT1 in NAFLD was investigated in normal and high-fat diet-induced obese mice. In this study, we found a significant upregulation of PRMT1 and downregulation of CFLAR after 48h of fasting, while the latter significantly rebounded after 12h of refeeding. The expression of PRMT1 increased in the livers of mice fed a methionine choline-deficient (MCD) diet and in hepatocytes challenged with oleic acid (OA)/palmitic acid (PA). Overexpression of PRMT1 not only inhibited the expression of genes involved in fatty acid oxidation (FAO) and promoted the expression of genes involved in fatty acid synthesis (FAS), resulting in increased triglyceride accumulation in primary hepatocytes, but also enhanced the gluconeogenesis of primary hepatocytes. Conversely, knockdown of hepatic PRMT1 significantly alleviated MCD diet-induced hepatic lipid metabolism abnormalities and liver injury in vivo, possibly through the upregulation of CFLAR protein levels. Knockdown of PRMT1 suppressed the expression of genes related to FAS and enhanced the expression of genes involved in FAO, causing decreased triglyceride accumulation in OA/PA-treated primary hepatocytes in vitro. Although short-term overexpression of PRMT1 had no significant effect on hepatic triglyceride levels under physiological conditions, it resulted in increased serum triglyceride and fasting blood glucose levels in normal C57BL/6J mice. More importantly, PRMT1 was observed to interact with and methylate CFLAR, ultimately leading to its ubiquitination-mediated protein degradation. This process subsequently triggered the activation of c-Jun N-terminal kinase 1 (JNK1) and lipid deposition in primary hepatocytes. Together, these results suggested that PRMT1-mediated methylation of CFLAR plays a critical role in hepatic lipid metabolism. Targeting PRMT1 for drug design may represent a promising strategy for the treatment of NAFLD.

The spin of electrons plays a vital role in chemical reactions and processes, and the excited state generated by the absorption of photons shows abundant spin-related phenomena. However, the importance of electron spin in photochemistry studies has been rarely mentioned or summarized. In this review, we briefly introduce the concept of spin photochemistry based on the spin multiplicity of the excited state, which leads to the observation of various spin-related photophysical properties and photochemical reactivities. Then, we focus on the recent advances in terms of light-induced magnetic properties, excited-state magneto-optical effects and spin-dependent photochemical reactions. The review aims to provide a comprehensive overview to utilize the spin multiplicity of the excited state in manipulating the above photophysical and photochemical processes. Finally, we discuss the existing challenges in the emerging field of spin photochemistry and future opportunities such as smart magnetic materials, optical information technology and spin-enhanced photocatalysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aβ), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aβ pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navβ2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aβ1-42 and AD mice, the possible effects and potential mechanisms induced by Navβ2. The results reveal that Aβ1-42 induces remarkable increases in Navβ2 intracellular domain (Navβ2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navβ2-ICD further enhances these effects induced by Aβ1-42, while interfering the generation of Navβ2-ICD and/or complementing BDNF neutralize the Navβ2-ICD-conducted effects. Luciferase reporter assay verifies that Navβ2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navβ2 induced by Aβ1-42-associated AD pathology leads to intracellular Navβ2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navβ2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Advances in mass spectrometry (MS) have enabled high-throughput analysis of proteomes in biological systems. The state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide-spectrum matches (PSMs), which convert mass spectra to peptide sequences. Different database search algorithms use distinct search strategies and thus may identify unique PSMs. However, no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and a control on the false discovery rate (FDR). To fill in this gap, we proposed a statistical framework, Aggregation of Peptide Identification Results (APIR), that is universally compatible with all database search algorithms. Notably, under an FDR threshold, APIR is guaranteed to identify at least as many, if not more, peptides as individual database search algorithms do. Evaluation of APIR on a complex proteomics standard dataset showed that APIR outpowers individual database search algorithms and empirically controls the FDR. Real data studies showed that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search algorithms. The APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis, e.g., differential gene expression analysis on RNA sequencing data. The APIR R package is available at https://github.com/yiling0210/APIR., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3'→5' exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII ( Escherichia coli ) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labeled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5'-bond of phosphodiester from 3' to 5' end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3'-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics., Competing Interests: HW, CY, QL, ZJ, CJ, CZ, NL, CZ, GZ, MY, YL No competing interests declared, (© 2024, Wang et al.)