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The confused gene expressions and molecular mechanisms for mitochondrial dysfunction of traditional nanoenzymes is a challenge for tumor therapy. Herein, a nano-bacilliform-enzyme obtains the ability to inhibit p52-ZER6 signal pathway, regulate the genes related to mitochondrial metabolism, and possess the GOx/CAT/POD-like property. NBE acquires catalytic activity from the electronic energy transition. The tannin of NBE as a mitochondrial (Mito)-targeting guide overloads MitoROS, and then metabolic disorder and lipid peroxidation of Mito membrane occurs, thus leading to a novel death pathway called PAFerroptosis (pyroptosis, apoptosis, and Ferroptosis). Simultaneously, in order to refrain from mitophagy, hydroxychloroquine is mixed with NBE to form a combo with strength pyroptosis. As a result, NBE/combo improves the PAFerroptosis obviously by activation of CD8+T cells and inactivation of MDSC cells, up-regulating expression of caspase-3 signal pathway, intercepting DHODH pathway to arrive excellent antitumor effect (93%). Therefore, this study establishes a rational nanoenzyme for mitochondrial dysfunction without mitophagy for effective antitumor therapy., (© 2024 Wiley‐VCH GmbH.)

Aim: To investigate the effects of fibrillin-1 (FBN1) deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions., Methods: Streptozotocin (STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy (DR) patients, and FBN1 expression was detected in retinas from STZ-diabetic mice and controls. In the Gene Expression Omnibus (GEO) database, the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients. Using lentivirus to knock down FBN1 levels, vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay, fluorescein fundus angiography (FFA) and immunofluorescence labeled with tight junction marker in vivo . High glucose-induced monkey retinal vascular endothelial cells (RF/6A) were used to investigate effects of FBN1 on the cells in vitro . The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance (TEER) assay and flow cytometry, respectively., Results: FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients (GSE60436 datasets) using RNA-seq approach. Besides, knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection. Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group, and knocking down of FBN1 increased the tight junction levels. In vitro , 30 mmol/L glucose could significantly inhibit viability of RF/6A cells, and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation. Down-regulation of FBN1 reduced high glucose (HG)-stimulated retinal microvascular endothelial cell permeability, increased TEER, and inhibited RF/6A cell apoptosis in vitro ., Conclusion: The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions. Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage, reduce vascular leakage, cell apoptosis, and maintain vascular endothelial cell barrier function., Competing Interests: Conflicts of Interest: Zhang Y, None; Liu XJ, None; Zhai XR, None; Yao Y, None; Shao B, None; Zhen YH, None; Zhang X, None; Xiao Z, None; Wang LF, None; Zhang ML, None; Chen ZM, None., (International Journal of Ophthalmology Press.)

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD., (© 2024. The Author(s).)

Background: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity., Results: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs., Conclusions: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity., (© 2024. The Author(s).)

Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Methods: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro , rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury in vitro . Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN., Competing Interests: Author BL was employed by Chengdu Hanpharm Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Min, Xie, Jiang, Rui, Li, Zeng and Liu.)

Chronic kidney disease (CKD) is a type of chronic disease in which multiple factors are responsible for the structural and functional disorders of the kidney. Piperazine ferulate (PF) has anti-platelet and anti-fibrotic effects, and its mechanism of action remains to be elucidated. This study aimed to investigate the protective effect of PF against CKD in rats and to determine its mechanism of action. Network pharmacology was used to predict potential PF action targets in the treatment of CKD and to further validate them. A rat model of CKD was established; blood was collected, etc., for the assessment of the renal function; renal pathologic damage was examined using hematoxylin and eosin (HE) staining and Masson staining; changes in the levels of TGF-β1 and α-SMA were determined with ELISA; EPOR, FN, and COL I expression were detected utilizing immunohistochemistry; and HIF-1α, HIF-2α, and EPO protein molecules were analyzed deploying western blotting. PF reduces Scr, BUN, and 24 h UP levels; decreases FN and COL I expression; and attenuates renal injury. Additionally, PF inhibited TGF-β1 and stimulated the production of HIF-1α and HIF-2α, which downregulated α-SMA and upregulated EPO. PF attenuated the progression of the CKD pathology, and the mechanism of its action is possibly associated with the promotion of HIF-1α/HIF-2α/EPO production and TGF-β1 reduction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cancer immunotherapy provides durable response and improves survival in a subset of head and neck squamous cell carcinoma (HNSC) patients, which may due to discriminative tumor microenvironment (TME). Epigenetic regulations play critical roles in HNSC tumorigenesis, progression, and activation of functional immune cells. This study aims to identify an epigenetic signature as an immunophenotype indicator of durable clinical immunotherapeutic benefits in HNSC patients., Methods: Unsupervised consensus clustering approach was applied to distinguish immunophenotypes based on five immune signatures in The Cancer Genome Atlas (TCGA) HNSC cohort. Two immunophenotypes (immune 'Hot' and immune 'Cold') that had different TME features, diverse prognosis, and distinct DNA methylation patterns were recognized. Immunophenotype-related methylated signatures (IPMS) were identified by the least absolute shrinkage and selector operation algorithm. Additionally, the IPMS score by deconvolution algorithm was constructed as an immunophenotype classifier to predict clinical outcomes and immunotherapeutic response., Results: The 'Hot' HNSC immunophenotype had higher immunoactivity and better overall survival (p = 0.00055) compared to the 'Cold' tumors. The immunophenotypes had distinct DNA methylation patterns, which was closely associated with HNSC tumorigenesis and functional immune cell infiltration. 311 immunophenotype-related methylated CpG sites (IRMCs) was identified from TCGA-HNSC dataset. IPMS score model achieved a strong clinical predictive performance for classifying immunophenotypes. The area under the curve value (AUC) of the IPMS score model reached 85.9% and 89.8% in TCGA train and test datasets, respectively, and robustness was verified in five HNSC validation datasets. It was also validated as an immunophenotype classifier for predicting durable clinical benefits (DCB) in lung cancer patients who received anti-PD-1/PD-L1 immunotherapy (p = 0.017) and TCGA-SKCM patients who received distinct immunotherapy (p = 0.033)., Conclusions: This study systematically analyzed DNA methylation patterns in distinct immunophenotypes to identify IPMS with clinical prognostic potential for personalized epigenetic anticancer approaches in HNSC patients. The IPMS score model may serve as a reliable epigenome prognostic tool for clinical immunophenotyping to guide immunotherapeutic strategies in HNSC., (© 2024. Springer Nature Switzerland AG.)

Protozoa play a pivotal role in the microbial cycle, and ciliated protozoan grazing habits are associated with dimethyl sulfide (DMS) cycle. Many studies have explored the impacts of nanoplastics (NPs) and microplastics (MPs) on ecotoxicological effects of ciliates. However, limited research exists on NPs and MPs influences on the production of organic sulfur compounds. The impact of NPs and MPs on the production of dimethyl sulfoxide (DMSO) and carbonyl sulfide (COS) remains unclear. Therefore, we examined the impacts of three concentrations (1 × 10 5 , 5 × 10 5 , and 1 × 10 6 items/mL) of polystyrene (PS) NPs (50 nm) and MPs (1 and 5 μm) on the ecotoxicology and DMS/dimethylsulfoniopropionate (DMSP)/DMSO/COS production in the ciliate Uronema marinum. NPs and MPs exposure were found to reduce the abundance, growth rate, volume, and biomass of U. marinum. Additionally, NPs and MPs increased the superoxide anion radical (O 2 ˙ ─ ) production rates and malondialdehyde (MDA) contents (24 h), leading to a decline in glutathione (GSH) content and an ascend in superoxide dismutase (SOD) activity to mitigate the effects of reactive oxygen species (ROS). Exposure to PS NPs and MPs decreased the ingestion rates of algae by 7.5-14.4%, resulting in decreases in DMS production by 56.8-85.4%, with no significant impact on DMSO production. The results suggest a distinct pathway for the production of DMSO or COS compared to DMS. These findings help us to understand the NPs and MPs impacts on the marine ecosystem and organic sulfur compound yield, potentially influencing the global climate., 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.)

Dimethyl sulfide (DMS) is a prevalent volatile organic sulfur compound relevant to the global climate. Ecotoxicological effects of nano- and microplastics (NPs and MPs) on phytoplankton, zooplankton, and bacteria have been investigated by numerous studies. Yet, the influences of NPs/MPs on dimethylated sulfur compounds remains understudied. Herein, we investigated the impacts of polystyrene (PS) NPs/MPs (80 nm, 1 μm, and 10 μm) on zooplankton grazing, chlorophyll a (Chl a) concentration, bacterial community, dimethylsulfoniopropionate (DMSP), and DMS production in the microcosms. Our findings revealed that rotifer grazing increased the production of DMS in the absence of NPs/MPs but did not promote DMS production when exposed to NPs/MPs. The ingestion rates of the rotifer and copepod exposed to NPs/MPs at high concentrations were significantly reduced. NPs/MPs exposure significantly decreased DMS levels in the treatments with rotifers compared to the animal controls. In the bacterial microcosms, smaller NPs/MPs sizes were more detrimental to Chl a concentrations compared to larger sizes. The study revealed a stimulatory effect on Chl a concentrations, DMSP d concentrations, and bacterial abundances when exposed to 10 μm MP with low concentrations. The effects of NPs/MPs on DMS concentrations were both dose- and size-dependent, with NPs showing greater toxicity compared to larger MPs. NPs/MPs led to changes in bacterial community compositions, dependent on both dosage and size. NPs caused a notable decrease in the alpha diversities and richness of bacteria compared to MPs. These results provide insights into the influences of NPs/MPs on food webs, and subsequently organic sulfur compounds cycles., 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.)

Polyhedral boranes have potential applications in medicine and material science due to their unique structure and stability. However, tedious and low-yield synthetic methods limited their application. Herein, we have developed a facile large-scale synthetic method for M 2 [B 12 H 12 ] (M = Na, K) by the reaction of MBH 4 with N , N -dipropylaniline borane in diglyme at 120 or 140 °C in up to 88% yield. The mechanistic studies indicated that intermediates, such as [B 3 H 8 ] - and [B 9 H 14 ] - , were formed in the formation process of [B 12 H 12 ] 2- anion, similar to previously reported. The formation of B 2 H 6 from the N , N -dipropylaniline borane adducts is most important. The developed method avoided using toxic materials, with high yield, easily scaled up, raw materials are readily available. Additionally, the starting material, N , N -dipropylaniline, could be repeatedly used at least three times with similar yields, which is an economical way to facilitate industrial synthesis. It is believed that this method will support further application of Na 2 [B 12 H 12 ] and K 2 [B 12 H 12 ] as solid electrolytes for an all-solid-state batteries.

Osteoporosis (OP) constitutes a notable public health concern that significantly impacts the skeletal health of the global aging population. Its prevalence is steadily escalating, yet the intricacies of its diagnosis and treatment remain challenging. Recent investigations have illuminated a profound interlink between gut microbiota (GM) and bone metabolism, thereby opening new avenues for probing the causal relationship between GM and OP. Employing Mendelian randomization (MR) as the investigative tool, this study delves into the causal rapport between 211 varieties of GM and OP. The data are culled from genome-wide association studies (GWAS) conducted by the MiBioGen consortium, in tandem with OP genetic data gleaned from the UK Biobank, BioBank Japan Project, and the FinnGen database. A comprehensive repertoire of statistical methodologies, encompassing inverse-variance weighting, weighted median, Simple mode, Weighted mode, and MR-Egger regression techniques, was adroitly harnessed for meticulous analysis. The discernment emerged that the genus Coprococcus3 is inversely associated with OP, potentially serving as a deterrent against its onset. Additionally, 21 other gut microbial species exhibited a positive correlation with OP, potentially accentuating its proclivity and progression. Subsequent to rigorous scrutiny via heterogeneity and sensitivity analyses, these findings corroborate the causal nexus between GM and OP. Facilitated by MR, this study successfully elucidates the causal underpinning binding GM and OP, thereby endowing invaluable insights for deeper exploration into the pivotal role of GM in the pathogenesis of OP., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Sensory intelligence in the brain helps listeners automatically extract abstract auditory rules formed by invariant acoustic features from complex speech sound streams, presumably serving as the neural basis for speech comprehension. However, whether this intelligence is deficient in children with cochlear implants (CIs) remains unclear., Methods: Mandarin Chinese monosyllables shared a flat lexical tone contour to form an abstract auditory rule but differed in other acoustic features to construct a complex speech sound stream. The abstract rule was occasionally violated by monosyllables with a rising or falling lexical tone., Results: In normal hearing (NH) children, the abstract auditory rule could be extracted, as revealed by a mismatch negativity (MMN) and a late discriminative negativity (LDN). However, the MMN and LDN were only evoked in CI children with good hearing and speech performance. NH children with a higher speech perception or spatial hearing score had a greater MMN. The LDN was attenuated with increasing age in NH children., Conclusions: The sensory intelligence for extraction of auditory abstract rules, associated with speech perception, is deficient in CI children. This intelligence may gradually develop during childhood and adolescence., Significance: Deficient sensory intelligence in CI children may aid in understanding poor speech comprehension in complex environments., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts., Methods: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management., Findings: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD., Conclusions: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD., Funding: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007)., Competing Interests: Declaration of interests M.-H.Z. has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. L.A.B. has received speaker fees from Novo Nordisk and is on the Steering Committee of ACTION Teens, a multicountry study of adolescent obesity sponsored by Novo Nordisk. All fees received are directed to L.A.B.’s hospital research cost center. M.K. is a consultant for Mirum and Medison Pharma. A.M. has received honoraria from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Janssen. N.B.H.N. has received honoraria for lectures and the role of advisory board member (Adolescents with Obesity) from Novo Nordisk. C.M. is chairman of the board and shareholder of DeFaire Medical AB, scientific advisor and shareholder of Oriflame Wellness AB, scientific advisor of Itrim AB, scientific advisor of and speaker for Novo Nordisk, scientific advisor of Rhythm, and speaker for Astra Zeneca, Semper, and Redeye. C.D.B. has received an independent research grant from Echosens. C.G. has acted as speaker for Merck, Gilead, Abbvie, and Novo Nordisk; has served as an advisory board member for Merck, Novo Nordisk, and Gilead; and has received unrestricted research funding from Theratechnologies Inc. M.T.A.-L. has obtained a grant from Novo Nordisk and has acted in an advisory capacity for MSD and Novo Nordisk and as speaker for Novo Nordisk, Gilead, and Abbie. J.M.P. has received consulting fees from Boehringer Ingelheim, MSD, and Novo Nordisk; speaking fees from Gilead, Intercept, and Novo Nordisk; travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk; educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD; and funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898. J.-G.F. has received honoraria for lectures from Sanofi, Echosens, Abbott, Novartis, AstraZeneca, Hisky Medical Technologies, and Novo Nordisk; consulting fees from Allergan, Echosens, Novartis, and Terns; and research grants from Sanofi. S.S.S. serves on Mirum and Alberio advisory boards., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dimethylsulfoniopropionate (DMSP), a key organic sulfur compound in marine and subseafloor sediments, is degraded by phytoplankton and bacteria, resulting in the release of the climate-active volatile gas dimethylsulfide (DMS). However, it remains unclear if dominant eukaryotic fungi in subseafloor sediments possess specific abilities and metabolic mechanisms for DMSP degradation and DMS formation. Our study provides the first evidence that fungi from coal-bearing sediments ∼2 km below the seafloor, such as Aspergillus spp., Chaetomium globosum, Cladosporium sphaerospermum, and Penicillium funiculosum, can degrade DMSP and produce DMS. In Aspergillus sydowii 29R-4-F02, which exhibited the highest DMSP-dependent DMS production rate (16.95 pmol/μg protein/min), two DMSP lyase genes, dddP and dddW, were identified. Remarkably, the dddW gene, previously observed only in bacteria, was found to be crucial for fungal DMSP cleavage. These findings not only extend the list of fungi capable of degrading DMSP, but also enhance our understanding of DMSP lyase diversity and the role of fungi in DMSP decomposition in subseafloor sedimentary 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.)

Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients. Methods: One hundred twenty-six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C-reactive protein (CRP), Interleukin 6 (IL-6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and the Epidemiological Research Center Depression Scale (CES-D), respectively. Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF-A and CES-D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF-A and CES-D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients. Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM-associated executive impairment and depression status., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Shuai He et al.)

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Urease-producing bacteria (UPB) are widely present in soil and play an important role in soil ecosystems. In this study, 65 UPB strains were isolated from cadmium (Cd)-polluted soil around a lead-zinc mine in Yunnan Province, China. The Cd tolerance, removal of Cd from aqueous solution, production of indoleacetic acid (IAA) and plant growth-promoting effects of these materials were investigated. The results indicate that among the 65 UPB strains, four strains with IAA-producing ability were screened and identified as Bacillus thuringiensis W6-11, B. cereus C7-4, Serratia marcescens W11-10, and S. marcescens C5-6. Among the four strains, B. cereus C7-4 had the highest Cd tolerance, median effect concentration (EC 50 ) of 59.94 mg/L. Under Cd 5 mg/L, S. marcescens C5-6 had the highest Cd removal from aqueous solution, up to 69.83%. Under Cd 25 mg/kg, inoculation with B. cereus C7-4 significantly promoted maize growth in a sand pot by increasing the root volume, root surface area, and number of root branches by 22%, 29%, and 20%, respectively, and plant height and biomass by 16% and 36%, respectively, and significantly increasing Cd uptake in the maize roots. Therefore, UPB is a potential resource for enhancing plant adaptability to Cd stress in plants with Cd-polluted habitats.

Background and Purpose: Compassion is increasingly considered essential to quality nursing care and is a concept that is strongly embedded across cultures, including Chinese culture. The Patient Compassion Model (PCM) depicts the unique yet overlapping domains of compassion. The Sinclair Compassion Questionnaire (SCQ) was directly developed and validated from this empirical model. In this study, we sought to establish initial validation of a translated SCQ among Mandarin-speaking patients by assessing the transferability of the PCM and the clinical sensibility of the SCQ. Methods: Forward and back-translation of the PCM and SCQ were performed in accordance with World Health Organization guidelines. Qualitative interviews were used to assess the transferability of the PCM with conceptualizations of compassion within a Chinese context. Cognitive interviews were conducted to assess the clarity, readability, wording, questions, and response scales of the Mandarin translation of the SCQ. Qualitative data were analyzed using constant comparative analysis, and cognitive interviews were analyzed using framework analysis. Results: The original categories of the PCM were verified in this Mandarin-speaking patient population. Specifically, participants' understanding of compassion is described as consisting of healthcare provider virtues, emphasizing the importance of a virtuous response that sought to understand the individual and their unique needs, to relationally communicate from a place of shared humanity and to ameliorate suffering. Participants were able to answer, comprehend, and endorse all 15 Mandarin SCQ items, resulting in no modifications to the Mandarin SCQ. Conclusions: This study provides initial validation of the Mandarin SCQ and PCM. Future studies should consider further establishing the validity and reliability of the Mandarin SCQ among a larger Chinese patient population., (© Copyright 2024 Springer Publishing Company, LLC.)

The prevalence of short stature among prepubertal children in China is relatively high. Early identification of the cause and timely intervention can bring greater benefits to children with short stature. This paper provides an overview of early diagnosis, intervention measures, and personalized medication dosage for prepubertal short stature children, aiming to provide references for clinical doctors.

Due to the potential impacts of microplastics (MPs) and nanoplastics (NPs) on algal growth and thereby affect the climate-relevant substances, dimethylsulfoniopropionate (DMSP) and dimethyl sulfide (DMS), we studied the polystyrene (PS) MPs and NPs of 1 μm and 80 nm impacts on the growth, chlorophyll content, reactive oxygen species (ROS), antioxidant enzyme activity, and DMS/DMSP production in Emiliania huxleyi. E. huxleyi is a prominent oceanic alga that plays a key role in DMS and DMSP production. The results revealed that high concentrations of MPs and NPs inhibited the growth, carotenoid (Car), and Chl a concentrations of E. huxleyi. However, short-time exposure to low concentrations of PS MPs and NPs stimulated the growth of E. huxleyi. Furthermore, high concentrations of MPs and NPs resulted in an increase in the superoxide anion radical (O 2 .- ) production rate and a decrease in the malondialdehyde (MDA) content compared with the low concentrations. Exposure to MPs and NPs at 5 mg L -1 induced superoxide dismutase (SOD) activity as a response to scavenging ROS. High concentrations of MPs and NPs significantly inhibited the production of DMSP and DMS. The findings of this study support the potential ecotoxicological impacts of MPs and NPs on algal growth, antioxidant system, and dimethylated sulfur compounds production, which maybe potentially impact the global climate., 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.)

Purpose: To investigate the inhibitory effect of sodium cantharidate (SCA) on human tongue squamous cell carcinoma CAL27 cells and its mechanism., Methods: CAL27 cells were pretreated with different concentrations of SCA. Cell viability was analyzed by CCK-8 method. The migration and invasion of CAL27 cells were measured by scratch test and Transwell chamber, and the apoptosis rate was measured by flow cytometry. p53 protein and its phosphorylation sites Ser33, Ser37, Ser46, expression of BCL-2, BAX, and cleaved caspase 3 in CAL27 cells were detected by Western blot. Statistical analysis was performed with Graphpad Prism 9.0 software package., Results: Compared with the blank control group, the proliferation, migration and invasion of CAL27 cells in sodium cantharidate group were significantly decreased, and the apoptosis rate was significantly increased(P＜0.01) in a dose-dependent manner. The expression of p53 protein and its phosphorylation sites Ser33, Ser37, Ser46 protein was significantly up-regulated(P＜0.05 or P＜0.01). The expression of BCL-2 protein was down-regulated and the expression of BAX protein was significantly up-regulated(P＜0.05 or P＜0.01). The ratio of BCL-2/BAX was significantly decreased and the expression of cleaved caspase 3 protein was significantly up-regulated(P＜0.05 or P＜0.01)., Conclusions: SCA can inhibit the proliferation, migration and invasion of human tongue squamous cell carcinoma CAL27 cells. It also down-regulates the ratio of BCL-2/BAX and up-regulates the expression of cleaved caspase 3 protein by regulating the phosphorylation of p53 protein, which induces apoptosis.

A dual-emission ratio-fluorescent sensing nanohybrid based on Radix Hedysari green-synthesized carbon quantum dots (CDs) and glutathione-functionalized gold nanoclusters (GSH-AuNCs) had been developed for the determination of cefodizime sodium (CDZM). The designed fluorescence nanohybrid had two significant fluorescence emission peaks at 458 nm and 569 nm when excited at 360 nm, which was attributed to the CDs and GSH-AuNCs. With the addition of CDZM, the fluorescence at 458 nm was slightly weakened while the fluorescence at 569 nm was enhanced obviously. Based on the relationship between the I 569 /I 458 fluorescence intensity ratio and the concentration of CDZM, the designed nanohybrid exhibited a good linearity range of 1.0-1000.0 μM and the limit of detection (LOD) was 0.19 μM. The method was finally applied in the detection of CDZM in urine, showing the potential applications in complicated biological samples.

Background: To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy., Methods: During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at -80 ℃. These samples were obtained from 105 pregnant women in a nested case-control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups., Results: It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05)., Conclusion: Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Broadening carborane applications has consistently been the goal of chemists in this field. Herein, compared to alkyl or aryl groups, a carborane cage demonstrates an advantage in stabilizing a unique bonding interaction: M⋯C-H interaction. Experimental results and theoretical calculations have revealed the characteristic of this two-center, two-electron bonding interaction, in which the carbon atom in the arene ring provides two electrons to the metal center. The reduced aromaticity of the benzene moiety, long distance between the metal and carbon atom in arene, and the upfield shift of the signal of M⋯C-H in the nuclear magnetic resonance spectrum distinguished this interaction from metal⋯C π interaction and metal-C(H) σ bonds. Control experiments demonstrate the unique electronic effects of carborane in stabilizing the M⋯C-H bonding interaction in organometallic chemistry. Furthermore, the M⋯C-H interaction can convert into C-H bond metallization under acidic conditions or via treatment with t -butyl isocyanide. These findings deepen our understanding regarding the interactions between metal centers and carbon atoms and provide new opportunities for the use of carboranes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Endogenous retroviruses (ERVs), a subset of genomic transposable elements (TEs) in a broader sense, have remained latent within mammalian genomes for tens of millions of years. These genetic elements are typically in a silenced state due to stringent regulatory mechanisms. However, under specific conditions, they can become activated, triggering inflammatory responses through diverse mechanisms. This activation has been shown to play a potential role in various neurological disorders, tumors, and cellular senescence. Consequently, the regulation of ERV expression through various methods holds promise for clinical applications in disease treatment. ERVs also engage in interactions with a variety of exogenous viruses, thereby influencing the outcomes of viral infectious diseases. This article comprehensively reviews the pathogenic cascade of ERVs, encompassing activation, inflammation, associated diseases, senescence, and interplay with viruses. Additionally, it outlines therapeutic strategies targeting ERVs with the aim of offering novel research directions for understanding the relationship between ERVs and diseases, along with corresponding treatment modalities.

Background: Teeth identification has a pivotal role in the dental curriculum and provides one of the important foundations of clinical practice. Accurately identifying teeth is a vital aspect of dental education and clinical practice, but can be challenging due to the anatomical similarities between categories. In this study, we aim to explore the possibility of using a deep learning model to classify isolated tooth by a set of photographs., Methods: A collection of 5,100 photographs from 850 isolated human tooth specimens were assembled to serve as the dataset for this study. Each tooth was carefully labeled during the data collection phase through direct observation. We developed a deep learning model that incorporates the state-of-the-art feature extractor and attention mechanism to classify each tooth based on a set of 6 photographs captured from multiple angles. To increase the validity of model evaluation, a voting-based strategy was applied to refine the test set to generate a more reliable label, and the model was evaluated under different types of classification granularities., Results: This deep learning model achieved top-3 accuracies of over 90% in all classification types, with an average AUC of 0.95. The Cohen's Kappa demonstrated good agreement between model prediction and the test set., Conclusions: This deep learning model can achieve performance comparable to that of human experts and has the potential to become a valuable tool for dental education and various applications in accurately identifying isolated tooth., (© 2024. The Author(s).)

Marine distribution of dimethylsulfoniopropionate (DMSP) and its cleavage product dimethyl sulfide (DMS) is greatly affected by the community structures of bacteria, phytoplankton, and zooplankton. Spatial distributions of dissolved and particulate DMSP (DMSP d,p ), and DMS were measured and their relationships with DMSP lyase activity (DLA), abundance of DMSP-consuming bacteria (DCB), and the community structures of phytoplankton, zooplankton, and bacteria were determined during summer in the South China Sea (SCS). The depth distributions of DMSP d,p exhibited a similar trend with Chl a, reaching their maxima in the mixing layer. The DMS concentration was positively correlated with DCB abundance and DLA, indicating that DCB and DMSP lyase had a significant effect on DMS production. High DMS concentrations in the horizontal distribution coincided with high DCB abundance and DLA and may be due to the rapid growth of phytoplankton resulting from the high dissolved inorganic nitrogen concentration brought by the cold vortices. Moreover, the highest copepod abundance at station G3 coincided with the highest DMS concentrations there among stations B4, F2, and G3. These results suggest that copepod may play an important role in DMS production. The bacterial SAR11 clade was positively correlated with DLA, indicating its significant contribution to DMSP degradation in the SCS. These findings contribute to the understanding of the effect of the community assemblage on DMSP/DMS distributions in the SCS dominated by mesoscale vortices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Labiaplasty is one of the top cosmetic procedures patients are seeking in the past two years. However, treatment of disease in posterior fourchette caused by various etiological factors was less investigated and neglected., Methods: Three types of posterior fourchette deformity were proposed: (1) Redundant posterior fourchette, (2) Relaxed posterior fourchette, and (3) Constricted posterior fourchette. Local flap transfer technique was applied. Y-V-plasty and 5-Z-Flap-plasty were used to treat web type and tight type of the constricted posterior fourchette, respectively. Follow-ups were arranged on the Internet or at the outpatient clinic. Visual analogue scale (VAS) was utilized to evaluate sexual discomfort in the satisfaction questionnaires during follow-up., Results: A total of 48 patients with constricted posterior fourchette deformity from May 2022 to May 2023 were reviewed in the study. Y-V-plasty could decrease VAS in patients with web-type deformity by 4.13 ± 1.46 (p＜0.001). 5-Z-Flap-plasty could decrease VAS in patients with tight-type deformity by 3.76 ± 1.53 (p＜0.05). Satisfaction rates of the web type and tight type were 93.1% (27/29) and 86.7% (13/15) respectively. Complications include two cases of hematoma, one case of persistent pain and two cases of dehiscence., Conclusion: Constricted posterior fourchette seriously affects the quality of life. Y-V-plasty and 5-Z-Flap-plasty can be utilized to treat the two subtypes of constricted posterior fourchette, which can effectively reduce the pain score of patients with high satisfaction and few long-term complications., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Silent information regulator type-1 (SIRT1), a nicotinamide adenine dinucleotide + -dependent deacetylase, is a member of the sirtuins family and has unique protein deacetylase activity. SIRT1 participates in physiological as well as pathophysiological processes by targeting a wide range of protein substrates and signalings. In this review, we described the latest progress of SIRT1 in pulmonary diseases. We have introduced the basic information and summarized the prominent role of SIRT1 in several lung diseases, such as acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung cancer, and aging-related diseases., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Reactive oxygen species (ROS) is a chemically reactive chemical substance containing oxygen and a natural by-product of normal oxygen metabolism. Excessive ROS affect the growth process of crops, which will lead to the decrease of yield. Nitrogen, as a critical nutrient element in plants and plays a vital role in plant growth and crop production. Nitrate is the primary nitrogen source available to plants in agricultural soil and various natural environments. However, the molecular mechanism of ROS-nitrate crosstalk is still unclear. In this study, we used the foxtail millet (Setaria italica L.) as the material to figure it out. Here, we show that excessive NaCl inhibits nitrate-promoted plant growth and nitrogen use efficiency (NUE). NaCl induces ROS accumulation in roots, and ROS inhibits nitrate-induced gene expression in a short time. Surprisingly, low concentration ROS slight promotes and high concentration of ROS inhibits foxtail millet growth under long-term H 2 O 2 treatment. These results may open a new perspective for further exploration of ROS-nitrate signaling pathway in plants., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Molecules with high point-group symmetry are interesting prototype species in the textbook. As transition metal-centered boron clusters tend to have highly symmetric structures to fulfill multicenter bonding and high stability, new boron clusters with rare point-group symmetry may be viable. Through in-depth scrutiny over the structures of experimentally already observed transition metal-centered boron-wheel complexes, geometric and electronic design principles are summarized, based on which we studied M©B 11 k - ( M = Y, La; Zr, Hf; k = 1, 2) clusters and found that a Y©B 11 2- boron-wheel complex has an unprecedented D 11 h point-group symmetry. The remarkable stability of the planar Y©B 11 2- complex is illustrated via extensive global-minimum structural search as well as comprehensive chemical bonding analyses. Similar to other boron-wheel complexes, the Y©B 11 2- complex is shown to possess σ and π double aromaticity, indeed following the electronic design principle previously summarized. This new compound is expected to be experimentally identified, which will extend the currently known largest possible planar molecular symmetry and enrich the metal-centered boron-wheel class.

As the most produced phthalate, di-(2-ethylhexyl) phthalate (DEHP) is a widely environmental pollutant primarily used as a plasticizer, which cause the harmful effects on human health. However, the impact of DEHP on spleen and its underlying mechanisms are still unclear. Pyroptosis is a novel form of cell death induced by activating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes and implicated in pathogenesis of numerous inflammatory diseases. The current study aimed to explore the impact of DEHP on immune inflammatory response in mouse spleen. In this study, the male ICR mice were treated with DEHP (200 mg/kg) for 28 days. Here, DEHP exposure caused abnormal pathohistological and ultrastructural changes, accompanied by inflammatory cells infiltration in mouse spleen. DEHP exposure arouse heat shock response that involves increase of heat shock proteins 60 (HSP60) expression. DEHP also elevated the expressions of toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) proteins, as well as the activation of NF-κB pathway. Moreover, DEHP promoted NLRP3 inflammasome activation and triggered NLRP3 inflammasome-induced pyroptosis. Mechanistically, DEHP drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis. Our findings reveal that targeting HSP60-mediated TLR4/NLRP3 signaling axis may be a promising strategy for inflammatory diseases treatment., 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.)

Aim: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children., Methods: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing., Results: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|>0.1 and Adj. P <0.05), and 328 of these were identified with a significance of Adj. P <0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like ( TCERG1L , cg07684215) gene was hypermethylated in the four T1DM children with DR ( P =0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P >0.05) between participants with and without DR., Conclusion: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM., Competing Interests: Conflicts of Interest: Qian Y, None; Xiao Y, None; Lin QR, None; Xiang ZY, None; Cui LP, None; Sun JQ, None; Li SC, None; Qin XR, None; Zou HD, None; Yang CH, None; Jin PY, None., (International Journal of Ophthalmology Press.)

Objective: Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer., Methods: CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan-Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay., Results: CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966-1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice., Conclusion: Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Polygonatum cyrtonema Hua is a traditional Chinese medicinal food herb which can regulate the liver and Qi, nourish the heart and blood, moisten the lungs and nourish the kidneys with the potential to treat emotional diseases. However, few studies have explored the effects of Polygonatum cyrtonema Hua on postpartum depression. Therefore, we investigated whether processed Polygonatum cyrtonema Hua could improve postpartum depression in rat models by regulating monoamines and hormones., Methods: Female Sprague-Dawley rats were randomized into normal control (0.9%Nacl), Sham operation (0.9%Nacl), postpartum depression model (0.9%Nacl), fluoxetine (2.5 mg/kg Fluoxetine), low, medium and high dose of processed Polygonatum cyrtonema Hua (2.5 g/kg, 5 g/kg, 10 g/kg) groups. Rats in these groups received drug intervention, and then subjected to Open-field test and Forced swimming test. Brain tissues and serum samples were collected and used to quantify levels of monoamines, hypothalamic-pituitary-adrenal axis and serum Estradiol. The status of neuronal cells in hippocampus 1 region was examined through hematoxylin-eosin staining, whereas expression of estrogen receptor α and β was detected by immunohistochemistry., Results: Rats in the model group showed decreased mobility time, the disorder of neuronal cells in hippocampus 1 area, and decreased concentration of 5-hydroxytryptamine and dopamine in brain tissue, norepinephrine and estradiol in serum as well as estrogen receptor α and β expression. They also exhibited increased adrenocorticotropic hormone, corticosterone and corticotropin releasing hormone in serum. However, the treatment with processed Polygonatum cyrtonem Hua or fluoxetine reversed the above abnormalities., Conclusion: The H group showed significant improvement in postpartum depression in rats, and processed Polygonatum cyrtonema Hua can be used as a developing drug for the prevention or treatment of depression., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Microplastics (MPs) and nanoplastics (NPs) have gained global concern due to their detrimental effects on marine organisms. We investigated the effects of 80 nm polystyrene (PS) NPs on life history traits, ingestion, and dimethyl sulfide (DMS) and dimethylsulfoniopropionate (DMSP) production in the rotifer Brachionus plicatilis. Fluorescently labeled 80 nm PS NPs were ingested by the rotifer B. plicatilis and accumulated in the digestive tract. The lethal rates of B. plicatilis exposed to NPs were dose-dependent. High concentrations of PS NPs exposure had negative effects on developmental duration, leading to prolonged embryonic development and pre-reproductive periods, shortened reproductive period, post-reproductive period, and lifespan in B. plicatilis. High concentrations of PS NPs exposure inhibited life table demographic parameters such as age-specific survivorship and fecundity, generation time, net reproductive rate, and life expectancy. Consequently, the population of B. plicatilis was adversely impacted. Furthermore, exposure to PS NPs resulted in a reduced ingestion rate in B. plicatilis, as well as a decreased in DMS, particulate DMSP (DMSP p ) concentration, and DMSP lyase activity (DLA), which exhibited a dose-response relationship. B. plicatilis grazing promoted DLA and therefore increased DMS production. PS NPs exposure caused a decline in the increased DMS induced by rotifer grazing. Our results help to understand the ecotoxicity of NPs on rotifer and their impact on the biogeochemical cycle of dimethylated sulfur compounds., 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.)

Purpose: This study aimed to investigate the effect of Marshall ethanol infusion (VOM-Et) in the vein on mitral isthmus (MI) ablation., Methods: Patients with persistent atrial fibrillation (AF) were grouped into vein of VOM-Et combined with radiofrequency (RF) ablation (VOM-Et-RF) and RF groups. The primary outcome was MI block immediate block rate after surgery. Stratified analysis was also performed for factors affecting the outcome measures., Results: A total of 118 consecutive patients underwent AF ablation at Taizhou Hospital of Zhejiang Province from January 2018 to December 2021. Successful bidirectional perimitral block was achieved in 96% of patients in VOM-Et-RF (69 of 72) and in 76% of patients in the RF group (35 of 46) ( P  < 0.01). In the subgroup analysis, male sex, elder than 60 years, Left atrial diameter <55 mm, and AF duration <3 years were associated with the benefits of VOM-Et in AF Patients., Conclusion: The vein of Marshall ethanol infusion for catheter ablation can improve the MI block rate. Male sex, elder age, smaller Left atrial diameter and shorter AF duration may have significant benefits for VOM-Et., 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., (© 2024 Ge, Lu, Li, Wang, Yin, Li, Jiang, Mi, Tung and Yan.)

Background: In time-of-flight PET, image quality and accuracy can be enhanced by improving the annihilation photon pair coincidence time resolution, which is the variation in the arrival time difference between the two annihilation photons emitted from each positron decay in the patient. Recent studies suggest direct detection of ionization tracks and their resulting modulation of optical properties, instead of scintillation, can improve the CTR significantly, potentially down to less than 10 ps CTR. However, the arrival times of the 511 keV photons are not predictable, leading to challenges in the spatiotemporal localization characterization of the induced charge carriers in the detector crystal., Purpose: To establish an optimized experimental setup for measuring ionization induced modulation of optical properties, it is critical to develop a versatile simulation algorithm that can handle multiple detector material properties and time-resolved charge carrier dynamics., Methods: We expanded our previous algorithm and simulated ionization tracks, cascade time and induced charge carrier density over time in different materials. For designing a proof-of-concept experiment, we simulated ultrafast electrons and free-electron x-ray photons for timing characterization along with alpha and beta particles for higher spatial localization., Results: With 3 MeV ultrafast electrons, by reducing detector crystal thickness, we can effectively reduce the ionization cascade time to 0.79 ps and deposited energy to 198.5 keV, which is on the order of the desired 511 keV energy. Alpha source simulations produced a cascade time of 2.45 ps and charge carrier density of 6.39 × 1020 cm -3 . Compared to the previous results obtained from 511 keV photon-induced ionization track simulations, the cascade time displayed similar characteristics, while the charge density was found to be higher. These findings suggest that alpha sources have the potential to generate a stronger ionization-induced signal using the modulation of optical properties as the detection mechanism., Conclusions: This work provides a guideline to understand, design and optimize an experimental platform that is highly sensitive and temporally precise enough to detect single 511 keV photon interactions with a goal to advance CTR for ToF-PET., (© 2023 American Association of Physicists in Medicine.)

A Personal Health Knowledge Graph (PHKG) facilitates the efficient integration of potential diagnostic clues from patients' electronic health records with medical knowledge, establishing diagnostic reasoning paths and ensuring accurate, individually interpretable results in the diagnosis of pelvic masses.

Ethnopharmacological Relevance: Interstitial lung disease (ILD) is a chronic lung dysfunction disease with a poor prognosis and poor recovery. The clinically used therapeutic drugs, such as glucocorticoids and immunosuppressants, have no significant therapeutic effect and are accompanied with severe side effects. In recent years, considerable progress has been made in exploring and applying natural herb components for treating ILD. Traditional Chinese Medicine (TCM) possesses innate, non-toxic characteristics and offers advantages in preventing and treating pulmonary ailments. However, a comprehensive study of TCM on ILD therapy has not yet been reviewed., Aim of the Review: This review aimed to provide a comprehensive summary of the monomer components, total extracts, and prescriptions of TCM for ILD therapy, elucidating their molecular mechanisms to serve as a reference in treating ILD., Materials and Methods: The literature information was searched in the PubMed, Web of Science databases. The search keywords included 'interstitial lung disease', 'lung fibrosis' or 'pulmonary fibrosis', and 'traditional Chinese medicine', 'traditional herbal medicine', or 'herb medicine'., Results: The active components of single herbs, such as alkaloids, flavonoids, terpenoids, phenols, and quinones, have potential therapeutic effects on ILD. The active extracts and prescriptions were also summarized and analyzed. The herbs, Glycyrrhiza uralensis Fisch. (Gancao), Astragalus membranaceus Fisch. Bunge. (Huangqi) and Angelicasinensis (Oliv.) Diels (Danggui), play significant roles in the treatment of ILD. The mechanisms involve the inhibition of inflammatory factor release, anti-oxidative injury, and interference with collagen production, etc. CONCLUSION: This review examines the therapeutic potential of TCM for ILD and elucidates its molecular mechanisms, demonstrating that mitigating inflammation and oxidative stress, modulating the immune system, and promoting tissue repair are efficacious strategies for ILD therapy. The depth research will yield both theoretical and practical implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Epimedium koreanum Nakai (E. koreanum), a member of the genus Epimedium in the family Berberidaceae, is a well-known and well-liked traditional herb used as a "kidney tonic". For thousands of years, it has been utilized for renal yang deficiency, impotence, spermatorrhea, impotence, weakness of tendons and bones, rheumatic paralysis and discomfort, numbness, and constriction., Aim of the Study: The paper aims to comprehensively in-depth, and methodically review the most recent research on the traditional uses, phytochemistry, pharmacology, and toxicity of E. koreanum., Materials and Methods: Scientific databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, Baidu Scholar, and CNKI and medicine books in China were searched for relevant information on E. koreanum., Results: In traditional uses, E. koreanum is frequently used to treat various diseases like erectile dysfunction, infertility, rheumatoid arthritis, osteoporosis, asthma, kidney-yang deficiency syndrome, etc. To date, more than 379 compounds have been discovered from various parts of E. koreanum, including flavonoids, lignans, organic acids, terpenoids, hydrocarbons, dihydrophenanthrene derivatives, alkaloids, and others. Research has revealed that the compounds and crude extracts have a wide range of pharmacological effects on the reproductive, cardiovascular, and nervous systems, as well as anti-osteoporosis, anti-tumor, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, and antiviral properties. Besides, the crude extracts show potential hepatotoxicity., Conclusion: Based on recent domestic and international research investigations, E. koreanum contains a wealth of chemical components with pronounced pharmacological activities. Its traditional uses are numerous, and the majority of these traditional uses have been supported by contemporary pharmacological investigations. Crude extracts, on the other hand, can result in hepatotoxicity. Therefore, additional in vivo and in vitro experimental research on the pharmacology and toxicology of E. koreanum are required in the future to assess its safety and efficacy. This will give a firmer scientific foundation for its safe application and the development of new drugs in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Reduced brain volume, impaired cognition, and possibly a range of psychoneurological disorders have been reported in patients with non-alcoholic fatty liver disease (NAFLD); however, no underlying cause has been specified. Here, Mendelian randomization (MR) was employed to determine the causative NAFLD effects on cortical structure., Methods: We used pooled-level data from FinnGen's published genome-wide association study (GWAS) of NAFLD (1908 cases and 340,591 healthy controls), as well as published GWAS with NAFLD activity score (NAS) and fibrosis stage-associated SNPs as genetic tools, in addition to the Enigma Consortium data from 51,665 patients, were used to assess genetic susceptibility in relation to changes with cortical thickness (TH) and surface area (SA). A main estimate was made by means of inverse variance weighted (IVW), while heterogeneity and pleiotropy were detected using MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier to perform a two-sample MR analysis., Results: At the global level, NAFLD reduced SA (beta = -586.72 mm 2 , se = 217.73, p  = 0.007) and several changes in the cortical structure of the cerebral gyrus were found, with no detectable pleiotropy., Conclusion: NAFLD causally affects cortical structures, which supports the presence of an intricate liver-brain axis., 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 Lin, Cai, Chen, Hong, Tu, Chen and Du.)

Pulmonary fibrosis is a chronic and progressive disease, current systemic administration is not fully effective with many side effects, such as gastrointestinal and liver injury. The pulmonary delivery system for pulmonary fibrosis may contribute to maximize therapeutic benefit. Natural compounds might have prominence as potential drug candidates, but the low bioavailabilities affect their clinical use. Tetrandrine is a natural alkaloid with good anti-inflammatory, antifibrogenetic and antioxidant effects, and it is used as a clinical therapeutic drug for the treatment of silicosis in China. In the present study, we explore a new strategy of pulmonary delivery system to improve low solubility and pesticide effect of tetrandrine. Tetrandrine was loaded into alginate nanogels by reverse microemulsion method. The release behavior of tetrandrine reached zero-order kinetics release and the maximum free radical clearance rates reached up to 90%. The pulmonary fibrosis rats were treated with tetrandrine nanogels by using ultrasonic atomizing inhalation. Tetrandrine nanogels decreased the development and progression of fibrosis by reducing inflammation response and bating the deposition of extra cellular matrix. In conclusion, ultrasonic atomizing inhalation of tetrandrine nanogels provided a new therapeutic strategy for pulmonary fibrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Two-dimensional (2D) MOFs exhibit unique periodicity in surface structures and thus have attracted much interest in the fields of catalysis, energy, and sensors. However, the expanded production scale of 2D MOFs had remained a great challenge in most previous studies. Herein, a controllable and efficient crystallization method for synthesizing 2D MOF nanosheets using high-gravity reactive precipitation is proposed, significantly improving heterogeneous catalysis efficiency. The two-dimensional ZIF-L nanosheets prepared in a rotating packed bed (RPB) reactor show a smaller lateral and lamellar thickness and a higher BET surface area compared to ZIF-L nanosheets prepared in a conventional stirred tank reactor (STR), with a greatly shortened reaction time. Applying the ZIF-L-RPB nanosheets as a catalyst, the catalytic Knoevenagel condensation as a probe reaction displays a high conversion rate of benzaldehyde (99.3%) within 2 h at room temperature, greatly exceeding that displayed by ZIF-L-STR and other reported catalysts. Furthermore, ZIL-L-RPB nanosheets of only 0.2 wt% enhanced the catalytic activity for the glycolysis of poly(ethylene terephthalate) (PET) with a PET conversion and a monomer yield of 90% in a short period of 15 min at 195 °C and almost completely depolymerized PET with a monomer yield of 94% in 30 min, which was far above that achieved by ZIL-L-STR. These results indicate the promising prospects of a high-gravity reactive precipitation strategy with precise size control in an economical way to prepare high-activity 2D MOF nanosheets for a wide range of heterogeneous catalysis.

This experiment aimed to establish a green, simple and highly sensitive method (supercritical fluid chromatography (SFC) coupled with ion mobility quadrupole time-of-flight mass spectrometry (IM-Q-TOF/MS)) for the detection of multiple pesticides in foods. During the experiments, several important SFC parameters, such as stationary phase, modifier, make-up solution, back-temperature and back-pressure were optimized. Here, single-field collision cross section (CCS) values and multifield CCS values of 20 pesticides were examined by IM-Q-TOF/MS as highly specific parameters with excellent experimental precision. In addition, based on accurate mass matching and fragment ion comparison, mass fragments were obtained by IM-Q-TOF/MS, which elucidated the regularities of compound structure and characteristic fragment ions. Under the optimized conditions, satisfactory linearity (R 2  ≥ 0.9989) and recoveries (79.60 % to 112.97 %) were obtained. The intra- and interday precisions were favorable, with RSDs lower than 4.91 and 7.65 %, respectively. Additionally, the method showed low limits of detection (0.1-8.8 ng/mL). The proposed method has been successfully applied to the highly sensitive detection of phenylurea herbicide, triazine herbicides, organophosphorus pesticide, pyrethroid insecticide and acaricide in yam and potato., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Diagnostic errors have become the biggest threat to the safety of patients in primary health care. General practitioners, as the "gatekeepers" of primary health care, have a responsibility to accurately diagnose patients. However, many general practitioners have insufficient knowledge and clinical experience in some diseases. Clinical decision making tools need to be developed to effectively improve the diagnostic process in primary health care. The long-tailed class distributions of medical datasets are challenging for many popular decision making models based on deep learning, which have difficulty predicting few-shot diseases. Meta-learning is a new strategy for solving few-shot problems., Methods and Materials: In this study, a few-shot disease diagnosis decision making model based on a model-agnostic meta-learning algorithm (FSDD-MAML) is proposed. The MAML algorithm is applied in a knowledge graph-based disease diagnosis model to find the optimal model parameters. Moreover, FSDD-MAML can learn learning rates for all modules of the knowledge graph-based disease diagnosis model. For n-way, k-shot learning tasks, the inner loop of FSDD-MAML performs multiple gradient update steps to learn internal features in disease classification tasks using n×k examples, and the outer loop of FSDD-MAML optimizes the meta-objective to find the associated optimal parameters and learning rates. FSDD-MAML is compared with the original knowledge graph-based disease diagnosis model and other meta-learning algorithms based on an abdominal disease dataset., Result: Meta-learning algorithms can greatly improve the performance of models in top-1 evaluation compared with top-3, top-5, and top-10 evaluations. The proposed decision making model FSDD-MAML outperforms all the other models, with a precision@1 of 90.02 %. We achieve state-of-the-art performance in the diagnosis of all diseases, and the prediction performance for few-shot diseases is greatly improved. For the two groups with the fewest examples of diseases, FSDD-MAML achieves relative increases in precision@1 of 29.13 % and 21.63 % compared with the original knowledge graph-based disease diagnosis model. In addition, we analyze the reasoning process of several few-shot disease predictions and provide an explanation for the results., Conclusion: The decision making model based on meta-learning proposed in this paper can support the rapid diagnosis of diseases in general practice and is especially capable of helping general practitioners diagnose few-shot diseases. This study is of profound significance for the exploration and application of meta-learning to few-shot disease assessment in general practice., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)