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Abstract Background Pediatric myelodysplastic syndromes (MDS) are rare disorders with an unrevealed pathogenesis. Our aim is to explore the role of genetic factors in the pathogenesis of MDS in children with different outcomes and to discover the correlation between genetic features and clinical outcomes as well as disease characteristics. Methods We conducted an analysis of archived genetic data from 26 patients diagnosed with pediatric MDS at our institution between 2015 and 2021, examining the association between different genetic characteristics and clinical manifestations as well as prognosis. Additionally, We presented three cases with distinct genetic background and outcomes as examples to elaborate the role of genetic factors in pediatric MDS with different prognoses. Results Genetic variations were detected in 13 out of the 26 patients, including 8 patients with co-occurrence of somatic and germline mutations (CSGMs) and 5 patients with somatic mutations alone. Our analysis revealed that advanced MDS (4/8, 50% vs. 1/5, 20% and 4/11, 36.4%), PD (3/8, 37.5% vs. 1/5, 20% and 1/11 9.1%), and TD (6/8, 75% vs. 2/5, 40% and 2/11, 18.2%) were more common in patients with CSGMs than those with somatic mutations alone or without any mutations. We also found out in our study that 8 patients with CSGMs had evidently different clinical outcomes, and we presented 3 of them as examples for elaboration. Case 1 with germline and somatic mutations of unknown significance had a relatively slow disease course and a good prognosis. Case 2 with compound heterozygous germline SBDS variants and somatic mutations like del20q had a stable disease course and a reversed outcome. Case 3 with a germline GATA2 variant and somatic mutations including − 7 had a rapidly progressive disease course and a worst prognosis. Conclusion Our findings indicate that genetic background of pediatric MDS is closely linked with disease characteristics as well as outcomes and that CSGMs may lead to disease progression. It should be emphasized that the interaction between certain germline variants and somatic mutations, such as SBDS and del20q, may result in hematopoietic stem cell adaptation (improved hematopoiesis) and reversed clinical outcomes, which can facilitate the development of targeted therapy.

Abstract Background China has the third-largest burden of tuberculosis (TB) cases in the world with great challenges towards ending TB. Primary health care (PHC) sectors play a critical role in TB prevention and control in communities under the Chinese integrated TB control model. However, there is a lack of comprehensive review of research evidence on TB control in PHC sectors under the integrated TB control model in China. Methods This review was conducted following the PRISMA guidelines. Articles published from 2012 to January 2022 were searched from four international and three Chinese databases. Studies conducted inside mainland China and relevant with TB control service in PHC sectors under the integrated model were included. After study selection, data extraction, and quality assessment, the meta-analysis was performed with RevMan using a random-effect model.When I2 was more than 50%, subgroup analysis was performed to explore possible reasons for heterogeneity. We also conducted a post hoc sensitivity analysis for outcomes after meta-analysis by exclusion of studies with a high risk of bias or classified as low quality. Results Forty-three studies from 16 provinces/municipalities in China were included in this review, and most studies included were of medium quality. PHC sectors in East China delivered TB control service better overall than that in West China, especially in tracing of patients and TB case management (TCM). In meta-analyses, both the pooled arrival rate of tracing and pooled TCM rate in East China were higher than those in West China. TB patients had a low degree of willingness to receive TCM provided by healthcare workers in PHC sectors nationwide, especially among migrant TB patients. There were 9 studies reporting factors related to TB control service in PHC sectors, 6 (2 in East and 4 in West China) of which indentified several characteristics of patients as associated factors. The context of PHC sectors was demonstrated to influence delivery of TB control service in PHC sectors in 5 studies (3 in East, 1 in Middle and 1 in West China). Most studies on strategies to promoting TB control services in PHC sectors were conducted in East China and some of these studies identified several online and offline interventions and strategies improving patients’ treatment compliance [pooled OR (95% CI): 7.81 (3.08, 19.19] and awareness of TB [pooled OR (95% CI): 6.86 (2.16, 21.72)]. Conclusion It is of urgent need to improve TB control in PHC sector in China, particularly in West China. Formative and implementation research with rigorous design are necessary to develop comprehensive, context-specific, and patient-centered TB control strategies to promote ending TB in China.

Abstract Purpose We evaluated the value of copy number variation sequencing (CNV-seq) and quantitative fluorescence (QF)-PCR for analyzing chromosomal abnormalities (CA) in spontaneous abortion specimens. Methods A total of 650 products of conception (POCs) were collected from spontaneous abortion between April 2018 and May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. The clinical features of the patients were recorded. Results Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, of which 217 (33.4%) were autosomal trisomies, 42(6.5%) were chromosomal monosomies and 40 (6.2%) were pathogenic CNVs (pCNVs). Chromosomal trisomy occurs mainly on chromosomes 15, 16, 18, 21and 22. Monosomy X was not associated with the maternal or gestational age. The frequency of chromosomal abnormalities in miscarriages from women with a normal live birth history was 55.3%; it was 54.4% from women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and with ≥ 2 previous miscarriages regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 and 30–34 years (P

Let $ \gamma(G) $ denote the domination number of a graph $ G $. A vertex $ v\in V(G) $ is called a critical vertex of $ G $ if $ \gamma(G-v) = \gamma(G)-1 $. A graph is called vertex-critical if its every vertex is critical. In this paper, we correspondingly introduce two such definitions: (i) A set $ S\subseteq V(G) $ is called a strong critical vertex-set of $ G $ if $ \gamma(G-S) = \gamma(G)-|S| $; (ii) A graph $ G $ is called strong $ l $-vertex-set-critical if $ V(G) $ can be partitioned into $ l $ strong critical vertex-sets of $ G $. Therefrom, we give some properties of strong $ l $-vertex-set-critical graphs by extending the previous results of vertex-critical graphs. As the core work, we study on the existence of this class of graphs and prove that there exists a strong $ l $-vertex-set-critical connected graph if and only if $ l\notin\{2, 3, 5\} $.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Abstract Background Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction. Methods A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed. Results Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P

Abstract Background The relationship between leukocyte telomere length (LTL) and mortality risk in individuals with metabolic syndrome (MetS) remains poorly understood. This study aimed to investigate the association between telomere length and long-term all-cause mortality, and cardiovascular disease (CVD) mortality, in individuals with MetS in the United States. Methods A total of 1980 participants with MetS aged 18 years or older from the National Health and Nutrition Examination Survey (NHANES) prospective cohort study (1999–2002) were included in this cohort study. Medical records review was used to identify the cause of deaths as of December 2018. We employed Kaplan-Meier curves, fitted curves, and Cox proportional hazards regression models to estimate hazard ratios (HRs) for all-cause and CVD mortality, stratified by tertiles of LTL. Results Over a median follow-up of 17.75 years of participants with metabolic syndrome, 819 deaths occurred, including 231 cardiovascular deaths. After adjusting for multiple covariates, participants with shorter telomere length had a significantly higher risk of all-cause mortality (HR, 1.33; 95% CI, 1.11–1.6) and CVD mortality (HR, 1.36; 95% CI, 0.96–1.93) compared with those in the highest tertile of telomere length. All-cause mortality (P

Abstract Exercise is an effective non-pharmacological strategy for ameliorating nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism needs further investigation. Cysteine dioxygenase type 1 (Cdo1) is a key enzyme for cysteine catabolism that is enriched in liver, whose role in NAFLD remains poorly understood. Here, we show that exercise induces the expression of hepatic Cdo1 via the cAMP/PKA/CREB signaling pathway. Hepatocyte-specific knockout of Cdo1 (Cdo1LKO) decreases basal metabolic rate of the mice and impairs the effect of exercise against NAFLD, whereas hepatocyte-specific overexpression of Cdo1 (Cdo1LTG) increases basal metabolic rate of the mice and synergizes with exercise to ameliorate NAFLD. Mechanistically, Cdo1 tethers Camkk2 to AMPK by interacting with both of them, thereby activating AMPK signaling. This promotes fatty acid oxidation and mitochondrial biogenesis in hepatocytes to attenuate hepatosteatosis. Therefore, by promoting hepatic Camkk2-AMPK signaling pathway, Cdo1 acts as an important downstream effector of exercise to combat against NAFLD.

The reliability analysis of vertically integrated protection devices is crucial for designing International Electrotechnical Commission (IEC) 61850-based substations. This paper presents the hardware architecture of a four-in- one vertically integrated device and the information transmission path of each function based on the functional information transmission chain of protection devices, measurement and control devices, merging units, and intelligent terminals. Additionally, a reliability analysis model of the protection device and its protection system is constructed using the fault tree analysis method while considering the characteristics of each module of the vertically integrated device. The stability probability of the protection system in each state is analyzed by combining the state-transfer equations of line and busbar protection with a Markov chain. Finally, the failure rate and availability of the protection device and its protection system are calculated under different ambient temperatures using a 110 kV intelligent substation as an example. The sensitivity of each device module is analyzed.

Background Inflammatory bowel disease (IBD) has become highly prevalent in recent years characterized by a prolonged disease course and high disease burden. However, there is a lack of data to understand the burden of IBD in China, which may hinder health care planning and resource allocation for the disease. Objective To investigate the burden of IBD and its variation tendency in China from 1990 to 2019, and analyze the influence of age, gender and period on IBD. Methods The incidence, mortality and disability adjusted life year (DALY) rate of IBD in China from 1990 to 2019 were collected using the Global Burden of Disease Database 2019. Joinpoint software was used to analyze the variation tendency and characteristics of standardized incidence, standardized mortality and standardized DALY rate of IBD, and Excel 2019 software was used for data processing. Results From 1990 to 2019, the standardized incidence increased from 1.47/100 000 to 3.01/100 000 with avevage annual percent change (AAPC) of 2.50%〔95%CI (2.4%, 2.6%) 〕, the standardized mortality decreased from 0.86/100 000 to 0.35/100 000 with AAPC of -1.6%〔95%CI (-3.8%, -3.4%) 〕, the standardized DALY rate decreased from 24.47/100 000 to 16.31/100 000, with AAPC of -2.2%〔95%CI (-2.3%, -2.0%) 〕, the changes of trends were all statistically significant (P

The progress of research and forecast techniques for tropical cyclone (TC) unusual tracks (UTs) in recent years is reviewed. A major research focus has been understanding which processes contribute to the evolution of the TC and steering flow over time, especially the reasons for the sharp changes in TC motion over a short period of time. When TCs are located in the vicinity of monsoon gyres, TC track forecast become more difficult to forecast due to the complex interaction between the TCs and the gyres. Moreover, the convection and latent heat can also feed back into the synoptic-scale features and in turn modify the steering flow. In this report, two cases with UTs are examined, along with an assessment of numerical model forecasts. Advances in numerical modelling and in particular the development of ensemble forecasting systems have proved beneficial in the prediction of such TCs. There are still great challenges in operational track forecasts and warnings, such as the initial TC track forecast, which is based on a poor pre-genesis analysis, TC track forecasts during interaction between two or more TCs and track predictions after landfall. Recently, artificial intelligence (AI) methods such as machine learning or deep learning have been widely applied in the field of TC forecasting. For TC track forecasting, a more effective method of center location is obtained by combining data from various sources and fully exploring the potential of AI, which provides more possibilities for improving TC prediction.

Abstract This work deals with the fabrication of one low density steel by mixing AISI S2 tool steel and AlSi10Mg powders using powder-based directed energy deposition (P-DED) technique. Two approaches of mixing powders were compared-continuous mixing during the process (in-situ) and mixing the powder prior to the process (premixed). The P-DED sample was characterised by a variety of techniques such as optical microscopy, scanning electron microscopy, electron backscatter diffraction, X-ray diffraction, and hardness measurement. Our findings demonstrate the successful achievement of steel with a 8 wt. % AlSi10Mg addition when two dissimilar powders are premixed, resulting in approximately 12% reduction in the density of S2 steel. Optimizing the powder feed rate and the ratio of AlSi10Mg powder contribute to an improvement of printability, eliminating materials separation, leading to a homogenous deposited part. Compared to the in-situ mixing case, the premixed process within the current process window generates a more homogeneous microstructure consisting of three phases: Ferrite, Fe3Al and Fe3AlC carbide. Whereas, the in-situ sample exhibits only two phases Ferrite and Fe3Al. The hardness of the premixed sample is found to be slightly higher compared to the in-situ sample.

Abstract Background The γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the “enteric nervous system–vagus nerve–brain” axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure. Methods Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice. Results The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system. Conclusions These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.

Abstract Background Hospice and Palliative Care (HPC) is in high demand in China; however, the country is facing the shortage of qualified HPC nurses. A well-suited competence framework is needed to promote HPC human resource development. Nevertheless, existing unstandardized single-structured frameworks may not be sufficient to meet this need. This study aimed at constructing a comprehensive multi-structured HPC competence framework for nurses. Methods This study employed a mixed-method approach, including a systematic review and qualitative interview for HPC competence profile extraction, a two-round Delphi survey to determine the competences for the framework, and a cross-sectional study for framework structure exploration. The competence profiles were extracted from publications from academic databases and interviews recruiting nurses working in the HPC field. The research team synthesized profiles and transferred them to competences utilizing existing competence dictionaries. These synthesized competences were then subjected to Delphi expert panels to determine the framework elements. The study analyzed theoretical structure of the framework through exploratory factor analysis (EFA) based on a cross-sectional study receiving 491 valid questionnaires. Results The systematic review involved 30 publications from 10 countries between 1995 and 2021, while 13 nurses from three hospitals were interviewed. In total, 87 and 48 competence profiles were respectively extracted from systematic review and interview and later synthesized into 32 competences. After the Delphi survey, 25 competences were incorporated into the HPC competence framework for nurses. The EFA found a two-factor structure, with factor 1 comprising 18 competences namely Basic Competences; factor 2 concluding 7 competences namely Developmental Competences. Conclusions The two-factor HPC competence framework provided valuable insights into the need and directions of Chinese HPC nurses’ development.

Abstract Background Musca domestica larvae are common saprophytes in nature, promoting the material—energy cycle in the environment. However, heavy metal pollution in the environment negatively affects their function in material circulation. Our previous research found that some intestinal bacteria play an important role in the development of housefly, but the responses of microbial community to heavy metal stresses in Musca domestica is less studied. Results In this study, CuSO4, CuSO4—Klebsiella pneumoniae mixture and CuSO4—K. pneumoniae phage mixture were added to the larval diet to analyze whether K. pneumoniae can protect housefly larvae against Cu2+ injury. Our results showed that larval development was inhibited when were fed with CuSO4, the bacterial abundance of Providencia in the intestine of larvae increased. However, the inhibition effects of CuSO4 was relieved when K. pneumoniae mixed and added in larval diets, the abundance of Providencia decreased. Electron microscope results revealed that K. pneumoniae showed an obvious adsorption effect on copper ion in vitro. Conclusions Based on the results we assume that K. pneumoniae could adsorb Cu2+, reduce Cu2+ impact on gut community structure. Our study explains the role of K. pneumoniae antagonizing Cu2+, which could be applied as a probiotic to saprophytic bioantagonistic metal contamination.

Abstract Background The incidence of refractive surgery-related dry eye disease (DED) is rising due to the increasing popularity of corneal refractive surgery. The moisture chamber goggles (MCGs) have been shown to tear evaporation by increasing local humidity and minimizing airflow. The current study aims to evaluate the efficacy of moisture chamber goggles for refractive surgery-related DED. Methods In this nonrandomized open-label controlled study, 78 participants (156 eyes) receiving refractive surgery were enrolled between July 2021 and April 2022, and sequentially allocated to MGC and control groups. 39 participants were allocated to the MGC groups, of which 53.8% received small-incision lenticule extraction (SMILE) and 46.2% received femtosecond laser-assisted in situ keratomileusis (FS-LASIK), and were instructed to wear MCGs for the duration of 1 month postoperatively, in addition to the standard postoperative treatment received by the control groups (56.4% SMILE, 43.6% FS-LASIK). Participants underwent full ophthalmic examinations, including visual acuity, manifest refraction, DED evaluations, and higher-order aberrations (HOAs), both preoperatively and at routine follow-ups 1 day, 1 week, and 1 month after surgery. DED parameters included non-invasive tear film break-up time (NIBUT), tear meniscus height (TMH), conjunctival congestion, lipid layer thickness (LLT), and ocular surface disease index (OSDI) questionnaires. Student’s t-test was used for comparisons between control and MCG groups, and between preoperative and postoperative parameters within groups. Results Postoperative NIBUT decreased in both SMILE and FS-LASIK control groups 1 day after the surgery (SMILE, P = 0.001; FS-LASIK, P = 0.008), but not in the corresponding MCG groups (SMILE, P = 0.097; FS-LASIK, P = 0.331). TMH in the MCG group was significantly higher at 1 week (P = 0.039) and 1 month (P = 0.015) in SMILE, and 1 day (P = 0.003) in FS-LASIK groups. In FS-LASIK participants, significantly lower HOAs and coma levels in the MCG group were observed 1 day (total HOAs, P = 0.023; coma, P = 0.004) and 1 week (total HOAs, P = 0.010, coma, P = 0.004) after surgery. No consistent statistically significant intergroup difference was observed between MCG and control groups in conjunctival congestion, LLT, and OSDI. Conclusions MCGs effectively slowed tear evaporation, increased tear film stability, and improved HOAs in patients receiving SMILE and FS-LASIK surgeries. MCG is an effective adjuvant therapy in the comprehensive management of refractive surgery-related DED.

Abstract Quantum error mitigation has been extensively explored to increase the accuracy of the quantum circuits in noisy-intermediate-scale-quantum (NISQ) computation, where quantum error correction requiring additional quantum resources is not adopted. Among various error-mitigation schemes, probabilistic error cancellation (PEC) has been proposed as a general and systematic protocol that can be applied to numerous hardware platforms and quantum algorithms. However, PEC has only been tested in two-qubit systems and a superconducting multi-qubit system by learning a sparse error model. Here, we benchmark PEC using up to four trapped-ion qubits. For the benchmark, we simulate the dynamics of interacting fermions with or without spins by applying multiple Trotter steps. By tomographically reconstructing the error model and incorporating other mitigation methods such as positive probability and symmetry constraints, we are able to increase the fidelity of simulation and faithfully observe the dynamics of the Fermi–Hubbard model, including the different behavior of charge and spin of fermions. Our demonstrations can be an essential step for further extending systematic error-mitigation schemes toward practical quantum advantages.

Abstract A set of high-quality pan-genomes would help identify important genes that are still hidden/incomplete in bird reference genomes. In an attempt to address these issues, we have assembled a de novo chromosome-level reference genome of the Silkie (Gallus gallus domesticus), which is an important avian model for unique traits, like fibromelanosis, with unclear genetic foundation. This Silkie genome includes the complete genomic sequences of well-known, but unresolved, evolutionarily, endocrinologically, and immunologically important genes, including leptin, ovocleidin-17, and tumor-necrosis factor-α. The gap-less and manually annotated MHC (major histocompatibility complex) region possesses 38 recently identified genes, with differentially regulated genes recovered in response to pathogen challenges. We also provide whole-genome methylation and genetic variation maps, and resolve a complex genetic region that may contribute to fibromelanosis in these animals. Finally, we experimentally show leptin binding to the identified leptin receptor in chicken, confirming an active leptin ligand-receptor system. The Silkie genome assembly not only provides a rich data resource for avian genome studies, but also lays a foundation for further functional validation of resolved genes.

Abstract Environmental stimuli trigger rapid transcriptional reprogramming of gene networks. These responses occur in the context of the local chromatin landscape, but the contribution of organ-specific dynamic chromatin modifications in responses to external signals remains largely unexplored. We treated tomato seedlings with a supply of nitrate and measured the genome-wide changes of four histone marks, the permissive marks H3K27ac, H3K4me3, and H3K36me3 and repressive mark H3K27me3, in shoots and roots separately, as well as H3K9me2 in shoots. Dynamic and organ-specific histone acetylation and methylation were observed at functionally relevant gene loci. Integration of transcriptomic and epigenomic datasets generated from the same organ revealed largely syngenetic relations between changes in transcript levels and histone modifications, with the exception of H3K27me3 in shoots, where an increased level of this repressive mark is observed at genes activated by nitrate. Application of a machine learning approach revealed organ-specific rules regarding the importance of individual histone marks, as H3K36me3 is the most successful mark in predicting gene regulation events in shoots, while H3K4me3 is the strongest individual predictor in roots. Our integrated study substantiates a view that during plant environmental responses, the relationships between histone code dynamics and gene regulation are highly dependent on organ-specific contexts.

Abstract Background Allele-specific binding (ASB) events occur when transcription factors (TFs) bind more favorably to one of the two parental alleles at heterozygous single nucleotide polymorphisms (SNPs). Evidence suggests that ASB events could reveal the impact of sequence variations on TF binding and may have implications for the risk of diseases. Results Here we present ASB-analyzer, a software platform that enables the users to quickly and efficiently input raw sequencing data to generate individual reports containing the cytogenetic map of ASB SNPs and their associated phenotypes. This interactive tool thereby combines ASB SNP identification, biological annotation, motif analysis, phenotype associations and report summary in one pipeline. With this pipeline, we identified 3772 ASB SNPs from thirty GM12878 ChIP-seq datasets and demonstrated that the ASB SNPs were more likely to be enriched at important sites in TF-binding domains. Conclusions ASB-analyzer is a user-friendly tool that enables the detection, characterization and visualization of ASB SNPs. It is implemented in Python, R and bash shell and packaged in the Conda environment. It is available as an open-source tool on GitHub at https://github.com/Liying1996/ASBanalyzer .

AbstractContext Paeoniflorin (PF) contributes to improving coronary artery disease (CAD).Objective This study clarified the efficiency of PF in CAD and the molecular mechanism.Materials and methods Human coronary artery endothelial cells (HCAECs) were treated with oxidized low-density lipoprotein (ox-LDL; 20, 40, 80 and 160 μg/mL) and PF (0.05, 0.1 0.2 and 0.4 mM). To study cell phenotypes, HCAECs were treated with 80 μg/mL ox-LDL with or without 0.1 mM PF for 24 h, and cell viability and apoptosis were evaluated using the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. In addition, inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). Western blot evaluated the Wnt/β-catenin pathway-related factors.Results ox-LDL and PF (0.2 and 0.4 mM) suppressed cell viability in a dose-dependent manner. The IC50 value of PF was 722.9 nM. PF facilitated cell viability (115.76%), inhibited apoptosis (46.28%), reduced IL-6 (63.43%) and IL-8 (66.70%) levels and increased IL-10 levels (181.15%) of ox-LDL-treated HCAECs. Additionally, PF inactivated the Wnt/β-catenin pathway, and XAV939 treatment further promoted cell viability (120.54%), suppressed apoptosis (56.92%), reduced the levels of IL-6 (76.16%) and IL-8 (86.82%) and increased the IL-10 levels (120.22%) of ox-LDL-induced HCAECs after PF treatment. Moreover, PF alleviated plaque lesions of the aorta and aorta root and serum lipid of ApoE−/− mice with a high-fat diet.Discussion and conclusions This study first revealed that PF inhibited ox-LDL-induced HCAECs apoptosis and inflammation via the Wnt/β-catenin pathway and alleviated CAD, suggesting the potential of PF as a drug for CAD treatment.

ABSTRACTThis study primarily analyzed the response of cold tolerance and phenology periods of four pear cultivars to climate differences in central (Gongzhuling) and eastern (Longjing) Jilin, which could provide a theoretical basis for the regional division and cultivation. It showed that there was a significant difference in the cold tolerance of the same cultivars between the two regions. Soluble sugar and soluble starch contents are the most important physiological indicators that determine the cold tolerance of the pear cultivars in Gongzhuling is stronger than that in Longjing. In phenology, only the cessation of terminal shoot extension and growing season length of pear cultivars were significantly related to their contents of soluble sugar and soluble starch. Furthermore, the gray correlation analysis identified the district’s effective accumulated temperature as the key meteorological factors affecting the cessation of terminal shoot extension. The precipitation in the growing season was another major meteorological factor affecting the growing season length. Therefore, in this study, the influence of the main district meteorological factors on the key phenology periods of four pear cultivars, which decided the different accumulation of sugar and starch, eventually lead to the difference in cold tolerance of the same pear cultivar in two regions.

AbstractContext Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application.Objective This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis.Materials and methods Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings.Results Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1β and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1β, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment.Discussion and conclusion Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1β, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.

ABSTRACTThe quality of cooked potato depends on its nutritional components. This study aimed to select suitable potato cultivars for cooking through correlation analysis of their nutritional composition and cooking characteristics. The nutritional components and sensory properties of 10 potatoes from the Xinjiang province were determined. Correlation analysis showed that protein and calcium, as well as the dietary fiber, iron, and phosphorus contents were significantly associated with the total colour difference (ΔE) and softening (p < .05). The umami and kokumi of potatoes after cooking were significantly correlated with isoleucine and tyrosine, as well as lysine, leucine, and isoleucine (p < .01). It could be deduced from the colour, texture characteristics and sensory properties that Longshu11 was suitable for processing mashed potato products, and that Jizhang12, Longshu10 and Heijingang were suitable for fresh-cut. The results provided new ideas and theoretical support for efficiently selecting suitable potato varieties for cooking and processing.

Abstract The fossils of Hamipterus tianshanensis (Wang et al. in Curr Biol 24:1323–1330, 2014) and their eggs have important scientific significance because they can provide unique information about the reproduction, development, and evolution of pterosaurs. The fossils and the rock surrounding them have, however, been weathered, which including powdering and flaking, since they were relocated from Xinjiang to Beijing. The high content of soluble salts is a significant factor in fossil deterioration because the dissolution–recrystallization process can generate tremendous pressure and lead to decreased mechanical strength. This study evaluated the electrokinetic desalination performance for the fossils, and two types of poultices employed including paper pulp from Bioline® and CKS121 (cellulose: kaolin: sand = 1:2:1, w/w). Mercury intrusion porosimetry (MIP), scanning electron microscopy (SEM), ion chromatography (IC), and other methods were applied to evaluate the desalination effect. The surface salt content reduction by applied direct current (DC) was about 70%, and the inner salt content reduction was about 80%. The experimental results suggest that the electrokinetic method is a promising way to desalinate fossils. Nonetheless, cracks appeared in the surrounding rock crack after electrokinetic desalination, which can be explained by the montmorillonite swelling-induced stresses. Pre-consolidation, especially for electro-chemical method may solve the cracking problem for the clay-rich sandstone desalination.

Abstract Background Acute kidney injury (AKI) is a frequent complication of cardiac surgery that poses significant risks for both the development of chronic kidney diseases and mortality. Our previous study illustrated that heightened expression levels of faecal and plasma indole metabolites before the operation were associated with ischemic AKI. In this study, we aimed to validate the supposition that plasma indole-3-aldehyde (I3A) could serve as a predictive biomarker for AKI in patients undergoing cardiac surgery. Methods This statistical reanalysis utilized AKI metabolomic data from patients scheduled for cardiac surgery between April 2022 and July 2022 in two tertiary hospitals. Faecal and blood samples were prospectively collected before surgery within 24 h, and variables related to the preoperative, intraoperative, and postoperative periods were recorded. AKI diagnosis was based on the Kidney Disease Improving Global Outcomes criteria. Results In this study, 55 patients who underwent cardiac surgery were analyzed, and 27 of them (49.1%) developed postoperative AKI. Before surgery, these patients had significantly higher levels of faecal indole metabolites, including skatole, trans-3-indoleacrylic acid, and 5-methoxyindoleacetic acid. The plasma I3A, clinical model that considered perioperative and intraoperative variables, and their combination had area under the receiver operating characteristic curve (ROC) values of 0.79 (95% CI 0.67–0.91), 0.78 (95% CI 0.66–0.90), and 0.84 (95% CI 0.74–0.94) for predicting AKI, respectively. Furthermore, by utilizing net reclassification improvement and integrated discrimination improvement, plasma I3A showed significant improvements in risk reclassification compared to the clinical model alone. Conclusions The dysregulation of gut microbiota metabolism in patients scheduled for cardiac surgery can result in an increase in indoles from tryptophan metabolism, which may be associated with postoperative acute kidney injury (AKI). This suggests that indoles may serve as a predictive biomarker for AKI in patients undergoing cardiac surgery.

Abstract Background Pulmonary nodule growth rate assessment is critical in the management of subsolid pulmonary nodules (SSNs) during clinical follow-up. The present study aimed to develop a model to predict the growth rate of SSNs. Methods A total of 273 growing SSNs with clinical information and 857 computed tomography (CT) scans were retrospectively analyzed. The images were randomly divided into training and validation sets. All images were categorized into fast-growth (volume doubling time (VDT) ≤ 400 days) and slow-growth (VDT > 400 days) groups. Models for predicting the growth rate of SSNs were developed using radiomics and clinical features. The models’ performance was evaluated using the area under the curve (AUC) values for the receiver operating characteristic curve. Results The fast- and slow-growth groups included 108 and 749 scans, respectively, and 10 radiomics features and three radiographic features (nodule density, presence of spiculation, and presence of vascular changes) were selected to predict the growth rate of SSNs. The nomogram integrating radiomics and radiographic features (AUC = 0.928 and AUC = 0.905, respectively) performed better than the radiographic (AUC = 0.668 and AUC = 0.689, respectively) and radiomics (AUC = 0.888 and AUC = 0.816, respectively) models alone in both the training and validation sets. Conclusion The nomogram model developed by combining radiomics with radiographic features can predict the growth rate of SSNs more accurately than traditional radiographic models. It can also optimize clinical treatment decisions for patients with SSNs and improve their long-term management.

Abstract Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

The COVID-19 pandemic significantly disrupted global healthcare systems. The impacts of SARS-CoV-2 infection on urticaria and its management are unknown. This study aimed to collect information about patients with urticaria infected with SARS-CoV-2 and to investigate the impact of SARS-CoV-2 infection on urticaria severity, course, and treatment to better support recovery. This was a questionnaire-based study of patients with urticaria infected with SARS-CoV-2. Changes in urticaria severity (measured with the urticaria activity score (UAS)), course, and treatment were assessed before, during, and after SARS-CoV-2 infection. The mean (±SD) UAS scores were 5.17 ± 1.67, 4.23 ± 1.98, and 4.37 ± 1.93 before, during, and after SARS-CoV-2 infection, respectively (F = 8.839, p < 0.01). The median (IQR) wheal score was 0.464 (0.464, 0.763), 0.464 (0.138, 0.763), and 0.464 (0.138, 0.763) before, during, and after infection, respectively (Kruskal–Wallis H-test, H = 12.230, p = 0.02). The median (IQR) pruritus score was 0.695 (0.395, 0.695), 0.394 (0.123, 0.695), and 0.394 (0.123, 0.695) before, during, and after infection, respectively (Kruskal–Wallis H-test, H = 21.001, p < 0.01). Within the limitations of a questionnaire study, urticaria appears to improve during SARS-CoV-2 infection and worsens slightly after recovery, and the frequency of Western medicine use increases.

Background The serum reverse triiodothyronine (rT3) values of heart failure patients who died during hospitalization were found significantly higher than the upper limit of the biological reference interval in the clinical work of the author. The prediction of thyroid hormones, especially rT3, on death during hospitalization of heart failure patients was rare reported in the previous studies, it is of great clinical significance to explore the indicators with predictive value for death during hospitalization in patients with heart failure. Objective To investigate the relationship between serum thyroid hormones and prognosis during hospitalization in patients with heart failure. Methods A total of 197 patients with heart failure admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from April 2019 to April 2022 were included in the study. Baseline data of the study subjects were collected by the electronic medical record system. Fasting venous blood of all subjects was collected within 24 h after admission for total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), rT3 and N-terminal brain natriuretic peptide precursor (NT-pro-BNP). Subjects were divided into death group (n=18) and non-death group (n=179) according to the occurrence of death during hospitalization. Multivariate Logistic regression analysis was used to investigate the influencing factors of death during hospitalization in patients with heart failure. Receiver operating curve (ROC curve) was plotted to evaluate the predictive value of related indicators on death during hospitalization in patients with heart failure, and the area under curve (AUC) of each indicator was calculated and compared by Delong test. Results The age and rT3 of death group were higher than those of non-death group, while FT3, TT3 and TSH of death group were lower than those of non-death group, with statistically significant differences (P

The laminar flow separation and separation-induced transition at low Reynolds number are complex, and have great difficulty in numerical simulation. Based on fully-connected back-propagation neural network, a data-driven model of intermittency at low Reynolds number was established. The input parameters of the data-driven model to reflect transition process and predict intermittency were selected through optimization design. By modifying the k-ω SST two equation turbulence model with a data-driven transition equation, the flow field evolution and unsteady aerodynamic characteristics of a two-dimensional airfoil under dynamic stall were solved. Results show that the data-driven transition equation combined with two equation turbulence model has the generalization ability for the angle of attack, and clearly reflects the typical flow conditions such as the growth and shedding of the leading-edge vortex and the reattachment of the flow under dynamic stall. The relative error of unsteady aerodynamic lift in dynamic stall between the data-driven transition model and the SST-γ three equation model is lower than 12%.

Reasonable artificial reef layout can provide suitable habitat, promote species diversity and ecosystem stability. However, affected by various factors, the actual location of the artificial reef may be different from the plan, resulting in the failure of the artificial reef construction to achieve the expected results. In this study, four indicators, including center of gravity error, peripheral area error, overlapping area error, and reef quantity error, were used to evaluate the status of artificial reef placement errors in Tianjin Ocean Ranching. The results showed that the error of the peripheral area and reef quantity is -0.11 and 0.067, respectively, it meant that the accuracy of delivery layout was relatively high; the average error of center of gravity and overlapping area was 0.59 and 0.73, respectively, and the accuracy of delivery positioning was relatively poor, which needed further improvement. From the perspective of actual changes, in 2018, the center of gravity error, overlapping area error, and reef quantity error of artificial reefs were significantly improved, and only the peripheral area error was slightly larger, indicating that the accuracy has achieved the expected effect. This study quantified the placement error of artificial reefs in Tianjin Ocean Ranching, and the results could provide useful reference for improving the effect of artificial reef placement, provide a scientific basis for relevant policy formulation, and guide management practices for Tianjin Ocean Ranching.

In order to reveal the differences in the biosynthesis and metabolism of the major bioactive composition in sea buckthorn berry pulp during ripening, non-targeted metabolomics based on ultra-high performance liquid chromatography coupled to mass spectrometry (UPLC-MS) was used to analyze the metabolites of sea buckthorn berry pulp from two strains at different developmental stages (green and orange pulp). The results showed that the four sample groups had significant metabolic differences. A total of 124 significantly differential metabolites were detected among the four groups based on variable importance in the projection (VIP) > 1 and t-test P < 0.05, including organic acids, carbohydrates, lipids, flavonoids and secondary metabolites. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, 15, 7 and 4 significantly differential metabolites associated with lipid, flavonoid and serotonin metabolism were identified, respectively, and eight significantly differential metabolites involved in anticancer function were selected. The significant up-regulation of phosphatidylcholine (PC) (16:0/16:0) and glycerophosphocholine could be the reason for the high accumulation of lipids in sea buckthorn berry pulp. The significant upregulation of isorhamnetin was key for the high flavonoid content in sea buckthorn berry pulp. Relatively high contents of N-acetylserotonin, capecitabine, γ-aminobutyric acid (GABA) and other bioactive composition involved in anticancer function were shown in sea buckthorn berry pulp during its development. These results provide a scientific basis for revealing the metabolic mechanism of bioactive composition of sea buckthorn berries and developing related functional products.

Precursor-derived ceramic SiOC (PDC-SiOC) microlattices exhibit excellent oxidation resistance, high-temperature stability, and superior mechanical properties. However, the printing accuracy of the PDC-SiOC microlattices by 3D printing is still limited, and mechanical properties of the PDC-SiOC microlattices have not been studied systematically. Here, PDC-SiOC octet microlattices were fabricated by projection micro stereolithography (PμSL) 3D printing, and photoabsorber (Sudan III)’s effect on the accuracy was systematically analyzed. The results showed that the addition of Sudan III improved the printing accuracy significantly. Then, the ceramization process of the green body was analyzed in detail. The order of the green body decreased, and most of their chemical bonds were broken during pyrolysis. After that, the PDC-SiOC microlattices with different truss diameters in the range of 52–220 μm were fabricated, and their mechanical properties were investigated. The PDC-SiOC microlattices with a truss diameter of 52 μm exhibited higher compression strength (31 MPa) than those with bigger truss diameters. The size effect among the PDC-SiOC microlattices was analyzed. Our work provides a deeper insight into the manufacturing of PDC-SiOC micro-scaled architectures by 3D printing and paves a path to the research of the size effect in ceramic structures.

The arid inland river basins in northwestern China have been experienced various stages of soil and water resources over-exploitation over the past 50 years, as well as ecological protection and restoration in recent years, which has significantly influenced the regional groundwater and ecological environment. However, the long-term evolution of groundwater and its ecological effects remain unclear. In this study, the Kongque River Basin is chosen as a study area, and the spatio-temporal evolution of groundwater flow field is analyzed based on the comparison of recent groundwater monitoring data and historical data. The ecological effects of long-term groundwater evolution are discussed by analyzing the influence of regional groundwater to Populus euphratica in the riparian zone. The results show that from 1971 to 2021, the groundwater flow in the Kongque River Basin has undergone drastic variation due to excessive groundwater exploitation, and the groundwater levels have shown a general downward trend. The total area where the groundwater levels have decreased by more than 40 m is 204.69 km2, as well as 1735.81 and 1018.56 km2 for 20−40 and 5−20 m, and eventually led to the formation of a regional drawdown funnel, which have seriously affected the water consumption of Populus euphratica in the middle and lower reaches. From 1971 to 2016, the regional groundwater level depth in the riparian zone of the Kongque River Basin decreased by more than 10 m, with a degradation and shrinkage of Populus euphratica. After the implementation of the ecological water transport project since 2016, the groundwater level depth has gradually increased by 2−4 m, and reached the critical groundwater level of Populus euphratica. From 2014 to 2018, the regional NDVI increased by 17%, which indicates that the coverage rate of natural vegetation has improved. This study can improve the understanding of evolution patterns in groundwater and ecological environment in arid inland river basins of the northwestern China, and provide scientific references for sustainable development and utilization of groundwater and ecological protection in similar regions.

Abstract Antrodia cinnamomea (AC) is a treasured Asian medicinal mushroom, which has attracted attention due to recent research on its effectiveness in targeting a variety of serious ailments such as cancer and liver diseases. Among different A. cinnamomea constituents, triterpenoids are regarded as the most therapeutically attractive components because of their anti-inflammatory and cytotoxic activities. In the present study, we proposed a mathematical and statistical extraction protocol to evaluate the concentrations of total ergostane and lanostane triterpenoid derivatives from the ethanolic extract of the wild fruiting bodies of A. cinnamomea (EEAC) by utilizing response surface methodology (RSM) and quantitative NMR (qNMR) approaches. The optimum response surface model showed that the variations of the investigated response variables reached more than 90%, suggesting that the developed model is accurate in explaining response variability. Furthermore, the EEAC major characteristic triterpenoids were quantified through the comparison of the HPLC-tandem MS results with those of the qNMR results. The precision of the used techniques was also evaluated. The experimental design of the EEAC optimum extraction procedure obtained by using RSM and qNMR enabled accurate characterization and quantitation of A. cinnamomea triterpenoids.

Abstract To evaluate the possibility of judging the degree of bone healing by wall thickness analysis provide reference for quantitative analysis of bone healing. Patients with lower limb fracture from April 2014 to October 2019 were recruited and divided into bone healing (group A), poor bone healing (group B), and nonunion (group C). Models were built in Mimics 20.0 with DICOM 3.0 data obtained from patient’s CT. Three-dimensional geometric models of unaffected limb and affected limb after simulated removal of internal fixation were established, corresponding to basic phase and simulated phase, respectively. Wall thickness analysis was performed to obtain median wall thickness after meshing. R2 (median wall thickness ratio), R4 (CT value ratio), and R5 (healing index ratio) were obtained by calculating the ratio of each value in simulated phase to that in basic phase. Receiver operating characteristic curve analysis was used to evaluate the ability of Wall Thickness Analysis to indicate fracture healing. 112 CT scans of 79 patients were included in the study. The frequency of categorization in groups A, B, and C was 49, 37 and 26, respectively. The median R2 in groups A, B, and C was 0.91, 0.80, and 0.67, respectively (group A > group B > group C, all P

Abstract Background Autistic traits (ATs) are frequently reported in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to examine ATs in children with ADHD from both behavioral and neuroimaging perspectives. Methods We used the Autism Spectrum Screening Questionnaire (ASSQ) to assess and define subjects with and without ATs. For behavioral analyses, 67 children with ADHD and ATs (ADHD + ATs), 105 children with ADHD but without ATs (ADHD − ATs), and 44 typically developing healthy controls without ATs (HC − ATs) were recruited. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the mean amplitude of low-frequency fluctuation (mALFF) values (an approach used to depict different spontaneous brain activities) in a sub-sample. The imaging features that were shared between ATs and ADHD symptoms or that were unique to one or the other set of symptoms were illustrated as a way to explore the “brain–behavior” relationship. Results Compared to ADHD-ATs, the ADHD + ATs group showed more global impairment in all aspects of autistic symptoms and higher hyperactivity/impulsivity (HI). Partial-correlation analysis indicated that HI was significantly positively correlated with all aspects of ATs in ADHD. Imaging analyses indicated that mALFF values in the left middle occipital gyrus (MOG), left parietal lobe (PL)/precuneus, and left middle temporal gyrus (MTG) might be specifically related to ADHD, while those in the right MTG might be more closely associated with ATs. Furthermore, altered mALFF in the right PL/precuneus correlated with both ADHD and ATs, albeit in diverse directions. Conclusions The co-occurrence of ATs in children with ADHD manifested as different behavioral characteristics and specific brain functional alterations. Assessing ATs in children with ADHD could help us understand the heterogeneity of ADHD, further explore its pathogenesis, and promote clinical interventions.

Abstract Parkinson’s disease (PD) is characterized by α-synuclein aggregation in dopaminergic (DA) neurons, which are sensitive to oxidative stress. Mitochondria aconitase 2 (ACO2) is an essential enzyme in the tricarboxylic acid cycle that orchestrates mitochondrial and autophagic functions to energy metabolism. Though widely linked to diseases, its relation to PD has not been fully clarified. Here we revealed that the peripheral ACO2 activity was significantly decreased in PD patients and associated with their onset age and disease durations. The knock-in mouse and Drosophila models with the A252T variant displayed aggravated motor deficits and DA neuron degeneration after 6-OHDA and rotenone-induction, and the ACO2 knockdown or blockade cells showed features of mitochondrial and autophagic dysfunction. Moreover, the transcription of autophagy-related genes LC3 and Atg5 was significantly downregulated via inhibited histone acetylation at the H3K9 and H4K5 sites. These data provided multi-dimensional evidences supporting the essential roles of ACO2, and as a potential early biomarker to be used in clinical trials for assessing the effects of antioxidants in PD. Moreover, ameliorating energy metabolism by targeting ACO2 could be considered as a potential therapeutic strategy for PD and other neurodegenerative disorders.

Abstract Objective To explore the histopathological features of glandular atrophy of the lamina propria of gastric mucosa during its occurrence and development. Method We performed detailed histological observation and immunohistochemical examination on the endoscopic biopsy and ESD endoscopic resection specimens of 896 patients with glandular atrophy of the lamina propria of gastric mucosa. The EnVision two-step method was used for immunohistochemical staining, and the slices were incubated with primary antibody CK7, CK20, villin, CDX2, MUC5AC, MUC6, p53 and ki-67. Hematoxylin staining was performed and observed under the microscope and statistically analyzed. Results In the initial stage of glandular atrophy of the lamina propria, the proliferation area of the deep gastric pits, and the isthmus and neck of the gastric glands are characterized by roughly normal structure of the glandular structure, increased mesenchyme, and widened space between glands. Subsequently, the gland becomes smaller in volume and less in number, especially at the base, in the gastric glandular part of the gastric unit. The disease at this stage has higher incidence, and occurs more often in the elderly who account for 64.0% (573/896) of our study group. The disease in this stage may exhibit some lesions that are physiologic (age-related degeneration) while others are pathological. Therefore, this condition is called simple glandular atrophy of the lamina propria of the gastric mucosa. When the gastric mucosal epithelium is subjected to infection or repeated infections, chemical stimuli, immune factors, and genetic factors, it can lead to the proliferation and transformation of stem cells in the proliferation area of the deep gastric pits, and the isthmus and neck of the gastric glands, forming single ducts, multiple ducts, or a proliferation of patchy cells. Then, atypical hyperplasia (intraepithelial neoplasia) presents, finally leading to gastric adenocarcinoma. Conclusion Understanding the histopathological characteristics of glandular atrophy of the lamina propria of gastric mucosa is of great significance in controlling the occurrence and development of gastric cancer.

Abstract Background Leeches are an integral component of aquatic biocenosis and can be found in a wide range of ecosystems such as freshwater, saltwater, flowing, and still-water ecosystems. It especially plays an important role in the freshwater benthic community and is an important part of the food web. In this study, a leech species was found in the mantle cavity of wild freshwater mussels in Zigong City, Sichuan Province, China, and its identity was determined through morphological analysis and molecular biological analysis. Results The leech is Hemiclepsis khankiana, a new species of Hemiclepsis that has been discovered in Russia in recent years. Through morphological analysis, the current survey observed that the morphological characteristics of Hemiclepsis khankiana eyespots were significantly different from the first reported description. The first pair of eyespots on the leech were separated and clear, while it had been reduced to unclear shadows in the previous report. The phylogenetic tree based on the COI gene showed that the COI gene sequence obtained in this study was in the same evolutionary branch as Hemiclepsis khankiana (MN295420, MN295421). Genetically, it was most closely related to Hemiclepsis kasmiana (mean COI p-distance = 3.98%). Conclusions The current study reported on the new distribution range of Hemiclepsis khankiana, which was initially discovered in China. This study indicates that the distribution range of the leech species has expanded, laying a foundation for further studies in China.

Abstract Autophagosomes are double-membrane vesicles generated intracellularly to encapsulate substrates for lysosomal degradation during autophagy. Phase separated p62 body plays pivotal roles during autophagosome formation, however, the underlying mechanisms are still not fully understood. Here we describe a spatial membrane gathering mode by which p62 body functions in autophagosome formation. Mass spectrometry-based proteomics reveals significant enrichment of vesicle trafficking components within p62 body. Combining cellular experiments and biochemical reconstitution assays, we confirm the gathering of ATG9 and ATG16L1-positive vesicles around p62 body, especially in Atg2ab DKO cells with blocked lipid transfer and vesicle fusion. Interestingly, p62 body also regulates ATG9 and ATG16L vesicle trafficking flux intracellularly. We further determine the lipid contents associated with p62 body via lipidomic profiling. Moreover, with in vitro kinase assay, we uncover the functions of p62 body as a platform to assemble ULK1 complex and invigorate PI3KC3-C1 kinase cascade for PI3P generation. Collectively, our study raises a membrane-based working model for multifaceted p62 body in controlling autophagosome biogenesis, and highlights the interplay between membraneless condensates and membrane vesicles in regulating cellular functions.

Abstract Cellular senescence is a hallmark of aging and has been linked to age-related diseases. Age-related macular degeneration (AMD), the most common aging-related retinal disease, is prospectively associated with retinal pigment epithelial (RPE) senescence. However, the mechanism of RPE cell senescence remains unknown. In this study, tert-butyl hydroperoxide (TBH)-induced ARPE-19 cells and D-galactose-treated C57 mice were used to examine the cause of elevated iron in RPE cell senescence. Ferric ammonium citrate (FAC)-treated ARPE-19 cells and C57 mice were used to elucidated the mechanism of iron overload-induced RPE cell senescence. Molecular biology techniques for the assessment of iron metabolism, cellular senescence, autophagy, and mitochondrial function in vivo and in vitro. We found that iron level was increased during the senescence process. Ferritin, a major iron storage protein, is negatively correlated with intracellular iron levels and cell senescence. NCOA4, a cargo receptor for ferritinophagy, mediates degradation of ferritin and contributes to iron accumulation. Besides, we found that iron overload leads to mitochondrial dysfunction. As a result, mitochondrial DNA (mtDNA) is released from damaged mitochondria to cytoplasm. Cytoplasm mtDNA activates the cGAS-STING pathway and promotes inflammatory senescence-associated secretory phenotype (SASP) and cell senescence. Meanwhile, iron chelator Deferoxamine (DFO) significantly rescues RPE senescence and retinopathy induced by FAC or D-gal in mice. Taken together, these findings imply that iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway. Inhibiting iron accumulation may represent a promising therapeutic approach for age-related diseases such as AMD.

Introduction: Given the high prevalence of thyroid nodules and the potential for malignancy, it is imperative to understand the various factors that contribute to their development. This study aimed to explore the relationship between metabolic syndrome, lifestyle, and thyroid nodules in adult men in southern China. Methods: This study enrolled a total of 183,990 subjects at a medical examination center in a general hospital in southern China between January 1, 2015, and December 31, 2020. Multivariate logistic regression analysis was utilized to evaluate the relationship between metabolic syndrome, lifestyle factors, and thyroid nodules. Furthermore, structural equation modeling elucidated the intricate relationships among these variables. Results: The prevalence of thyroid nodules among Chinese adult males was 14.9%. Several factors were identified as risk factors for thyroid nodules, including advanced age, irregular meal time, smoking or quitting smoking, quitting drinking, heavy manual labor, hypertension, diabetes, dyslipidemia and centripetal obesity, and those belonging to ethnic minorities and drinking alcohol were found to be protective factors against thyroid nodules. Structural equation modeling highlighted metabolic syndrome's mediating role amidst lifestyle influences on thyroid nodules. Conclusion: The prevalence of thyroid nodules in Chinese adult males is relatively moderate to low. The factors identified in this study can help clinicians identify high-risk patients and develop targeted screening strategies for the timely detection of thyroid nodules. However, further mechanistic research and longitudinal studies are necessary to explore the underlying causes and establish causal relationships.

Background and aim: Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway. Experimental procedure: The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN. Results and conclusion: The most frequent Chinese medicine component in XLW was Coptis chinensis. Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.