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Density matrix embedding theory (DMET) is a quantum embedding theory for strongly correlated systems. From a computational perspective, one bottleneck in DMET is the optimization of the correlation potential to achieve self-consistency, especially for heterogeneous systems of large size. We propose a new method, called projected DMET (p-DMET), which achieves self-consistency without needing to optimize the correlation potential. We demonstrate the performance of p-DMET on the two-dimensional Hubbard model.

Objective Summarize the clinical and genetic characteristics of atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation. Methods and Results From May 2020 to April 2022, Anhui Provincial Children's Hospital diagnosed and treated 4 children with atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation, including 2 males and 2 females were a pair of identical twins. They all had comprehensive developmental delay before onset. At the age of 2 years, all cases gradually exhibited clinical manifestations of atypical Rett syndrome, such as frequent clapping, biting, sleep disorders (increased sleep or difficulty falling asleep), and grinding teeth, followed by developmental regression and seizures. The initial age of epilepsy was from 2 years and 2 months to 2 years and 10 months. All cases started with generalized tonic-clonic seizure, with epileptic spasm occurring between 2 and 11 months of course. Case 2, Case 3 and Case 4 were also accompanied by focal seizures. Four cases with VEEG background of 4-6 Hz θ wave, the VEEG during the interictal phase was a broad multifocal sharp slow complex wave. In Case 2, Case 3 and Case 4,MRI was abnormal, mainly with increased depth of cerebral hemispheric sulcus and gyrus. The whole exome sequencing suggested pathogenicity and possible pathogenic variations in the IQSEC2 gene, Case 1 and Case 2 were frameshift mutations of c. 608dup (p. Gln204Profs*35), while Case 3 and Case 4 were nonsense mutations of c.2231C > A (p.Ser744Ter) and c.2521C > T (p.Gln841Ter), respectively. The four mutation sites have not been reported domestically or internationally. All cases received treatment with multiple antiepileptic seizure medicine. The last follow-up age was from 4 years and 3 months to 6 years and 3 months. All cases were unable to walk alone and had no active language. There were no seizures in Case 1 for 3 years, occasional seizures in Case 2 and Case 4, and frequent seizures in Case 3. Conclusions IQSEC2 gene variation can manifest as atypical Rett syndrome, which can be accompanied by refractory epileptic spasms. Both males and females have severe phenotypes, and the severity of clinical phenotypes at the same mutation site varies. Our report enriches the variation spectrum and clinical phenotype spectrum of the IQSEC2 gene, expands the genetic spectrum of Rett syndrome and developmental epileptic encephalopathy, and provides value for the clinical diagnosis, treatment and subsequent research of this disease.

Objective To investigate the long-term efficacy of amygdala-hippocampus deep brain stimulation (AH - DBS) in treating refractory medial temporal lobe epilepsy (mTLE) and its impact on cognitive function. Methods Seven patients with refractory mTLE who were treated at The First Medical Center of Chinese PLA General Hospital from January 2014 to December 2018 were enrolled in this study. All 7 patients underwent AH -DBS. Seizure types, seizure frequency, and antiepileptic seizure medicine (ASM) usage were compared before and after surgery. Cognitive function was assessed using Wechsler Adult Intelligence Scale - Revised (WAIS - R). Post - operative stimulation parameters and surgery - related complications were recorded. Results Of the 7 patients, 4 patients received bilateral AH-DBS, 2 patients received left AH - DBS, and one patient received left AH - DBS combined with right anterior temporal lobectomy. There were 6 patients underwent the occipital approach, and one patient underwent the frontal approach. Only one patient experienced poor healing of the scalp incision, which healed after local skin grafting. The mean follow-up period was (73.00 ± 8.98) months. During the follow-up period, there were reductions in complex partial seizure (CPS) frequency [1.00 (0.00, 31.00) times per month vs. 2.00 (1.50, 60.00) times per month; Z = - 2.207, P = 0.027], secondary generalized tonic - clonic seizure (SGTCS) frequency [0.00 (0.00, 1.00) times per month vs. 2.00 (1.00, 3.00) times per month; Z = - 2.428, P = 0.015], and the total seizure frequency [1.00 (0.50, 31.00) times per month vs. 5.00 (2.50, 64.00) times per month; Z = - 2.366, P = 0.018]. However, there were no significant differences in the number of ASM types [1.00 (1.00, 2.00) types vs. 1.00 (1.00, 3.00) types; Z = - 1.633, P = 0.102] or WAIS-R [(85.50 ± 7.09) scores vs. (89.00 ± 9.47) scores; t = - 1.761, P = 0.078] before and after surgery. Conclusions As a novel anti - epileptic treatment method, AH-DBS can reduce the frequency of refractory mTLE without serious adverse events and has no significant impact on cognitive function.

Abstract Background There are significant geographic inequities in COVID-19 case fatality rates (CFRs), and comprehensive understanding its country-level determinants in a global perspective is necessary. This study aims to quantify the country-specific risk of COVID-19 CFR and propose tailored response strategies, including vaccination strategies, in 156 countries. Methods Cross-temporal and cross-country variations in COVID-19 CFR was identified using extreme gradient boosting (XGBoost) including 35 factors from seven dimensions in 156 countries from 28 January, 2020 to 31 January, 2022. SHapley Additive exPlanations (SHAP) was used to further clarify the clustering of countries by the key factors driving CFR and the effect of concurrent risk factors for each country. Increases in vaccination rates was simulated to illustrate the reduction of CFR in different classes of countries. Findings Overall COVID-19 CFRs varied across countries from 28 Jan 2020 to 31 Jan 31 2022, ranging from 68 to 6373 per 100,000 population. During the COVID-19 pandemic, the determinants of CFRs first changed from health conditions to universal health coverage, and then to a multifactorial mixed effect dominated by vaccination. In the Omicron period, countries were divided into five classes according to risk determinants. Low vaccination-driven class (70 countries) mainly distributed in sub-Saharan Africa and Latin America, and include the majority of low-income countries (95.7%) with many concurrent risk factors. Aging-driven class (26 countries) mainly distributed in high-income European countries. High disease burden-driven class (32 countries) mainly distributed in Asia and North America. Low GDP-driven class (14 countries) are scattered across continents. Simulating a 5% increase in vaccination rate resulted in CFR reductions of 31.2% and 15.0% for the low vaccination-driven class and the high disease burden-driven class, respectively, with greater CFR reductions for countries with high overall risk (SHAP value > 0.1), but only 3.1% for the ageing-driven class. Conclusions Evidence from this study suggests that geographic inequities in COVID-19 CFR is jointly determined by key and concurrent risks, and achieving a decreasing COVID-19 CFR requires more than increasing vaccination coverage, but rather targeted intervention strategies based on country-specific risks.

Abstract Background Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. However, the predictive value of single indictor still remains controversial. This study aimed to assess the predictive value of combining preoperative left atrial volume index (LAVI) and postoperative interleukin-6 (IL-6) for POAF in the patients receiving cardiac surgery. Methods Patients who admitted to Nanjing First Hospital during the study period between December 2022 and June 2023, and underwent open-heart surgery without a history of atrial fibrillation (AF) were enrolled. The relationships between predictors and POAF were investigated using logistic regression analysis. We determined the combined predictive value of LAVI and IL-6 for POAF by measuring the changes in the area under the receiver operating characteristic curve (AUC) and calculating the net reclassification improvements (NRIs) and integrated discrimination improvement (IDIs). Results 102 patients were enrolled in this study, and 50 participants developed POAF (49.0%). Patients who experienced POAF had higher levels of preoperative LAVI and postoperative IL-6 than those who did not. Regression analysis revealed that larger LAVI and higher level of IL-6 were independently associated with increased risk of POAF. The combined addition of LAVI and IL-6 to the predictive model resulted in an evident increase in the AUC. Incorporating both LAVI and IL-6 increased IDIs in all models. Conclusion Our results demonstrated that combined LAVI and IL-6 achieved a higher prediction performance for POAF.

A2/O is a common domestic sewage treatment process.The aeration method of aerobic section is usually the traditional bottom aeration, which has low oxygen dissolution efficiency. In order to achieve high quality and efficient treatment of sewage, a static spiral cutter without power drive was developed based on gas-liquid mass transfer enhancement and fluid mechanics theory. Large bubbles in gas-liquid mixture could be cut into micro-nanometer scale small bubbles, which can improve dissolved oxygen in a short time, and control gas flow to achieve the adjustment of dissolved oxygen. Experiments with no aeration, traditional bottom aeration, and static spiral cutting were carried out. The results showed that compared with the traditional bottom aeration process, with the static spiral cutting, the removal rate of solid suspended solids(SS) increased by 12.3%,the removal rate of COD by 5.6%, the removal rates of ammonia nitrogen (NH3-N) and total phosphorus (TP) were increased by 8.1% and 8.5% respectively, and the concentration of saturated dissolved oxygen (DO) was increased by 48.2%. Overall,static spiral cutter has advantages of simple structure and good economy, it has a promising application for the optimization of sewage treatment aeration.

ObjectiveTo explore the relationship between the exposure level of particulate matter 2.5 (PM2.5) and particulate matter 10 (PM10) in the air of pregnant women during preconception and first trimester of pregnancy and the risk of gestational diabetes mellitus (GDM).MethodsThe data of pregnant women delivered in 22 monitoring hospitals in Hebei Province from 2019 to 2021 were collected, and the daily air quality data of their cities were used to calculate the exposure levels of PM2.5 and PM10 in different pregnancy stages, and logistic regression model was used to analyze the impact of exposure levels of PM2.5 and PM10 on GDM during preconception and first trimester of pregnancy.Results108,429 singleton live deliveries were included in the study, of which 12,967 (12.0%) women had a GDM diagnosis. The prevalence of GDM increased over the course of the study from 10.2% (2019) to 14.9% (2021). From 2019 to 2021, the average exposure of PM2.5 and PM10 was relatively 56.67 and 103.08μg/m3 during the period of preconception and first trimester of pregnancy in Hebei Province. Handan, Shijiazhuang, and Xingtai regions had the most severe exposure to PM2.5 and PM10, while Zhangjiakou, Chengde, and Qinhuangdao had significantly lower exposure levels than other regions. The GDM group had statistically higher exposure concentrations of PM2.5 and PM10 during the period of preconception, first trimester, preconception and first trimester (P

Objective: Anxiety disorder (AD) is a common mental disorder related to cardiovascular disease morbidity. Oxidative stress plays a crucial role in the anxiety state and can lead to cardiac remodeling. Over-activation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in cardiomyocytes and neurons can cause oxidative stress. Additionally, the AMPAR inhibitor—2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline-2,3-dione (NBQX) plays an important role in ameliorating oxidative stress. This study aimed to explore the anti-arrhythmic effects of NBQX in a rat model of anxiety. Methods: The AD model was induced using empty bottle stimulation. Male Sprague Dawley rats were randomly divided into four groups: control + saline, control + NBQX, AD + saline, and AD + NBQX. Open field test was conducted to measure anxiety-like behavior. Electrophysiological experiments, histological analysis, biochemical detection and molecular biology were performed to verify the effects of NBQX on the amelioration of electrical remodeling and structural remodeling. Furthermore, the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) was used in vitro to demonstrate the signaling pathway. Results: Oxidative stress levels increased with AMPAR over-activation in AD rats, leading to heightened vulnerability to ventricular fibrillation (VF). NBQX reverses anxiety and VF susceptibility. Our results showed that NBQX activated the Nrf2/heme oxygenase-1 (HO-1) pathway, leading to a decline in oxidative stress levels. Connexin 43 and ion channel expression was upregulated. NBQX treatment attenuated fibrosis and apoptosis. This effect was diminished by ML385 treatment in vitro. Conclusion: NBQX can alleviate VF susceptibility in rat models of anxiety by alleviating electrical remodeling, structural remodeling via regulating the Nrf2/HO-1 pathway to some extent.

IntroductionAnalyzing the correlation between planktonic eukaryotic communities (PECs) and aquatic physicochemical parameters (APPs) provides important references for predicting the impact of climate change and human activities on aquatic ecosystems.MethodsTo assess the influence of seasons and APPs on PEC structures in lakes and rivers, we utilized high-throughput sequencing of the 18S rRNA gene to analyze PEC structures in a lake and seven rivers in the Chaohu Lake Basin and analyzed their correlations with APPs.ResultsOur results revealed that PEC structure was significantly affected by season, with the highest α-diversity observed in summer. Furthermore, we identified several APPs, including water temperature, conductivity, dissolved oxygen, pH, phosphate, total phosphorus, trophic level index (TLI), nitrate, ammonia nitrogen, and total nitrogen, that significantly influenced PEC structures. Specifically, we found that Stephanodiscus hantzschii, Simocephalus serrulatus, Cryptomonas sp. CCAC_0109, Pedospumella encystans, Actinochloris sphaerica, Chlamydomonas angulosa, Gonyostomum semen, Skeletonema potamos, Chlamydomonas klinobasis, Pedospumella sp., and Neochlorosarcina negevensis were significantly correlated to TLI, while Limnoithona tetraspina, Theileria sp., and Pseudophyllomitus vesiculosus were significantly correlated to the water quality index (WQI). However, our random forest regression analysis using the top 100 species was unable to accurately predict the WQI and TLI.DiscussionThese results provide valuable data for evaluating the impact of APPs on PEC and for protecting water resource in the Chaohu Lake Basin.

ABSTRACT Antimicrobial resistance has become a growing public health threat in recent years. Klebsiella pneumoniae is one of the priority pathogens listed by the World Health Organization. Antimicrobial peptides are considered promising alternatives to antibiotics due to their broad-spectrum antibacterial activity and low resistance. In this study, we investigated the antibacterial activity of antimicrobial peptide A20L against K. pneumoniae. In vitro antibacterial activity of A20L against K. pneumoniae was demonstrated by broth microdilution method. We confirmed the in vivo efficacy of A20L by Galleria mellonella infection model. In addition, we found that A20L also had certain antibiofilm activity by crystal violet staining. We also evaluated the safety and stability of A20L, and the results revealed that at a concentration of ≤128 µg/mL, A20L exhibited negligible toxicity to RAW264.7 cells and no substantial toxicity to G. mellonella. A20L was stable at different temperatures and with low concentration of serum [5% fetal bovine serum (FBS)]; however, Ca2+, Mg2+, and high serum concentrations reduced the antibacterial activity of A20L. Scanning electron microscope (SEM) and membrane permeability tests revealed that A20L may exhibit antibacterial action by damaging bacterial cell membranes and increasing the permeability of outer membrane. Taken together, our results suggest that A20L has significant development potential as a therapeutic antibiotic alternative, which provides ideas for the treatment of K. pneumoniae infection.IMPORTANCEA20L showed antibacterial and anti-infective efficacy in vitro and in vivo against Klebsiella pneumoniae. It can have an antibacterial effect by disrupting the integrity of cell membranes. A20L displayed anti-biofilm and anti-inflammatory activity against carbapenem-resistant K. pneumoniae and certain application potential in vivo, which provides a new idea for the clinical treatment of biofilm-associated infections.

Acute large hemispheric infarction (ALHI) is an overwhelming emergency with a great challenge of gastrointestinal dysfunction clinically. Here, we initially proposed delayed bowel movements as the clinical phenotype of strike to gut-brain axis (GBA) in ALHI patients by epidemiological analysis of 499 acute ischemic stroke (AIS) patients. 1H NMR-based metabolomics revealed that AIS markedly altered plasma global metabolic profiling of patients compared with healthy controls. Risk factors of strike on GBA were the National Institutes of Health Stroke Scale (NIHSS) score ≥ 5 and stroke onset time ≤ 24 h. As a result, first defecating time after admission to the hospital ≥2 days could be considered as a potential risk factor for strike on GBA. Subsequently, the ALHI Bama miniature (BM) pig model with acute symptomatic seizure was successfully established by ligation of the left ascending pharyngeal artery combined with local air injection. Clinical phenotypes of brain necrosis such as hemiplegia were examined with brain diffusion-weighted imaging (DWI) and pathological diagnosis. In addition to global brain injury and inflammation, we also found that ALHI induced marked alterations of intestinal barrier integrity, the gut microbial community, and microbiota-derived metabolites including serotonin and neurotransmitters in both plasma and multiple brain tissues of BM pigs. These findings revealed that microbiota-gut-brain axis highly contributed to the occurrence and development of ALHI.

[ Objective ] As an important regulator involved in protein synthesis and gene expression , riboso- mal proteins are crucial for plant growth and development and stress response. In this study , a ribosomal protein family gene OsRPL36A was cloned from rice , and a preliminary study was performed for its bio- logical function , providing a basis for the study of OsRPL36A function. [ Methods ] Bioinformatics tech- niques were used to analysis gene structure , cis -regulatory elements , and evolution process of OsRPL36A . Meanwhile , the expression of OsRPL36A in different tissues and under diurnal rhythm , different hor- mones , and abiotic stresses were analyzed by quantitative real-time PCR ( qRT-PCR ) . [ Results ] ( 1 ) OsR- PL36A encoded 98 amino acids with a 297 bp coding region , which belonged to the ribosomal protein L36 supergene family , and was named as OsRPL36A . ( 2 ) The promoter region of OsRPL36A contained 3 rhythmic expression-related elements , 10 light-responsive elements , 14 hormone-responsive elements , and 27 environmental stress response elements. ( 3 ) The expression of OsRPL36A in leaves was relatively higher than that in other tissues and presented a typical rhythmic expression pattern. The expression of OsRPL36A was in- duced by IAA , high temperature , low temperature , osmotic stress , and so on. [ Conclusion ] OsRPL36A was highly expressed in leaves and presented a typical rhythmic expression pattern. OsRPL36A responded to IAA and might be involved in response to heat shock , low temperature , salt , and osmotic stresses.

Weighted total least squares (WTLS) have been regarded as the standard tool for the errors-in-variables (EIV) model in which all the elements in the observation vector and the coefficient matrix are contaminated with random errors. However, in many geodetic applications, some elements are error-free and some random observations appear repeatedly in different positions in the augmented coefficient matrix. It is called the linear structured EIV (LSEIV) model. Two kinds of methods are proposed for the LSEIV model from functional and stochastic modifications. On the one hand, the functional part of the LSEIV model is modified into the errors-in-observations (EIO) model. On the other hand, the stochastic model is modified by applying the Moore-Penrose inverse of the cofactor matrix. The algorithms are derived through the Lagrange multipliers method and linear approximation. The estimation principles and iterative formula of the parameters are proven to be consistent. The first-order approximate variance-covariance matrix (VCM) of the parameters is also derived. A numerical example is given to compare the performances of our proposed three algorithms with the STLS approach. Afterwards, the least squares (LS), total least squares (TLS) and linear structured weighted total least squares (LSWTLS) solutions are compared and the accuracy evaluation formula is proven to be feasible and effective. Finally, the LSWTLS is applied to the field of deformation analysis, which yields a better result than the traditional LS and TLS estimations.

Abstract Rice bacterial leaf streak (BLS), caused by Xanthomonas oryzae pv. oryzicola (Xoc), is a worldwide destructive rice bacterial disease, and seriously affects the global rice industry. Effective integrated management measures for BLS depend on the timely and proper detection of Xoc. Here, two highly specific and super-sensitive monoclonal antibodies (MAbs) against Xoc were first prepared using the cultured Xoc RS105 as an immunogen. Then, two serological assays, Dot enzyme-linked immunosorbent assay (Dot-ELISA) and Colloidal gold immunochromatographic strip (CGICS), were developed for the super-sensitive and broad-spectrum detection of Xoc in homogenates prepared from field-collected rice plants. The newly created Dot-ELISA and CGICS assays can detect ten different Xoc strains from various provinces in China and other countries without cross-reactivity with the other ten tested plant bacteria. Furthermore, Dot-ELISA and CGICS can detect Xoc in bacterial suspensions diluted up to 9.78 × 103 CFU/mL and 4.88 × 103 CFU/mL, respectively, or in rice plant tissue homogenates diluted up to 1:51,200 (w/v, g/mL). Surprisingly, both Dot-ELISA and CGICS serological assays were more sensitive than the conventional PCR. Additionally, analysis results using field-collected rice samples showed that the newly created Dot-ELISA and CGICS were reliable in detecting Xoc in rice tissues. Thus, the two serological assays were highly valuable and effective for the diagnosis of rice bacterial leaf streak in rice-grown areas and for inspection and quarantine of Xoc.

In order to explore the adaptability and failure mechanism of landing gear materials for amphibious aircraft in the marine environment. By preparing a high-speed flame sprayed WC coating on the surface of hot-rolled 300M high-strength steel, the corrosion behavior of the coating in an artificial seawater environment was studied using electrochemical testing, salt spray testing, tensile testing, fatigue testing, and characterization by SEM, EDS, XRD, and CLSM. The research results indicate that the WC coating undergoes significant passivation and exhibits good corrosion resistance in an artificial seawater environment with pH value 8.2, which is related to the passivation of Co in the coating under alkaline conditions. The long-term electrochemical impedance results indicate that the corrosion resistance of the coating increases after soaking for 28 days, which is related to the oxide formed by the surface binder. Compared with the 300 M substrate, the tensile strength of the sprayed material slightly increases, which is related to the residual stress releasing inside the coating. Its cracking in artificial seawater is mainly controlled by the anodic dissolution process. As the pre corrosion time increases, the fatigue life of the material significantly decreases. The corrosive medium from the environment enters the interior of the coating during the pre corrosion process, which increases the number of defects, causes premature failure of the coating, and leads to an increase in material fracture sensitivity. WC coatings have good corrosion resistance, and the release of residual stress during the tensile process slightly increases the tensile strength of the material. The coating fails prematurely after pre corrosion, which results in a reduced fatigue life of the material.

To address the challenge of retrieving subcanopy topography using single-baseline single-polarization TanDEM-X interferometric synthetic aperture radar (InSAR) data, we propose a novel InSAR processing framework. Our methodology begins by employing the SINC model to estimate the penetration depth (PD). Subsequently, we establish a linear relationship between PD and phase center height (PCH) to generate a wall-to-wall PCH product. To achieve this, spaceborne light detection and ranging (LiDAR) data are employed to capture the elevation bias between actual ground elevation and InSAR-derived elevation. Finally, the subcanopy topography is derived by subtracting the PCH from the conventional InSAR-based digital elevation model (DEM). Moreover, this approach enables the simultaneous estimation of forest height from single-baseline TanDEM-X data by combining the estimated PD and PCH components. The approach has been validated against airborne LiDAR scanning (ALS) data over four diverse sites encompassing different forest types, terrain conditions, and climates. The derived subcanopy topography in the boreal and hemiboreal forest sites (Krycklan and Remningstorp) demonstrated notable improvement in accuracy. Additionally, the winter acquisitions outperformed the summer ones in terms of inversion accuracy. The achieved root-mean-square errors (RMSEs) for the winter scenarios were 2.45 m and 3.83 m, respectively, representing a 50% improvement over the InSAR-based DEMs. The forest heights are also close to the ALS measurements, with RMSEs of 2.70 m and 3.33 m, respectively. For the Yanguas site in Spain, characterized by rugged terrain, subcanopy topography in forest areas was estimated with an accuracy of 4.27 m, a 35% improvement over the original DEM. For the denser tropical forest site, only an average elevation bias could be corrected.

The existing salient object detection in optical remote sensing images methods mostly employ the same strategy to handle features at different levels without fully considering the distinct characteristics these features possess at various levels. This results in the neglect of some high-level semantics and low-level details during the feature extraction process. Furthermore, existing methods often rely on simple convolution operations to construct modules for feature extraction and fusion. Due to the inherent locality of convolution operations, these models are limited in their performance. To address these challenges, we propose a novel progressive complementation network with semantics and details (SDPCNet) consisting of three parts: Deep semantics aggregation module (DSAM), semantics-guided feature complement module (SFCM), and detail feature enhancement module (DFEM). Specifically, the DSAM is applied on the two highest-level features, guided by the global view with global long-range dependencies and local context generated by transformer and dilated convolution. The DSAM deeply delves the semantic information in high-level features to perceive the object positions and alleviate the adverse effects of cluttered backgrounds. The SFCM operates on the intermediate two levels of features, performing global correlation modeling on the aggregated cross-level features. It enhances multiscale semantic information and edge details using multiple sets of dilated convolutions to address the challenges posed by the uncertainty in the size and number of salient objects. The DFEM acts on the lowest two levels of features, enhancing edge details in spatial dimension and emphasizing semantics in different channel dimensions. It is then fused with high-level features to augment feature diversity and reduce the impact of background noise. Extensive experiments conducted on the ORSSD, EORSSD, and ORSI-4199 datasets demonstrate that our proposed SDPCNet outperforms 23 state-of-the-art methods across eight evaluation metrics.

Abstract Background Since the Z0011 trial, the assessment of axillary lymph node status has been redirected from the previous assessment of the occurrence of lymph node metastasis alone to the assessment of the degree of lymph node loading. Our aim was to apply preoperative breast ultrasound and clinicopathological features to predict the diagnostic value of axillary lymph node load in early invasive breast cancer. Methods The 1247 lesions were divided into a high lymph node burden group and a limited lymph node burden group according to axillary lymph node status. Univariate and multifactorial analyses were used to predict the differences in clinicopathological characteristics and breast ultrasound characteristics between the two groups with high and limited lymph node burden. Pathological findings were used as the gold standard. Results Univariate analysis showed significant differences in ki-67, maximum diameter (MD), lesion distance from the nipple, lesion distance from the skin, MS, and some characteristic ultrasound features (P

Abstract Objective To analyse the relationship between the polymorphisms of the H-type hypertensive methylenetetrahydrofolate reductase (MTHFR) C677T gene and neutrophil gelatinase-associated lipocalin (NGAL) in early kidney injury. Method A total of 279 hospitalised patients with hypertension were selected and grouped according to their homocysteine (Hcy) level. If their blood Hcy level was ≥ 10 µmol/L they were assigned to the H-type hypertensive group, and if it was

Abstract Background Some studies have assessed the predictive role of the atherogenic index of plasma (AIP) for macrovascular diseases. This prospective investigation aimed to elucidate whether AIP is associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR) incidence. Methods The data were extracted from 4831 participants, of whom 2943 and 3360 participants with type 2 diabetes (T2D) were included in the DKD and DR follow-up analyses, respectively. Cox regression models were performed to test the relationships of AIP value at baseline with the risk of incident DKD and DR. Group-based trajectory modelling was utilized to discern AIP trajectories during the follow-up period. Subsequently, logistic regressions were applied to ascertain the influence of AIP trajectories on the incidence of DKD and DR. Results During the follow-up period, 709 (24.1%) and 193 (5.7%) participants developed DKD and DR, respectively. The median (interquartile range) follow-up time was 24.2 (26.3) months for DKD and 25.7 (27.0) months for DR. According to the multivariate Cox regression models, baseline AIP was positively and linearly related to the occurrence of DKD, with a hazard ratio of 1.75 (95% confidence interval [CI] 1.36–2.26). Three distinct trajectories of AIP were identified throughout the follow-up time: Low (31.4%), Median (50.2%), and High (18.3%). Compared to participants with the Low AIP trajectory, those with High and Median AIP trajectories presented 117% (95% CI: 1.62–2.91) and 84% (95% CI 1.46–2.32) greater odds of developing DKD, respectively. However, neither baseline levels nor trajectories of AIP were shown to be related to DR after adjusting for confounding factors. Conclusions Baseline levels and trajectories of AIP were independently related to elevated DKD risk, indicating that AIP could be used as a predictor for identifying T2D participants at higher risk of DKD. No association between AIP and DR was detected.

This study is intended to explore the effect of hypoxia-inducible factor-1α (HIF-1α) activation on lipid accumulation in the diabetic kidney. A type 1 diabetic rat model was established by STZ intraperitoneal injection. Cobalt chloride (CoCl2) and YC-1 were used as the HIF-1α activator and antagonist, respectively. CoCl2 treatment significantly increased HIF-1α expression, accelerated lipid deposition, and accelerated tubular injury in diabetic kidneys. In vitro, CoCl2 effectively stabilized HIF-1α and increased its transportation from the cytoplasm to the nucleus, which was accompanied by significantly increased lipid accumulation in HK-2 cells. Furthermore, results obtained in vivo showed that HIF-1α protein expression in the renal tubules of diabetic rats was significantly downregulated by YC-1 treatment. Meanwhile, lipid accumulation in the tubules of the DM + YC-1 group was markedly decreased in comparison to the DM + DMSO group. Accordingly, PAS staining revealed that the pathological injury caused to the tubular epithelial cells was alleviated by YC-1 treatment. Furthermore, the blood glucose level, urine albumin creatinine ratio, and NAG creatinine ratio in the DM + YC-1 group were significantly decreased compared to the DM + DMSO group. Moreover, the protein expression levels of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) in diabetic kidneys were decreased by YC-1 treatment. Our findings demonstrate that the activation of HIF-1α contributed to interstitial injury in a rat model of diabetic nephropathy and that the underlying mechanism involved the induction of lipid accumulation.

AbstractIntroduction Establishing reference ranges for central airway parameters and exploring their influencing factors in Han Chinese non-smoking adults.Methods This prospective cross-sectional study was conducted on Han Chinese non-smoking adults who underwent chest CT scans at the Tongzhou Campus of Dongzhimen Hospital Affiliated with the Beijing University of Chinese Medicine between September 2022 and November 2022. The SYNAPSE 3D image analysis software was utilized, enabling the extraction of critical parameters such as central airway length, airway wall thickness (AWT), airway lumen area (ALA), and subcarinal angle (SCA). Pearson’s correlation coefficient analysis and multiple linear regression analysis methods were employed to evaluate the relationship between central airway parameters and age, sex, weight, and height.Results The study encompassed 888 Han Chinese non-smoking adults, comprising 456 females and 432 males. Significant sex differences were noted in central airway length, AWT, and ALA, with measurements in males exceeding those in females (p

Post-stroke depression (POSD) is a common difficulty and most predominant emotional syndrome after stroke often consequences in poor outcomes. In the present investigation, we have designed and studied the neurologically active celastrol/minocycline encapsulated with macrophages-derived exosomes functionalized PLGA nanoformulations (CMC-EXPL) to achieve enhanced anti-inflammatory behaviour and anti-depressant like activity in a Rat model of POSD. The animal model of POSD was established through stimulating process with chronic unpredictable mild stress (CUM) stimulations after procedure of middle cerebral artery occlusion (MCAO). Neuronal functions and Anti-inflammation behaviours were observed by histopathological (H&E) examination and Elisa analyses, respectively. The anti-depressive activity of the nanoformulations treated Rat models were evaluated by open-field and sucrose preference test methods. Microglial polarization was evaluated via flow-cytometry and qRT-PCR observations. The observed results exhibited that prepared nanoformulations reduced the POSD-stimulated depressive-like activities in rat models as well alleviated the neuronal damages and inflammatory responses in the cerebral hippocampus. Importantly, prepared CMC-EXPL nanoformulation effectively prevented the M1 pro-inflammatory polarization and indorsed M2 anti-inflammatory polarization, which indicates iNOS and CD86 levels significantly decreased and upsurged Arg-1 and CD206 levels. CMC-EXPL nanoformulation suggestively augmented anti-depressive activities and functional capability and also alleviated brain inflammation in POSD rats, demonstrating its therapeutic potential for POSD therapy.

Abstract Purpose To characterize the phenotype and genotype of a Chinese family with autosomal‐dominant retinitis pigmentosa (RP) accompanied by iris coloboma. Methods The proband, a 34‐year‐old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full‐field electroretinography (ffERG). Genetic analyses were conducted through whole‐exome sequencing (WES) to screen for variations. Results Three members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR‐204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members. Conclusions In this third independent and the first Asian family, the existence of a miR‐204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR‐204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal‐dominant pattern, including in Chinese patients, miR‐204 aberrations should be considered.

Abstract Chloroplasts play a vital role in plant growth and development, which are the main sites of photosynthesis and the production of hormones and metabolites. Despite their significance, the regulatory mechanisms governing chloroplast development remain unclear. In our investigation, we identified a rice mutant with defective chloroplasts in rice (Oryza sativa L.), named albino lethal 13 (osal13), which displayed a distinct albino phenotype in leaves, ultimately resulting in seedling lethality. Molecular cloning revealed that OsAL13 encodes a novel rice protein with no homologous gene or known conserved domain. This gene was located in the chloroplast and exhibited constitutive expression in various tissues, particularly in green tissues and regions of active cell growth. Our study's findings reveal that RNAi‐mediated knockdown of OsAL13 led to a pronounced albino phenotype, reduced chlorophyll and carotenoid contents, a vesicle chloroplast structure, and a decrease in the expression of chloroplast‐associated genes. Consequently, the pollen fertility and seed setting rate were lower compared with the wild type. In contrast, the overexpression of OsAL13 resulted in an increased photosynthetic rate, a higher total grain number per panicle, and enhanced levels of indole‐3‐acetic acid (IAA) in the roots and gibberellin A3 (GA3) in the shoot. These outcomes provide new insights on the role of OsAL13 in regulating chloroplast development in rice.

This study mainly investigated the effects of berberine (BBR) on the bile acid metabolism in gut-liver axis and the microbial community in large intestine of weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC) by microbiome and metabolome analyses. Sixty-four piglets were randomly assigned to four groups including Control group, BBR group, ETEC group, and BBR + ETEC group. Dietary BBR supplementation upregulated the colonic mRNA expression of Occludin, Claudin-5, trefoil factor 3 (TFF3), and interleukin (IL)-10, and downregulated colonic IL-1β and IL-8 mRNA expression in piglets challenged with ETEC K88 (p

Chinese herbal medicine (CHM) is integral to a traditional Chinese medicine (TCM) system. Accurately identifying Chinese herbal medicine is crucial for quality control and prescription compounding verification. However, with many Chinese herbal medicines and some with similar appearances but different therapeutic effects, achieving precise identification is a challenging task. Traditional manual identification methods have certain limitations, including labor-intensive, inefficient. Deep learning techniques for Chinese herbal medicine identification can enhance accuracy, improve efficiency and lower coats. However, few high-quality Chinese herbal medicine datasets are currently available for deep learning applications. To alleviate this problem, this study constructed a dataset (Dataset 1) containing 3,384 images of 20 common Chinese herbal medicine fruits through web crawling. All images are annotated by TCM experts, making them suitable for training and testing Chinese herbal medicine identification methods. Furthermore, this study establishes another dataset (Dataset 2) of 400 images by taking pictures using smartphones to provide materials for the practical efficacy evaluation of Chinese herbal medicine identification methods. The two datasets form a Ningbo Traditional Chinese Medicine Chinese Herb Medicine (NB-TCM-CHM) Dataset. In Dataset 1 and Dataset 2, each type of Chinese medicine herb is stored in a separate folder, with the folder named after its name. The dataset can be used to develop Chinese herbal medicine identification algorithms based on deep learning and evaluate the performance of Chinese herbal medicine identification methods.

To solve the current situation of low vehicle-to-pile ratio, charging pile (CP) operators incorporate private CPs into the shared charging system. However, the introduction of private CP has brought about the problem of poor service quality. Reputation is a common service evaluation scheme, in which the third-party reputation scheme has the issue of single point of failure; although the blockchain-based reputation scheme solves the single point of failure issue, it also brings the challenges of storage and query efficiency. It is a feasible solution to classify and store information on multiple chains, and at this time, reputation needs to be calculated in a cross-chain mode. Crosschain reputation calculation faces the problems of correctness verification, integrity verification and efficiency. Therefore, this paper proposes a verifiable and efficient cross-chain calculation model for CP reputation. Specially, in this model, we propose a verifiable cross-chain contract calculation scheme that adopts polynomial commitment to solve the problems of polynomial damage and tampering that may be encountered in the crosschain process of outsourced polynomials, so as to ensure the integrity and correctness of polynomial calculations. In addition, the miner selection and incentive mechanism algorithm in this scheme ensures the correctness of extracted information when the outsourced polynomial is calculated on the blockchain. The security analysis and experimental results demonstrate that this scheme is feasible in practice.

With the proliferation of the consumer's awareness of wine provenance, wines with unique origin characteristics are increasingly in demand. This study aimed to investigate the influence of geographical origins and climatological characteristics on grapes and wines. A total of 94 anthocyanins and 78 non-anthocyanin phenolic compounds in grapes and wines from five Chinese viticultural vineyards (CJ, WH, QTX, WW, and XY) were identified by UHPLC-QqQ-MS/MS. Chemometric methods PCA and OPLS-DA were established to select candidate differential metabolites, including flavonols, stilbenes, hydroxycinnamic acids, peonidin derivatives, and malvidin derivatives. CCA showed that malvidin-3-O-glucoside had a positive correlation with mean temperature, and quercetin-3-O-glucoside had a negative correlation with precipitation. In addition, enrichment analysis elucidated that the metabolic diversity in different origins mainly occurred in flavonoid biosynthesis. This study would provide some new insights to understand the effect of geographical origins and climatological characteristics on phenolic compounds in grapes and wines.

Purpose: This study aimed to explore the test-retest reliability of fNIRS in measuring frontal and parietal cortices activation during straight walking and turning walking in older adults, in order to provide a theoretical foundation for selecting assessment tools for clinical research on motor control and some diseases such as Parkinson's disease in older adults. Methods: 18 healthy older participants (69.1 ± 0.7 years) were included in this study. The participants completed straight walking and figure-of-eight turning walking tasks at self-selected speeds. Intra-class correlation coefficients (ICCs) and Bland-Altman scatter plots were used to assess the test-retest reliability of oxyhemoglobin (HbO2) changes derived from fNIRS. p

ContextThe prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically.ObjectiveTo investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population.DesignRetrospective cohort study.MethodsWe recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion.ResultsUPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0–120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P

ABSTRACT Purpose: Pre-eclampsia (PE) is a pregnancy-related complication. Eucommia is effective in the treatment of hypertensive disorders in pregnancy, but the specific effects and possible mechanisms of Eucommia granules (EG) in PE remain unknown. The aim of this study was to investigate the effects and possible mechanisms of EG in PE rats. Methods: Pregnant Sprague Dawley rats were divided into five groups (n = 6): the control group, the model group, the low-dose group, the medium-dose group, and the high-dose group of EG. The PE model was established by subcutaneous injection of levonitroarginine methyl ester. Saline was given to the blank and model groups, and the Eucommia granules were given by gavage to the remaining groups. Blood pressure and urinary protein were detected. The body length and weight of the pups and the weight of the placenta were recorded. Superoxide dismutase (SOD) activity and levels of malondialdehyde (MDA), placental growth factor (PIGF), and soluble vascular endothelial growth factor receptor-1 (sFIt-1) were measured in the placenta. Pathological changes were observed by hematoxylin-eosin staining. Wnt/β-catenin pathway-related protein expression was detected using Western blot. Results: Compared with the model group, the PE rats treated with EG had lower blood pressure and urinary protein. The length and weight of the pups and placental weight were increased. Inflammation and necrosis in the placental tissue was improved. SOD level increased, MDA content and sFIt-1/PIGF ratio decreased, and Wnt/β-catenin pathway-related protein expression level increased. Moreover, the results of EG on PE rats increased with higher doses of EG. Conclusions: EG may activate the Wnt/β-catenin pathway and inhibit oxidative stress, inflammation, and vascular endothelial injury in PE rats, thereby improving the perinatal prognosis of preeclamptic rats. EG may inhibit oxidative stress, inflammation, and vascular endothelial injury through activation of the Wnt/β-catenin pathway in preeclampsia rats, thereby improving perinatal outcomes in PE rats.

Abstract Obesity increases the risk of cognitive impairment and dementia, and the gut microbiota can affect brain cognitive function and obesity through a variety of pathways such as the gut-brain axis. This study aimed to discover how fatty acid affect cognitive function by regulating intestinal flora in obesity. Obese subjects were recruited for cognitive function assessment, and participants were divided into obese group with cognitive impairment (MCI, n = 49) and obese cognitively normal group (Non_MCI, n = 55). In the erythrocyte membrane, the proportion of polyunsaturated fatty acids (PUFA), linoleic acid (C18:2 n-6) and arachidonic acid (C20:4 n-6) and n-6/n-3 ratio was higher in the MCI group than in the Non_MCI group. However, the α-linolenic acid (C18:3 n-3) percentage of the erythrocyte membrane was lower in the MCI group. We found that Coriobacteriales_Incertae_Sedis was positively correlated with erythrocyte membrane C20:4 n-6 and n-6 PUFA and negatively correlated with cognitive scores in obese patients. In addition, several of the functional pathways we predicted were significantly different in the MCI and Non_MCI groups. Higher levels of n-6/n-3 polyunsaturated fatty acids ratio in the erythrocyte membranes may influence the inflammatory response in the organism causing obesity induced cognitive damage. Moreover, high levels of n-6/n-3 polyunsaturated fatty acids ratio may also affect the intestinal flora of obese patients, which in turn may affect the cognitive function of obese patients.

ABSTRACT: Objectives: The emergence of carbapenem-resistant Escherichia coli (CREC) is a global concern as its prevalence restricts treatment options and poses a considerable threat to public health. In this study, in vitro and in vivo activity of the antimicrobial peptide Octominin against CREC was investigated to reveal possible mechanisms of action. Furthermore, its safety and factors influencing its antibacterial effect were assessed. Additionally, the anti-inflammatory effects of Octominin were examined. Methods: The antimicrobial activity of Octominin against 11 strains of CREC was determined using the broth microdilution method, growth curve, and time-kill assay. Its possible mechanism of action was unraveled using the propidium iodide and N-phenyl-1-naphthylamine fluorochrome and lipopolysaccharide-binding assays. To understand the safety and stability of Octominin, its cytotoxicity, hemolysis, and antibacterial activity under various conditions (i.e, temperature, ions) were estimated. Additionally, a Galleria mellonella infection model was utilized to evaluate the efficacy of Octominin in vivo, and qRT-PCR was performed to assess its effect on the expression of proinflammatory cytokines. Results: Octominin displayed a significant antibacterial effect, with MICs of 4–8 µg/mL and MBCs of 8–16 µg/mL. Octominin exerted its antibacterial effect by disrupting bacterial membranes. Cytotoxicity and hemolysis tests demonstrated the potential application of Octominin in vivo. The G. mellonella infection model asserted the in vivo efficacy of Octominin. Furthermore, Octominin inhibited the expression of proinflammatory cytokines. Although the temperature had little effect on its the activity, serum and ions reduced activity. Conclusion: Octominin is a promising alternative agent with remarkable antibacterial and anti-inflammatory effects for treating infections caused by CREC.

Olefin solution polymerization can be used to obtain high-performance polyolefin materials that cannot be obtained via other polymerization processes. Polyolefin elastomers (POE) are a typical example. Due to cost, only a few linear α-olefins (e.g., 1-butene, 1-hexene, and 1-octene) are used as comonomers in solution polymerization in industry. However, α-olefin comonomers with other structures may have different effects on polymerization in comparison with common linear ones. Moreover, the properties of the corresponding materials may differ significantly. In this work, copolymers of ethylene with linear and end-cyclized α-olefins are synthesized using a metallocene catalyst. The copolymerization of ethylene with linear α-olefins results in a higher turn-over frequency (TOF) and lower incorporation than copolymerization with end-cyclized α-olefins, which may indicate that end-cyclized α-olefins have a higher coordination probability and lower insertion rate. In this reaction, the comonomer is distributed randomly in the polymer chain and efficiently destroys crystallization. End-cyclized α-olefins exhibit a much stronger crystallization destructive capacity (CDC) in the copolymer than linear α-olefins, possibly because linear α-olefins act mainly in the radial direction of the main chain of the polymer, while end-cyclized α-olefins act mainly in the axial direction of the main chain.

Caffeic acid (CA) is a phenolic acid compound widely used in pharmaceutical and food applications. However, the efficient synthesis of CA is usually limited by the resources of individual microbial platforms. Here, a cross-kingdom microbial consortium was developed to synthesize CA from sugarcane bagasse hydrolysate using Escherichia coli and Candida glycerinogenes as chassis. In the upstream E. coli module, shikimate accumulation was improved by intensifying the shikimate synthesis pathway and blocking shikimate metabolism to provide precursors for the downstream CA synthesis module. In the downstream C. glycerinogenes module, conversion of p-coumaric acid to CA was improved by increasing the supply of the cytoplasmic cofactor FAD(H2). Further, overexpression of ABC transporter-related genes promoted efflux of CA and enhanced strain resistance to CA, significantly increasing CA titer from 103.8 mg/L to 346.5 mg/L. Subsequently, optimization of the inoculation ratio of strains SA-Ec4 and CA-Cg27 in this cross-kingdom microbial consortium resulted in an increase in CA titer to 871.9 mg/L, which was 151.6% higher compared to the monoculture strain CA-Cg27. Ultimately, 2311.6 and 1943.2 mg/L of CA were obtained by optimization of the co-culture system in a 5 L bioreactor using mixed sugar and sugarcane bagasse hydrolysate, respectively, with 17.2-fold and 14.6-fold enhancement compared to the starting strain. The cross-kingdom microbial consortium developed in this study provides a reference for the production of other aromatic compounds from inexpensive raw materials.

Objective: The aim of this study was to investigate the diagnostic value of HPV (human papillomavirus) E6/E7 mRNA combined with thin-layer liquid-based cytology test (TCT) detection in patients with cervical intraepithelial neoplasia (CIN) in the residual and recurrence of lesions after cervical conization. Methods: A total of 154 patients who had undergone cervical conization and were diagnosed with high-grade cervical intraepithelial neoplasia (CIN 1 and CIN 3) by histopathology and had complete follow-up data were enrolled. TCT, HPV-DNA detection, and HPV E6/E7 mRNA detection combined with TCT detection in 12 months can be used to detect abnormal cytology (>atypical squamous epithelium of undetermined significance). Patients with atypical squamous cell of undetermined significance or high-risk HPV-DNA (+) or HPV E6/E7 mRNA combined with TCT (+) underwent colposcopy and cervical biopsy again for pathological diagnosis. Results: There were 9 cases of residual lesions and 22 cases of recurrence. Thirty of the 57 cases with positive HPV-DNA after surgery were still there or came back. Of the 26 cases with positive HPV E6/E7 mRNA combined with TCT, 24 were still there or came back. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy rate of HPV-DNA detection were 96.8%, 78.0%, 52.6%, 99.0%, and 81.8%, respectively; the sensitivity and specificity of HPV E6/E7 mRNA were combined with TCT detection of sex. Conclusion: HPV E6/E7 mRNA combined with TCT detection can be included in follow-up examinations, which can timely and effectively predict the risk of CIN residual or recurrence after cervical conization and reduce excessive examination and treatment.

Under the background of the development of new media technology, the attention of wushu events in the society is gradually increasing, which makes the competition in the event broadcasting market more and more intense. This paper focuses on the problem of predicting the operational risk of wushu event broadcasting rights, based on the GBRT algorithm, innovatively improves the traditional loss function, introduces the regular term, and proposes the application of XGBoost algorithm in the operational risk prediction of wushu event broadcasting rights. The improved algorithm divides the operational risk of broadcasting rights into two main levels, covering three primary and 10 secondary indicators. In this study, the XGBoost algorithm is applied in the early warning of informing proper operation risk, which is classified into two main levels, covering 3 primary and 10 secondary indicators. The article also conducts an in-depth experimental analysis of the risk of overpremium of the event rights and the risk of matching the audience’s demand. In addition, according to the results of audience analysis, men have become the primary audience of wushu events, with a frequency of up to 401 times. Based on the XGBoost algorithm, the wushu event broadcasting right operation risk warning system can effectively predict and help the event broadcasting platform to avoid the potential operation risk, which provides valuable data support for the market decision-making.

Deregulation of cell cycles can result in a variety of cancers, including breast cancer (BC). In fact, abnormal regulation of cell cycle pathways is often observed in breast cancer, leading to malignant cell proliferation. CDK4/6 inhibitors (CDK4/6i) can block the G1 cell cycle through the cyclin D-cyclin dependent kinase 4/6-inhibitor of CDK4-retinoblastoma (cyclinD-CDK4/6-INK4-RB) pathway, thus blocking the proliferation of invasive cells, showing great therapeutic potential to inhibit the spread of BC. So far, three FDA-approved drugs have been shown to be effective in the management of advanced hormone receptor positive (HR+) BC: palbociclib, abemaciclib, and ribociclib. The combination strategy of CDK4/6i and endocrine therapy (ET) has become the standard therapeutic regimen and is increasingly applied to advanced BC patients. The present study aims to clarify whether CDK4/6i can also achieve a certain therapeutic effect on Human epidermal growth factor receptor 2 positive (HER2+) BC. Studies of CDK4/6i are not limited to patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced BC, but have also expanded to other types of BC. Several pre-clinical and clinical trials have demonstrated the potential of CDK4/6i in treating HER2+ BC. Therefore, this review summarizes the current knowledge and recent findings on the use of CDK4/6i in this type of BC, and provides ideas for the discovery of new treatment modalities.

ContextAdrenocortical carcinoma (ACC) is rare and have high rates of recurrence and mortality. The role of adjuvant radiation therapy (RT) in localized ACC was controversial.MethodsWe conducted a retrospective study in our center between 2015 and 2021 to evaluate the efficacy and safety of adjuvant RT in localized ACC. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to estimate the independent risk factors. Adverse events associated with RT were documented according to the toxicity criteria of the radiation therapy oncology group (RTOG) and the common terminology criteria for adverse events (CTCAE v5.0).ResultsOf 105 patients with localized ACC, 46 (43.8%) received adjuvant RT after surgery. The median radiation dose was 45.0Gy (range:30.0-50.4) and median follow up time was 36.5 (IQR: 19.7-51.8) months. In comparison to the no adjuvant RT group, patients with adjuvant RT had better 3-year OS (87.9% vs 79.5%, P=0.039), especially for patients with ENSAT I/II stage (P=0.004). Adjuvant RT also improved the median DFS time from 16.5months (95%CI, 12.0-20.9) to 34.6months (95%CI, 16.1-53.0). Toxicity of RT was generally mild and moderate with six grade 3 events.ConclusionsPostoperative adjuvant RT significantly improved OS and DFS compared with the use of surgery alone in resected ACC patients. Although this retrospective study on RT in localized ACC indicates that RT is effective in ACC, its findings need to be prospectively confirmed.

BackgroundNeonatal-onset multisystem inflammatory disease (NOMID) is a rare and severe autoinflammatory disease caused by mutations of the NLRP3 gene and is characterized by a skin rash, fever, arthropathy, and neurologic manifestations. We herein report a neonatal case with recurrent rash, fever, and meningitis from 12 h after birth, and NOMID was diagnosed during the neonatal period. We also reviewed the clinical characteristics and genetic mutations of previously reported Chinese neonates with NOMID.Case presentation and literature reviewNOMID is rare in China, and there have been over 100 cases uncovered thus far, including ours. The patient we reported here was the youngest among the confirmed Chinese cases and had the de novo mutation c.1210G>C (p.V404L) in exon 4 of the NLRP3 gene, which has not been reported previously. All 25 patients manifested recurrent urticaria-like rash, and 24 were febrile. Of the 23 patients with genetic data available, all had NLRP3 mutations. The primary treatment of these patients entailed glucocorticoids and immunosuppressants; however, the IL-1 inhibitor was rarely used due to its current unavailability in China. One patient was cured by umbilical cord blood stem cell transplantation (UCBT), which provided an alternative treatment.ConclusionWe recommend that NOMID be considered for neonates with recurrent rash, fever, and aseptic meningitis. However, further research on underlying mechanisms and therapeutic regimens in China is necessary to provide improved management.

Objective·To study whether mutations at the I72 site of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) can induce resistance in acute lymphoblastic leukemia (ALL) cells to thiopurine chemotherapy drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), and explain their mechanisms of action.Methods·The PRPS1 gene mutations (I72F, R177S and V316L) found in clinical practice and PRPS1 gene mutations (V208A and V289A) present in two ALL cell lines (KOPN72bi and RS4;11) were constructed into the vector pGV303 fused with green fluorescent protein (GFP), respectively. The PRPS1 A190T mutation that has been proven to be resistant to thiopurine chemotherapy drugs was used as the positive control, and the empty vector pGV303 (Vector), PRPS1 wild-type (WT) and PRPS1 I72V were used as the negative controls. The various mutants of PRPS1 were transiently transfected into HEK-293T cells (referred to as 293T cells), and the expression of these exogenous PRPS1 was detected by Western blotting. The half maximal inhibitory concentration (IC50) of 6-MP or 6-TG on the above 293T cell lines transiently transfected with PRPS1 mutants was detected and calculated by drug sensitivity experiments. Subsequently, in addition to PRPS1 I72F and I72V, multiple mutations I72M, I72L, I72N, I72S and I72T were constructed into the vector pGV303, respectively, by changing the isoleucine (I) at position 72 into other amino acids. The various mutants were transiently transfected into 293T cells, respectively, and the protein expression of each mutant and IC50 values of 6-MP or 6-TG were detected by Western blotting and drug sensitivity experiments. PRPS1 WT, I72F, I72V, A190T and pGV303 vectors were transfected into REH cell lines by lentivirus infection, and GFP-positive cells were sorted by flow cytometry to obtain cells with stable expression of PRPS1 mutants. The protein expression of each mutant in REH cells and IC50 values of 6-MP or 6-TG were detected by Western blotting and drug sensitivity experiments to verify the results of drug sensitivity experiments obtained by 293T cells. Annexin V/DAPI double staining was used to evaluate the apoptosis of each REH cell line, and Western blotting was used to detect the levels of DNA damage-related proteins [phosphorylation at S139 of histone H2AX (phosphorylated H2AX-S139, γ-H2AX), phosphorylated check point kinase 2 (pCHK2)], and apoptosis-related protein cleaved poly (ADP-ribose) polymerase (cleaved PARP) in each REH cell line. The diagrams of amino acid residues and spatial conformations of I72 locus, I72V and I72F were predicted and drawn through three-dimensional imaging and PyMOL software by using the crystal structure data of PRPS1-numbered 2HCR (PDB code 2HCR) in the PDB (Protein Data Bank) database.Results·Western blotting results showed that the transiently transfected exogenous PRPS1-mutated proteins were successfully expressed in 293T cells. The drug sensitivity experiment results showed that the IC50 values of 6-MP or 6-TG in 293T cells expressing PRPS1 I72F, R177S, V316L, V208A and the positive control A190T were much higher than those in cells expressing V289A and the negative control Vector, PRPS1 WT and I72V (all P =0.000). After mutating the isoleucine (I) at position 72 with other amino acids, Western blotting results showed successful expression of exogenous PRPS1-mutated proteins at position I72 after transient transfection in 293T cells. Drug sensitivity experiments revealed the IC50 values of 6-MP or 6-TG in 293T cells expressing PRPS1 I72M, I72F, I72L, I72N, I72S, I72T and positive control A190T were much higher than those in cells expressing negative control Vector, PRPS1 WT and I72V (all P=0.000). Western blotting results showed that the protein expression levels of PRPS1 WT, A190T, I72F and I72V in the REH stable cell lines constructed by lentivirus were high and similar. The drug sensitivity experiment results showed that the IC50 values of 6-MP or 6-TG in REH cells expressing PRPS1 I72F and positive control A190T were much higher than those in cells expressing negative control Vector, PRPS1 WT and I72V (all P=0.000), which was consistent with the drug sensitivity results obtained by transient transfection in 293T cells. The results of Annexin V/DAPI double staining method and the detection of DNA damage and apoptosis-related proteins by Western blotting showed that after 6-MP treatment, the DNA damage and apoptosis rates of REH cell lines expressing PRPS1 A190T and I72F were significantly lower than those of cells expressing negative control Vector, PRPS1 WT and I72V (all P=0.000). The protein structure analysis results showed that PRPS1 I72F could change the conformation of PRPS1.Conclusion·The PRPS1 I72F, R177S, V316L, V208A, I72M, I72L, I72N, I72S and I72T mutations can confer drug resistance to the thiopurine chemotherapy drugs in cells, while the PRPS1 V289A and I72V mutations do not affect cell sensitivity to the thiopurine chemotherapy drugs. The drug sensitivity experiment results in 293T cells are consistent with those in REH cells, demonstrating that 293T cells can serve as a rapid research model for detecting the resistance of PRPS1 mutations to thiopurine chemotherapy drugs. The effects of the PRPS1 I72 mutations on the resistance of the thiopurine chemotherapy drugs may be related to changes in the structure of PRPS1.

Biotechnology is crucial for the sustainable development of the aquatic seed industry. Therefore, improving the innovation capability in aquatic breeding and making seed sources independent are significant for ensuring food security in China. This study summarizes the development status and problems of aquatic breeding in China and analyzes the status of research and application of seven types of biotechnology for aquatic breeding, namely, transgenic breeding, ploidy breeding, molecular-marker-assisted breeding, genomic selection breeding, genome editing breeding, molecular design breeding, and germline stem cell transplantation; future research and development demand for these technical fields in China is further analyzed. Moreover, future development goals and major tasks are suggested, including collecting, preserving, and accurately identifying excellent germplasm resources of aquatic organisms, profoundly analyzing the genetic basis and regulatory mechanism of critical traits, developing efficient and accurate breeding technologies, and achieving breakthroughs in the creation of new varieties. Furthermore, following suggestions are proposed: optimizing development policies of the aquatic seed industry, promoting technological innovation in aquatic breeding, establishing platforms for aquatic variety creation and transformation, and setting up special projects to accelerate technological innovation and development of the aquatic seed industry.

Abstract Backgroud To predict the malignancy of 1–5 cm gastric gastrointestinal stromal tumors (GISTs) by machine learning (ML) on CT images using three models - Logistic Regression (LR), Decision Tree (DT) and Gradient Boosting Decision Tree (GBDT). Methods 231 patients from Center 1 were randomly assigned into the training cohort (n = 161) and the internal validation cohort (n = 70) in a 7:3 ratio. The other 78 patients from Center 2 served as the external test cohort. Scikit-learn software was used to build three classifiers. The performance of the three models were evaluated by sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC). Diagnostic differences between ML models and radiologists were compared in the external test cohort. Important features of LR and GBDT were analyzed and compared. Results GBDT outperformed LR and DT with the largest AUC values (0.981 and 0.815) in the training and internal validation cohorts and the greatest accuracy (0.923, 0.833 and 0.844) across all three cohorts. However, LR was found to have the largest AUC value (0.910) in the external test cohort. DT yielded the worst accuracy (0.790 and 0.727) and AUC values (0.803 and 0.700) in both the internal validation cohort and the external test cohort. GBDT and LR performed better than radiologists. Long diameter was demonstrated to be the same and most important CT feature for GBDT and LR. Conclusions ML classifiers, especially GBDT and LR with high accuracy and strong robustness, were considered to be promising in risk classification of 1–5 cm gastric GISTs based on CT. Long diameter was found the most important feature for risk stratification.

Stout beer was selected as the research object to screen angiotensin-converting enzyme (ACE) inhibitory peptides. The peptide sequences of stout beer were identified using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry with de novo, and 41 peptides were identified with high confidence. Peptide Ranker was used to score the biological activity and six peptides with a score ≥ 0.5 were screened to predict their potential ACE inhibitory (ACEI) activity. The toxicity, hydrophilicity, absorption, and excretion of these peptides were predicted. In addition, molecular docking between the peptides and ACE revealed a significant property of the peptide DLGGFFGFQR. Furthermore, molecular docking conformation and molecular dynamics simulation revealed that DLGGFFGFQR could be tightly bound to ACE through hydrogen bonding and hydrophobic interaction. Lastly, the ACEI activity of DLGGFFGFQR was confirmed using in vitro evaluation and the IC50 value was determined to be 24.45 μM.

The abnormality in N6-methyladenosine (m6A) methylation is involved in the course of Alzheimer’s disease (AD), while the intervention of 27-Hydroxycholesterol (27-OHC) can affect the m6A methylation modification in the brain cortex. Disordered gut microbiota is a key link in 27-OHC leading to cognitive impairment, and further studies have found that the abundance of Roseburia intestinalis in the gut is significantly reduced under the intervention of 27-OHC. This study aims to investigate the association of 27-OHC, Roseburia intestinalis in the gut, and brain m6A modification in the learning and memory ability injury. In this study, 9-month-old male C57BL/6J mice were treated with antibiotic cocktails for 6 weeks to sweep the intestinal flora, followed by 27-OHC or normal saline subcutaneous injection, and then Roseburia intestinalis or normal saline gavage were applied to the mouse. The 27-OHC level in the brain, the gut barrier function, the m6A modification in the brain, and the memory ability were measured. From the results, we observed that 27-OHC impairs the gut barrier function, causing a disturbance in the expression of m6A methylation-related enzymes and reducing the m6A methylation modification level in the brain cortex, and finally leads to learning and memory impairment. However, Roseburia intestinalis supplementation could reverse the negative effects mentioned above. This study suggests that 27-OHC-induced learning and memory impairment might be linked to brain m6A methylation modification disturbance, while Roseburia intestinalis, as a probiotic with great potential, could reverse the damage caused by 27-OHC. This research could help reveal the mechanism of 27-OHC-induced neural damage and provide important scientific evidence for the future use of Roseburia intestinalis in neuroprotection.

Cyclic olefin copolymer is a type of high-performance polyolefin material, which is prepared by using a single-site catalyst in solution polymerization. The common activator of this system is alkyl aluminoxane or organic boron/aluminum system. Among them, organic boron is mostly triphenylcarbenium tetrakis(pentafluorophenyl)borate or dimethylanilinium tetrakis(pentafluorophenyl)borate. In this study, ethylene and norbornene were copolymerized with metallocene catalyst activated with the combination of tris(pentafluorophenyl)boron and triisobutylaluminium. Compared with homopolymerization of ethylene, copolymerization shows high activity. The molecular weight of the polymer increased significantly with the increase of the insertion rate of norbornene. Fineman-Ross method was used to calculate the reactivity ratio, which showed that the reactivity ratio of norbornene was much lower than that of ethylene. The high copolymerization activity may indicate that, although norbornene has a lower coordination probability, its insertion rate is higher than ethylene. The copolymer with higher norbornene incorporation has a higher glass transition temperature, and the relationship between them is linear.