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Abstract Background The metabolomic profiles of individuals with different clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have not been clearly characterized. Methods We performed metabolomics analysis of 166 individuals, including 62 healthy controls, 16 individuals with asymptomatic SARS-CoV-2 infection, and 88 patients with moderate (n = 42) and severe (n = 46) symptomatic 2019 coronavirus disease (COVID-19; 17 with short-term and 34 with long-term nucleic-acid test positivity). By examining differential expression, we identified candidate metabolites associated with different SARS-CoV-2 infection presentations. Functional and machine learning analyses were performed to explore the metabolites’ functions and verify their candidacy as biomarkers. Results A total of 417 metabolites were detected. We discovered 70 differentially expressed metabolites that may help differentiate asymptomatic infections from healthy controls and COVID-19 patients with different disease severity. Cyclamic acid and N-Acetylneuraminic Acid were identified to distinguish symptomatic infected patients and asymptomatic infected patients. Shikimic Acid, Glycyrrhetinic acid and 3-Hydroxybutyrate can supply significant insights for distinguishing short-term and long-term nucleic-acid test positivity. Conclusion Metabolomic profiling may highlight novel biomarkers for the identification of individuals with asymptomatic SARS-CoV-2 infection and further our understanding of the molecular pathogenesis of COVID-19.

Abstract Wastewater produced in beryllium mining seriously affects ecological balance and causes great environmental pressure. We designed a novel porous lotus leaf biochar modified with PO4 3−/NH4 + multifunctional groups (MLLB) and used it for beryllium(Be) removal from beryllium mining wastewater. Kinetic and thermodynamic experiments showed that the adsorption capacity (Qe) of Be with MLLB from the simulated beryllium mining wastewater could reach 40.38 g kg−1 (35 °C, pH = 5.5), and the adsorption process was spontaneous and endothermic. The dispersion coefficient Kd of Be with MLLB was 2.6 × 104 mL g−1, which proved that MLLB had strong selective adsorption capacity for Be. Phosphoric acid, ammonia, and hydroxyl groups on the MLLB surface would complex with Be to form Be(OH)2 and Be(NH4)PO4 complexation products, which implied that surface complexation and precipitation reactions might co-existed in the adsorption process. The above results showed that MLLB could effectively adsorb Be and prevent beryllium exposure in a beryllium mining process. Graphical Abstract

Abstract Background There are some changes in the new 9th edition Tumor-Node-Metastases (TNM) staging system for lung cancer, including subdividing M1c into M1c1 and M1c2 stage. The aim of this study was to assess the prognostic performance of the updated classification system and try to provide some real-world application data among advanced lung adenocarcinoma patients with bone metastases. Methods Advanced lung adenocarcinoma patients in M1c stage with bone metastases who receiving first-line first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and T790M-guided osimertinib as the second-line therapy were retrospectively screened from December 2016 to December 2021. A total of 126 patients were enrolled in this study. 62 patients and 64 patients were subdivided into M1c1 and M1c2 groups according to the 9th edition of TNM staging system.The first-line real-world progression-free survival (1LrwPFS), the second-line real-world progression-free survival (2LrwPFS), post-progression survival (PPS) and real-world overall survival (rwOS) were analyzed. Results The overall median rwOS was 40.1 months (95% CI 35.996–44.204). 1LrwPFS was 13.9 months (95% CI 12.653–15.147) and 2LrwPFS was 14.5 months (95% CI 11.665–17.335) for all patients.Patients in M1c2 stage was inferior to M1c1 stage patients in rwOS (35.2 months vs. 42.9 months, HR = 0.512, P = 0.005). 2LrwPFS was moderately correlated with rwOS (r = 0.621, R2 = 0.568, P = 0.000). Multivariate analysis showed performance status (PS) score ≥ 2 and TP53 alteration positive were independent prognostic factors of worse rwOS. Conclusions More refined stratification of M1c according to the 9th edition of TNM staging system is conducive to the judgment of prognosis and the implementation of precision medicine for patients.

Objective To explore the intervention effect of health education based on the concept of Oren's self-care theory in elderly patients with acute ischemic stroke. Methods A total of 138 elderly acute ischemic stroke patients admitted to Handan Central Hospital from November 2021 to November 2023 were selected and randomly separated into two groups using a random number table method, each had 69 cases. The control group received routine health education, while the research group received health education based on the concept of Oren's self-care theory on the top of control group. Rehabilitation compliance, self-care ability, limb function, 10-meter walk test (10MWT), Timed up and go test (TUGT), healthy behavior, and self-care ability were compared between two groups. Results The compliance rate of research group was higher than that in control group (P

Objective To investigate the relationship between serum miR-340-5p and stimulator of interferon gene (STING) levels in elderly patients with acute ischemic stroke and their condition and prognosis. Methods A total of 113 elderly patients with acute ischemic stroke admitted to Handan Central Hospital from May 2020 to May 2022 were selected as the study group, and 113 normal healthy patients during the same period were selected as the control group, according to the neurological impairment was assessed according to the National Institutes of Health Stroke Scale (NIHSS) score on the day of admission (< 6 scores as mild, 6- moderate > mild (P

Studies on the prognosis of hepatitis B virus (HBV) reactivation following modern therapies for newly diagnosed MM (NDMM) are lacking. In this retrospective study, we aimed to assess the incidence, risk factors and prognosis of HBV reactivation in NDMM. A total of 33 of 355 patients with NDMM and HBV reactivation were included in this study. Multivariable analysis showed that hepatitis B surface antigen-positivity, hepatitis B core antibody-positivity, bortezomib-containing regimens, autologous stem cell transplantation, and gain of 1q21 were identified as independent risk factors of HBV reactivation in NDMM patients. The NDMM patients with HBV reactivation had poorer 3-year overall survival (OS) and progression-free survival (PFS) than did those without HBV reactivation, as confirmed by multivariate analysis. In conclusion, HBV reactivation in patients with NDMM constitutes a significant complication, correlating with reduced OS and PFS, and emerges as a potential adverse prognostic factor in the contemporary era of treatment.

Abstract Fluorogens with aggregation‐induced emission (AIEgens) are promising agents for two‐photon fluorescence (TPF) imaging. However, AIEgens’ photophysical properties are fixed and unoptimizable once synthesized. Therefore, it is urgent and meaningful to explore an efficient post‐regulation strategy to optimize AIEgens’ photophysical properties. Herein, a general and efficient post‐regulation strategy is reported. By simply tuning the ratio of inert AIEgens within binary nanoparticles (BNPs), the fluorescence quantum yield and two‐photon absorption cross‐section of functional AIEgens are enhanced by 8.7 and 5.4 times respectively, which are not achievable by conventional strategies, and the notorious phototoxicity is almost eliminated. The experimental results, theoretical simulation, and mechanism analysis demonstrated its feasibility and generality. The BNPs enabled deep cerebrovascular network imaging with ≈1.10 mm depth and metastatic cancer cell detection with single‐cell resolution. Furthermore, the TPF imaging quality is improved by the self‐supervised denoising algorithm. The proposed binary molecular post‐regulation strategy opened a new avenue to efficiently boost the AIEgens’ photophysical properties and consequently TPF imaging quality.

Abstract Background The 9th edition of the TNM Classification for lung cancer delineates M1c into two subcategories: M1c1 (Multiple extrathoracic lesions within a single organ system) and M1c2 (Multiple extrathoracic lesions involving multiple organ systems). Existing research indicates that patients with lung cancer in stage M1c1 exhibit superior overall survival compared to those in stage M1c2. The primary frontline therapy for patients with advanced non‐small cell lung cancer (NSCLC), lacking driver gene mutations, involves the use of immune checkpoint inhibitors (ICIs) combined with chemotherapy. Nevertheless, a dearth of evidence exists regarding potential survival disparities between NSCLC patients with M1c1 and M1c2 undergoing first‐line immune‐chemotherapy, and reliable biomarkers for predicting treatment outcomes are elusive. Serum metabolic profiles may elucidate distinct prognostic mechanisms, necessitating the identification of divergent metabolites in M1c1 and M1c2 undergoing combination therapy. This study seeks to scrutinize survival discrepancies between various metastatic patterns (M1c1 and M1c2) and pinpoint metabolites associated with treatment outcomes in NSCLC patients undergoing first‐line ICIs combined with chemotherapy. Method In this study, 33 NSCLC patients lacking driver gene mutations diagnosed with M1c1, and 22 similarly diagnosed with M1c2 according to the 9th edition of TNM Classification, were enrolled. These patients received first‐line PD‐1 inhibitor plus chemotherapy. The relationship between metastatic patterns and progression‐free survival (PFS) in patients undergoing combination therapy was analyzed using univariate and multivariate Cox regression models. Serum samples were obtained from all patients before treatment initiation for untargeted metabolomics analysis, aiming to identify differential metabolites. Results In the univariate analysis of PFS, NSCLC patients in M1c1 receiving first‐line PD‐1 inhibitor plus chemotherapy exhibited an extended PFS (HR = 0.49, 95% CI, 0.27–0.88, p = 0.017). In multivariate PFS analyses, these M1c1 patients receiving first‐line PD‐1 inhibitor plus chemotherapy also demonstrated prolonged PFS (HR = 0.45, 95% CI, 0.22–0.92, p = 0.028). The serum metabolic profiles of M1c1 and M1c2 undergoing first‐line PD‐1 inhibitors plus chemotherapy displayed notable distinctions. In comparison to M1c1 patients, M1c2 patients exhibited alterations in various pathways pretreatment, including platelet activation, linoleic acid metabolism, and the VEGF signaling pathway. Diminished levels of lipid‐associated metabolites (diacylglycerol, sphingomyelin) were correlated with adverse outcomes. Conclusion NSCLC patients in M1c1, devoid of driver gene mutations, receiving first‐line PD‐1 inhibitors combined with chemotherapy, experienced superior outcomes compared to M1c2 patients. Moreover, metabolomic profiles strongly correlated with the prognosis of these patients, and M1c2 patients with unfavorable outcomes manifested distinct changes in metabolic pathways before treatment. These changes predominantly involved alterations in lipid metabolism, such as decreased diacylglycerol and sphingomyelin, which may impact tumor migration and invasion.

Background: Buyang Huanwu Decoction (BHD) is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. This study was designed to investigate the effects of BHD on ischemic stroke (IS) and its underlying mechanism. Methods: The middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation and reoxygenation (OGD/R) rat brain microvascular endothelial cell (RBMVEC) models were established. Brain infarction size and neurological score were calculated following MCAO surgery. Evans blue was used to measure blood brain barrier (BBB) permeability. Cell counting kit-8 (CCK-8) and TUNEL assays were performed to evaluate the cell viability and apoptosis of RBMVECs. Dual-luciferase reporter assay was used to analyze the transcriptional activities of apoptosis-related genes. Results: Results showed that higher infarction volume, neurological scores, and BBB permeability in the MCAO group rats were reduced after BHD treatment. Drug serum (DS) treatment had no impact on the normal RBMVECs’ cell viability and cell apoptosis. Besides, DS treatment decreased the lactate production, glucose uptake, and extracellular acidification rate in normal and OGD/R-induced RBMVECs. DS treatment downregulated the protein levels of pan-lysine lactylation (kla), histone H3 lysine 18 lactylation (H3K18la), and the transcriptional of apoptotic protease activating factor-1 (Apaf-1) in OGD/R-treated RBMVECs. In addition, Apaf-1 overexpression decreased cell viability and increased apoptosis and glycolysis activity of OGD/R-treated RBMVECs. Conclusion: In summary, BHD inhibited glycolysis and apoptosis via suppressing the pan-kla and H3K18la protein levels and the Apaf-1 transcriptional activity, thus restraining the progression of IS.

Objective To explore the impacts of health empowerment model combined with binary coping intervention on neurological function,coping style,and hope level in elderly stroke patients. Methods A total of 144 elderly stroke patients admitted to Handan Central Hospital from October 2020 to October 2022 were selected as the research subjects,they were randomly separated into a reference group and an observation group,with 72 cases in each group.The reference group received routine nursing intervention,while observation group received health empowerment combined with binary coping intervention,The neurological function [National Institutes of Health Stroke Scale(NIHSS)] ,coping style [Simplified coping style questionnaire(SCSQ)] ,and hope level [Herth hope index(HHI)] of both groups were evaluated before and after intervention. Results There was no statistically significant difference in NIHSS scores,SCSQ scores,and HHI scores between the two groups before intervention(P>0.05).After intervention,the NIHSS scores of the observation group were lower than those in the control group(P

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia (CNS-ALL). Integrin α6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression. The targeted peptide D(RWYD) (abbreviated RD), with nanomolar affinity to integrin α6 was identified by peptide scanning techniques such as alanine scanning, truncation, and D-substitution. Herein, we developed a therapeutic nanoparticle based on the integrin α6-targeted peptide for treating CNS-ALL. The self-assembled proapoptotic nanopeptide D(RWYD)-D(KLAKLAK)2-GD(FFY) (abbreviated RD-KLA-Gffy) contains the integrin α6-targeted peptide RD, the well-known proapoptotic peptide D(KLAKLAK)2 (abbreviated KLA), and the self-assembling tetrapeptide GD(FFY) (abbreviated Gffy). The functional mechanism of RD-KLA-Gffy is clarified using different experiments. Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis, thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity. Moreover, the combined use of RD-KLA-Gffy and methotrexate (MTX) shows a potent antitumor effect in treating CNS-ALL, indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX, which shows promise for application in CNS-ALL therapy.

Abstract As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice.

Objective To investigate the impacts of Xinglou Tongluo drink combined with clopidogrel on cognitive function, cerebral blood circulation, and serum Netrin-1 level in elderly patients with acute ischemic stroke. Methods A total of 80 elderly patients with acute ischemic stroke admitted to Handan Central Hospital from January 2022 to May 2023 were selected as the study subjects.They were randomly divided into an observation group(40 cases) and a control group(40 cases) using a random number table method.The control group received treatment with clopidogrel, while the observation group received treatment with Xinglou Tongluo Yin combined with clopidogrel.The clinical efficacy, cerebral blood circulation indicators [blood flow resistance index(RI), mean blood flow velocity(Vm), and vascular pulsatility index(PI)] , serum indicators [Netrin-1 and matrix metalloproteinase-9] and Neurological function [National Institutes of Health Stroke Scale(NIHSS) score] and cognitive function [Montreal Cognitive Assessment Scale(MoCA) score] were compared between the two groups. Results The overall response rate in the observation group was higher than that in the control group(P

Abstract Deep learning‐based image registration (DLIR) has been widely developed, but it remains challenging in perceiving small and large deformations. Besides, the effectiveness of the DLIR methods was also rarely validated on the downstream tasks. In the study, a multi‐scale complexity‐aware registration network (MSCAReg‐Net) was proposed by devising a complexity‐aware technique to facilitate DLIR under a single‐resolution framework. Specifically, the complexity‐aware technique devised a multi‐scale complexity‐aware module (MSCA‐Module) to perceive deformations with distinct complexities, and employed a feature calibration module (FC‐Module) and a feature aggregation module (FA‐Module) to facilitate the MSCA‐Module by generating more distinguishable deformation features. Experimental results demonstrated the superiority of the proposed MSCAReg‐Net over the existing methods in terms of registration accuracy. Besides, other than the indices of Dice similarity coefficient (DSC) and percentage of voxels with non‐positive Jacobian determinant (|Jϕ|≤0), a comprehensive evaluation of the registration performance was performed by applying this method on a downstream task of multi‐atlas hippocampus segmentation (MAHS). Experimental results demonstrated that this method contributed to a better hippocampus segmentation over other DLIR methods, and a comparable segmentation performance with the leading SyN method. The comprehensive assessment including DSC, |Jϕ|≤0, and the downstream application on MAHS demonstrated the advances of this method.

Lake regime shift theory provides effective support for managing lake eutrophication. However, there are limited studies on identifying lake regime status using mathematical methods. Based on the similarities in characteristics and evolutionary patterns of lake ecosystems, and utilizing long-term lake water ecological monitoring data, this study introduces a method for evaluating lake regime status using total nitrogen (TN), total phosphorus (TP), and chlorophyll-a (Chl-a) as evaluation indices. Taking Poyang Lake as an example, the lake regime status was evaluated. The results showed that: The weights of total nitrogen (TN), total phosphorus (TP), and chlorophyll a (Chl-a) in Poyang Lake were 0.207, 0.234 and 0.559, respectively, with Chl-a being the main controlling factor for evaluating the lake regime. The lake regime of Poyang Lake is in the Algae-Macrophytes Coexist state. The similarity assessment method has been proven effective for determining a lake regime using sparse water eco-environmental data.

Lake eutrophication has become a significant water environmental issue worldwide. In order to further explore the mechanism of hydrologic connectivity on lake eutrophication and effectively control it, this study selected Poyang Lake, Junshan Lake, Chi Lake, Taibo Lake, and Yao Lake with varying degrees of hydrological connectivity in the Poyang Lake region as research subjects. The study utilized the comprehensive Trophic Level Index (TLI) method to assess the eutrophication of lakes. It also examined the impact of hydrological connectivity on eutrophication evaluation indices and the eutrophication state on a spatiotemporal scale. The results showed that the change in the hydrological period has little effect on the eutrophication of lakes, whether they are connected or obstructed. Except for Yao Lake, which was in a moderately eutrophic state (60, 70], the other four lakes were in a mildly eutrophic state (50, 60], consistent with the Trophic State Index (TSI) evaluation results. The eutrophication evaluation indices of obstructed lakes were significantly different from those of river-connected lakes. The change in eutrophication evaluation index of obstructed lakes was more likely to be influenced by human factors, whereas that of rivers-connected lakes was closely associated with hydrological connectivity. At present, there is a risk of a cyanobacteria bloom outbreak in Poyang Lake and its surrounding lakes. Therefore, this study suggests that strict control of point and non-point source pollution in the lake region, along with the scientific and reasonable formulation of a cultivation model, will effectively prevent lake eutrophication and cyanobacteria bloom outbreaks. This study provides theoretical support for investigating the mechanisms of lake eutrophication.

ABSTRACTLong noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model. RNA expression was detected by qRT-PCR. The protein expression of Apelin, NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and up-frameshift suppressor 1 (UPF1) was assessed using western blot. Cell injury was evaluated using flow cytometry, enzyme-linked immunosorbent assay, and oxidative stress kit assays. RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin. NEAT1 expression was upregulated in the aortic vascular tissues of mice with T2DM exposed to IH and HMEC-1 cells stimulated with HG and IH, whereas Apelin expression was downregulated. The absence of NEAT1 protected HMEC-1 cells from HG- and IH-induced damage. Furthermore, NEAT1 destabilized Apelin mRNA by recruiting UPF1. Apelin overexpression decreased HG- and IH-induced injury to HMEC-1 cells by activating the Nrf2/HO-1 pathway. Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA.Abbreviations: LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1β, interleukin-1β; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4.

BackgroundSensorineural hearing loss (SNHL) children have difficulty living and limited movement due to impaired vestibular function and reduced balance ability.ObjectivesThe present study evaluated the effects of Latin dance training on the vestibular function and balance of SNHL children.MethodsThirty SNHL children with no difference in vestibular function and balance ability were randomly divided into two groups, the Latin dance training group (LTG, n = 15) and the control group (CONG, n = 15). Vestibular function, timed eyes-closed static (ECS) and functional reach test (FRT) were measured before and after the intervention, and a two-way repeated-measures analysis of variance was performed.ResultsAfter training, the vestibular function performance of LTG was higher than that of CONG (CONG: 16.425 ± 3.616 vs. LTG: 12.241 ± 2.610, p = 0.0411, ES = 1.3914), the left foot ECS performance of LTG was higher than that of CONG (CONG: 2.765 ± 0.872 vs. LTG: 4.688 ± 1.113, p = 0.0026, ES = 1.9857), the right foot ECS performance of LTG was higher than that of CONG (CONG: 3.113 ± 0.639 vs. LTG: 4.797 ± 1.071, p = 0.0137, ES = 2.01), the FRT performance of LTG was higher than that of CONG (CONG: 32.009 ± 6.134 vs. LTG: 43.797 ± 6.616, p = 0.0021, ES = 1.9135).ConclusionsAfter Latin dance training, SNHL children improved vestibular function and balance. The static balance ability of the left foot has been improved significantly than right foot.

The interaction between tumor fatty acid metabolism and immune microenvironment is a novel topic in oncology research, and the relationship of lipid-derived factors with immune editing in tumor is unclear. The breast cancer samples from the TCGA database were used as the training set, and samples from GSE42568 were employed as the validation set for constructing a model to identify a signature associated with fatty acid metabolism through Lasso Cox regression. And the changes in immune related signatures and risk score before and after anti-PD-1 monotherapy were caught by the differential analysis in GSE225078. A 14-gene prognostic risk scoring model identifying by fatty acid metabolism relevant signature was conducted, and the high risk group had shorter overall survival and progression free survival than low risk group. Many metabolism-related pathways were enriched in the high risk group, and many immune-related pathways were enriched in low risk group. The crucial differentially expressed genes between the high/low risk groups, CYP4F8 and CD52, were found to be strongly associated with SUCLA2 and ACOT4 of 14-gene model, and strongly related to immune infiltration. Immune related signatures, fatty acid metabolism-risk score and the expression level of ALDH1A1 (in 14-gene-model) changed after anti-PD-1 monotherapy. And the mice model results also showed anti-PD-1 mAb could significantly reduce the expression level of ALDH1A1 (p < 0.01). These results brought up the crosstalk between immune components and fatty acid metabolism in breast cancer microenvironment, which provided a new possibility of targeting fatty acid metabolism for combination therapy in breast cancer immunotherapy.

Fruit wart is an important appearance trait influencing consumer preferences of bitter gourd (Momordica charantia L.). The molecular genetic mechanisms underlying fruit wart formation in bitter gourd are largely unknown. In this study, genetic analysis based on four generations showed that fruit wart formation in bitter gourd was controlled by a single dominant locus named as Fwa. The Fwa locus was initially mapped into a 4.82 Mb region on pseudochromosome 4 by BSA-seq analysis and subsequently narrowed down to a 286.30 kb region by linkage analysis. A large F2 population consisting of 2 360 individuals was used to screen recombinants, and the Fwa locus was finally fine mapped into a 22.70 kb region harboring four protein-coding genes through recombination analysis. MC04g1399, encoding an epidermal patterning factor 2-like protein, was proposed as the best candidate gene for Fwa via sequence variation and expression analysis. In addition, a 1-bp insertion and deletion (InDel) variation within MC04g1399 was converted to a cleaved amplified polymorphic sequence (CAPS) marker that could precisely distinguish between the warty and non-warty types with an accuracy rate of 100% among a wide panel of 126 bitter gourd germplasm resources. Our results not only provide a scientific basis for deciphering the molecular mechanisms underlying fruit wart formation but also provide a powerful tool for efficient genetic improvement of fruit wart via marker-assisted selection.

ObjectivesThe effects of cold exposure on whole-body metabolism in humans have gained increasing attention. Brown or beige adipose tissues are crucial in cold-induced thermogenesis to dissipate energy and thus have the potential to combat metabolic disorders. Despite the immune regulation of thermogenic adipose tissues, the overall changes in vital immune cells during distinct cold periods remain elusive. This study aimed to discuss the overall changes in immune cells under different cold exposure periods and to screen several potential immune cell subpopulations on thermogenic regulation.MethodsCibersort and mMCP-counter algorithms were employed to analyze immune infiltration in two (brown and beige) thermogenic adipose tissues under distinct cold periods. Changes in some crucial immune cell populations were validated by reanalyzing the single-cell sequencing dataset (GSE207706). Flow cytometry, immunofluorescence, and quantitative real-time PCR assays were performed to detect the proportion or expression changes in mouse immune cells of thermogenic adipose tissues under cold challenge.ResultsThe proportion of monocytes, naïve, and memory T cells increased, while the proportion of NK cells decreased under cold exposure in brown adipose tissues.ConclusionOur study revealed dynamic changes in immune cell profiles in thermogenic adipose tissues and identified several novel immune cell subpopulations, which may contribute to thermogenic activation of adipose tissues under cold exposure.

Background Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy.Method 200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS1 and p

Abstract Background Pulmonary rehabilitation training is of great significance for the prognosis of chronic obstructive pulmonary disease (COPD) patients. The purpose of this study was to investigate the therapeutic effect and pathway of a new sequential noninvasive positive pressure ventilation (NIPPV) + inspiratory muscle training (IMT) therapy. Methods A total of 100 COPD patients were enrolled and randomly divided into oxygen therapy (OT), NIPPV, IMT and sequential (NIPPV + IMT) group. Lung function, exercise endurance, quality of life, and dyspnea symptoms were examined and recorded. Then, reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) levels were detected by enzyme-linked immunoassay, and suppressor of cytokine signaling 5 (SOCS5)/janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway expression changes were detected by quantitative real time-polymerase chain reaction (qRT-PCR) and western blot. A mouse model of COPD was then established to further verify the effects of SOCS5/JAK2/STAT3 pathways on lung function and oxidative stress. Results After 8 weeks of treatment, NIPPV, IMT or sequential (NIPPV + IMT) significantly improved exercise endurance, quality of life and dyspnea, reduced oxidative stress, promoted SOCS5 expression and inhibited the activation of JAK2/STAT3 pathway, and no significant effect was observed on lung function of COPD patients. Notably, sequential (NIPPV + IMT) showed better therapeutic outcomes than either IMT or NIPPV alone. Moreover, results at the animal level showed that overexpression of SOCS5 significantly reduced pulmonary inflammatory infiltration, pathological changes and oxidative stress levels in COPD mice, enhanced lung function, and inhibited the activation of JAK2/STAT3 pathway. Conclusion Our results elucidated that sequential (NIPPV + IMT) significantly relieved COPD development by regulating SOCS5/JAK2/STAT3 signaling-mediated oxidative stress.

During its shelf life, sedimentation and discoloration occurred in purple rice wine, severely diminishing its marketability. To improve the stability of the wine body, the effects of clarifier and membrane filtration treatments on the clarity and anthocyanin content of purple rice wine were investigated in this paper. This study used purple rice as the raw material to produce purple rice wine, and the best of six clarifiers was chosen. The clarification process of clarifiers was optimized using single-factor experiments and response surface experiments, and then five distinct filter membranes were used to filter the wine's supernatant. Clarity and anthocyanin concentration selected the optimal filter membrane, and membrane flux was analyzed. From the results, the optimal clarifying process had a diatomite concentration of 0.83 g/L, pH4.55, and a temperature of 29 ℃. The comprehensive clarification value was 69.72±1.03 under these conditions. The wine's supernatant clarity and anthocyanin concentration decreased significantly after filtration with various filter membranes (P

ObjectiveSome studies have associated frailty and prognostic outcomes in geriatric hip fracture patients, but whether frailty can predict postoperative outcomes remains controversial. This review aims to assess the relationship between frailty and adverse postoperative outcomes in geriatric patients with hip fracture.MethodsBased on electronic databases, including PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang Data, we systematically searched for studies that investigated the association between frailty and adverse outcomes among patients aged 60 or over after hip fracture surgery. Stata 17.0 and Trial Sequential Analysis viewer software were used to obtain pooled estimates and verify whether the sample size was sufficient and the evidence robust.ResultsTwenty-one studies involving 49,196 patients were included for quantitative analysis. Compared with nonfrail patients, frail patients had a higher risk of inpatient mortality (risk ratio [RR] = 1.93, 95% confidence interval [CI]: 1.66-2.23), 30-day mortality (RR = 2.13, 95% CI: 1.23-3.70), and 1-year mortality (RR = 2.44, 95% CI: 1.47-4.04). Frailty can significantly predict postoperative complications (RR = 1.76, 95% CI: 1.38-2.23), including delirium, pneumonia, cardiac complications, urinary tract infection, and surgical site infection; the association between frailty and deep venous thrombosis/pulmonary embolism and acute kidney injury needs further analysis. Trial sequential analysis showed that the findings regarding mortality were reliable and robust.ConclusionThis meta-analysis provides detailed information indicating that frailty is a substantial predictor of mortality and selected postoperative complications.

Abstract With the increasing prevalence of infectious diseases caused by drug‐resistant bacteria, there is an urgent need to develop innovative therapies alternative to antibiotics. Among these alternatives, the aggregation‐induced emission (AIE) photosensitizers (PSs) stand out with their integrated imaging and therapeutic functionalities, allowing for early monitoring and image‐guided ablation of bacteria. AIE fluorescent probes with unique optical properties excel in selective bacterial imaging. Furthermore, AIE‐enabled reactive oxygen species (ROS)‐mediated antibacterial photodynamic therapy can operate on multiple targets to oxidize bacteria. Also, as they are able to specifically target bacteria, AIE PSs can ameliorate the limitations of the small‐scale action of ROS. This review methodically discusses the different strategies that can be employed using AIE PSs for targeting bacteria, including sheltered bacteria. The challenges and future opportunities of using AIE PSs in this emerging field are also briefly discussed.

Abstract The titer of anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) neutralizing antibodies (NAbs) in the human body is an essential reference for evaluating the acquired protective immunity and resistance to SARS‐CoV‐2 infection. In this study, a fluorescence‐quenching lateral flow immunoassay (FQ‐LFIA) is established for quantitative detection of anti‐SARS‐CoV‐2 NAbs in the sera of individuals who are vaccinated or infected within 10 min. The ultrabright aggregation‐induced emission properties encapsulated in nanoparticles, AIE490NP, are applied in the established FQ‐LFIA with gold nanoparticles to achieve a fluorescence “turn‐on” competitive immunoassay. Under optimized conditions, the FQ‐LFIA quantitatively detected 103 positive and 50 negative human serum samples with a limit of detection (LoD) of 1.29 IU mL−1. A strong correlation is present with the conventional pseudovirus‐based virus neutralization test (R2 = 0.9796, P

ObjectiveThis network meta-analysis (NMA) was conducted to compare and rank the effects of training interventions including aerobic exercise (AE), resistance training (RT), combined aerobic and resistance training (CT), and high-intensity interval training (HIIT) on vital metabolic indicators in adults with overweight and obesity.MethodsPubMed, Cochrane, Embase, and Web of Science were searched from 1990 to February 2023. Articles were included if they described randomized controlled trials (RCTs) examining the effects of exercise training on anthropometry parameters, lipid profiles, glucose metabolism, blood pressure, and cardiorespiratory fitness in adults with overweight and obesity. Weighted mean difference with 95% CI was calculated.ResultsA total of 28 studies with 1,620 patients were included. Results revealed that AE exerts best effects on weight loss (−2.35 [−4.05, −0.64]) and body mass index (−0.9 [−1.38, −0.42]), while HIIT is the most effective in reducing waist circumference (−5.93 [10.71, −1.15]), percentage body fat (−3.93 [−5.73, −2.12]), serum triglycerides (−20.55 [−37.20, −3.91]), and fasting blood glucose (−14.31 [−22.47, −6.16]) and improving VO2 max (7.41 [4.37, 10.45]). However, no significant benefit was observed in terms of total cholesterol and blood pressure.ConclusionsAE is the optimal exercise type for reducing body weight and BMI, while HIIT exerts the most beneficial effects on improving body composition, cardiorespiratory fitness, and metabolic abnormalities in adults with overweight and obesity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023444322, identifier CRD42023444322.

Background: Greenness surrounding residential places has been found to significantly reduce the risk of diseases such as hypertension, obesity, and metabolic syndrome (MetS). However, it is unclear whether visible greenness exposure at the workplace has any impact on the risk of MetS. Methods: Visible greenness exposure was assessed using a Green View Index (GVI) based on street view images through a convolutional neural network model. We utilized logistic regression to examine the cross-sectional association between GVI and MetS as well as its components among 51,552 adults aged 18–60 in the city of Hangzhou, China, from January 2018 to December 2021. Stratified analyses were conducted by age and sex groups. Furthermore, a scenario analysis was conducted to investigate the risks of having MetS among adults in different GVI scenarios. Results: The mean age of the participants was 40.1, and 38.5% were women. We found a statistically significant association between GVI and having MetS. Compared to the lowest quartile of GVI, participants in the highest quartile of GVI had a 17% (95% CI: 11–23%) lower odds of having MetS. The protective association was stronger in the males, but we did not observe such differences in different age groups. Furthermore, we found inverse associations between GVI and the odds of hypertension, low high-density lipoprotein cholesterol, obesity, and high levels of FPG. Conclusions: Higher exposure to outdoor visible greenness in the workplace environment might have a protective effect against MetS.

Yellow horn grows in northern China and has a high tolerance to drought and poor soil. Improving photosynthetic efficiency and increasing plant growth and yield under drought conditions have become important research content for researchers worldwide. Our study goal is to provide comprehensive information on photosynthesis and some candidate genes breeding of yellow horn under drought stress. In this study, seedlings’ stomatal conductance, chlorophyll content, and fluorescence parameters decreased under drought stress, but non-photochemical quenching increased. The leaf microstructure showed that stomata underwent a process from opening to closing, guard cells from complete to dry, and surrounding leaf cells from smooth to severe shrinkage. The chloroplast ultrastructure showed that the changes of starch granules were different under different drought stress, while plastoglobules increased and expanded continuously. In addition, we found some differentially expressed genes related to photosystem, electron transport component, oxidative phosphate ATPase, stomatal closure, and chloroplast ultrastructure. These results laid a foundation for further genetic improvement and deficit resistance breeding of yellow horn under drought stress.

IntroductionBrown adipose tissue (BAT) is mainly responsible for mammalian non-shivering thermogenesis and promotes energy expenditure. Meanwhile, similar to white adipose tissue (WAT), BAT also secretes a variety of adipokines to regulate metabolism through paracrine, autocrine, or endocrine ways. The chemokine C-X-C motif chemokine ligand-13 (CXCL13), a canonical B cell chemokine, functions in inflammation and tumor-related diseases. However, the role of CXCL13 in the adipose tissues is unclear.MethodsThe expression of CXCL13 in BAT and subcutaneous white adipose tissue (SWAT) of mice under cold stimulation were detected. Local injection of CXCL13 into BAT of normal-diet and high-fat-diet induced obese mice was used to detect thermogenesis and determine cold tolerance. The brown adipocytes were treated with CXCL13 alone or in the presence of macrophages to determine the effects of CXCL13 on thermogenic and inflammation related genes expression in vitro.ResultsIn this study, we discovered that the expression of CXCL13 in the stromal cells of brown adipose tissue significantly elevated under cold stimulation. Overexpression of CXCL13 in the BAT via local injection could increase energy expenditure and promote thermogenesis in obese mice. Mechanically, CXCL13 could promote thermogenesis via recruiting M2 macrophages in the BAT and, in the meantime, inhibiting pro-inflammatory factor TNFα level. DiscussionThis study revealed the novel role of adipose chemokine CXCL13 in the regulation of BAT activity and thermogenesis.

In Cucurbitaceae crops, the first flower node (FFN) is an important agronomic trait which can impact the onset of maturity, the production of female flowers, and yield. However, the gene responsible for regulating FFN in bitter gourd is unknown. Here, we used a gynoecious line (S156G) with low FFN as the female parent and a monoecious line (K8-201) with high FFN as the male parent to obtain F1 and F2 generations. Genetic analysis indicated that the low FFN trait was incompletely dominant over the high FFN trait. A major quantitative trait locus (QTL)-Mcffn and four minor effect QTLs-Mcffn1.1, Mcffn1.2, Mcffn1.3, and Mcffn1.4 were detected by whole-genome re-sequencing-based QTL mapping in the S156G×K8-201 F2 population (n=234) cultivated in autumn 2019. The Mcffn locus was further supported by molecular marker-based QTL mapping in three S156G×K8-201 F2 populations planted in autumn 2019 (n=234), autumn 2020 (n=192), and spring 2022 (n=205). Then, the Mcffn locus was fine-mapped into a 77.98-kb physical region on pseudochromosome MC06 using a large S156G×K8-201 F2 population (n=2,402). MC06g1112, which is a homolog of FLOWERING LOCUS T (FT), was considered as the most likely Mcffn candidate gene according to both expression and sequence variation analyses between parental lines. A point mutation (C277T) in MC06g1112, which results in a P93S amino acid mutation between parental lines, may be responsible for decreasing FFN in bitter gourd. Our findings provide a helpful resource for the molecular marker-assisted selective breeding of bitter gourd.

Abstract Background The American Society of Clinical Oncology (ASCO) has strived to address racial/ethnic disparities in cancer care since 2009. Surgery plays a pivotal role in cancer care; however, it is unclear whether and how racial/ethnic disparities in cancer surgery have changed over time. Methods This cohort study included 1,113,256 White and Black cancer patients across 9 years (2007–2015) using patient data extracted from the Surveillance, Epidemiology, and End Results (SEER)‐18 registries. Patient data were included from 2007 to adjust insurance status and by 2015 to obtain at least a 3‐year survival follow‐up (until 2018). The primary outcome was a surgical intervention. The secondary outcomes were the use of (neo)adjuvant chemotherapy and cancer‐specific survival (CSS). Adjusted associations of the race (Black/White) with the outcomes were measured in each cancer type and year. Results The gap between surgery rates for Black and White patients narrowed overall, from an adjusted odds ratio (aOR) of 0.621 (0.592–0.652) in 2007 to 0.734 (0.702–0.768) in 2015. However, the racial gap persisted in the surgery rates for lung, breast, prostate, esophageal, and ovarian cancers. In surgically treated patients with lymph node metastasis, Black patients with colorectal cancer (CRC) were less likely to receive (neo)adjuvant chemotherapy than White patients. Black patients undergoing surgery were more likely to have a worse CSS rate than White patients undergoing surgery. In breast cancer patients, the overall trend was narrow, but continuously present, with an adjusted hazard ratio (aHR) of 1.224 (1.278–1.173) in 2007 and 1.042 (1.132–0.96) in 2015. Conclusions Overall, progress has been made toward narrowing the Black‐White gap in cancer surgical opportunity and survival. Future efforts should be directed toward those specific cancers for which the Black‐White gap continues. Additionally, it is worth addressing the Black‐White gap regarding the use of (neo)adjuvant chemotherapy for CRC treatment.

Because of the high complementarity between global navigation satellite systems (GNSSs) and visual-inertial odometry (VIO), integrated GNSS-VIO navigation technology has been the subject of increased attention in recent years. In this paper, we propose an embedded high-precision multi-sensor fusion suite that includes a multi-frequency and multi-constellation GNSS module, a consumption-grade inertial measurement unit (IMU), and a grayscale camera. The suite uses an NVIDIA Jetson Xavier NX as the host and develops a Field Programmable Gate Array-based controller for hardware time synchronization between heterogeneous sensors. A multi-state constraint Kalman filter is used to generate the tightly-coupled estimation from the camera and the IMU. As a result, the GNSS output is loosely coupled to facilitate the acquisition of the global drift-free estimation. Results from the calibration reveal that the time synchronization accuracy of the suite is better than 30 µs (standard deviation [STD]) and that the projection error of camera-IMU is less than 0.1 pixels (STD); these results highlight the advantage of this hardware time synchronization mechanism. Results from the vehicle-mounted tests reveal reductions in the three-dimensional (3D) positioning error from 8.455 m to 5.751 m (root mean square) on experimental urban roads, which significantly improves the accuracy and continuity of GNSS individual positioning. In underground sites where the satellite signal is completely unavailable, the 3D position error drift of the suite is only 1.58 ‰, which also shows excellent performance.

BackgroundCOVID-19 is a highly infectious respiratory disease that can manifest in various clinical presentations. Although many studies have reported the lipidomic signature of COVID-19, the molecular changes in asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain elusive.MethodsThis study combined a comprehensive lipidomic analysis of 220 plasma samples from 166 subjects: 62 healthy controls, 16 asymptomatic infections, and 88 COVID-19 patients. We quantified 732 lipids separately in this cohort. We performed a difference analysis, validated with machine learning models, and also performed GO and KEGG pathway enrichment analysis using differential lipids from different control groups.ResultsWe found 175 differentially expressed lipids associated with SASR-CoV-2 infection, disease severity, and viral persistence in patients with COVID-19. PC (O-20:1/20:1), PC (O-20:1/20:0), and PC (O-18:0/18:1) better distinguished asymptomatic infected individuals from normal individuals. Furthermore, some patients tested positive for SARS-CoV-2 nucleic acid by RT-PCR but did not become negative for a longer period of time (≥60 days, designated here as long-term nucleic acid test positive, LTNP), whereas other patients became negative for viral nucleic acid in a shorter period of time (≤45 days, designated as short-term nucleic acid test positive, STNP). We have found that TG (14:1/14:1/18:2) and FFA (4:0) were differentially expressed in LTNP and STNP.ConclusionIn summary, the integration of lipid information can help us discover novel biomarkers to identify asymptomatic individuals and further deepen our understanding of the molecular pathogenesis of COVID-19.

Gastric cancer is a malignant tumor with high mortality and high incidence. This study aims to explore the function and molecular mechanism of Cortactin on gastric cancer progression in vitro and in vivo. A bioinformatics analysis from TCGA displayed that Cortactin was highly expressed in gastric cancer samples, and patients with a high Cortactin level had a worse survival rate. Subsequently, we investigated the specific mechanism of action of A in gastric cancer by collecting patient samples for immunohistochemistry, WB, qRT-PCR, cell transfection, cell invasion and metastasis, and constructing tumor xenografts in nude mice. Overexpression of Cortactin inhibited apoptosis and enhanced cellular proliferation and mobility in AGS cells, while those activities were reversed by the knockdown of MMP2 or MMP9. Conversely, the deletion of Cortactin induced apoptosis and suppressed cell growth and metastasis in SGC7901 cells, whereas those behaviors were inhibited by overexpression of MMP2 or MMP9. Additionally, the ERK pathway was activated by Cortactin upregulation. In vivo studies presented that overexpression of Cortactin promoted tumor growth, increased Ki67 expression, and reduced caspase 3 expression, which was reversed by ERK inhibitor treatment. In conclusion, Cortactin acted as an oncogene in gastric cancer and exerted its function by ERK/MMP2/MMP9 signaling pathway.

Abstract Background Albuminuria is a hallmark of diabetic kidney disease (DKD) that promotes its progression, leading to renal fibrosis. Renal macrophage function is complex and influenced by macrophage metabolic status. However, the metabolic state of diabetic renal macrophages and the impact of albuminuria on the macrophage metabolic state are poorly understood. Methods Extracellular vesicles (EVs) from tubular epithelial cells (HK-2) were evaluated using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Glycolytic enzyme expression in macrophages co-cultured with HSA-treated HK-2 cell-derived EVs was detected using RT-qPCR and western blotting. The potential role of EV-associated HIF-1α in the mediation of glycolysis was explored in HIF-1α siRNA pre-transfected macrophages co-cultured with HSA-treated HK-2 cell-derived EVs, and the extent of HIF-1α hydroxylation was measured using western blotting. Additionally, we injected db/db mice with EVs via the caudal vein twice a week for 4 weeks. Renal macrophages were isolated using CD11b microbeads, and immunohistofluorescence was applied to confirm the levels of glycolytic enzymes and HIF-1α in these macrophages. Results Glycolysis was activated in diabetic renal macrophages after co-culture with HSA-treated HK-2 cells. Moreover, HSA-treated HK-2 cell-derived EVs promoted macrophage glycolysis both in vivo and in vitro. Inhibition of glycolysis activation in macrophages using the glycolysis inhibitor 2-DG decreased the expression of both inflammatory and fibrotic genes. Mechanistically, EVs from HSA-stimulated HK-2 cells were found to accelerate macrophage glycolysis by stabilizing HIF-1α. We also found that several miRNAs and lncRNAs, which have been reported to stabilize HIF-1α expression, were increased in HSA-treated HK-2 cell-derived EVs. Conclusion Our study suggested that albuminuria induced renal macrophage glycolysis through tubular epithelial cell-derived EVs by stabilizing HIF-1α, indicating that regulation of macrophage glycolysis may offer a new treatment strategy for DKD patients, especially those with macroalbuminuria.

BackgroundGrowth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported.ObjectivesThis study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center.MethodsWe retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital’s information system.ResultsBased on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P

The Cortical 3-Hinges Folding Pattern (i.e., 3-Hinges) is one of the brain's hallmarks, and it is of great reference for predicting human intelligence, diagnosing eurological diseases and understanding the brain functional structure differences among gender. Given the significant morphological variability among individuals, it is challenging to identify 3-Hinges, but current 3-Hinges researches are mainly based on the computationally expensive Gyral-net method. To address this challenge, this paper aims to develop a deep network model to realize the fast identification of 3-Hinges based on cortical morphological and structural features. The main work includes: (1) The morphological and structural features of the cerebral cortex are extracted to relieve the imbalance between the number of 3-Hinges and each brain image's voxels; (2) The feature vector is constructed with the K nearest neighbor algorithm from the extracted scattered features of the morphological and structural features to alleviate over-fitting in training; (3) The squeeze excitation module combined with the deep U-shaped network structure is used to learn the correlation of the channels among the feature vectors; (4) The functional structure roles that 3-Hinges plays between adolescent males and females are discussed in this work. The experimental results on both adolescent and adult MRI datasets show that the proposed model achieves better performance in terms of time consumption. Moreover, this paper reveals that cortical sulcus information plays a critical role in the procedure of identification, and the cortical thickness, cortical surface area, and volume characteristics can supplement valuable information for 3-Hinges identification to some extent. Furthermore, there are significant structural differences on 3-Hinges among adolescent gender.

Arsenic pollution is a global environmental concern. Arsenic-induced chronic liver injury and its irreversible outcomes, including liver cirrhosis and liver cancer, threaten the health of residents in arsenic-contaminated areas. Liver fibrosis is a reversible pathological stage in the progression of arsenic-induced chronic liver injury to cirrhosis and liver cancer. The aim of this study is to identify the epigenetic mechanism of arsenic-induced liver fibrosis based on the dedifferentiation of liver sinusoidal endothelial cells (LSECs). Rats were treated with 0.0, 2.5, 5.0, or 10.0 mg/kg sodium arsenite for 36 weeks. Marked fibrotic phenotypes were observed in the rat livers, manifested by hepatic stellate cell activation and an increased extracellular matrix, as well as the deposition of collagen fibers. The reduced fenestrations on the cells’ surface and the increased expression of the dedifferentiation marker CD31 corroborated the LSECs’ dedifferentiation in the liver tissue, which was also found to be significantly associated with fibrotic phenotypes. We further revealed that arsenic exposure could inhibit the enrichment of histone H3 lysine 18 acetylation (H3K18ac) in the promoters of Fcgr2b and Lyve1, two key genes responsible for maintaining the differentiation phenotype of LSECs. This inhibition subsequently suppressed the genes’ expression, promoting LSEC dedifferentiation and subsequent liver fibrosis. In conclusion, arsenic can trigger liver fibrosis by inhibiting H3K18ac-dependent maintenance of LSEC differentiation. These findings uncover a novel mechanism of arsenic-induced liver fibrosis based on a new insight into epigenetically dependent LSEC dedifferentiation.

Due to its advantages of low latency, low power consumption, and high flexibility, FPGA-based acceleration technology has been more and more widely studied and applied in the field of computer vision in recent years. An FPGA-based feature extraction and tracking accelerator for real-time visual odometry (VO) and visual simultaneous localization and mapping (V-SLAM) is proposed, which can realize the complete acceleration processing capability of the image front-end. For the first time, we implement a hardware solution that combines features from accelerated segment test (FAST) feature points with Gunnar Farneback (GF) dense optical flow to achieve better feature tracking performance and provide more flexible technical route selection. In order to solve the scale invariance and rotation invariance lacking problems of FAST features, an efficient pyramid module with a five-layer thumbnail structure was designed and implemented. The accelerator was implemented on a modern Xilinx Zynq FPGA. The evaluation results showed that the accelerator could achieve stable tracking of features of violently shaking images and were consistent with the results from MATLAB code running on PCs. Compared to PC CPUs, which require seconds of processing time, the processing latency was greatly reduced to the order of milliseconds, making GF dense optical flow an efficient and practical technical solution on the edge side.

Glufosinate is a broad-spectrum herbicide used to control most weeds in agriculture worldwide. Goosegrass (Eleusine indica L.) is one of the top ten malignant weeds across the world, showing high tolerance to glufosinate via different mechanisms that are not yet fully understood. This study revealed that nitrogen metabolism could be a target-resistant site, providing clues to finally clarify the mechanism of glufosinate resistance in resistant goosegrass populations. Compared to susceptible goosegrass (NX), the resistant goosegrass (AUS and CS) regarding the stress of glufosinate showed stronger resistance with lower ammonia contents, higher target enzyme GS (glutamine synthetase) activity, and lower GOGAT (glutamine 2-oxoglutarate aminotransferase) activity. The GDH (glutamate dehydrogenase) activity of another pathway increased, but its gene expression was downregulated in resistant goosegrass (AUS). Analyzing the transcriptome and proteome data of goosegrass under glufosinate stress at 36 h showed that the KEGG pathway of the nitrogen metabolism was enriched in glufosinate-susceptible goosegrass (NX), but not in glufosinate-resistant goosegrass (CS and AUS). Several putative target genes involved in glufosinate stress countermeasures were identified. This study provides specific insights into the nitrogen metabolism of resistant goosegrass, and gives a basis for future functional verification of glufosinate-tolerance genes in plants.

Abstract Background Molecular markers play an important role in predicting clinical outcomes in pancreatic adenocarcinoma (PAAD) patients. Analysis of the ferroptosis-related genes may provide novel potential targets for the prognosis and treatment of PAAD. Methods RNA-sequence and clinical data of PAAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The PAAD samples were clustered by a non-negative matrix factorization (NMF) algorithm. The differentially expressed genes (DEGs) between different subtypes were used by “limma_3.42.2” package. The R software package clusterProfiler was used for functional enrichment analysis. Then, a multivariate Cox proportional and LASSO regression were used to develop a ferroptosis-related gene signature for pancreatic adenocarcinoma. A nomogram and corrected curves were constructed. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, migration and invasion assays. Results The 173 samples were divided into 3 categories (C1, C2, and C3) and a 3-gene signature model (ALOX5, ALOX12, and CISD1) was constructed. The prognostic model showed good independent prognostic ability in PAAD. In the GSE62452 external validation set, the molecular model also showed good risk prediction. KM-curve analysis showed that there were significant differences between the high and low-risk groups, samples with a high-risk score had a worse prognosis. The predictive efficiency of the 3-gene signature-based nomogram was significantly better than that of traditional clinical features. For comparison with other models, that our model, with a reasonable number of genes, yields a more effective result. The results obtained with qPCR and IHC assays showed that ALOX5 was highly expressed, whether ALOX12 and CISD1 were expressed at low levels in tissue samples. Finally, function assays results suggested that ALOX5 may be an oncogene and ALOX12 and CISD1 may be tumor suppressor genes. Conclusions We present a novel prognostic molecular model for PAAD based on ferroptosis-related genes, which serves as a potentially effective tool for prognostic differentiation in pancreatic cancer patients.

Abstract Objectives The purpose of this study was to investigate the incidence of deep vein thrombosis (DVT) and clarify the risk factors of DVT in patients with femoral neck fracture. Methods A self-designed questionnaire was used to collect the clinical data of 1209 patients with femoral neck fracture in our hospital from January 2019 to December 2019. The content of the questionnaire mainly includes general information, past medical history, history of present illness, operation related information, occurrence of DVT. The collected data were entered into Excel to analyze the incidence and risk factors of DVT in patients with femoral neck fracture. Chi square test and binary logistic regression model was used to screen the risk factors of DVT. Results 1209 cases of femoral neck fracture were included in this study. The incidence of DVT was 28.0% (339 patients). Among them, 71.7% (243 patients) were preoperative DVT and 28.3% (96 patients) were postoperative DVT. For the risk-factor analysis, gender, age, time from injury to hospitalization, operative method, anesthesia method and intraoperative blood loss were independent risk factors for DVT. Conclusion The incidence of DVT in patients with femoral neck fracture is relatively high, and there are many related risk factors.

Lipoxygenase (LOX) gene plays an essential role in plant growth, development, and stress response. 15 LOX genes were identified, which were unevenly distributed on chromosomes and divided into three subclasses in this study. In promoter region analysis, many cis-elements were identified in growth and development, abiotic stress response, hormonal response, and light response. qRT-PCR showed that the LOX gene showed tissue specificity in seven tissues, especially XsLOX1, 3, and 7 were relatively highly expressed in roots, stems, and axillary buds. The different expression patterns of LOX genes in response to abiotic stress and hormone treatment indicate that different XsLOX genes have different reactions to these stresses and play diversified roles. This study improves our understanding of the mechanism of LOX regulation in plant growth, development, and stress and lays a foundation for further analysis of biological functions.

Background. The role of disulfidptosis-related lncRNAs remains unclear in lung adenocarcinoma. Methods. Analysis in R software was conducted using different R packages, which are based on the public data from The Cancer Genome Atlas (TCGA) database. The transwell assay was used to evaluate the invasion and migration abilities of lung cancer cells. Results. In our study, we identified 1401 lncRNAs significantly correlated with disulfidptosis-related genes (|Cor| > 0.3 and P

Some cells within a diffuse large B-cell lymphoma (DLBCL) have the genotype of a stem cell, the proportion of which is termed degree of stemness. We interrogated correlations between the degree of stemness with immune and stromal cell scores and clinical outcomes in persons with DLBCL. We evaluated gene expression data on 1,398 subjects from Gene Expression Omnibus to calculate the degree of stemness. Subjects were classified into low- and high-stemness cohorts based on restricted cubic spline plots. Weighted gene co-expression network analysis (WGCNA) was used to screen for stemness-related genes. Immune and stromal scores correlated with the degree of stemness (both P < 0.001). A high degree of stemness correlated with a shorter progression-free survival (PFS; Hazard Ratio [HR; 95% Confidence Interval [CI] =1.90 (1.37, 2.64; P < 0.001) and a shorter survival (HR = 2.29 (1.53, 3.44; P < 0.001). CDC7 expression correlated with the degree of stemness, and CDC7-inhibitors significantly increased apoptosis (P < 0.01), the proportion of cells in G1 phase (P < 0.01), and inhibited lymphoma growth in a mice xenograft model (P = 0.04). Our data indicate correlations between the degree of stemness, immune and stromal scores, PFS, and survival. These data will improve the prediction of therapy outcomes in DLBCL and suggest potential new therapies.

BackgroundRegional citrate anticoagulation (RCA) is increasingly used for continuous renal replacement therapy (CRRT) in children, but it is rarely used in children with liver injury, especially liver failure (LF). We analyze this issue through the following research.MethodsWe retrospectively analyzed 75 children with liver injury who underwent RCA-CRRT in the Pediatric Intensive Care Unit (PICU) of Children's Hospital of Chongqing Medical University. The patients were divided into the LF group and liver dysfunction (LD) group. The two groups were compared to evaluate the clinical safety and efficacy of RCA-CRRT in children with liver injury and to explore RCA-CRRT management strategies, in terms of the following indicators: the incidence of bleeding, clotting, citrate accumulation (CA), acid–base imbalance, and electrolyte disturbance, as well as filter lifespans, changes in biochemical indicators, and CRRT parameters adjustment.ResultsThe total incidence of CA (TCA) and persistent CA (PCA) in the LF group were significantly higher than those in the LD group (38.6 vs. 16.2%, p < 0.001; 8.4 vs. 1.5%, p < 0.001); and the CA incidence was significantly reduced after adjustment both in the LF (38.6 vs. 8.4%, p < 0.001) and LD groups (16.2 vs. 1.5%, p < 0.001). The incidence of hypocalcemia was significantly higher in the LF group than in the LD group either before (34.9 vs. 8.8%, p < 0.001) or after treatment (12.0 vs. 0%, p < 0.001). The speed of the blood and citrate pumps after adjustment was lower than the initial setting values in both the LF and LD groups. The dialysis speed plus replacement speed were higher than the initial settings parameters.ConclusionFor children undergoing RCA-CRRT, the risks of CA and hypocalcemia are significantly higher in children with liver failure than those with liver dysfunction, but through the proper adjustment of the protocol, RCA-CRRT can still be safely and effectively approached for children with LD and even LF.

Sinocyclocheilus wenshanensis is a cyprinid fish species endemic to Southwestern China. In this study, we first sequenced and characterized the complete mitochondrial genome (mitogenome) of S. wenshanensis by next-generation sequencing method. The entire length of mitogenome is 16,595 base pairs (bp), containing 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. Its gene arrangement pattern was identical to other previously reported Sinocyclocheilus fishes. The overall base composition is 31.12% A, 16.63% G, 25.45% T, and 26.80% C, with AT content of 56.57%. Phylogenetic analysis using mitogenome of 26 Cyprinidae fishes showed that S. wenshanensis are closely related to S. aluensis and S. oxycephalus. This work would provide molecular information fundamental to future phylogenetic analyses among Sinocyclocheilus species.