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The multifunctional linker molecules are crucial for the bio-orthogonal reaction for proteomic target profiling. Herein, we wish to present a novel type of biotin-based tetra-functional bio-orthogonal linkers 3a–3h named BPPA which, possessing a unique photolabile phenacyl ester motif, were readily prepared in 85–90% yields by a simple and green one-step protocol from commercially available and inexpensive reagents of biotin acids and 4’-ethynyl/azido 2-bromoacetophenones. The typical click reaction of BPPA linkers 3a and 3e via copper-catalyzed azide–alkyne cycloaddition (CuAAC) took place easily, resulting in the corresponding BPPA-triazole adducts 4a and 4b in nearly quantitative yields. A further cleavability evaluation of 4a and 4b demonstrated that the expected C-O bond detachment could be accomplished efficiently and rapidly by UV irradiation or by ammonia hydrolysis, respectively, resulting in the residual (hydroxyl)acetylphenyl triazole fragment supposed to be attached to proteins during biological manipulations. The BPPA linkers, with dual clickable options of either the terminal azide or alkyne clickable group, exhibit high potentials for various CuAAC-oriented bio-orthogonal reactions.

Point cloud registration is widely used in autonomous driving, SLAM, and 3D reconstruction, and it aims to align point clouds from different viewpoints or poses under the same coordinate system. However, point cloud registration is challenging in complex situations, such as a large initial pose difference, high noise, or incomplete overlap, which will cause point cloud registration failure or mismatching. To address the shortcomings of the existing registration algorithms, this paper designed a new coarse-to-fine registration two-stage point cloud registration network, CCRNet, which utilizes an end-to-end form to perform the registration task for point clouds. The multi-scale feature extraction module, coarse registration prediction module, and fine registration prediction module designed in this paper can robustly and accurately register two point clouds without iterations. CCRNet can link the feature information between two point clouds and solve the problems of high noise and incomplete overlap by using a soft correspondence matrix. In the standard dataset ModelNet40, in cases of large initial pose difference, high noise, and incomplete overlap, the accuracy of our method, compared with the second-best popular registration algorithm, was improved by 7.0%, 7.8%, and 22.7% on the MAE, respectively. Experiments showed that our CCRNet method has advantages in registration results in a variety of complex conditions.

Succinate dehydrogenase (SDH, EC 1.3.5.1) is one of the most promising targets for fungicide development and has attracted great attention worldwide. However, existing commercial fungicides targeting SDH have led to the increasingly prominent problem of pathogen resistance, so it is necessary to develop new fungicides. Herein, we used a structure-based molecular design strategy to design and synthesize a series of novel SDHI fungicides containing an N-(alkoxy)diphenyl ether carboxamide skeleton. The mycelial growth inhibition experiment showed that compound M15 exhibited a very good control effect against four plant pathogens, with inhibition rates of more than 60% at a dose of 50 μg/mL. A structure–activity relationship study found that N-O-benzyl-substituted derivatives showed better antifungal activity than others, especially the introduction of a halogen on the benzyl. Furthermore, the molecular docking results suggested that π–π interactions with Trp35 and hydrogen bonds with Tyr33 and Trp173 were crucial interaction sites when inhibitors bound to SDH. Morphological observation of mycelium revealed that M15 could inhibit the growth of mycelia. Moreover, in vivo and in vitro tests showed that M15 not only inhibited the enzyme activity of SDH but also effectively protected rice from damage due to R. solani infection, with a result close to that of the control at a concentration of 200 μg/mL. Thus, the N-(alkoxy)diphenyl ether carboxamide skeleton is a new starting point for the discovery of new SDH inhibitors and is worthy of further investigation.

Abstract Background and Aims Previous research has shown that socioeconomic factors, such as income and education, are associated with blood donation behavior. This study aims to investigate the factors that influence blood donation behavior using a large database of blood donation records and to provide further empirical evidence and insights into the factors that influence blood donation behavior and to identify potential strategies to increase blood donation rates in China. Methods This study employed correlation analysis and regression analysis to investigate the impact of socioeconomic factors on blood donation rates in 36 major cities in China. The study also used the K‐Means clustering algorithm to identify the socioeconomic factors that influence blood donation behavior at the per capita level. Additionally, the study conducted correlation analysis between the donor's age groups and the socioeconomic factors. The indices of economy and education were determined by correlation analysis. Results At the city level, overall economic output and university student populations were positively correlated with total blood donation times. However, at the per capita level, this linear relationship disappeared. By applying the K‐Means clustering algorithm, the cities were divided into subgroups where the linear relationship reemerged. The study also found that the number of college students had a linear relationship with blood donors between the ages of 18–34. Conclusion City characteristics and demographics significantly impact blood donation rates in different ways. A universal policy may have limited effect given the heterogeneity across cities. Tailored interventions targeting specific city clusters and education levels are needed to promote blood donation behavior, especially among youth and students. Investment in education and targeted education on blood donation appear particularly impactful. A combined approach integrating social and economic policies will likely be most effective.

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation and gradual joint degeneration, resulting in function disability. Recently, ferroptosis, a novel form of regulated cell death that involves iron-dependent lipid peroxidation, has been implicated in the pathogenesis of RA. However, the underlying molecular mechanisms and key genes involved in ferroptosis in RA remain largely unknown.MethodsThe GSE134420 and GSE77298 datasets were downloaded and DEGs were identified using R software. The DEGs were then mapped to the dataset of 619 ferroptosis-related genes obtained from the GeneCards database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to investigate the possible biological functions. Protein-protein interaction (PPI) networks were constructed to identify the hub genes. The relationship between hub genes and immune infiltration was estimated using the CIBERSORT algorithms. Gene Set Enrichment Analysis (GSEA) was used to explore the underlying signaling pathways of hub genes. Genome-wide association studies (GWAS) analysis was performed to confirm the pathogenic regions of the hub genes. RcisTarget and Gene-motif ranking databases were used to identify transcription factors (TFs) associated with the hub genes. The miRcode databases were utilized to construct the microRNA (miRNA)-messenger RNA (mRNA) network. Single-cell analysis was utilized to cluster cells and display the expression of hub genes in cell clusters. Finally, the expression and potential mechanism of hub genes were investigated in human and experimental samples.ResultsThree hub genes PTGS2, ENO1, and GRN highly associated with ferroptosis were identified. Four pathogenic genes HLA-B, MIF, PSTPIP, TLR1 were identified that were significantly and positively correlated with the expression levels of hub genes. The results of the GSEA showed that the hub genes were significantly enriched in pathways related to immunity, lysosome, phagocytosis and infection. ENO1 and PTGS2 were enriched in the TF-binding motif of cisbp_M5493. The hub genes were validated in experimental and patient samples and highly level of ENO1 expression was found to inhibit ACO1, which reduces ferroptosis in proliferating fibroblast-like synoviocytes (FLS).ConclusionPTGS2, ENO1 and GRN were identified and validated as potential ferroptosis-related biomarkers. Our work first revealed that ENO1 is highly expressed in RA synovium and that ferroptosis may be regulated by the ENO1-ACO1 axis, advancing the understanding of the underlying ferroptosis-related mechanisms of synovial proliferation and providing potential diagnostic and therapeutic targets for RA.

An eight-year-old girl was admitted with vomiting, gross hematuria, and progressive renal dysfunction. A renal biopsy revealed endocapillary proliferative glomerulopathy and crescent formation. Immunofluorescence staining revealed diffuse granular deposits of IgG and C3. Post-streptococcal acute glomerulonephritis (PSAGN) was suspected, based on the elevated anti-streptolysin O levels, decreased serum C3 concentrations, and histologic findings. The myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) test was positive, and the young patient gradually developed palisaded neutrophilic and granulomatous dermatitis (PNGD), orbital and paranasal sinus granulomatous neoplasms, along with intermittent nose, head, and orbital pain. Finally, she was diagnosed with the rare MPO-ANCA-associated granulomatosis with polyangiitis (GPA) superimposed on PSAGN. The patient was treated with aggressive renal replacement therapy, methylprednisolone pulse therapy, and intravenous pulse cyclophosphamide; her renal function normalized, and her pain symptoms improved.

Background: Guidewire fracture and dislodgment are very rare but can cause serious complications.Method: A case was reported where part of the guidewire was blocked to the posterior tibial. We attempted to remove it using a Solitaire AB Neurovascular Remodeling Device.Result: A Solitaire AB Neurovascular Remodeling Device was successfully used to remove the fracture and dislodgment of a guidewire. There were no complications during the removal of the guidewire.Conclusion: A Solitaire AB can be used to remove a fractured guidewire, which is a simple and effective method to reduce complications. The Solitaire stent gradually crimped and tightened to form a dense inverted conical meshwork, similar to the “trans embolic protection device.” We can use minimally invasive methods to remove a broken and displaced guidewire within the vascular lumen.

Hydrogen (H2) energy is presumed to be the most promising alternative to replacing traditional fossil fuels to achieve the global mission of carbon neutrality. Electrocatalytic water splitting driven by green electricity has been regarded as an ideal method for large‐scale green hydrogen production with a minimal CO2 footprint. However, most of the reported electrocatalysts still suffer from large overpotentials and severe activity degradation at high current density (>1000 mA cm−2). Therefore, a comprehensive review to summarize the representative alkaline hydrogen evolution reaction (HER) electrocatalysts with large current densities is essential to guide the fabrication of promising industrial electrocatalysts. In this review, starting from the fundamental of water electrolysis, the design principles to acquire alkaline electrocatalysts with large current density and high stability are elaborated. The critical factors for achieving high‐performance electrocatalysts to meet industrial H2 production are proposed. Additionally, the key processes for preparing self‐supported electrodes are clarified. Afterward, the recently advanced self‐supported transition metal‐based electrocatalysts with high current density for alkaline HER are systematically summarized. Finally, personal perspective on future opportunities and challenges is highlighted. It is hoped this review can guide the rational design of self‐supported high‐current density electrocatalysts for future commercial H2 production.

Objectives: This study aimed to evaluate the risk of venous thrombosis (VTE) associated with Janus kinase (JAK) inhibitors in patients diagnosed with immune-mediated inflammatory diseases.Methods: We conducted a comprehensive search of PUBMED, Cochrane, and Embase databases for randomized controlled trials evaluating venous thromboembolic incidence after administering JAK inhibitors in patients with immune-mediated inflammatory diseases. The studies were screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and a meta-analysis was performed.Results: A total of 16 studies, enrolling 17,242 participants, were included in this review. Four approved doses of JAK inhibitors were administered in the included studies. The meta-analysis revealed no significant difference in the incidence of VTE between patients receiving JAK inhibitors, a placebo, or tumor necrosis factor (TNF) inhibitors (RR 0.72, 95% CI (0.33-1.55); RR 0.94, 95%CI (0.33-2.69)). Subgroup analysis showed a lower risk of VTE with lower doses of JAK inhibitors [RR 0.56, 95%CI (0.36-0.88)]. Compared with the higher dose of tofacitinib, the lower dose was associated with a lower risk of pulmonary embolism [RR 0.37, 95%CI (0.18-0.78)].Conclusion: Our meta-analysis of randomized controlled trials observed a potential increase in the risk of VTE in patients with immune-mediated inflammatory diseases treated with JAK inhibitors compared to placebo or tumor necrosis factor inhibitors, though statistical significance was not attained. Notably, a higher risk of pulmonary embolism was observed with high doses of tofacitinib. Our findings provide valuable insights for physicians when evaluating the use of JAK inhibitors for patients with immune-mediated inflammatory diseases.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023382544, identifier CRD42023382544

In traditional medicine, Plagiorhegma dubia Maxim (PD) is used to treat diabetes, irritability, insomnia, high fever, and coma. In this study, to identify the components in PD, we first performed three preliminary phytochemical tests, which were all positive for the presence of alkaloids. Next, we evaluated the total alkaloid content and performed 13 different in vitro antioxidant experiments for three solvent extracts of PD. According to the results, the methanol extract was selected for further research. Ultra-performance liquid chromatography with electrospray ionization Orbitrap mass spectrometry was used to identify 41 compounds in the methanol extract. Thirty-eight of these compounds were alkaloids, and the main components were magnoflorine, berberrubine, and betaine. Addition of the methanol extract to cooking oil increased the stability against oxidation and greatly reduced the peroxide value. Cell viability and oral acute toxicity studies in mice indicated that the methanol extract was relatively non-toxic. Histopathological examination and biochemical analysis showed that the methanol extract was protective against liver damage in rats induced by d-galactosamine. The methanol extract also showed a good antidiabetic effect for streptozotocin-induced diabetes in rats, where it lowered blood sugar levels and protected vital organs against damage. Lipid profile parameters and oxidative stress parameters also improved. The therapeutic effects towards diabetes and liver damage were attributed to the ability of the three main components in the methanol extract to resist oxidative stress. Our results show that the alkaloid-rich methanol extract of PD is potential candidate for treatment of diseases associated with oxidative imbalances. This understanding of the hepatoprotective effect and antidiabetic activity of PD provides new insight for its use as a substitute for Coptis chinensis and establishes a foundation for development of PD as an economic crop.

Background: The purpose of this research was to establish a safe, effective, and simple nervous system aneurysm model. This method could quickly and stably establish an exact canine tongue aneurysm model. This paper summarizes the technique and key points of the method.Methods: Under the condition of anesthesia by inhaling isoflurane with a mask, we punctured the femoral artery of the canine, and the tip of the catheter was placed in the common carotid artery for intracranial arteriography. The positions of the lingual artery, external carotid artery, and internal carotid artery were identified. Then, the skin near the mandible was cut according to the positioning and separated layer by layer until the bifurcation of the lingual artery and external carotid artery was exposed. The lingual artery were then sutured with 2–0 silk sutures approximately 3 mm from the external carotid/lingual artery bifurcation. The final angiographic review showed that the aneurysm model was successfully established.Results: The lingual artery aneurysm was successfully established in all 8 canines. All canines obtained a stable model of nervous system aneurysm and confirmed by DSA angiography.Conclusion: We have established a safe, effective, stable and simple method to establish a canine nervous system aneurysm model with controllable size. In addition, this method has the advantages of no arteriotomy, less trauma, constant anatomical location, and low risk of stroke.

The majority of gastric cancer (GC) patients are in a progressive stage at the initial stage of treatment, and the overall response rate to immunotherapy remains unsatisfactory largely due to the lack of effective prognostic biomarkers. Immunogenic cell death (ICD) was identified as a new form of regulated cell death that can activate adaptive immune responses and further promote immunotherapy efficacy. Therefore, we attempted to characterize the ICD-associated signature to stratify patients who could benefit from immunotherapy. In our study, two subgroups of patients were identified based on the data of 34 ICD-related genes extracted from The Cancer Genome Atlas database via consensus clustering. The estimated scores, stromal scores, immune scores, tumor purity, and survival rate showed significant differences between the low and high ICD groups. Then, we constructed an ICD-related risk signature, including IFNB1, IL6, LY96, and NT5E, using least absolute shrinkage and selection operator Cox regression analysis; then, high- and low-risk groups could be clearly distinguished. Notably, the risk score is a reliable predictor of the prognosis and immunotherapy outcome in GC, which was further validated in an immunohistochemistry assay. These results suggest that ICD is closely associated with the prognosis and tumor immune microenvironment in GC. Taken together, this study first constructed and validated a prognostic ICD-related signature to predict the survival and effect of immunotherapy in GC, which provided new insight for potent individualized immunotherapy strategies.

To investigate the possible risk factors for proximal pulmonary embolism (PE) in patients with lower extremity deep vein thrombosis (LEDVT). A single-center, retrospective cohort study was conducted. Consecutive patients diagnosed with unilateral LEDVT and confirmed PE by computed tomography (CT) pulmonary angiography and indirect CT venography between September 2015 and January 2022 were included. Patient demographics, presentation of LEDVT, laboratory examination, thrombus characteristics, comorbidities and risk factors for LEDVT, and imaging findings were analyzed to determine the univariable and multivariable associations. The associations between thrombus location, stenosis, and proximal PE were assessed using a stratified analysis. A total of 115 eligible patients (60.08 ± 15.18 years, 59.1% male) were included. Of these patients, 40 (34.8%) were in the proximal PE group (proximal thrombus involved main or lobar pulmonary artery), and 75 (65.2%) were in the distal PE group (without main and labor pulmonary artery involvement). The univariable analysis showed that onset time of LEDVT symptoms ≤ 7 days ( P = .041), inferior vena cava (IVC) involvement ( P = .035), and severe iliac vein stenosis (IVS) (stenosis ratio > 61.3%) ( P = .010) were associated with the occurrence of proximal PE. Further multivariant analysis showed that IVC involvement was associated with an increased odds of proximal PE (OR: 4.45, 95% CI: 1.083 − 18.248, P = .038), whereas severe IVS (stenosis ratio > 61.3%) was associated with a decreased odds of proximal PE (OR: 0.294, 95% CI: 0.110-0.783, P = .014). Among patients with unilateral LEDVT, IVC involvement increased the risk of proximal PE; patients with severe IVS (stenosis ratio > 61.3%) had a lower risk of developing proximal PE compared with distal PE; and severe IVS seemed to be a protective factor for proximal PE.

Objective: To investigate the safety and effectiveness of catheter-based therapy (CBT) compared to conventional catheter-directed thrombosis (CDT) for non-oncological patients with inferior vena cava thrombosis (IVCT), as well to evaluate the differences between CBTs using AngioJet rheolytic thrombectomy (ART) and large lumen catheter aspiration (LLCA). Methods: This retrospective single-center study included eligible patients with IVCT treated with CBTs coupled with/without CDT or CDT alone as the first-line treatment between January 3, 2015 and January 28, 2022. The baseline demographics, comorbidities, clinical characteristics, treatment details, course data were all reviewed. Results: A total of 106 patients (128 limbs) were included, with 42 cases were treated with ART, 30 with LLCA, and 34 with CDT alone. Technical success rates were 100% (128/128), and 95.5% (84/88) limbs treated with CBT subsequently underwent CDT. The mean duration of CDT time and total infusion agent dosage in patients with CBTs were lower than those who underwent CDT alone ( P < .05). Similarities were observed in ART compared to LLCA ( P < .05). At the end of CDT, clinical success was achieved in 85.2% (75/88) of limbs treated with CBTs and 77.5% (31/40) of limbs with CDT alone, and 88.5% (46/52) in ART and 80.6% (29/36) in LLCA. The 12-month follow-up showed slightly lower incidences of recurrent thrombosis (7.7% vs 15.2%) and post-thrombotic syndrome (14.1% vs 21.2%), which persisted in patients who underwent ART compared to LLCA (4.3% vs 12.9% and 8.5% vs 22.6%). Patients who underwent CBTs tended to have lower minor complications (5.6% vs 17.6%) but were at higher risk of transient macroscopic hemoglobinuria (58.3% vs 0%) and recoverable acute kidney injury (11.1% vs 2.9%) compared to CDT alone. These findings were similar in ART compared to LLCA (2.4% vs 10.0%, 100% vs 0%, and 16.7% vs 3.3%, respectively). LLCA seemed to have more hemoglobin losses (10.50 ± 9.20 vs 5.57 ± 10. 42 g/L, P < .05). Conclusion: CBTs coupled with/without CDT are safe and effective in patients with IVCT, reducing the clot burden in a moderate time, restoring blood flow rapidly, minimizing thrombolytic drug requirement and lowering minor bleeding complication compared to CDT alone. ART and LLCA have comparable outcomes but with different adverse event profiles.

Résumé Contexte À l’heure actuelle, la L-carnitine (LC) et le coenzyme Q10 (CoQ10), tels qu’utilisés en clinique pour traiter l’infertilité masculine due à une asthénozoospermie (AZS), sont encore principalement administrés par voie orale, mais certains patients atteints d’AZS ne montrent pas toujours d’amélioration significative de la motilité des spermatozoïdes, ni de grossesse chez la conjointe. Prodom™ est. un dispositif utilisé pour aider à la reproduction, qui est. temporairement installé sur le pénis pour faciliter la conception en aidant la femme à injecter certains médicaments dans le vagin. Cette étude a utilisé une association CL + CoQ10 assistée par Prodom™ pour traiter des patients atteints d’AZS et a évalué l’effet de cette méthode sur la mobilité des spermatozoïdes et la grossesse clinique, dans le but de trouver une méthode confortable, peu coûteuse et efficace. Résultats Au cours de cet essai thérapeutique, 232 cas sont allés au bout de l’étude, alors que 25 se sont arrêtés. Au cours des tests in vitro, la mobilité progressive des spermatozoïdes dans le groupe LC, le groupe CoQ10, le groupe CL + CoQ10 et dans le groupe témoin de sperme, était respectivement de 24,3 ± 4,6% et 38,1 ± 5,1%, de 23,0 ± 4,8% et 36,9 ± 4,4%, de 28,4 ± 5,0% et 43,8 ± 5,4%, et de 19,7 ± 4,4% et 26,0 ± 4,9%. La mobilité progressive des spermatozoïdes était significativement différentes entre les groupes (toutes les valeurs de P

Abstract The aim of this study was to evaluate the relationship between polymorphisms in CYP2C19 and the single‐dose pharmacokinetics (PKs) of omeprazole in healthy Chinese volunteers. A 20 mg single dose of omeprazole (Losec) enteric‐coated capsules or tablets was orally administered to 656 healthy subjects from eight subcenters. The polymorphic alleles of CYP2C19*2, *3, and *17 were determined by Sanger sequencing and Agena mass array. Plasma concentrations of omeprazole were determined by high‐performance liquid‐chromatography tandem mass spectrometry. PK parameters of area under the concentration versus time curve (AUC)0‐t, AUC from zero to infinity (AUC0‐∞), maximum plasma concentration (Cmax), and terminal half‐life (t1/2) were significantly influenced by CYP2C19 phenotype (all p

Abstract Background Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined. Results In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence. Conclusions Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.

Abstract The choice of the ideal material employed in selector devices is a tough task both from the theoretical and experimental side, especially due to the lack of a synergistic approach between techniques able to correlate specific material properties with device characteristics. Using a material‐to‐device multiscale technique, a reliable protocol for an efficient characterization of the active traps in amorphous GeSe chalcogenide is proposed. The resulting trap maps trace back the specific features of materials responsible for the measured findings, and connect them to an atomistic description of the sample. The metrological approach can be straightforwardly extended to other materials and devices, which is very beneficial for an efficient material‐device codesign and the optimization of novel technologies.

BackgroundPancreatic cancer is one of most aggressive malignancies with a dismal prognosis. Activation of PI3K/AKT signaling is instrumental in pancreatic cancer tumorigenesis. The aims of this study were to identify the molecular clustering, prognostic value, relationship with tumor immunity and targeting of PI3K/AKT-related genes (PARGs) in pancreatic cancer using bioinformatics.MethodsThe GSEA website was searched for PARGs, and pancreatic cancer-related mRNA data and clinical profiles were obtained through TCGA downloads. Prognosis-related genes were identified by univariate Cox regression analysis, and samples were further clustered by unsupervised methods to identify significant differences in survival, clinical information and immune infiltration between categories. Next, a prognostic model was constructed using Lasso regression analysis. The model was well validated by univariate and multivariate Cox regression analyses, Kaplan−Meier survival analysis and ROC curves, and correlations between risk scores and patient pathological characteristics were identified. Finally, GSEA, drug prediction and immune checkpoint protein analyses were performed.ResultsPancreatic cancers were divided into Cluster 1 (C1) and Cluster 2 (C1) according to PARG mRNA expression. C1 exhibited longer overall survival (OS) and higher immune scores and CTLA4 expression, whereas C2 exhibited more abundant PD-L1. A 6-PARG-based prognostic model was constructed to divide pancreatic cancer patients into a high-risk score (HRS) group and a low-risk score (LRS) group, where the HRS group exhibited worse OS. The risk score was defined as an independent predictor of OS. The HRS group was significantly associated with pancreatic cancer metastasis, aggregation and immune score. Furthermore, the HRS group exhibited immunosuppression and was sensitive to radiotherapy and guitarbine chemotherapy. Multidrug sensitivity prediction analysis indicated that the HRS group may be sensitive to PI3K/AKT signaling inhibitors (PIK-93, GSK2126458, CAL-101 and rapamycin) and ATP concentration regulators (Thapsigargin). In addition, we confirmed the oncogenic effect of protein phosphatase 2 regulatory subunit B’’ subunit alpha (PPP2R3A) in pancreatic cancer in vitro and in vivo.ConclusionsPARGs predict prognosis, tumor immune profile, radiotherapy and chemotherapy drug sensitivity and are potential predictive markers for pancreatic cancer treatment that can help clinicians make decisions and personalize treatment.

Abstract Immunotherapy is an attractive treatment strategy for cancer, while its efficiency and safety need to be improved. A dual‐cascade activatable nanopotentiator for sonodynamic therapy (SDT) and chemodynamic therapy (CDT)‐cooperated immunotherapy of deep tumors via reshaping adenosine metabolism is herein reported. This nanopotentiator (NPMCA) is constructed through crosslinking adenosine deaminase (ADA) with chlorin e6 (Ce6)‐conjugated manganese dioxide (MnO2) nanoparticles via a reactive oxygen species (ROS)‐cleavable linker. In the tumor microenvironment with ultrasound (US) irradiation, NPMCA mediates CDT and SDT concurrently in deep tumors covered with 2‐cm tissues to produce abundant ROS, which results in dual‐cascade scissoring of ROS‐cleavable linkers to activate ADA within NCMCA to block adenosine metabolism. Moreover, immunogenic cell death (ICD) of dying tumor cells and upregulation of the stimulator of interferon genes (STING) is triggered by the generated ROS and Mn2+ from NPMCA, respectively, leading to activation of antitumor immune response. The potency of immune response is further reinforced by reducing the accumulation of adenosine in tumor microenvironment by the activated ADA. As a result, NPMCA enables CDT and SDT‐cooperated immunotherapy, showing an obviously improved therapeutic efficacy to inhibit the growths of bilateral tumors, in which the primary tumors are covered with 2‐cm tissues.

Regulatory T cells (Tregs) display great promise in rheumatoid arthritis (RA) therapy. However, their low number and differentiation rate limit their further application in the clinics. In the present study, we first optimized a combination of IL-2, TGF-β and cyclin dependent kinase inhibitor AS2863619 (IL-2/TGF-β/AS), which could induce Tregs with high efficiency in vitro. After the induced Tregs (iTregs) were confirmed to suppress lymphocyte proliferation and pro-inflammatory T help cells (Th1 and Th17) activation, a chitosan-stabilized nanoparticle drug delivery system (NDDS) was developed according to the optimized formula of IL-2/TGF-β/AS. In vivo study, the NDDS was injected into the knees of mice with collagen-induced arthritis (CIA). As a result, the NDDS remarkably reduced the pathological score of the CIA, alleviated the inflammatory cell infiltration and synovial hyperplasia, and minimized cartilage tissue damage in the knee joint of the CIA mice. Mechanically, the NDDS administration promoted Treg differentiation and decreased Th17 production, consequently reversing the ratio of Treg/Th17, and reducing the secretion of TNF-α in the sera, which facilitated to relieve the severity and progression of arthritis. In sum, NDDS capable of efficiently inducing Tregs were constructed successfully and provided a potential platform for treating RA by restoring the equilibrium of Treg/Th17 destroyed in RA.

Integrins are main cell adhesion receptors serving as linker attaching cells to extracellular matrix (ECM) and bidirectional hubs transmitting biochemical and mechanical signals between cells and their environment. Integrin αvβ3 is a critical family member of integrins and interacts with ECM proteins containing RGD tripeptide sequence. Accumulating evidence indicated that the abnormal expression of integrin αvβ3 was associated with various tumor progressions, including tumor initiation, sustained tumor growth, distant metastasis, drug resistance development, maintenance of stemness in cancer cells. Therefore, αvβ3 has been explored as a therapeutic target in various types of cancers, but there is no αvβ3 antagonist approved for human therapy. Targeting-integrin αvβ3 therapeutics has been a challenge, but lessons from the past are valuable to the development of innovative targeting approaches. This review systematically summarized the structure, signal transduction, regulatory role in cancer, and drug development history of integrin αvβ3, and also provided new insights into αvβ3-based therapeutics in cancer from bench to clinical trials, which would contribute to developing effective targeting αvβ3 agents for cancer treatment.

The purpose of this study was to investigate whether serum B-endorpin and neuropeptide Y were associated with changes in levels of thyroid hormones in children suffering from anorexia. One hundred and five anorexic children admitted to Xianning City Central Hospital, China, from August 2019 to July 2021, were selected as case group, while 105 normal children were selected as normal control group. Serum B-endorpin and neuropeptide Y levels in the case group were lower than those in the normal control group (both P

Renal cell carcinoma (RCC) is the most frequent renal malignancy in the world, and its incidence is increasing year by year. RCC is a well-known drug resistant tumor, and the treatment methods are limited. Most patients with RCC are discovered at the advanced stage, and thus have poor prognosis even after treatment. Therefore, it is very urgent to find new markers for the diagnosis and treatment of RCC. Accumulating evidence shows that lncRNAs participate in the occurrence and progression of RCC, which is achieved by the lncRNA-miRNA-mRNA axis. It is widely known that metabolic defect is an essential pathogenesis in RCC. As is the case with other tumors, RCC can satisfy the demands of cancerous cells for uncontrolled proliferation through aerobic glycolysis. However, whether lncRNAs can modulate RCC progression through metabolic pathway is still not clarified. Taken together, this review mainly summarized the metabolic regulatory mechanisms of lncRNAs in RCC progression, especially their roles in glucose metabolism, lipid metabolism, amino acid metabolism and mitochondrial dynamics, as well as the clinical applications of lncRNAs via targeting metabolism in RCC therapy. It will provide the new targets and approaches for early clinical diagnosis, treatment and prognosis of RCC.

Non-alcoholic steatohepatitis (NASH) has become a major cause of liver transplantation and liver-associated death. The gut-liver axis is a potential therapy for NASH. Sodium cholate (SC) is a choleretic drug whose main component is bile acids and has anti-inflammatory, antifibrotic, and hepatoprotective effects. This study aimed to investigate whether SC exerts anti-NASH effects by the gut-liver axis. Mice were fed with an high-fat and high-cholesterol (HFHC) diet for 20 weeks to induce NASH. Mice were daily intragastric administrated with SC since the 11th week after initiation of HFHC feeding. The toxic effects of SC on normal hepatocytes were determined by CCK8 assay. The lipid accumulation in hepatocytes was virtualized by Oil Red O staining. The mRNA levels of genes were determined by real-time quantitative PCR assay. SC alleviated hepatic injury, abnormal cholesterol synthesis, and hepatic steatosis and improved serum lipid profile in NASH mice. In addition, SC decreased HFHC–induced hepatic inflammatory cell infiltration and collagen deposition. The target protein-protein interaction network was established through Cytoscape software, and NR1H4 [farnesoid x receptor (FXR)] was identified as a potential target gene for SC treatment in NASH mice. SC-activated hepatic FXR and inhibited CYP7A1 expression to reduce the levels of bile acid. In addition, high-dose SC attenuated the abnormal expression of cancer markers in NASH mouse liver. Finally, SC significantly increased the expression of FXR and FGF15 in NASH mouse intestine. Taken together, SC ameliorates steatosis, inflammation, and fibrosis in NASH mice by activating hepatic and intestinal FXR signaling so as to suppress the levels of bile acid in NASH mouse liver and intestine.

Objective The objective of this study was to investigate the risk of acute kidney injury in elderly patients compared with nonelderly patients undergoing AngioJet rheolytic thrombectomy for treatment of acute deep vein thrombosis. Methods A retrospective review of all patients who underwent AngioJet rheolytic thrombectomy for the treatment of acute deep vein thrombosis between November 1, 2014 and August 1, 2022 was conducted. Their baseline demographics, comorbidities, clinical characteristics, procedural details, and postoperative course were reviewed. Results A total of 105 eligible patients were reviewed; 45 patients were in the elderly group, and 60 were in the nonelderly group. Except for age ( p < 0.001), no significant differences regarding demographics were detected ( p >0.05). Transient macroscopic hemoglobinuria occurred in all patients during the first 24 h post-AngioJet rheolytic thrombectomy. The overall morbidity of acute kidney injury in the two groups was 11.4%, and the nonelderly group had a similar rate of acute kidney injury (8.3%) to the elderly group (15.6%). None of the 12 patients progressed to dialysis within the postoperative period, and the mean acute kidney injury recovery time of the elderly group was 5.86 ± 1.57 days, which was longer than the 3.60 ± .89 days of the nonelderly group ( p = 0.017). Conclusion The use of AngioJet rheolytic thrombectomy for the treatment of patients with acute deep vein thrombosis is associated with a potential risk of acute kidney injury, which seems to have a comparable rate in elderly and nonelderly patients. acute kidney injury in the elderly group tends to need a longer recovery time, which requires postoperative vigilance for this population.

The association between excessive screen media use and mental health problems has attracted widespread attention. The literature to date has neglected the biological mechanisms underlying such a relationship and failed to distinguish between different types of screen media activities. A sample from the Adolescent Brain and Cognitive Development study was used in the present study to elucidate the longitudinal associations between specific types of screen media use, brain development, and diverse mental health problems. The results showed that different types of screen media use have differentiated associations with mental health problems, subcortical volume, and cortical–subcortical connectivity. Specifically, more passive media use was associated with increased rule-breaking behavior, while more video game playing was associated with increased withdrawn/depressed symptoms. In addition, more social media use was associated with a reduced volume of the hippocampus, caudate, and thalamus proper. More research is needed to examine the differential effects of screen media use on neurodevelopmental processes and mental health problems across adolescence.

Picea koraiensis Nakai (PK) is an evergreen tree. It plays an important role in landscaping and road greening. Insect galls of PK are formed by parasitism of the adelgid Adelges laricis. Except for phenolics, other chemical constituents and biological activity of insect gall from PK are still unknown. Thus, here, we performed phytochemical and biological activity analyses of PK insect gall extracts, aiming to turn waste into treasure and serve human health. PK insect gall extracts were prepared using seven solvents. Antioxidant activities of the extracts were examined via antioxidant assays (radical and oxidizing substance quenching, metal chelating, and reducing power). The inhibitory activities of the extracts were determined toward the key human-disease-related enzymes α-glucosidase, α-amylase, cholinesterase, tyrosinase, urease, and xanthine oxidase. The content of numerous active constituents was high in the methanol and ethanol extracts of PK insect gall, and these extracts had the highest antioxidant and enzyme-inhibitory activities. They also showed excellent stability and low toxicity. These extracts have potential for use as stabilizers of olive and sunflower seed oils.

Electromagnetic vortex carries the orbital angular momentum, one of the most fundamental properties of waves. The order of such vortex can be unbounded in principle, thus facilitating high-capability wave technologies for optical communications, photonic integrated circuits and others. However, it remains a key challenge to generate the high-order vortex beams in a reconfigurable, broadband and cost-effective manner. Here, inspired by the balanced-ternary concept, we demonstrate the reconfigurable generation of order-controllable vortices via cascaded N-layer metasurfaces. We theoretically showed that 3N−1${3}^{N}-1$ different vortex modes can be generated by cascading N metasurfaces, each one serving as an individual vortex beam generator for the order of 3k${3}^{k}$ (k = 0,1,2 …, N−1$N-1$). As a proof-of-concept demonstration, a reconfigurable generation of 26 different vortex beams, with orders from 1 to 13 and from −1 to −13, is showcased in a broad millimeter-wave region by a cascade of 3 metasurfaces. Our method can be easily extended to vortex beam generator of arbitrary orders in a reconfigurable and easily implementable manner, paving a new avenue towards tremendous practical applications.

Abstract Background With the aggravation of the aging of the world population, frailty has become one of the common complications in elderly people. Its diagnosis is not objective, the pathogenesis is not clear, and interventions are not sound, thus intensifying the problem. Furthermore, frailty is closely associated with the occurrence and poor prognosis of coronary atherosclerotic heart disease. Moreover, few studies report on the prevalence of frailty in elderly patients with the chronic coronary syndrome (CCS). Objective We aimed to investigate the prevalence of frailty in elderly patients with CCS. We analyzed the correlation between the blood serum levels of interleukin‐6 (IL‐6), albumin (Alb), and 25‐hydroxyvitamin D (25(OH)D) with frailty in elderly patients with CCS. We have also provided recommendations for helping the objective diagnosis as well as proposed new intervention methods in the future. Methods Two hundred eight‐eight inpatients (≥60 years) with the chronic coronary syndrome were recruited at the Department of Geriatrics, the First People's Hospital of Yunnan Province, China. General information and laboratory examination data were collected. The comprehensive geriatric assessment was conducted via an internet‐based platform of the Comprehensive Geriatric Assessment (inpatient version) developed by us, among which frailty was assessed by the Chinese version of Fried Frailty Phenotype, a component of the assessment scale. Results Among the total number of old patients with CCS, 87 (30.2%) had no frailty, 93 (32.3%) had early frailty, and 108 (37.5%) had frailty. According to the multivariate logistic regression analysis, after adjusting for confounding factors, IL‐6 (OR = 1.066, 95% CI 1.012–1.127), Alb (OR = 0.740, 95% CI 0.560–0.978), and 25(OH)D (OR = 0.798, 95% CI 0.670–0.949) were independently associated with frailty in the three groups of models. Conclusion IL‐6 proved to be a risk factor for frailty in elderly patients with CCS, while Alb and 25(OH)D were protective factors, which make the potential targets for predicting and intervening frailty in elderly patients with CCS.

Objective: To compare the safety of conventional transarterial chemoembolization (cTACE) vs drug-eluting bead TACE (DEB-TACE) in very early- and early-stage hepatocellular carcinoma (HCC). Methods: Data of patients with early- and very early-stage HCC treated with cTACE or DEB-TACE were evaluated retrospectively in this study. A total of 40 patients were included, 20 treated with cTACE and 20 with DEB-TACE. The cTACE and DEB-TACE groups were comprised of 80% and 75% males, while there were 20% females in cTACE group and 25% in Deb-TACE group respectively. The mean age of patients in cTACE group was 57.43 ​+ ​5.6 years, while it was 56.4 ​+ ​5.5 years in DEB-TACE group. All patients had liver status of Child–Pugh Class A and a score ≤ 7 in Child-Pugh class type B in very early- (stage 0) or early-phase (stage A) stages according to the Barcelona Clinic Liver Cancer (BCLC) system. Results: The Child-Pugh class degradation in the cTACE group was slightly higher than that in the DEB-TACE group. Serious complications like peritumoral parenchymal ischemia were observed in 4 patients in the cTACE group and 5 in the DEB-TACE group. Localized bile duct dilation was seen in 2 patients in the cTACE group and 6 in the DEB-TACE group.No significant variation in serious complications between the two groups was established in localized bile duct dilatation. Other minor complications noted were liver failure, liver abscess, liver infarction, acute cholecystitis, biliary tree necrosis, and mortality. Further, no substantial variation in tumor response between the groups was reported immediately and 1-year post-procedural assessment. Conversion rate to other treatment modalities such as surgical resection, radiofrequency ablation (RFA), or swap between cTACE and DEB-TACE was substantially higher in the DEB-TACE group (40%) than in the cTACE group (10%) at the 1-year completion period of the study. Conclusion: In terms of tumor response, the DEB-TACE group showed a better response, to some extent, as an initial therapy for HCC in the early stages as compared to the cTACE group, and DEB-TACE also exhibited better clinical efficacy in patients with HCC.

Accurately monitoring and predicting the large-scale dynamic changes of water levels in coastal zones is essential for its protection, restoration and sustainable development. However, there has been a challenge for achieving this goal using a single radar altimeter and retracking technique due to the diversity and complexity of coastal waveforms. To solve this issue, we proposed an approach of estimating water level of the coastal zone in Beibu Gulf, China, by combination of waveform classifications and multiple sub-waveform retrackers. This paper stacked Random Forest (RF), XGBoost and CatBoost algorithms for building an ensemble learning (SEL) model to classify coastal waveforms, and further evaluated the performance of three retracking strategies in refining waveforms using Cryosat-2, SARAL, Sentinel-3 altimeters. We compared the estimation accuracy of the coastal water levels between the single altimeter and synergistic multi-altimeter, and combined Breaks for Additive Season and Trend (BFAST), Mann-Kendall mutation test (MK) with Long Short-Term Memory (LSTM) algorithms to track the historical change process of coastal water levels, and predict its future development trend. This paper found that: (1) The SEL algorithm achieved high-precision classification of different coastal waveforms with an average accuracy of 0.959, which outperformed three single machine learning algorithms. (2) Combination of Threshold Retracker and ALES+ Retracker (TR_ALES+) achieved the better retracking quality with an improvement of correlation coefficient (R, 0.089~0.475) and root mean square error (RMSE, 0.008∼ 0.029 m) when comparing to the Threshold Retracker & Primary Peak COG Retracker and Threshold Retracker & Primary Peak Threshold Retracker. (3) The coastal water levels of Cryosat-2, SARAL, Sentinel-3 and multi-altimeter were in good agreement (R>0.66, RMSE

ObjectiveNonfilter-associated inferior vena cava thrombosis (IVCT) is an under-recognized but severe state of venous thromboembolism. The aims of this study were to investigate risk factors and develop a prediction model based on clinical data and imaging findings to evaluate the probability of IVCT in patients with lower extremity deep vein thrombosis (LEDVT).MethodsA single-center retrospective cohort study was conducted. We analyzed the clinical data and multimodal imaging findings of consecutive patients with confirmed LEDVT between February 2016 and January 2022. The demographics, presentation of LEDVT, laboratory examination, thrombus characteristics, comorbidities and risk factors for LEDVT, and imaging findings were analyzed using an independent t-test, Chi-square test, Fisher's exact test, and regression analysis to determine the univariable and multivariable associations and to establish a predictive model to assess the probability of IVCT.ResultsA total of 267 eligible patients were included, of whom 40 were in the IVCT group and 227 were in the non-IVCT group. The incidence of nonfilter-associated IVCT was 15.0% (40/267). Age < 63.5 years [odds ratio (OR) 2.54; 95% confidence interval (CI), 1.10–5.85, p = 0.029], male sex (OR 2.82; 95% CI, 1.19–6.72, p = 0.019), proximal DVT (OR 8.21; 95% CI, 1.01–66.76, p = 0.049), bilateral DVT (OR 7.30; 95% CI, 3.28–16.21, p < 0.001), and D-dimer >4.72 μg/ml (OR 4.64; 95% CI, 1.80–11.72, p = 0.001) were risk factors for IVCT's occurrence. Then, we established a prediction model based on these risk factors. The diagnostic efficiency [area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.858] for predicting IVCT was superior to that of isolated risk factors, including age < 63.5 years (AUC of ROC curve was 0.624) or D-dimer >4.72 μg/ml (AUC of ROC curve was 0.656).ConclusionAge < 63.5 years, male sex, proximal LEDVT, bilateral LEDVT and D-dimer >4.72 μg/ml were risk factors. The diagnostic efficiency of the predictive model for predicting IVCT was superior to that of a single risk factor alone. It may be used for predicting the probability of nonfilter-associated IVCT in patients with LEDVT.

Fu brick tea (FBT) and its extracts have good lipid-lowering effects and have been used in the treatment of obesity in previous studies. Unfortunately, the therapeutic effect of FBT on non-alcoholic fatty liver disease (NAFLD) has not been thoroughly studied. In this study, we explored the mechanism by which FBT alleviates NAFLD from the perspective of the gut microbiota and liver metabolites. The results showed that FBT could reduce the body weight, liver weight and abdominal fat of NAFLD mice, and improve liver pathological morphology, liver lipid deposition, blood lipids and liver function. Moreover, FBT improved the diversity of the gut microbiota and changed the profile of liver metabolism in NAFLD mice. Further studies showed that FBT could ameliorate the cecum barrier, and regulate the effects of factors related to lipid synthesis in the cecum and liver of NAFLD mice. In conclusion, the present study confirmed that FBT can alleviate high fat induced NAFLD by regulating the homeostasis of the gut microbiota and liver metabolites.

The rapid classification of micro-particles has a vast range of applications in biomedical sciences and technology. In the given study, a prototype has been developed for the rapid detection of particle size using multi-angle dynamic light scattering and a machine learning approach by applying a support vector machine. The device consisted of three major parts: a laser light, an assembly of twelve sensors, and a data acquisition system. The laser light with a wavelength of 660 nm was directed towards the prepared sample. The twelve different photosensors were arranged symmetrically surrounding the testing sample to acquire the scattered light. The position of the photosensor was based on the Mie scattering theory to detect the maximum light scattering. In this study, three different spherical microparticles with sizes of 1, 2, and 4 μm were analyzed for the classification. The real-time light scattering signals were collected from each sample for 30 min. The power spectrum feature was evaluated from the acquired waveforms, and then recursive feature elimination was utilized to filter the features with the highest correlation. The machine learning classifiers were trained using the features with optimum conditions and the classification accuracies were evaluated. The results showed higher classification accuracies of 94.41%, 94.20%, and 96.12% for the particle sizes of 1, 2, and 4 μm, respectively. The given method depicted an overall classification accuracy of 95.38%. The acquired results showed that the developed system can detect microparticles within the range of 1–4 μm, with detection limit of 0.025 mg/ml. Therefore, the current study validated the performance of the device, and the given technique can be further applied in clinical applications for the detection of microbial particles.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers worldwide, with high mortality. However, the molecular regulatory mechanisms of liver cancer, especially transcriptional and post-transcriptional mechanisms, should be further studied. Here we used chromatin and cross-linking immunoprecipitation with high throughput sequencing methods (ChIP-seq and CLIP-seq) to capture the global binding profiles on RNAs and DNAs of Enhancer of zeste homolog 2 (EZH2) and its partner Jumonji And AT-Rich Interaction Domain Containing 2 (JARID2) in liver carcinoma cell lines (HepG2) and normal liver cell line (THLE-2), respectively. We also integrated HCC transcriptome data from the TCGA to analyze the expression pattern of bound genes. We found that EZH2 and JARID2 both showed distinct binding profiles between HepG2 and THLE-2 cells. By binding to the primary RNAs, bound transcripts of EZH2 and JARID2 in HepG2 showed significantly increased transcriptional levels in HCC patients. By performing gene set enrichment analysis (GSEA), the bound transcripts were also highly related to HCC development. We also found EZH2 and JARID2 could specifically bind to several long noncoding RNAs (lncRNAs), including H19. By exploring the DNA binding profile, we detected a dramatically repressed DNA binding ability of EZH2 in HepG2 cells. We also found that the EZH2-bound genes showed slightly increased transcriptional levels in HepG2 cells. Integrating analysis of the RNA and DNA binding profiles suggests EZH2 and JARID2 shift their binding ability from DNA to RNA in HepG2 cells to promote cancer development in HCC. Our study provided a comprehensive and distinct binding profile on RNAs and DNAs of EZH2 and JARID2 in liver cancer cell lines, suggesting their potential novel functional manners to promote HCC development.

Lakes potentially provide sensitive indicators of global climate change, but water pollution seriously affects the lake ecosystem. Therefore, mapping and monitoring water quality of lake has attracted extensive attention from scholars. However, estimating optically active (OAPs) and non-optically water quality parameters (NOAPs) and clarifying their response relationship with hydro-meteorology still face great challenges. To resolve these issues, this paper presents an approach for assessing OAPs (Chlorophyll a (Chla), Total suspended matter (TSM)) and NOAPs (total phosphorus (TP), total nitrogen (TN), ammonia nitrogen (NH4-N), five-day biochemical oxygen demand (BOD5)) in Poyang Lake, the largest freshwater lake in China, by using ensemble learning (SEL), combing leave-one-out validation and machine learning (LOOCV-ML) algorithms with multi-source remote sensing images. We further quantitatively evaluated retrieval accuracy differences between OAPs and NOAPs using multispectral and hyperspectral images. Meanwhile, a novel automatic extraction method was proposed in this paper for mapping water bodies. We systematically explored the response relationship between water quality (OAP and NOAP) and hydro-meteorology. We found that NOAPs achieved higher estimation accuracy than OAPs. The LOOCV-XGBoost and LOOCV-GradientBoost provided higher inversion accuracy of OAP and NOAP than SEL, demonstrating the great potential of combining OHS-2A hyperspectral images with LOOCV-ML to estimate the water quality in inland lakes. We revealed that the estimation accuracy (MRE) of TN and TP was 1.09 %-18.03 % higher than NH4-N and BOD5. Finally, we clarified that water temperature had a significantly negative effect on NH4-N and BOD5 (Projected importance of variables (VIP) > 1, Coefficient 1, Coefficient > 1), further revealing that water temperature, water body area, wind speed, rainfall, mean relative humidity and sunshine hours were important divers of OAPs and NOAPs changes. These results provide a scientific basis for restoration and protection of water quality in lake ecosystems.

Purpose Acute massive pancreaticoduodenal artery (PDA) hemorrhage represents an urgent condition. Here, we report our experience in transcatheter arterial embolization (TAE) using N-butyl-2 cyanoacrylate (NBCA) Glubran® 2 for this condition. Methods A retrospective study of 10 consecutive patients (mean, 55.2 ± 15.9 years; range, 27–74 years) was conducted from April 2015 to April 2021. The data, including baseline characteristics, control of active PDA hemorrhage (the technical and clinical outcomes), volumes of Glubran 2, and related complications, were collected from medical archives. Technical success was defined as complete occlusion of bleeding vessels on the final arteriogram. Clinical success was defined as the sustained resolution of symptoms or signs of PDA hemorrhage without the need for repeat endovascular or surgical treatment after TAE. Safety was evaluated based on the occurrence of complications. Results Glubran 2 was empirically used for six patients (6/10) with PDA hemorrhage without pseudoaneurysm (PSA), and a combination of Glubran 2 and microcoils (n = 13) was used for four patients (4/10) with PSA. The concentration ratios were 1:2–1:4 mixtures of Glubran 2 and ethiodized oil, and the median total volume injected was 1.1 ml (range, 0.7–1.6 ml). Technical success based on 10 episodes of TAEs was 100% (10/10). Early rebleeding did not occur, and repeat TAE was not necessary. Clinical success was 100% (10/10). No nontarget embolization or embolization-related complications occurred. Two patients (2/10) experienced minor complications of postembolization syndrome. During a median follow-up time of 3 months, no recurrent hemorrhage was recorded. Conclusion Urgent TAE with the use of NBCA Glubran 2 plays an important role in controlling massive PDA hemorrhage. It is minimally invasive, effective, relatively safe, and likely to reduce the need for immediate traditional surgery. The condition with PSA may determine the microcoils employed.

BackgroundIron is an essential nutrient element, and iron metabolism is related to many diseases. Ferroptosis is an iron-dependent form of regulated cell death associated with ischemic stroke (IS). Hence, this study intended to discover and validate the possible ferroptosis-related genes involved in IS.Materials and methodsGSE16561, GSE37587, and GSE58294 were retrieved from the GEO database. Using R software, we identified ferroptosis-related differentially expressed genes (DEGs) in IS. Protein-protein interactions (PPIs) and enrichment analyses were conducted. The ROC curve was plotted to explore the diagnostic significance of those identified genes. The consistent clustering method was used to classify the IS samples. The level of immune cell infiltration of different subtypes was evaluated by ssGSEA and CIBERSORT algorithm. Validation was conducted in the test sets GSE37587 and GSE58294.ResultsTwenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls. Enrichment analysis shows that the 21 DEGs are involved in monocarboxylic acid metabolism, iron ion response, and ferroptosis. Moreover, their expression levels were pertinent to the age and gender of IS patients. The ROC analysis demonstrated remarkable diagnostic values of LAMP2, TSC22D3, SLC38A1, and RPL8 for IS. Transcription factors and targeting miRNAs of the 21 DEGs were determined. Vandetanib, FERRIC CITRATE, etc., were confirmed as potential therapeutic drugs for IS. Using 11 hub genes, IS patients were categorized into C1 and C2 subtypes. The two subtypes significantly differed between immune cell infiltration, checkpoints, and HLA genes. The 272 DEGs were identified from two subtypes and their biological functions were explored. Verification was performed in the GSE37587 and GSE58294 datasets.ConclusionOur findings indicate that ferroptosis plays a critical role in the diversity and complexity of the IS immune microenvironment.

The early detection of skin cancer substantially improves the five-year survival rate of patients. It is often difficult to distinguish early malignant tumors from skin images, even by expert dermatologists. Therefore, several classification methods of dermatoscopic images have been proposed, but they have been found to be inadequate or defective for skin cancer detection, and often require a large amount of calculations. This study proposes an improved capsule network called FixCaps for dermoscopic image classification. FixCaps has a larger receptive field than CapsNets by applying a high-performance large-kernel at the bottom convolution layer whose kernel size is as large as $31\,\times \,31$ , in contrast to commonly used $9\,\times \,9$ . The convolutional block attention module was used to reduce the losses of spatial information caused by convolution and pooling. The group convolution was used to avoid model underfitting in the capsule layer. The network can improve the detection accuracy and reduce a great amount of calculations, compared with several existing methods. The experimental results showed that FixCaps is better than IRv2-SA for skin cancer diagnosis, which achieved an accuracy of 96.49% on the HAM10000 dataset.

Whether there is a transition underway, from a warm-dry climate to a warm-wet climate in Northwest China remains a controversial and scientifically significant issue. Will this trend continue in the future? Another hot issue is whether the climate in Northwest China will continue to be warm and humid over the next few decades. In this paper, eight CMIP6 models were employed to investigate temperature and precipitation changes under five principal Shared Socioeconomic Pathway (SSP) scenarios (from 2015 to 2099) to project the future warming and humidification in Northwest China using the SPEI (standardized precipitation evapotranspiration index) method. The results revealed that (1) the simulated temperature and precipitation of eight CMIP6 models were consistent with that of observed data during 1961–2014, which showed an increase of approximately 28.2 mm, while simulated data revealed an increase of approximately 9.4 mm. The annual precipitation gradually decreased from Eastern Inner Mongolia and the Southern Northwest Mongolia region (>700 mm) to the Central Northwest Mongolia region (

In order to get blueberries goes on sale in advance and obtain greater economic benefits, southern blueberries were moved to an intelligent greenhouse with controllable environment for experimental production. The early maturing production control technology of southern blueberry intelligent greenhouse was explored and studied. First, a detailed and comprehensive investigation and summary were conducted on the production factors of blueberry soilless cultivation, such as the production characteristics of various blueberry varieties, the pH and composition of the substrate, the key points of water and fertilizer irrigation, and the scope of the microenvironment climate. Then, the existing Venlo-type greenhouse was deployed for blueberry production, and the geography, climate and internal structural conditions of the greenhouse were briefly described, and the greenhouse blueberry full-cycle control goal was planned. Finally, the production control system was designed and implemented based on the Internet of Things technology, and the overall framework of the software layer, the hardware layer and the cloud were introduced. Based on multi-factor coordinated control model of greenhouse environment, according to the characteristics of blueberry growth environment, a set of blueberry greenhouse multi-factor coordinated control algorithms were proposed and used for environmental regulation. The experimental greenhouse is located in the southeast of Huaqiao Town, Kunshan city, Suzhou city, Jiangsu province. It has been verified that the overall control system has a significant effect, and the first wave of fruits was harvested in early May 2021, making the southern variety of blueberry enter the fruit picking period nearly one month earlier. Compared with the blueberry plants without cold storage, the yields per plant of "Star" "Emerald" "Lanmei No. 1", and "Coast" after cold storage increased by 51.5%, 85.5%, 43.8%, and 94.7%, respectively, and the weight of each fruit was increased 10.9%, 7.2%, 2.6%, and 5.3%, respectively. Experiments proved that the use of multi-factor coordinated control algorithms for regulation can increase the yield and quality of blueberries and achieve significant economic benefits and provide a demonstration for the industrialization of blueberry plants in southern greenhouses to promote early maturity production and management.

Abstract Background Acute limb ischemia (ALI) is an important clinical event threatening both life and the affected limbs, but the optimal treatment for ALI remains undefined. The aim of this study was to compare the safety and effectiveness of thrombectomy approaches via either catheter-based thrombectomy (CBT) or catheter-directed thrombolysis (CDT). Methods A total of 98 patients (mean age 69.7 years, 60 male) who underwent endovascular intervention for ALI from January 2015 to July 2019 were included. Of these, 57 were treated with primary CBT via a large-bore catheter, an AngioJet catheter or Rotarex catheter, and/or underwent low-dose CDT, and 41 were treated with primary CDT. The safety and effectiveness of CBT compared to conventional CDT and other various endovascular techniques were evaluated. Results More Rutherford IIb patients were treated with primary CBT (68.4%) than CDT (26.8%; P .05). Clinical success was estimated to be achieved in 98.2% of patients who underwent CBT, which is similar to the 97.6% estimated in those who underwent primary CDT (P = 1.000), and this finding was similar among the CBT subgroups. Patients who underwent CBT had a higher procedure-related distal embolization rate and economic cost than those who underwent primary CDT (P

Ionizing radiation (IR) is an important treatment for nasopharyngeal carcinoma (NPC) that mainly kills tumor cells by producing large amounts of reactive oxygen species (ROS). Intracellular ROS levels affect the sensitivity of tumor cells to IR. Recently, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-converting enzyme (ACE) have been found to affect the intracellular levels of ROS. Therefore, we performed a health informatics assessment of ACE in the TCGA database. We explored the effect of ACE in NPC cells. We found that either knockdown of ACE or inhibition of ACE by enalaprilat could decrease ROS levels in NPC cells. Furthermore, knockdown of ACE or inhibition of ACE by enalaprilat could reduce IR-induced ROS levels. ACE knockdown or inhibition reduced IR-induced DNA damage and apoptosis. ACE overexpression increased the level of ROS in NPC cells and further increased sensitivity to IR. These findings indicate that ACE influences the effect of IR by regulating the level of ROS in NPC cells.

In this work, we propose a 3D occlusion facial recognition network based on a multi-feature combination threshold (MFCT-3DOFRNet). First, we design and extract the depth information of the 3D face point cloud, the elevation, and the azimuth angle of the normal vector as new 3D facially distinctive features, so as to improve the differentiation between 3D faces. Next, we propose a multi-feature combinatorial threshold that will be embedded at the input of the backbone network to implement the removal of occlusion features in each channel image. To enhance the feature extraction capability of the neural network for missing faces, we also introduce a missing face data generation method that enhances the training samples of the network. Finally, we use a Focal-ArcFace loss function to increase the inter-class decision boundaries and improve network performance during the training process. The experimental results show that the method has excellent recognition performance for unoccluded faces and also effectively improves the performance of 3D occlusion face recognition. The average Top-1 recognition rate of the proposed MFCT-3DOFRNet for the Bosphorus database is 99.52%, including 98.94% for occluded faces and 100% for unoccluded faces. For the UMB-DB dataset, the average Top-1 recognition rate is 95.08%, including 93.41% for occluded faces and 100% for unoccluded faces. These 3D face recognition experiments show that the proposed method essentially meets the requirements of high accuracy and good robustness.

Laminin is an extracellular matrix multidomain trimeric glycoprotein, that has a potential role in tumor progression. Here, we studied the effects of non-small cell lung cancer (NSCLC) cells interaction on laminin and explored the underlying mechanism of laminin associated NSCLC progression. Culture of A549 and NCI-1299 cells on 2D collagen gels (containing laminin) significantly promoted the proliferative and tumorigenic characteristics, as well as cell invasion of tumor cells in vitro. Consistently, comparing the clinical NSCLC tumor tissues, a poor overall survival was observed in patients with high laminin expression. Mechanistically, the expression of integrin α6β4 was required for the pro-tumor effects of laminin. Meanwhile, we showed that the downstream signaling of integrin α6β4, involved the focal adhesion kinase (FAK)/Yes-Associated Protein (YAP)/TAZ signaling pathway. The activation of FAK/YAP/TAZ signaling pathway induced by laminin was validated in tumor tissues from NSCLC patients. Suppression of integrin α6β4/FAK/YAP/TAZ signaling pathway efficiently suppressed the laminin-induced tumor growth, and strengthened the anticancer effects of chemotherapy, describing a novel target for NSCLC treatment.

Mangroves are highly productive wetland ecosystems, located at the interlocking area of tropical and subtropical coastal zones. Accurately mapping the distribution, quality and quantity of species are crucial for mangrove management, protection, and restoration. This study proposed a mangrove species mapping approach by combining recursive feature elimination (RFE) with deep learning (DL) algorithms, and further assess the effectiveness of feature selection for DL (DeeplabV3+ and PSPNet) algorithm to improve classification accuracy under the high dimensional UAV image datasets. We constructed an ensemble learning models (SEL) by stacking five base models (Random Forest, XGBoost, LightGBM, CatBoost, and AdaBoost), and evaluate the classification ability of mangrove species between SEL and RFE-DL algorithms. Comparison of the classifications of mangrove species was to evaluate the accuracy differences between SEL and base models. Results indicated that: (1) RFE algorithm could improve the classification accuracy of DL algorithms. RFE-DL models using the optimal features achieved 94.8% of overall accuracy (OA), which was 0.2%-8.5% higher than only using the original multispectral bands; (2) SEL algorithm produced better classification performance than RFE-DL with a higher 1.6%-12.7% of overall accuracy. Mcnemar's test showed the classifications of mangrove species were significant differences between the three algorithms; (3) the SEL algorithm had a strong and stable ability for classifying mangrove species. The OA of six classification scenarios was from 75.5% to 92.2%, and the highest OA using SEL algorithm was 0.8%-4.2% higher than base models; (4) XGBoost algorithm had the highest importance, while AdaBoost had the lowest importance in the SEL-based classifications.