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Abstract Background Innominate artery aneurysms (IAAs) are rare and may result in rupture, distal arterial embolization, or local compression without timely treatment. Rupture is the most dangerous of these complications. This article reports a case of innominate artery bifurcation pseudoaneurysm. Case presentation The patient was a 45-year-old man who was admitted to the emergency department due to chest discomfort. The computed tomographic angiography (CTA) imaging indicated the presence of a 3.6*2.4 cm saccular aneurysm in the bifurcation of the innominate artery, involving both the right proximal subclavian and common carotid arteries. The patient’s vital signs were normal, there was equal blood pressure in the upper arms and no neurological dysfunction was observed. Gadolinium-enhanced magnetic resonance angiography indicated that the circle of Willis was intact. The treatment involved open surgery combined with endovascular therapy. The external carotid artery was first transposed to the right subclavian artery (RSA) and an 8-mm woven Dacron graft was inserted in the middle. The covered stent graft was then placed in the proximal part of the innominate artery to close the entrance of the aneurysm. Lastly, an occluder was implanted at the origin of the RSA. There were no perioperative or postoperative complications. At 1-year follow-up, no aneurysm was observed on CTA and the right vertebral artery was patent. Conclusions This study indicated that the combined use of endovascular therapy and open repair surgery is an effective strategy to treat innominate artery bifurcation pseudoaneurysm.

Fluid intelligence is an individual's innate ability to cope with complex situations and is gradually reduced across adults aging. The realization of fluid intelligence requires the simultaneous activity of multiple brain regions and depends on the structural connection of distributed brain regions. Uncovering the structural features of brain connections associated with fluid intelligence decline will provide reference for the development of intervention and treatment programs for cognitive decline. Using structural magnetic resonance imaging data of 454 healthy participants (18–87 years) from the Cam-CAN dataset, we constructed structural similarity network for each participant and calculated the node degree. Spearman correlation analysis showed that age was positively correlated with degree centrality in the cingulate cortex, left insula and subcortical regions, while negatively correlated with that in the orbito-frontal cortex, right middle temporal and precentral regions. Partial least squares (PLS) regression showed that the first PLS components explained 32 % (second PLS component: 20 %, pperm < 0.001) of the variance in fluid intelligence. Additionally, the degree centralities of anterior insula, supplementary motor area, prefrontal, orbito-frontal and anterior cingulate cortices, which are critical nodes of the multiple-demand network (MDN), were linked to fluid intelligence. Increased degree centrality in anterior cingulate cortex and left insula partially mediated age-related decline in fluid intelligence. Collectively, these findings suggest that the structural stability of MDN might contribute to the maintenance of fluid intelligence.

Abstract The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S. In this study, we examined different clinically relevant anthracycline drugs for a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. The different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical studies, as it potently kills cancer cells, lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Retrospective analysis of aclarubicin used as second-line treatment for relapsed/refractory AML patients showed survival effects similar to its use in first line, leading to a notable 23% increase in 5-year overall survival compared to other intensive chemotherapies. Considering individual anthracyclines as distinct entities unveils new treatment options, such as the identification of aclarubicin, which significantly improves the survival outcomes of AML patients while mitigating the treatment-limiting side-effects. Building upon these findings, an international multicenter Phase III prospective study is prepared, to integrate aclarubicin into the treatment of relapsed/refractory AML patients.

Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8+ T cells and the prognosis of AML patients. To develop a CD8+ T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8+ T cells in bulk RNA-seq and found it significantly correlated with observed single-cell RNA sequencing data and the proportions of CD8+ T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8+ THigh and CD8+ TLow groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8+ T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML.

Abstract Objectives Emerging evidence suggests a potential relationship between body composition and short-term prognosis of ulcerative colitis (UC). Early and accurate assessment of rapid remission based on conventional therapy via abdominal computed tomography (CT) images has rarely been investigated. This study aimed to build a prediction model using CT-based body composition parameters for UC risk stratification. Methods In total, 138 patients with abdominal CT images were enrolled. Eleven quantitative parameters related to body composition involving skeletal muscle mass, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured and calculated using a semi-automated segmentation method. A prediction model was established with significant parameters using a multivariable logistic regression. The receiver operating characteristic (ROC) curve was plotted to evaluate prediction performance. Subgroup analyses were implemented to evaluate the diagnostic efficiency of the prediction model between different disease locations, centers, and CT scanners. The Delong test was used for statistical comparison of ROC curves. Results VAT density, SAT density, gender, and visceral obesity were significantly statistically different between remission and invalidation groups (all p 0.05). Conclusions The predicting model constructed with CT-based body composition parameters is a potential non-invasive approach for short-term prognosis identification and risk stratification. Additionally, VAT density was an independent predictor for escalating therapeutic regimens in UC cohorts. Critical relevance statement The CT images were used for evaluating body composition and risk stratification of ulcerative colitis patients, and a potential non-invasive prediction model was constructed to identify non-responders with conventional therapy for making therapeutic regimens timely and accurately. Key points • CT-based prediction models help divide patients into invalidation and remission groups in UC. • Results of the subgroup analysis confirmed the stability of the prediction model with a high AUC (all > 0.820). • The visceral adipose tissue density was an independent predictor of bad short-term prognosis in UC. Graphical Abstract

Multi-category text classification aims to assign labels under multiple categories to each sample in the dataset. However, most researchers overlook the relationship between labels and do not effectively incorporate text and label information. To address these problems, we propose a label embedding joint cross-attention (LEJCA) model for multi-category text classification using label relations and text information. Specifically, we first input the characters of the text into the Pre-training Language Model to obtain the representation of the text. In addition, a label embedding method based on graph representation is proposed to realize multi-dimensional mining and quantitative description of label relations. Finally, a joint cross-attention (JCA) model is proposed to integrate text and label embedding representations. Experimental results on our own constructed dataset E-government document show that LEJCA ’s micro-average F1 score is improved by $9.7~{\%}$ compared to the baseline’s best result.

Improvement of integrated battlefield situational awareness in complex environments involving dynamic factors such as restricted communications and electromagnetic interference (EMI) has become a contentious research problem. In certain mission environments, due to the impact of many interference sources on real-time communication or mission requirements such as the need to implement communication regulations, the mission stages are represented as a dynamic combination of several communication-available and communication-unavailable stages. Furthermore, the data interaction between unmanned aerial vehicles (UAVs) can only be performed in specific communication-available stages. Traditional cooperative search algorithms cannot handle such situations well. To solve this problem, this study constructed a distributed model predictive control (DMPC) architecture for a collaborative control of UAVs and used the Voronoi diagram generation method to re-plan the search areas of all UAVs in real time to avoid repetition of search areas and UAV collisions while improving the search efficiency and safety factor. An attention mechanism ant-colony optimization (AACO) algorithm is proposed for UAV search-control decision planning. The search strategy is adaptively updated by introducing an attention mechanism for regular instruction information, a priori information, and emergent information of the mission to satisfy different search expectations to the maximum extent. Simulation results show that the proposed algorithm achieves better search performance than traditional algorithms in restricted communication constraint scenarios.

Introduction: The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance. Methods: A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction. Results: Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively). Conclusion: MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders.

Abstract Immunotherapy has emerged as a promising modality for addressing advanced or conventionally drug-resistant malignancies. When it comes to lung adenocarcinoma (LUAD), T cells have demonstrated significant influence on both antitumor activity and the tumor microenvironment. However, their specific contributions remain largely unexplored. This investigation aimed to delineate molecular subtypes and prognostic indicators founded on T cell marker genes, thereby shedding light on the significance of T cells in LUAD prognosis and precision treatment. The cellular phenotypes were identified by scrutinizing the single-cell data obtained from the GEO repository. Subsequently, T cell marker genes derived from single-cell sequencing analyses were integrated with differentially expressed genes from the TCGA repository to pinpoint T cell-associated genes. Utilizing Cox analysis, molecular subtypes and prognostic signatures were established and subsequently verified using the GEO dataset. The ensuing molecular and immunological distinctions, along with therapy sensitivity between the two sub-cohorts, were examined via the ESTIMATE, CIBERSORT, and ssGSEA methodologies. Compartmentalization, somatic mutation, nomogram development, chemotherapy sensitivity prediction, and potential drug prediction analyses were also conducted according to the risk signature. Additionally, real-time qPCR and the HPA database corroborated the mRNA and protein expression patterns of signature genes in LUAD tissues. In summary, this research yielded an innovative T cell marker gene-based signature with remarkable potential to prognosis and anticipate immunotherapeutic outcomes in LUAD patients.

Background: Benign prostatic hyperplasia (BPH) is prevalent among the aging male population and often presents with distressing lower urinary tract symptoms. There is emerging evidence that commercial oral poly-herbal traditional Chinese medicine (TCM) formulation combined with Western medicine (WM) may offer enhanced therapeutic effects compared to WM alone in BPH treatment. Nevertheless, determining the optimal formulations for BPH remains controversial. We aimed to employ a network meta-analysis to compare and assess differences among commonly used and recommended poly-herbal TCM formulations outlined in the Chinese guidelines for BPH treatment, providing clinical medication recommendations and guidance.Methods: We extensively searched for RCTs of BPH patients that had oral poly-herbal TCM formulations and WM treatment, covering both English and Chinese databases up to 31 October 2023. The quality of the included studies was evaluated using the Cochrane risk-of-bias tool Version 2 (ROB2). A Bayesian network meta-analysis was performed to assess the effectiveness of various formulations, followed by sensitivity and subgroup analyses.Results: Our meta-analysis included 107 RCTs involving 11,037 patients across 16 oral poly-herbal TCM formulations. The quality of the selected studies was assessed as “Some concerns”. Most formulations combined with WM demonstrated superior therapeutic efficacy compared to WM alone. For clinical effective rate, Jingui Shenqi pill (JGSQ) + WM had the highest-ranking probability (87.38%). Concerning International Prostate Symptom Score (IPSS) and maximum flow rate of urine, Guizhi Fuling capsule (GZFL) + WM was most effective (91.10% and 98.55%). Regarding the quality of life score and postvoid residual urine, Pulean tablet (PLA) + WM ranked first (86.71% and 91.81%). In controlling prostate volume, Huange capsule (HE) + WM demonstrated the highest efficacy (95.65%). Additionally, among the interventions, Lingze (LZ) + WM capsule exhibited the lowest incidence of adverse drug reactions (2.32%).Conclusion: Combining oral poly-herbal TCM formulations with WM may provide greater therapeutic benefits in BPH treatment compared to WM alone. JGSQ, GZFL, PLA, and HE emerged as promising treatment options. However, further rigorous empirical studies are essential to substantiate these findings.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459651, CRD 42023459651.

Summary: Background: The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value in bladder cancer (BCa) is unclear. Methods: In this multicentre, retrospective study, we included 830 patients with BCa from six independent cohorts. Differences in overall survival (OS) and cancer-specific survival (CSS) were investigated between high-tumour stroma ratio (TSR) and low-TSR groups. Multi-omics analyses, including RNA sequencing, immunohistochemistry, and single-cell RNA sequencing, were performed to study stroma-immune interactions. TSR prediction models were developed based on pelvic CT scans, and the best performing model was selected based on receiver operator characteristic analysis. Findings: Compared to low-TSR tumours, high-TSR tumours were significantly associated with worse OS (HR = 1.193, 95% CI: 1.046–1.361, P = 0.008) and CSS (HR = 1.337, 95% CI: 1.139–1.569, P

Summary: Background: The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods: In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings: In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64–73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953–0.998) to 0.992 (0.982–1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908–1.000]) surpassed that of two junior pathologists (0.862 [0.746–0.939], P = 0.023; 0.879 [0.767–0.950], P = 0.041) by 10–12% and showed no difference to that of two senior pathologists (both 0.983 [0.908–1.000], both P > 0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists’ slide reviewing time (−31%, P

Summary: Background: Urine cytology is an important non-invasive examination for urothelial carcinoma (UC) diagnosis and follow-up. We aimed to explore whether artificial intelligence (AI) can enhance the sensitivity of urine cytology and help avoid unnecessary endoscopy. Methods: In this multicentre diagnostic study, consecutive patients who underwent liquid-based urine cytology examinations at four hospitals in China were included for model development and validation. Patients who declined surgery and lacked associated histopathology results, those diagnosed with rare subtype tumours of the urinary tract, or had low-quality images were excluded from the study. All liquid-based cytology slides were scanned into whole-slide images (WSIs) at 40 × magnification and the WSI-labels were derived from the corresponding histopathology results. The Precision Urine Cytology AI Solution (PUCAS) was composed of three distinct stages (patch extraction, features extraction, and classification diagnosis) and was trained to identify important WSI features associated with UC diagnosis. The diagnostic sensitivity was mainly used to validate the performance of PUCAS in retrospective and prospective validation cohorts. This study is registered with the ChiCTR, ChiCTR2300073192. Findings: Between January 1, 2018 and October 31, 2022, 2641 patients were retrospectively recruited in the training cohort, and 2335 in retrospective validation cohorts; 400 eligible patients were enrolled in the prospective validation cohort between July 7, 2023 and September 15, 2023. The sensitivity of PUCAS ranged from 0.922 (95% CI: 0.811–0.978) to 1.000 (0.782–1.000) in retrospective validation cohorts, and was 0.896 (0.837–0.939) in prospective validation cohort. The PUCAS model also exhibited a good performance in detecting malignancy within atypical urothelial cells cases, with a sensitivity of over 0.84. In the recurrence detection scenario, PUCAS could reduce 57.5% of endoscopy use with a negative predictive value of 96.4%. Interpretation: PUCAS may help to improve the sensitivity of urine cytology, reduce misdiagnoses of UC, avoid unnecessary endoscopy, and reduce the clinical burden in resource-limited areas. The further validation in other countries is needed. Funding: National Natural Science Foundation of China; Key Program of the National Natural Science Foundation of China; the National Science Foundation for Distinguished Young Scholars; the Science and Technology Planning Project of Guangdong Province; the National Key Research and Development Programme of China; Guangdong Provincial Clinical Research Centre for Urological Diseases.

A pH-responsive colorimetric method based on dual-enzyme catalysis for rapid and facile detection and quantification of nanoPET at environment-dependent concentration is proposed. The nanoPET was hydrolyzed by the synergistic catalysis of cutinase and lipase to terephthalic acid which can be sensitive detected using bromocresol purple as the indicator. The color changed from purple to bright yellow as the nanoPET detection concentration increased from 0 mg/mL to 2 mg/mL which can be detected by UV–Vis. This naked-eye method has a high sensitivity for nanoPET detection with the visual detection cutoff of 31.00 μg/mL, and has a good linearity in the range of 0 ∼ 1 mg/mL with LOD of 22.84 μg/mL. The reliability of this method is verified in the detection of nanoPET in lake water and beer samples, with an average recovery of 87.1 %. The as-developed dual-enzyme colorimetric chemosensor holds promising potential as a robust and effective platform for the sensitive detection of nanoPET.

Abstract At present, medical image classification algorithm plays an important role in clinical diagnosis. However, due to the scarcity of data labels, small sample size, uneven distribution, and poor domain generalization, many algorithms still have limitations. Therefore, a deep learning training network for disease classification and recognition of multimodal few‐shot medical images are proposed, trying to solve the above problems and limitations. The network is based on the idea of meta‐learning for training. Specifically, the technology of transfer learning and few‐shot learning are used. In the process of building and improving the network structure, the multi‐source domain generalization method, which performs well in the field of person re‐identification, is combined. Finally, the applicability and effectiveness of the model are verified by using Grad‐CAM tool. The experiments show that the accuracy of classification and recognition of the model is better than the advanced model in this field. The concerned areas of model classification are similar or the same as the manually labelled areas. It is of far‐reaching significance to improve the efficiency of future clinical auxiliary diagnosis and patient diversion, as well as to promote the development of the Wise Information Technology of Med in the future.

Summary: Kinesin 1 (KIF5) is one major type of motor protein in neurons, but its members’ function in the intact brain remains less studied. Using in vivo two-photon imaging, we find that conditional knockout of Kif5b (KIF5B cKO) in CaMKIIα-Cre-expressing neurons shows heightened turnover and lower stability of dendritic spines in layer 2/3 pyramidal neurons with reduced spine postsynaptic density protein 95 acquisition in the mouse cortex. Furthermore, the RNA-binding protein fragile X mental retardation protein (FMRP) is translocated to the proximity of newly formed spines several hours before the spine formation events in vivo in control mice, but this preceding transport of FMRP is abolished in KIF5B cKO mice. We further find that FMRP is localized closer to newly formed spines after fear extinction, but this learning-dependent localization is disrupted in KIF5B cKO mice. Our findings provide the crucial in vivo evidence that KIF5B is involved in the dendritic targeting of synaptic proteins that underlies dendritic spine plasticity.

Objective Electronic mental health interventions are effective but not well promoted currently among older adults. This study sought to systematically review and summarize the barriers and facilitators of accepting and implementing electronic mental health interventions among older adults. Methods We comprehensively retrieved six electronic databases from January 2012 to September 2022: PubMed, Web of Science, Embase, Scopus, PsycINFO, and CINAHL. The JBI-QARI was used to assess the quality of the research methodology of each publication. Eligible studies underwent data coding and synthesis aligned to inductive and deductive methods. The Consolidated Framework for Implementation Research 2.0 was used as a deductive framework to guide a more structured analysis. Results The systematic review screened 4309 articles, 17 of which were included (eight with mixed methods and nine with qualitative methods). We identified and extracted the barriers and facilitators of accepting and implementing electronic mental health interventions among older adults: (1) innovation: technology challenges, optimized functions, and contents, security and privacy; (2) outer setting: community engagement and partnerships, financing; (3) inner setting: leadership engagement, available resources, incompatibility, intergenerational support, training and guidance; (4) individuals: perceptions, capability, motivation of older adults and healthcare providers; and (5) implementation process: recruit, external assistance, and team. Conclusion These findings are critical to optimizing, promoting, and expanding electronic mental health interventions among older adults. The systematic review also provides a reference for better evidence-based implementation strategies in the future.

Six new polyketides, which includes three new lactones (talarotones A–C) (1–3), one new polyketide (talarotide A) (4), two new polyenes (talaroyenes A, B) (5, 6), together with one new meroterpenoid (talaropenoid A) (7) and 13 known compounds (8–20) were isolated from the mangrove-derived fungus Talaromyces flavus TGGP35. The structure and configuration of the compounds 1–7 were elucidated from the data obtained from HR-ESI-MS, IR, 1D/2D NMR spectroscopy, Mo2 (OAc)4-induced electronic circular dichroism (ECD), CD spectroscopy, and modified Mosher's method. Compounds 5 and 20 displayed antioxidant activity with IC50 values of 0.40 and 1.36 mM, respectively. Compounds 3, 6, 11, 16, and 17 displayed cytotoxic activity against human cancer cells Hela, A549, and had IC50 values ranging from 28.89 to 62.23 μM. Compounds 7, 10–12, and 14–18 exhibited moderate or potent anti-insect activity against newly hatched larvae of Helicoverpa armigera Hubner, with IC50 values in the range 50–200 μg/mL. Compound 18 showed antibacterial activity against Ralstonia solanacearum with the MIC value of 50 μg/mL.

Background The goal of this study was to evaluate the global burden of malignant skin melanoma (MSM) from 1990 to 2019 using MSM-related data from the Global Burden of Disease study. Methods The incidences’ relationships with the social-demographic index (SDI) and human developmental index (HDI) were investigated. To determine significant changes in incidence trends, the joinpoint regression model was used. To demonstrate trends in MSM mortality rates, an Age-Period-Cohort framework was conducted. For the projection of new cases and the age-standardized incidence rate (ASR) of MSM incidence to 2034, the Nordpred method was used. Results In 2019, the ASR incidence per 100, 000 people for MSM was 3.6 (95% UI, 2.6–4.2). MSM prevalence increased in most countries between 1990 and 2019 (average annual percentage change >0). HDI and annual percentage change (APC) (ρ = .63, P < .001), as well as SDI and ASR, had a positive correlation. The total MSM mortality rate declined globally, with an APC of −.61%. Likewise, the mortality rate for the age group of people with ages

Background: This investigation studied the clinical features and outcomes of synovial sarcoma (SS) patients from a single institution. Methods: A retrospective clinicopathologic study was conducted on 129 postoperative SS patients during 2003–2018. Kaplan-Meier curves and Cox proportional hazards regression (Cox) models were performed to determine the parameters associated with recurrence-free survival (RFS), metastasis-free survival (MFS), and cancer-specific survival (CSS) via univariate and multivariate analysis. The impact of unplanned excision (UE) and residual tumor in re-excision specimens was evaluated. Results: The 3-year RFS, MFS and 5-year CSS were 72 %, 70 %, and 76 %, respectively. Independent factors associated with significantly inferior survival included older age, UE without re-excision, UE with residual tumors, high grade, and deep tumor for RFS, trunk-related tumor, UE without re-excision, UE with residual tumors, and deep tumor for MFS, UE with residual tumors, high grade, and deep tumor for CSS. Re-excision after UE was significantly associated with better RFS (P

Objective: To analyze the image performance of colon innervation defect with multilayer spiral CT (MSCT) and clinical manifestations, summarize its image characteristics and make correct diagnosis. Methods: The clinical features of colonic innervations deficiency present with prolonged constipation and incomplete ileus. MSCT imaging data using GE gem energy spectrum, CT 750 HD, and Philips MSCT. 1 mm layer thickness, 1 mm layer spacing, tube voltage, 120 kV, automatic tube current from the diaphragm to the bilateral pubic joint. Scan in the natural state of the intestine (No bowel preparation, no cleansing enema and bowel cleansing), after scanning, conduct MPR 3D reconstruction at the CT workstation, and the reconstructed data were archived and analyzed in the PACS system. Clarify the intestinal location of the diseased segment, measure intestinal wall thickness of dilated segment and narrow segment respectively; measure intestinal tube length of diseased segment (narrow segment); observe intestinal peristalsis with multiple-stage MSCT; and observe intestinal blood transport through enhancement. Results: The clinical features of colon innervations defect was constipation and incomplete ileus. In this study group, there were 5 adult patients with colon innervations defect, and the lesion site was located in the spleen and descending colon respectively, among which the diseased segment was located in 3 cases and the spleen was located in 2 cases of colon; MSCT shows relative narrowing of the colon and expansion of the proximal colon; The intestinal wall thickness was normal in the diseased area, and the intestinal wall thickness of the dilated colon section was normal or somewhat thickened, and the thickened intestinal wall in this group is less than 0.9 cm; The intestinal length of the diseased segment in this group was somewhere between 4.3~8.6 cm. The MSCT enhancement scan of mesangic vessels and mesangial density showed no abnormal changes, and no abnormal enhancement of the colon wall in the diseased section, suggesting normal blood supply; MSCT enhanced scan showed rigidity and no peristalsis in the diseased segment, suggesting loss of peristaltic function in the diseased segment. Conclusion: Colonic innervations defect has imaging findings of characteristic post dilating stenosis and clinical features of prolonged constipation and incomplete obstruction in adults, The MSCT combined with clinical data was able to indicate the diagnosis of colonic innervations defect before surgery.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound 25c exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, 25c exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of 25c as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.

Abstract Background Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with high incidence in China. The molecular mechanisms of vasculogenic mimicry (VM) and angiogenesis are not fully elucidated in NPC. More specially, it has seldomly been reported that Epstein–Barr virus‐encoded miRNA can regulate VM and angiogenesis in NPC. The aim of this study was to investigate the function and molecular mechanism of a targeting exosome system (iRGD‐exo‐antagomiR) against VM and angiogenesis in NPC, and to provide new approaches for improving the comprehensive treatment of NPC. Methods Exosomes were isolated by differential ultracentrifugation. Dynamic light scattering, transmission electron microscopy and western blotting were performed to characterize the exosomes. The 3D‐Culture assay, tube formation assay, chicken chorioallantoic membrane assay, Matrigel plug assay, mouse xenograft tumor modeling and immunohistochemical staining were applied to evaluate the anti‐VM and anti‐angiogenic effects of the targeting exosome system in vitro and in vivo. Western blot was performed to detect the changes of downstream regulated networks following interference and recovery of the target gene. Results In vitro or in vivo treatment with iRGD‐tagged exosome containing antagomiR‐BART1‐5p specifically suppressed VM and angiogenesis in NPC. EBV‐miR‐BART1‐5p promoted VM and angiogenesis in vitro and in vivo by regulating VEGF, PI3K, Akt, mTOR and HIF1‐α in a Spry2‐dependent manner. Conclusions Our findings demonstrated that targeting exosomes enveloped EBV‐miR‐BART1‐5p‐antagomiRs in a Spry2‐dependent manner for NPC therapy through both anti‐VM and anti‐angiogenesis in vitro and in vivo.

BackgroundHearing loss can exacerbate cognitive decline; therefore, exploring the mechanisms through which hearing loss affects cognitive function is crucial. The current study aimed to investigate the impact of hearing loss on cognitive function and the mediating role played by self-rated health and depressive anxiety symptoms.MethodsUsing stratified whole-group random sampling, the study employed a cross-sectional design and included 624 participants aged ≥65 years from three communities in Urumqi, China. Cognitive function was assessed using the Mini-Mental State Examination. Hearing function and self-rated health were determined by self-report. The 15-item Geriatric Depression Scale and the 7-item Generalized Anxiety Disorder Scale were used to assess depressive anxiety symptoms. Serial mediation analysis was performed using AMOS 26.0.ResultsHearing loss can not only negatively affect cognitive function in older adults directly (direct effect = −0.106; SE = 0.045; 95% confidence interval (CI): −0.201 to −0.016), but also indirectly affect the relationship between hearing loss and cognitive function through self-rated health and depressive anxiety symptoms. The results of the serial mediation analysis showed that the total indirect effect of self-rated health and depressive anxiety symptoms was −0.115 (95% CI: −0.168 to −0.070), and the total effect of the model was −0.221 (95% CI: −0.307 to −0.132), with the total indirect effect accounting for 52.04% of the total effect of the model.ConclusionOur study discovered that there is a partial mediation of the relationship between hearing loss and cognitive function by self-rated health and depressive anxiety symptoms. It is suggested that by enhancing self-rated health and ensuring good mental health, the decline in cognitive function among older adults with hearing loss can be delayed.

BackgroundMiddle-aged and older adults frequently experience hearing loss and a decline in cognitive function. Although an association between hearing difficulty and cognitive function has been demonstrated, its temporal sequence remains unclear. Therefore, we investigated whether there are bidirectional relationships between hearing difficulty and cognitive function and explored the mediating role of depressive symptoms in this relationship.MethodWe used the cross-lagged panel model and the random-intercept cross-lagged panel model to look for any possible two-way link between self-reported hearing difficulty and cognitive function. To investigate depressive symptoms’ role in this association, a mediation analysis was conducted. The sample was made up of 4,363 adults aged 45 and above from the China Health and Retirement Longitudinal Study (CHARLS; 2011–2018; 44.83% were women; mean age was 56.16 years). One question was used to determine whether someone had a hearing impairment. The tests of cognitive function included episodic memory and intelligence. The Center for Epidemiologic Studies Depression Scale, which consists of 10 items, was used to measure depressive symptoms.ResultsA bidirectional association between hearing and cognition was observed, with cognition predominating (Wald χ2 (1) = 7.241, p

Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease mainly involving the colon and rectum, which features recurrent mucosal inflammation. The excessive production of reactive oxygen species (ROS) is a trigger for pathological changes such as cell apoptosis and disordered immune microenvironments, which are crucial for the progression of UC and can be a promising therapeutic target. Nowadays, the development of targeted therapeutic strategies for UC is still in its infancy. Thus, developing effective therapies based on ROS scavenging and elucidating their molecular pathways are urgently needed. Herein, a biomimetic nanoformulation (Pd@M) with cubic palladium (Pd) as the core and macrophage‐derived extracellular vesicles (MEVs) as the shell is synthesized for the treatment of UC. These Pd@M nanoformulations exhibit multienzyme‐like activities for effective ROS scavenging, excellent targeting ability as well as good biocompatibility. It is verified that Pd@M can regulate the polarization state of macrophages by inhibiting glycolysis, and decrease neutrophil infiltration and recruitment. In this way, the colonic inflammatory and immune microenvironment is remodeled, and apoptosis is prevented, ultimately improving colonic mucosal barrier function and alleviating colitis in the mouse model. This finding provides a promising alternative option for the treatment of UC patients.

Conventional polyvinyl alcohol (PVA) cementitious composites are susceptible to macroscopic cracking when subjected to reduced compressive strength, diminished toughness, tensile impact and other external loads. In order to address these issues, this study investigates the mechanism of the modifier's influence by modifying PVA fibers with a silane coupling agent (KH560) through experimental studies and molecular dynamics simulations for multiscale computational analyses. Macro test results showed that the mechanical properties of PVA fiber concrete were significantly improved after silane coupling agent modified PVA fiber. The microscopic test results showed that the SCA-modified polymer film acted as a bridging ligament in the interfacial transition zone, effectively prevented crack extension, and enhanced the interfacial adhesion between the organic components of the PVA fibers and the cement matrix. Nanoscale molecular dynamics simulations showed that the hydrated calcium silicate exhibited a stable skeletal structure, while the introduction of SCA expanded the hydrogen bonding interactions at the interface, thus enhancing its stability.

Abstract This paper concentrates on robust deadlock control problems for an automated manufacturing system with uncontrollable, unobservable events and resource failures, which is modeled by a subclass of Petri nets. A recovery subnet is added to the holder of each unreliable resource to model resource failure and recovery. In order to prevent a strict minimal siphon in a Petri net model from being emptied, an extended constraint set is constructed based on the complementary set of a strict minimal siphon to obtain a robust liveness constraint. Due to the uncontrollability and unobservability of the transitions, an automated manufacturing system cannot enforce inadmissible robust liveness constraints. It is necessary to decide the admissibility of robust liveness constraints and transform the inadmissible constraints into admissible ones. To this end, a monitor is designed for each admissible robust liveness constraint such that it can be enforced. Finally, an iterative algorithm is developed to perform the above steps and a robust liveness controlled system is obtained. The feasibility of the control strategy is demonstrated by examples.

Abstract To provide evidence-based medicine references for formulating prevention and control policies in plateau areas, we explore the characteristics of anemia patients in Tibet (the plateau areas of China), especially those located at an altitude above 4500 m. We collected clinical data from 379 Tibetan anemia patients over the age of 18 years. We found those female patients accounted for the majority of Tibetan anemia patients. Almost half of the anemia patients aged from 28 to 47 years. The percentage of severe anemia and extremely severe anemia was 45.4% and 2.4%, respectively. 88.7% of patients are engaged in agriculture and animal husbandry, and 81.5% of patients just graduated from primary school or below. The most common causes of anemia were nutritional anemia, especially iron-deficiency anemia. At high-altitude localities, folic acid-deficiency anemia needs more attention. Overall, this study showed that altitude influences the incidence, severity, and cause of anemia. Peasants and herdsmen, low education levels, young and middle-aged women, and nutrition status should be paid attention to in future anemia control.

Highly accurate data on urban and rural settlement (URS) are essential for urban planning and decision-making in response to climate and environmental changes. This study developed an optimal random forest classification model for URSs based on spectral–topographic–radar polarization features using Landsat 8, NASA DEM, and Sentinel-1 SAR as the remote-sensing data sources. An optimal urban and rural settlement boundary (URSB) extraction technique based on morphological and pixel-level statistical methods was established to link discontinuous URSs and improve the accuracy of URSB extraction. An optimal random forest classification model for URSs was developed, as well as a technique to optimize URSB, using the Google Earth Engine (GEE) platform. The URSB of Xining, China, in 2020 was then extracted at a spatial resolution of 30 m, achieving an overall accuracy and Kappa coefficient of 96.21% and 0.92, respectively. Compared to using a single spectral feature, these corresponding metrics improved by 16.21% and 0.35, respectively. This research also demonstrated that the newly constructed Blue Roof Index (BRI), with enhanced blue roof features, is highly indicative of URSs and that the URSB was best extracted when the window size of the structural elements was 13 × 13. These results can be used to provide technical support for obtaining highly accurate information on URSs.

The calculation of a cockpit’s transient thermal load is important for determining the capacity of the cockpit environmental control system, ensuring the safety of electronic equipment and increasing the health and comfort of cockpit occupants. According to the structural parameters of the cockpit of a sightseeing airship, a physical model is established. The turbulence model and calculation method are selected and verified. The transient thermal load within full flight envelope, the cockpit thermal loads at different times of the day, and the cockpit thermal loads under different free-flow velocities are obtained based on the Computational Fluid Dynamics (CFD) method. The cockpit transient thermal loads during different seasons are also obtained. The results show that solar radiation has a great influence on the cockpit transient thermal load. As the flight altitude increases, the thermal load decreases from 8.8 kW (H = 0 m) to 4.7 kW (H = 3000 m). With the change in the solar radiation intensity and solar radiation angle, the thermal load increases considerably, from 2.2 kW (8:00 a.m.) to 5.4 kW (12:00 a.m.). The influence of the free-flow velocity is not very obvious at an altitude of 3000 m, as discussed in this study. The influence of seasons is significant. Finally, the influence of the solar absorptivity and infrared emissivity of the cockpit surface material are studied, and the temperature distribution on the cockpit’s surface is determined.

Invasive cardiac lipoma is a rare type of primary cardiac tumor that is composed of adipose tissue but infiltrating the adjacent structures. It is a benign tumor that can cause significant morbidity and mortality due to its size and location within the heart. We describe a giant invasive intracardiac lipoma across atrial wall extending to the ascending aorta and the superior vena cava. This review will provide an overview of invasive cardiac lipoma, including its clinical presentation, diagnosis, and management.

Abstract Background Carbon monoxide (CO) is an important signaling molecule participating in multiple biological functions. Previous studies have confirmed the valuable roles of CO in cancer therapies. If the CO concentration and distribution can be controlled in tumors, new cancer therapeutic strategy may be developed to benefit the patient survival. Results In this study, a UiO-67 type metal–organic framework (MOF) nanoplatform was produced with cobalt and ruthenium ions incorporated into its structure (Co/Ru-UiO-67). Co/Ru-UiO-67 had a size range of 70–90 nm and maintained the porous structure, with cobalt and ruthenium distributed uniformly inside. Co/Ru-UiO-67 was able to catalyze carbon dioxide into CO upon light irradiation in an efficient manner with a catalysis speed of 5.6 nmol/min per 1 mg Co/Ru-UiO-67. Due to abnormal metabolic properties of tumor cells, tumor microenvironment usually contains abundant amount of CO2. Co/Ru-UiO-67 can transform tumor CO2 into CO at both cellular level and living tissues, which consequently interacts with relevant signaling pathways (e.g. Notch-1, MMPs etc.) to adjust tumor microenvironment. With proper PEGylation (pyrene-polyacrylic acid-polyethylene glycol, Py-PAA-PEG) and attachment of a tumor-homing peptide (F3), functionalized Co/Ru-UiO-67 could accumulate strongly in triple-negative MDA-MB-231 breast tumors, witnessed by positron emission tomography (PET) imaging after the addition of radioactive zirconium-89 (89Zr) into Co-UiO-67. When applied in vivo, Co/Ru-UiO-67 could alter the local hypoxic condition of MDA-MB-231 tumors, and work synergistically with tirapazamine (TPZ). Conclusion This nanoscale UiO-67 MOF platform can further our understanding of CO functions while produce CO in a controllable manner during cancer therapeutic administration. Graphical Abstract

Abstract Objective To investigate the influence of diverse bone cement distribution patterns in patients with metastatic vertebral lesions after bilateral percutaneous kyphoplasty (PKP). Methods Fifty-nine patients with single-level metastatic vertebral lesions who received bilateral PKP were retrospectively reviewed. According to the different bone cement distribution patterns, patients were divided into confluent (n = 35, CF) and separated (n = 24, SP) groups. Indicators including visual analogue scale (VAS), Oswestry Disability Index (ODI), vertebral body height (VBH) variation, quality of life (QoL), and related complications were reviewed and compared between the two groups. Results No statistically significant differences were observed between the two groups in age, sex, types of lesions, locations of lesions, posterior vertebral body and/or pedicle involvement, percentage of vertebral invasion, procedure duration or cement volume (p > 0.05). There was significant improvement in VAS, ODI, VBH and QoL at any follow-up examination (p 0.05). No statistically significant differences were observed between the two groups in terms of ODI, VBH or QoL (p > 0.05). There was no statistically significant difference in the incidence of complications between the two groups (p > 0.05). Conclusions More rapid pain relief was achieved with confluent rather than separated bone cement distribution patterns in PKP for patients with metastatic vertebral lesions.

Abstract Background Increasing evidence indicates that myocardial oxidative injury plays a crucial role in the pathophysiology of cardiac hypertrophy (CH) and heart failure (HF). The active component of rhubarb, rhein exerts significant actions on oxidative stress and inflammation. Nonetheless, its role in cardiac remodeling remains unclear. Methods CH was induced by angiotensin II (Ang II, 1.4 mg/kg/d for 4 weeks) in male C57BL/6 J mice. Then, rhein (50 and 100 mg/kg) was injected intraperitoneally for 28 days. CH, fibrosis, oxidative stress, and cardiac function in the mice were examined. In vitro, neonatal rat cardiomyocytes (CMs) and cardiac fibroblasts (CFs) pre-treated with rhein (5 and 25 μM) were challenged with Ang II. We performed RNA sequencing to determine the mechanistic role of rhein in the heart. Results Rhein significantly suppressed Ang II-induced CH, fibrosis, and reactive oxygen species production and improved cardiac systolic dysfunction in vivo. In vitro, rhein significantly attenuated Ang II-induced CM hypertrophy and CF collagen expression. In addition, rhein obviously alleviated the increased production of superoxide induced by Ang II. Mechanistically, rhein inhibited FGF23 expression significantly. Furthermore, FGF23 overexpression abolished the protective effects of rhein on CMs, CFs, and cardiac remodeling. Rhein reduced FGF23 expression, mostly through the activation of AMPK (AMP-activated protein kinase). AMPK activity inhibition suppressed Ang II-induced CM hypertrophy and CF phenotypic transformation. Conclusion Rhein inhibited Ang II-induced CH, fibrosis, and oxidative stress during cardiac remodeling through the AMPK–FGF23 axis. These findings suggested that rhein could serve as a potential therapy in cardiac remodeling and HF.

ObjectivePulmonary cement embolism is a rare but underestimated complication of vertebroplasty due to the relative lack of study and examination. This study aims to investigate the incidence of pulmonary cement embolism in patients with spinal metastasis who undergo PVP with RFA and to analyze the relative risk factors.MethodsA total of 47 patients were retrospectively included and classified into pulmonary cement embolism (PCE) group and non-pulmonary cement embolism (NPCE) group by comparing pre- and postoperative pulmonary CT scan images. The demographic and clinical information of the patients was obtained. Demographic data in the two groups were compared using the chi-square test for qualitative data and the unpaired t test for quantitative data. Multiple logistic regression analysis was used to identify risk factors related to pulmonary cement embolism.ResultsPulmonary cement embolism was detected in 11 patients (23.4%), and all patients were asymptomatic and followed up regularly. Risk analysis showed that multiple segments (≥3, p=0.022), thoracic vertebrae (p=0.0008), and unipedicular puncture approach (p=0.0059) were risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra (p

Acute myeloid leukemia (AML) is a highly aggressive cancer with great heterogeneity and variability in prognosis. Though European Leukemia Net (ELN) 2017 risk classification has been widely used, nearly half of patients were stratified to “intermediate” risk and requires more accurate classification via excavating biological features. As new evidence showed that CD8+ T cell can kill cancer cells through ferroptosis pathway. We firstly use CIBERSORT algorithm to divide AMLs into CD8+ high and CD8+ low T cell groups, then 2789 differentially expressed genes (DEGs) between groups were identified, of which 46 ferroptosis-related genes associated with CD8+ T cell were sorted out. GO, KEGG analysis and PPI network were conducted based on these 46 DEGs. By jointly using LASSO algorithm and Cox univariate regression, we generated a 6-gene prognostic signature comprising VEGFA, KLHL24, ATG3, EIF2AK4, IDH1 and HSPB1. Low-risk group shows a longer overall survival. We then validated the prognostic value of this 6-gene signature using two independent external datasets and patient sample collection dataset. We also proved that incorporation of the 6-gene signature obviously enhanced the accuracy of ELN risk classification. Finally, gene mutation analysis, drug sensitive prediction, GSEA and GSVA analysis were conducted between high-risk and low-risk AML patients. Collectively, our findings suggested that the prognostic signature based on CD8+ T cell-related ferroptosis genes can optimize the risk stratification and prognostic prediction of AML patients.

Bare permafrost refers to permafrost with almost no vegetation on the surface, which is an essential part of the ecosystem of the Tibetan Plateau. An accurate extraction of the boundaries of bare permafrost is vital for studying how it is being impacted by climate change. The accuracy of permafrost and bare land distribution maps is inadequate, and the spatial and temporal resolution is low. This is due to the challenges associated with obtaining significant amounts of data in high-altitude and alpine regions and the limitations of current mapping techniques in effectively integrating multiple factors. This study introduces a novel approach to extracting information about the distribution of bare permafrost. The approach introduced here involves amalgamating a sample extraction method, the fusion of multi-source remote sensing information, and a hierarchical classification strategy. Initially, the available multi-source permafrost data, expert knowledge, and refinement rules for training samples are integrated to produce extensive and consistent permafrost training samples. Using the random forest method, these samples are then utilized to create features and classify permafrost. Subsequently, a methodology utilizing a hierarchical classification approach in conjunction with machine learning techniques is implemented to identify an appropriate threshold for fractional vegetation cover, thereby facilitating the extraction of bare land. The bare permafrost boundary is ultimately derived through layer overlay analysis. The permafrost classification exhibits an overall accuracy of 90.79% and a Kappa coefficient of 0.806. The overall accuracies of the two stratified extractions in bare land were 97.47% and 96.99%, with Kappa coefficients of 0.954 and 0.911. The proposed approach exhibits superiority over the extant bare land and permafrost distribution maps. It is well-suited for retrieving vast bare permafrost regions and is valuable for acquiring bare permafrost distribution data across a vast expanse. It offers technical assistance in acquiring extended-term data on the distribution of exposed permafrost on the Tibetan Plateau. Furthermore, it facilitates the elucidation of the impact of climate change on exposed permafrost.

Abstract Background As a widely distributed and aerial migratory bird, the Common Swift (Apus apus) flies over a wide geographic range in Eurasia and Africa during migration. Although some studies have revealed the migration routes and phenology of European populations, A. a. apus (from hereon the nominate apus), the route used by its East Asian counterpart A. a. pekinensis (from hereon pekinensis) remained a mystery. Methods Using light level geolocators, we studied the migration of adult pekinensis breeding in Beijing from 2014 to 2018, and analysed full annual tracks obtained from 25 individuals. In addition, we used the mean monthly precipitation to assess the seasonal variations in humidity for the distribution ranges of the nominate apus and pekinensis. This environmental variable is considered to be critically relevant to their migratory phenology and food resource abundance. Results Our results show that the swifts perform a round-trip journey of ca 30,000 km each year, representing a detour of 26% in autumn and 15% in spring compared to the shortest route between the breeding site in Beijing and wintering areas in semi-arid south-western Africa. Compared to the nominate apus, pekinensis experiences drier conditions for longer periods of time. Remarkably, individuals from our study population tracked arid habitat along the entire migration corridor leading from a breeding site in Beijing to at least central Africa. In Africa, they explored more arid habitats during non-breeding than the nominate apus. Conclusions The migration route followed by pekinensis breeding in Beijing might suggest an adaptation to semi-arid habitat and dry climatic zones during non-breeding periods, and provides a piece of correlative evidence indicating the historical range expansion of the subspecies. This study highlights that the Common Swift may prove invaluable as a model species for studies of migration route formation and population divergence.

Abstract Background Screening is often recommended as a first step in frailty management. Many guidelines call to implicate frailty screening into practice in the primary care setting. However, few countries or organizations implement it. Understanding and clarifying the stakeholders’ views and issues faced by the implementation is essential to the successful implementation of frailty screening. However, the systematic review on stakeholders’ views of frailty screening in primary care is decidedly limited. Our objective was to explore the perspective of older adults, caregivers, and healthcare providers on frailty screening and determine the enablers and barriers to implementing frailty screening in primary care. Methods A systematic search of six databases and other resources was conducted following JBI’s three-step search strategy. The search resulted in 7362 articles, of which 97 were identified for further assessment according to the inclusion criteria. After the full-text screening, quality assessment and data extraction were carried out using the tools from Joanna Briggs Institute (JBI). Moreover, reviewers used the approach of meta-aggregative of JBI to analyze data and synthesis the findings. Results Six studies were included. A total of 63 findings were aggregated into 12 categories and then further grouped into three synthesized findings:1) capacity of healthcare providers and older adults; 2) opportunity in the implementation of frailty screening; 3) motivation in the implementation of frailty screening. These themes can help identify what influences the implementation of screening from the perspective of stakeholders. Conclusions This meta-synthesis provides evidence on the barriers and enablers of frailty screening in primary care, from the aspects of psychological, physical, social, material, etc. However, stakeholder perspectives of frailty screening have not been adequately studied. More research and efforts are needed to explore the influencing factors and address the existing barriers.

Single atom catalysts have been described for efficient and selective metal catalysis, while enzymes have been known for their recognition and binding. In this manuscript, the authors develop a photochemical method to combine the two platforms in one, and demonstrate it by anchoring Pd atoms on Candida Antarctic lipase B, for highly efficient alkyl-alkyl cross-coupling reactions.

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) is a serious threat to the global swine industry. As a typical immunosuppressive virus, PRRSV has developed a variety of complex mechanisms to escape the host innate immunity. In this study, we uncovered a novel immune escape mechanism of PRRSV infection. Here, we demonstrate for the first time that the endoplasmic reticulum (ER)-resident N-acetyltransferase Nat9 is an important host restriction factor for PRRSV infection. Nat9 inhibited PRRSV proliferation in an acetyltransferase activity-dependent manner. Mechanistically, glycoprotein 5 (GP5) of PRRSV was identified as interacting with Nat9 and being N-terminally acetylated by it, which generates a GP5 degradation signal, promoting the K27-linked-ubiquitination degradation of GP5 to decrease virion assembly. Meanwhile, the expression of Nat9 was inhibited during PRRSV infection. In detail, two transcription factors, ETV5 and SP1, were screened out as the key transcription factors binding to the core promoter region of Nat9, and the PRRSV nonstructural protein 1β (Nsp1β), Nsp4, Nsp9, and nucleocapsid (N) proteins were found to interfere significantly with the expression of ETV5 and SP1, thereby regulating the transcription activity of Nat9 and inhibiting the expression of Nat9. The findings suggest that PRRSV decreases the N-terminal acetylation of GP5 to support virion assembly by inhibiting the expression of Nat9. Taken together, our findings showed that PRRSV has developed complex mechanisms to inhibit Nat9 expression and trigger virion assembly. IMPORTANCE To ensure efficient replication, a virus must hijack or regulate multiple host factors for its own benefit. Understanding virus-host interactions and the molecular mechanisms of host resistance to PRRSV infection is necessary to develop effective strategies to control PRRSV. The N-acetyltransferase Nat9 plays important roles during virus infection. Here, we demonstrate that Nat9 exhibits an antiviral effect on PRRSV proliferation. The GP5 protein of PRRSV is targeted specifically by Nat9, which mediates GP5 N-terminal acetylation and degradation via a ubiquitination-dependent proteasomal pathway. However, PRRSV manipulates the transcription factors ETV5 and SP1 to inhibit the expression of Nat9 and promote virion assembly. Thus, we report a novel function of Nat9 in PRRSV infection and elucidate a new mechanism by which PRRSV can escape the host innate immunity, which may provide novel insights for the development of antiviral drugs.

Laser quenching is one of the most outstanding gear tooth surface quenching methods due to its high efficiency, environmental friendliness, and performance consistency. Since gear tooth surface laser quenching requires repeated scanning, changing the laser scanning velocity and power by program control can meet the needs of variable depth quenching. The effects of laser scanning velocity and output power on the quenching depth and surface Rockwell hardness after quenching were studied and experimentally analyzed. The result shows that by adjusting the parameters, the surface hardness of the specimen changes slightly with the actual received laser energy. However, the quenching depth can be consistent with the laser scanning velocity. The maximum surface Rockwell hardness that a laser quenched material can achieve depends on the material itself, not on the laser power or scanning velocity. Compared with accelerated laser quenching, decelerated laser quenching is more suitable for tooth surface machining due to the cumulative effect of energy within the quenching depth range of metal materials.

Three-dimensional cancer organoids derived from self-organizing cancer stems are ex vivo miniatures of tumors that faithfully recapitulate their structure, distinctive cancer features, and genetic signatures. As novel tools, current cancer organoids have been well established and rapidly applied in drug testing, genome editing, and transplantation, with the ultimate aim of entering clinical practice for guiding personalized therapy. However, given that the lack of a tumor microenvironment, including immune cells and fibrous cells, is a major limitation of this emerging methodology, co-culture models inspire high hope for further application of this technology in cancer research. Co-culture of cancer organoids and immune cells or fibroblasts is available to investigate the tumor microenvironment, molecular interactions, and chimeric antigen receptor-engineered lymphocytes in cancer treatment. In light of the recent progress in cancer organoid co-culture models, it is only possible to recognize the advantages and drawbacks of this novel model to exploit its full potential. In this review, we summarize the recent advances in the application of cancer organoids and co-culture models and how they could be improved in the future to benefit cancer research, especially precision medicine.

SAR offset and optical offset are important techniques for glacier movement monitoring, but there are few researches on 3D deformation by integrating images from different platforms. In this paper, large glaciers in The Shisha Pangma area of Nyalam County, Tibet from November 2019 to January 2021 were selected as the research area. Based on variance component estimation, Sentinel-1 and Landsat8 data of the study area were combined for three-dimensional glacier calculation. Optical images of the same period were selected for comparative analysis of the offset estimation results. At the same time, the accuracy of the method was evaluated by selecting the stable area, and the applicability and accuracy of the method in glacier movement monitoring were analyzed. The results show that the maximum velocity of the glacier is 21 cm/day in the east-west direction, 68 cm/day in the north-south direction, and 17 cm/day in the vertical direction. Compared with the glacier displacement results obtained from a single image, the multi-image joint algorithm can compensate for the incoherence of SAR data and the low quality pixel values of optical data, and obtain more complete and detailed glacier information and higher accuracy of monitoring results. This paper can provide reference and technical support for using data from different platforms to jointly monitor multi-dimensional and high-precision changes of mountain glaciers.

A highly efficient and environmentally benign 1,3-dipolar cycloaddition of C,N - cyclic azomethine imines with 5-alkenyl thiazolones and 2-arylidenindane-1,3-diones is developed for the construction of congested quaternary spiro-carbon centers. All these transformations can be smoothly performed in ethanol at room temperature, providing a catalyst-free and atom-economical access to diversely substituted novel isoquinoline-fused spirocycles in almost quantitative yields with high diastereoselectivities. The promising anti-tumor activity of these structurally novel spirocyclic compounds is reported as well.

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. The proteasome inhibitor ixazomib is a landmark drug in the treatment of multiple myeloma with a high anti-cancer activity. Herein, we conjugated the pharmacophore of ubenimex and the boric acid of ixazomib to obtain a dual CD13 and proteasome inhibitor 7 (BC-05). BC-05 exhibited potent inhibitory activity on both human CD13 (IC50 = 0.13 μM) and the 20S proteasome (IC50 = 1.39 μM). Although BC-05 displayed lower anti-proliferative activity than that of ixazomib in vitro, an advantage was established in the in vivo anti-cancer efficacy and prolongation of survival time, which may be due to its anti-metastatic and immune-stimulating activity. A pharmacokinetic study revealed that BC-05 is a potentially orally active agent with an F% value of 24.9%. Moreover, BC-05 showed more favorable safety profiles than those of ixazomib in preliminary toxicity studies. Overall, the results indicate that BC-05 is a promising drug candidate for the treatment of multiple myeloma.

Epsilon toxin (ETX) is an exotoxin produced by type B and D Clostridium perfringens that causes enterotoxemia or necrotic enteritis in animals such as goats, sheep, and cattle. Vaccination is a key method in preventing such diseases. In this study, we developed a new type of dissolving microneedle patch (dMN) with a nanoparticle adjuvant for enhanced immune response to deliver the rETXY196E-C protein vaccine. We chose FDA-approved poly(lactic-co-glycolic acid) (PLGA) to prepare nanospheres as the vaccine adjuvant and introduced dimethyldioctadecylammonium bromide (DDAB) to make the surface of PLGA nanoparticles (PLGA NPs) positively charged for antigen adsorption. PLGA NPs with a diameter of 100~200 nm, a surface ZETA potential of approximately +40 mV, and good safety were successfully prepared and could effectively adsorb rETXY196E-C protein. Using non-toxic and antibacterial fish gelatin as the microneedle (MN) matrix, we prepared a PLGA-DDAB dMN vaccine with good mechanical properties that successfully penetrated the skin. After immunization of subcutaneous (SC) and dMN, antibody titers of the PLGA and Al adjuvant groups were similar in both two immune ways. However, in vivo neutralization experiments showed that the dMN vaccines had a better protective effect. When challenged with 100 × LD50 GST-ETX, the survival rate of the MN group was 100%, while that of the SC Al group was 80%. However, a 100% protective effect was achieved in both immunization methods using PLGA NPs. In vitro neutralization experiments showed that the serum antibodies from the dMN and SC PLGA NPs groups both protect naive mice from 10 × LD50 GST-ETX attack after being diluted 20 times and could also protect MDCK cells from 20 × CT50 GST-ETX attack. In conclusion, the PLGA-DDAB dMN vaccine we prepared has good mechanical properties, immunogenicity, and protection, and can effectively prevent ETX poisoning. This provides a better way of delivering protein vaccines.