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Abstract Alzheimer’s disease (AD) is the leading form of dementia, characterized by the accumulation and aggregation of amyloid in brain. Transient receptor potential vanilloid 2 (TRPV2) is an ion channel involved in diverse physiopathological processes, including microglial phagocytosis. Previous studies suggested that cannabidiol (CBD), an activator of TRPV2, improves microglial amyloid-β (Aβ) phagocytosis by TRPV2 modulation. However, the molecular mechanism of TRPV2 in microglial Aβ phagocytosis remains unknown. In this study, we aimed to investigate the involvement of TRPV2 channel in microglial Aβ phagocytosis and the underlying mechanisms. Utilizing human datasets, mouse primary neuron and microglia cultures, and AD model mice, to evaluate TRPV2 expression and microglial Aβ phagocytosis in both in vivo and in vitro. TRPV2 was expressed in cortex, hippocampus, and microglia.Cannabidiol (CBD) could activate and sensitize TRPV2 channel. Short-term CBD (1 week) injection intraperitoneally (i.p.) reduced the expression of neuroinflammation and microglial phagocytic receptors, but long-term CBD (3 week) administration (i.p.) induced neuroinflammation and suppressed the expression of microglial phagocytic receptors in APP/PS1 mice. Furthermore, the hyper-sensitivity of TRPV2 channel was mediated by tyrosine phosphorylation at the molecular sites Tyr(338), Tyr(466), and Tyr(520) by protein tyrosine kinase JAK1, and these sites mutation reduced the microglial Aβ phagocytosis partially dependence on its localization. While TRPV2 was palmitoylated at Cys 277 site and blocking TRPV2 palmitoylation improved microglial Aβ phagocytosis. Moreover, it was demonstrated that TRPV2 palmitoylation was dynamically regulated by ZDHHC21. Overall, our findings elucidated the intricate interplay between TRPV2 channel regulated by tyrosine phosphorylation/dephosphorylation and cysteine palmitoylation/depalmitoylation, which had divergent effects on microglial Aβ phagocytosis. These findings provide valuable insights into the underlying mechanisms linking microglial phagocytosis and TRPV2 sensitivity, and offer potential therapeutic strategies for managing AD.

Abstract Objective This research aimed to identify the fundamental and geographic characteristics of the primary healthcare personnel mobility in Nanning from 2000 to 2021 and clarify the determinants that affect their transition to non-primary healthcare institutions. Methods Through utilizing the Primary Healthcare Personnel Database (PHPD) for 2000–2021, the study conducts descriptive statistical analysis on demographic, economic, and professional aspects of healthcare personnel mobility across healthcare reform phases. Geographic Information Systems (QGIS) were used to map mobility patterns, and R software was employed to calculate spatial autocorrelation (Moran’s I). Logistic regression identified factors that influenced the transition to non-primary institutions. Results Primary healthcare personnel mobility is divided into four phases: initial (2000–2008), turning point (2009–2011), rapid development (2012–2020), and decline (2021). The rapid development stage saw increased mobility with no spatial clustering in inflow and outflow. From 2016 to 2020, primary healthcare worker mobility reached its peak, in which the most significant movement occurred between township health centers and other institutions. Aside from their transition to primary medical institutions, the primary movement of grassroots health personnel predominantly directs towards secondary general hospitals, tertiary general hospitals, and secondary specialized hospitals. Since 2012, the number and mobility distance of primary healthcare workers have become noticeably larger and remained at a higher level from 2016 to 2020. The main migration of primary healthcare personnel occurred in their districts (counties). Key transition factors include gender, education, ethnicity, professional category, general practice registration, and administrative division. Conclusions This study provides evidence of the features of primary healthcare personnel mobility in the less developed western regions of China, in which Nanning was taken as a case study. It uncovers the factors that impact the flow of primary healthcare personnel to non-primary healthcare institutions. These findings are helpful to policy refinement and support the retention of primary healthcare workers.

Poor seedling emergence is a challenge for direct seeding of rice under deep-sowing field conditions. Here we reveal that UDP-glucosyltransferase OsUGT75A promotes rice seedling emergence under deep-sowing conditions by increasing shoot length. Expression of OsUGT75A was higher in the middle regions of the shoot and in shoots under deep-sowing conditions. Levels of free abscisic acid (ABA) and jasmonates (JA) were higher in shoots of OsUGT75A mutants than in those of wild-type plants, and OsUGT75A mutants were more sensitive to ABA and JA treatments. Reduced shoot length was attributed to higher ABA INSENSITIVE 3 (OsABI3) expression and lower JASMONATE-ZIM domain protein (OsJAZ) expression in shoots. Shoot extension by OsUGT75A is achieved mainly by promotion of cell elongation. An elite haplotype of OsUGT75A associated with increased shoot length was identified among indica rice accessions. OsUGT75A acts to increase seedling emergence under deep-sowing conditions.

Abstract Objective Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. This study aimed to identify potential biomarkers and possible pathogenesis of RA using various bioinformatics analysis tools. Methods The GMrepo database provided a visual representation of the analysis of intestinal flora. We selected the GSE55235 and GSE55457 datasets from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) separately. With the intersection of these DEGs with the target genes associated with RA found in the GeneCards database, we obtained the DEGs targeted by RA (DERATGs). Subsequently, Disease Ontology, Gene Ontology, and the Kyoto Encyclopedia of Genes and Genomes were used to analyze DERATGs functionally. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed on the data from the gene expression matrix. Additionally, the protein-protein interaction network, transcription factor (TF)-targets, target-drug, microRNA (miRNA)-mRNA networks, and RNA-binding proteins (RBPs)-DERATGs correlation analyses were built. The CIBERSORT was used to evaluate the inflammatory immune state. The single-sample GSEA (ssGSEA) algorithm and differential analysis of DERATGs were used among the infiltration degree subtypes. Results There were some correlations between the abundance of gut flora and the prevalence of RA. A total of 54 DERATGs were identified, mainly related to immune and inflammatory responses and immunodeficiency diseases. Through GSEA and GSVA analysis, we found pathway alterations related to metabolic regulations, autoimmune diseases, and immunodeficiency-related disorders. We obtained 20 hub genes and 2 subnetworks. Additionally, we found that 39 TFs, 174 drugs, 2310 miRNAs, and several RBPs were related to DERATGs. Mast, plasma, and naive B cells differed during immune infiltration. We discovered DERATGs’ differences among subtypes using the ssGSEA algorithm and subtype grouping. Conclusions The findings of this study could help with RA diagnosis, prognosis, and targeted molecular treatment.

This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P

ABSTRACTFollowing the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9–45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported ≥ 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9–45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size.Clinical trial registration: NCT03438006.

BackgroundIt has been reported that decreased muscle mass combined with excessive visceral adipose tissue are significantly correlated with the risk of non-alcoholic fatty liver disease (NAFLD). However, it has not been explored among populations with metabolic dysfunction-associated fatty liver disease (MAFLD) subtypes. We aimed to investigate whether appendicular skeletal muscle mass to visceral fat area ratio (SVR), an indicator of sarcopenic obesity, influences on the risk of MAFLD subtypes and its hepatic condition in middle-aged and elderly population.MethodsA total of 4,003 middle-aged and elderly subjects were finally enrolled in this single-center retrospective study. Abdominal ultrasonography was employed for hepatic steatosis diagnosis. Participants were divided into four groups: diabetes-MAFLD, overweight/obese-MAFLD, lean-MAFLD and no MAFLD. Appendicular skeletal muscle mass as well as visceral fat area (VAF) was estimated by bioimpedance analysis measurements. Liver fibrosis was defined as a Fibrosis-4 index (FIB-4) and the NAFLD Fibrosis Score (NFS). Multivariate logistic regression analysis was performed to estimate the odds ratio and 95% confidence interval between SVR and MAFLD subtypes/hepatic condition stratified by sex.ResultsParticipants with MAFLD subtypes had a significant lower value of SVR compared with those without MAFLD (P0.05). The lowest quartile of SVR also increases the risk of MAFLD fibrosis in both males and females.ConclusionOur study concluded that a decrease in SVR (appendicular skeletal muscle mass divided by visceral fat area) is significantly associated with an increased prevalence of developing MAFLD subtypes and liver fibrosis in middle-aged and older persons of both genders.

Abstract Background In recent years, immune checkpoint inhibitor (ICI) therapy has greatly changed the treatment prospects of patients with non-small cell lung cancer (NSCLC). Among the available ICI therapy strategies, programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors are the most widely used worldwide. At present, immunohistochemistry (IHC) is the main method to detect PD-L1 expression levels in clinical practice. However, given that IHC is invasive and cannot reflect the expression of PD-L1 dynamically and in real time, it is of great clinical significance to develop a new noninvasive, accurate radiomics method to evaluate PD-L1 expression levels and predict and filter patients who will benefit from immunotherapy. Therefore, the aim of our study was to assess the predictive power of pretherapy [18F]-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT)-based radiomics features for PD-L1 expression status in patients with NSCLC. Methods A total of 334 patients with NSCLC who underwent [18F]FDG PET/CT imaging prior to treatment were analyzed retrospectively from September 2016 to July 2021. The LIFEx7.0.0 package was applied to extract 63 PET and 61 CT radiomics features. In the training group, the least absolute shrinkage and selection operator (LASSO) regression model was employed to select the most predictive radiomics features. We constructed and validated a radiomics model, clinical model and combined model. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the predictive performance of the three models in the training group and validation group. In addition, a radiomics nomogram to predict PD-L1 expression status was established based on the optimal predictive model. Results Patients were randomly assigned to a training group (n = 233) and a validation group (n = 101). Two radiomics features were selected to construct the radiomics signature model. Multivariate analysis showed that the clinical stage (odds ratio [OR] 1.579, 95% confidence interval [CI] 0.220–0.703, P

Interaction diversity and interaction identity, as two classic interaction patterns in real-world systems, are frequently employed to probe into the cooperative dilemmas among participants with diverse interaction identities within groups. Considering the influence of factors such as hyperlink configurations on the evolution of cooperation within complex networks, this study particularly focuses on the organic integration of hypergraphs and diverse interaction modes. Employing the public goods game model in uniformly stochastic hypergraphs, we explore the effects of synergy factors and diverse interacting individuals on the cooperation rate and strategy consistency within hyperlinks. We emphasize that the diverse interacting individuals are a double-edged sword, and the controlled number of such individuals is conducive to the evolution of cooperation. The findings of this study reveal the significance of these two typical interaction patterns and provide valuable insights for coordinating them to achieve social optimality in cooperation.

Proton dose deposition results are influenced by various factors, such as irradiation angle, beamlet energy and other parameters. The calculation of the proton dose deposition matrix (DDM) can be highly complex but is crucial in intensity-modulated proton therapy (IMPT). In this work, we present a novel deep learning (DL) approach using multi-source features for proton DDM prediction. The DL5 proton DDM prediction method involves five input features containing beamlet geometry, dosimetry and treatment machine information like patient CT data, beamlet energy, distance from voxel to beamlet axis, distance from voxel to body surface, and pencil beam (PB) dose. The dose calculated by Monte Carlo (MC) method was used as the ground truth dose label. A total of 40 000 features, corresponding to 8000 beamlets, were obtained from head patient datasets and used for the training data. Additionally, seventeen head patients not included in the training process were utilized as testing cases. The DL5 method demonstrates high proton beamlet dose prediction accuracy, with an average determination coefficient R ^2 of 0.93 when compared to the MC dose. Accurate beamlet dose estimation can be achieved in as little as 1.5 milliseconds for an individual proton beamlet. F or IMPT plan dose comparisons to the dose calculated by the MC method, the DL5 method exhibited gamma pass rates of γ (2 mm, 2%) and γ (3 mm, 3%) ranging from 98.15% to 99.89% and 98.80% to 99.98%, respectively, across all 17 testing cases. On average, the DL5 method increased the gamma pass rates to γ (2 mm, 2%) from 82.97% to 99.23% and to γ (3 mm, 3%) from 85.27% to 99.75% when compared with the PB method. The proposed DL5 model enables rapid and precise dose calculation in IMPT plan, which has the potential to significantly enhance the efficiency and quality of proton radiation therapy.

Objectives: Depression is a common disease of elderly population, with a global prevalence of more than 20%. Few studies have involved the associations of constipation and overeating with depression, especially in the elderly population. We aimed to address these associations in Chinese oldest-old and centenarians. Methods: A total of 1863 elderly individuals from 18 regions of Hainan, China, were investigated from July 2014 to December 2016. Health survey, physical examination, and blood analyses were performed through structured questionnaires and standard procedures. The Geriatric Depression Scale (GDS-15) was used to measure depression. Results: The proportions of elderly individuals with depression, constipation, and overeating were 20.80% (349), 15.14% (254), and 26.52% (445), respectively. The prevalence of constipation and overeating was significantly higher in the elderly group with depression than in those without depression (P < 0.05, all). In the multiple linear regression analyses, higher prevalence of constipation and overeating had positive and significant associations with the GDS-15 (P < 0.05, all). In the multiple logistic regression analyses, constipation (odds ratio [OR]: 2.328; 95% confidence interval [CI]: 1.540–3.521) and overeating (OR: 2.735; 95% CI: 1.920–3.898) had positive and significant associations with depression (P < 0.05, in all). Conclusions and Implications: This study provides epidemiological evidence that constipation and overeating have positive associations with depression in Chinese oldest-old and centenarians. The interventions for constipation and overeating should be improved to promote prevention and treatment for depression and achieve successful aging and healthy longevity.

Glutamine supplementation has been reported to affect blood pressure (BP). However, its role in the progression of hypertension induced by high salt diet (HSD) has not been elucidated. Male normotensive Wistar rats were exposed to high salt diet and treated with different doses of glutamine supplementation. Rats aged 6 weeks were assigned to five groups: (1) Normal-salt diet (0.3% NaCl, NSD); (2) High-salt diet (8% NaCl, HSD); (3) High-salt + low-dose diet (8% NaCl, 0.5 g of L-glutamine/kg body weight, HSLGD); (4) High-salt + middle-dose diet (8% NaCl, 1.5 g of L-glutamine/kg body weight, HSMGD); and (5) High-salt + high-dose diet (8% NaCl, 2.5 g of L-glutamine/kg body weight, HSHGD). After supplementing different doses of glutamine to male Wistar 6-week-old rats fed with HSD for 7 weeks, we found no difference in body weight among groups. Importantly, we showed that dietary L-glutamine supplementation could prevent the development of hypertension in a dose-dependent manner [dramatically lowering systolic blood pressure (SBP) and slightly reducing diastolic blood pressure (DBP) of hypertensive rats, while the differences of DBP between groups did not reach statistical significance]. Our data further elucidated that dietary glutamine supplementation mildly alleviated the degree of left ventricular hypertrophy, including interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in hypertensive rats. Together, our results offer evidence that the dietary uptake of glutamine may be associated with attenuating the development of high salt-induced hypertension and slightly alleviating the degree of left ventricular hypertrophy in hypertensive rats. Therefore, glutamine supplementation may act as a prospective dietary intervention for the treatment of hypertension.

Abstract Objective Galuteolin (Galu) is a substance extracted and purified from honeysuckle. The purpose of this study was to explore the effects of Galu on the TNF-α-induced RA-FLS cells (synoviocytes) and reveal its potential molecular mechanism from the perspectives of anti-apoptosis and anti-inflammation. Methods After TNF-α stimulation, cell proliferation of RA-FLS was assessed by CCK-8 assay. TUNEL staining was used to detect the apoptosis. Western blot was used to detect the expressions of Iκκβ, p-p65, p65, p-IκB, IκB, Cleaved-caspase3, Caspase-3, Bcl-2, and Bax. HO-1 were determined by RT-PCR. The contents of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MMP-1 were determined by ELISA. Results Galu significantly suppressed cell proliferation in a dose-dependent manner. Additionally, Galu obviously promotes cell apoptosis rate of RA-FLS cells and elevated the expression levels of HO-1, caspase-3, and Bax, while reducing the expression level of Bcl-2. Furthermore, Galu apparently inhibited the levels of Iκκβ, p-p65, and p-IκB. Moreover, Galu also significantly reduced the levels of pro-inflammatory factors IL-1β, IL-6, IL-8, and MMP-1 in RA-FLS cells. Conclusion Galuteolin exerts protective effects against TNF-α-induced RA-FLS cells by inhibiting apoptosis and inflammation, which can guide the clinical use of rheumatoid arthritis.

Objective: To investigate the predictors of acute cardiovascular events within 90 days after an acute lower respiratory tract infection (ALRTI) in elderly patients with stable coronary artery disease (sCAD).Methods: Observational analyses were conducted in a prospective cohort of the elderly with sCAD, during 90 days after they were hospitalized for ALRTI. Multiple logistic regression analysis was performed to identify predictors for acute cardiovascular events and all-cause mortality.Results: The present study comprised 426 patients with sCAD (median age: 88 years; IQR: 84–91; range: 72–102). Among these patients, 257 suffering from ALRTI were enrolled in the infection group. Meanwhile, 169 patients who did not suffer from ALRTI were regarded as the non-infection group. Compared with the non-infection group, patients in the infection group had a higher incidence of acute cardiovascular events (31.9 vs. 13.6%, p < 0.001) and all-cause mortality (13.2 vs. 1.8%, p < 0.001) during the 90-day follow-up. In addition, in the infection group, the incidence of cardiovascular events was also higher than those in the non-infection group during the 7-day and 30-day follow-up (10.9 vs. 2.4%, p = 0.001; 20.6 vs. 6.5%, p < 0.001). The same difference in the incidence of all-cause mortality during 7 and 30 days (1.2 vs. 0%, p = 0.028; 3.9 vs. 0.6%, p = 0.021) was observed between the two groups. Furthermore, multiple regression analysis found that ALRTI was independently associated with increased risk of cardiovascular events and all-cause mortality in elderly patients with sCAD.Conclusion: In elderly patients with sCAD, ALRTI was an independent predictor for both cardiovascular events and all-cause mortality.

In recent years, the rapid development of mobile communication technology has led to the development of positioning services, and the demand for indoor positioning technology has been increasing strictly. In the Internet information era, location-based services (LBS) have been applied in various fields after the emergence of location-based information technology, which brings new experience and convenience to people. In order to improve the indoor positioning accuracy of wireless sensor networks, an indoor positioning algorithm with a rotating arc triangle layout is proposed. This layout uses a circular arc triangle to deploy the beacon nodes and changes the position of the beacon nodes by rotating. Compared with the square, triangle, and equi-arc triangle layout, the rotating arc triangle layout reduces beacon nodes and is easy to rotate, but the layout after rotation has not changed. Experiments show that the layout of the rotating arc triangle layout is simple. By rotating the beacon node, multiple positioning prediction positions are superposed, and the positioning accuracy is improved. The rotating arc triangle layout is better than the square, the traditional triangle, the improved triangle, and the equal arc triangle. The average positioning accuracy of the arc triangle has been increased by 69.9%, 51.8%, 16.6%, 35.6%, and 32.9% respectively, which has certain use value and popularization.

Airborne laser scanning (ALS) data is one of the most commonly used data for terrain products generation. Filtering ground points is a prerequisite step for ALS data processing. Traditional filtering methods mainly use handcrafted features or predefined classification rules with preprocessing/post-processing operations to filter ground points iteratively, which is empirical and cumbersome. Deep learning provides a new approach to solve classification and segmentation problems because of its ability to self-learn features, which has been favored in many fields, particularly remote sensing. In this article, we proposed a point-based fully convolutional neural network (PFCN) which directly consumed points with only geometric information and extracted both point-wise and tile-wise features to classify each point. The network was trained with 37449157 points from 14 sites and evaluated on 6 sites in various forested environments. Additionally, the method was compared with five widely used filtering methods and one of the best point-based deep learning methods (PointNet++). Results showed that the PFCN achieved the best results in terms of mean omission error (T1 = 1.10%), total error (Te = 1.73%), and Kappa coefficient (93.88%), but ranked second for the root mean square error of the digital Terrain model caused by the worst commission error. Additionally, our method was on par with or even better than PointNet++ in accuracy. Moreover, the method consumes one-third of the computational resource and one-seventh of the training time. We believe that PFCN is a simple and flexible method that can be widely applied for ground point filtering.

Alzheimer’s disease (AD) is a common age-related neurodegenerative disease that leads to memory loss and cognitive function damage due to intracerebral neurofibrillary tangles (NFTs) and amyloid-β (Aβ) protein deposition. The phosphoinositide-dependent protein kinase (PDK1)/protein kinase B (Akt) signaling pathway plays a significant role in neuronal differentiation, synaptic plasticity, neuronal survival, and neurotransmission via the axon–dendrite axis. The phosphorylation of PDK1 and Akt rises in the brain, resulting in phosphorylation of the TNF-α-converting enzyme (TACE) at its cytoplasmic tail (the C-terminal end), changing its internalization as well as its trafficking. The current review aimed to explain the mechanisms of the PDK1/Akt/TACE signaling axis that exerts its modulatory effect on AD physiopathology. We provide an overview of the neuropathological features, genetics, Aβ aggregation, Tau protein hyperphosphorylation, neuroinflammation, and aging in the AD brain. Additionally, we summarized the phosphoinositide 3-kinase (PI3K)/PDK1/Akt pathway-related features and its molecular mechanism that is dependent on TACE in the pathogenesis of AD. This study reviewed the relationship between the PDK1/Akt signaling pathway and AD, and discussed the role of PDK1/Akt in resisting neuronal toxicity by suppressing TACE expression in the cell membrane. This work also provides a perspective for developing new therapeutics targeting PDK1/Akt and TACE for the treatment of AD.

Abstract Background Based on previous findings, we hypothesized that Vasohibin 2 (VASH2) protein may induce epithelial‐mesenchymal transition (EMT) of pancreatic cancer (PC) cells by promoting the malignant behaviors of these cells. The present study aimed to test this hypothesis and explore the possible mechanisms involved. Methods The expression of VASH2 in PC tissues and cell lines was detected by quantitative real‐time PCR and Western blot. PC cells with overexpression or knockdown of VASH2 were used to examine the involvement of VASH2 in EMT by detecting the expression of epithelial (E‐cadherin) and mesenchymal (vimentin) markers and EMT‐related transcription factor ZEB1/2, in gemcitabine resistance and tumor cell invasion by apoptosis and invasion assays, and in cancer stem cell‐like phenotypes by detecting the proportion of CD24+CD44+ and side population (SP) cells in PC cells with flow cytometry. The impact of VASH2 overexpression and knockdown on components of the Hedgehog signaling pathway was also assessed. Results We found that VASH2 was highly expressed in PC tissues and cells. It promoted the EMT of PC cells by altering ZEB1/2 expression. VASH2 also stimulated invasion and chemotherapeutic resistance of PC cells and increased the proportion of cancer stem‐like cells in PC cells. VASH2 did so by upregulating the expression of multiple molecules in the Hedgehog signaling pathway of PC cells. Conclusion VASH2 promotes malignant behaviors of PC cells by inducing EMT via activation of the Hedgehog signaling pathway.

Filtering of airborne light detection and ranging (LiDAR) data is a challenging task in vegetated mountain areas. Environmental features and LiDAR data characteristics have significant impacts on the performance of filtering algorithms. This study aims to determine the effects of topographic and environmental features such as slope, canopy cover, elevation variability, and LiDAR point density on five widely used filtering algorithms, including multi-scale curvature classification (MCC), interpolation-based filtering (IBF) algorithm, morphological filtering (MF) algorithm, progressive triangulated irregular network densification filtering (PTDF) algorithm, and slope-based filtering (SBF). The results show that the performances of these filtering algorithms are all significantly influenced by the chosen factors, but the dominant influential factor varies with algorithms. The MCC works well in steep and dense forests; IBF and MCC outperform the rest of filtering algorithms in areas with steep terrain but low vegetation coverage; and PTDF is more reliable for low-density LiDAR data. Our results can provide guidance for choosing the appropriate filtering algorithm based on the specific topographic and environmental features of a study area.

Abstract Background Immuno-inflammation plays a major role in the process of hypertension. We aimed to evaluate the association between inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW) and all-cause mortality in elderly patients with hypertension. Methods A total of 341 hypertensive patients over 80 years of age were included to this study. The NLR and RDW were measured on admission and all the selected patients were followed up for up to 90 days. Kaplan–Meier curves were plotted to evaluate the association between the NLR and the all-cause mortality at follow-up. Using Cox regression models, we investigated the prognostic value of NLR and RDW for all-cause mortality. Results Patients with higher quartile of NLR linked to high mortality in hypertensive patients at 90 day after admission (16.47%,13.25%,1.14%,1.17% respectively; χ2 = 20.581,P = 0.000). Surviving patients had lower RDW (13.61 ± 1.37 VS 14.18 ± 1.38, p = 0.041) and NLR (4.97 ± 5.72 VS 7.95 ± 6.88,p = 0.011). The receiver operating curve (ROC) of the NLR for all-cause mortality had an area under the curve (AUC) =0.714 (95%CI: 0.629–0.798, P = 0.000), with acritical value of 2.97, with sensitivity of 92.6%, and a specificity of 52.5%. The ROC of the RDW to predict all-cause mortality, had an AUC =0.654 (95%CI:0.548–0.761, P = 0.008), with acritical value of 13.2%.The Kaplan–Meier curve showed a significant difference between different NLR levels (p = 0.002). Multivariate Cox proportional hazard analysis shown 3rd quartile of NLR(RR = 9.646, 95% CI 1.302–34.457, P = 0.041) and 4th quartiles(RR = 16.451, 95% CI 2.137–66.643, P = 0.007) were found to independently predict all-cause death in hypertensive patients over 80 years of age. Higher rank of NLR was link to higher incidence of all-cause death for such patients. Conclusion The findings of the present study demonstrate the potential utility of NLR in risk stratification of elderly patients with hypertension to provide information for clinical treatment strategies.

As a large carbon pool, global forest ecosystems are a critical component of the global carbon cycle. Accurate estimations of global forest aboveground biomass (AGB) can improve the understanding of global carbon dynamics and help to quantify anthropogenic carbon emissions. Light detection and ranging (LiDAR) techniques have been proven that can accurately capture both horizontal and vertical forest structures and increase the accuracy of forest AGB estimation. In this study, we mapped the global forest AGB density at a 1-km resolution through the integration of ground inventory data, optical imagery, Geoscience Laser Altimeter System/Ice, Cloud, and Land Elevation Satellite data, climate surfaces, and topographic data. Over 4000 ground inventory records were collected from published literatures to train the forest AGB estimation model and validate the resulting global forest AGB product. Our wall-to-wall global forest AGB map showed that the global forest AGB density was 210.09 Mg/ha on average, with a standard deviation of 109.31 Mg/ha. At the continental level, Africa (333.34 ± 63.80 Mg/ha) and South America (301.68 ± 67.43 Mg/ha) had higher AGB density. The AGB density in Asia, North America and Europe were 172.28 ± 94.75, 166.48 ± 84.97, and 132.97 ± 50.70 Mg/ha, respectively. The wall-to-wall forest AGB map was evaluated at plot level using independent plot measurements. The adjusted coefficient of determination (R2) and root-mean-square error (RMSE) between our predicted results and the validation plots were 0.56 and 87.53 Mg/ha, respectively. At the ecological zone level, the R2 and RMSE between our map and Intergovernmental Panel on Climate Change suggested values were 0.56 and 101.21 Mg/ha, respectively. Moreover, a comprehensive comparison was also conducted between our forest AGB map and other published regional AGB products. Overall, our forest AGB map showed good agreements with these regional AGB products, but some of the regional AGB products tended to underestimate forest AGB density.