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This paper presents a novel low-cost and fully-portable instrumented shoe system for gait phase detection. The instrumented shoe consists of 174 independent sensing units constructed based on an off-the-shelf force-sensitive film known as the Velostat conductive copolymer. A zero potential method was implemented to address the crosstalk effect among the matrix-formed sensing arrays. A customized algorithm for gait event and phase detection was developed to estimate stance sub-phases including initial contact, flat foot, and push off. Experiments were carried out to evaluate the performance of the proposed instrumented shoe system in gait phase detection for both straight-line walking and turning walking. The results showed that the mean absolute time differences between the estimated phases by the proposed instrumented shoe system and the reference measurement ranged from 45 to 58 ms during straight-line walking and from 51 to 77 ms during turning walking, which were comparable to the state of art.Clinical and Translational Impact Statement—By allowing convenient gait monitoring in home healthcare settings, the proposed system enables extensive ADL data collection and facilitates developing effective treatment and rehabilitation strategies for patients with movement disorders.

ABSTRACTEquid alphaherpesvirus 8 (EqHV-8) is one of the most economically important viruses that is known to cause severe respiratory disease, abortion, and neurological syndromes in equines. However, no effective vaccines or therapeutic agents are available to control EqHV-8 infection. Heme oxygenase-1 (HO-1) is an antioxidant defense enzyme that displays significant cytoprotective effects against different viral infections. However, the literature on the function of HO-1 during EqHV-8 infection is little. We explored the effects of HO-1 on EqHV-8 infection and revealed its potential mechanisms. Our results demonstrated that HO-1 induced by cobalt-protoporphyrin (CoPP) or HO-1 overexpression inhibited EqHV-8 replication in susceptible cells. In contrast, HO-1 inhibitor (zinc protoporphyria) or siRNA targeting HO-1 reversed the anti-EqHV-8 activity. Furthermore, biliverdin, a metabolic product of HO-1, mediated the anti-EqHV-8 effect of HO-1 via both the protein kinase C (PKC)β/extracellular signal-regulated kinase (ERK)1/ERK2 and nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP)–protein kinase G (PKG) signaling pathways. In addition, CoPP protected the mice by reducing the EqHV-8 infection in the lungs. Altogether, these results indicated that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.IMPORTANCEEqHV-8 infections have threatened continuously donkey and horse industry worldwide, which induces huge economic losses every year. However, no effective vaccination strategies or drug against EqHV-8 infection until now. Our present study found that one host protien HO-1 restrict EqHV-8 replication in vitro and in vivo. Furthermore, we demonstrate that HO-1 and its metabolite biliverdin suppress EqHV-8 relication via the PKCβ/ERK1/ERK2 and NO/cGMP/PKG pathways. Hence, we believe that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.

Procollagen c-protease enhancer protein (PCOLCE) performs an essential action in improving the recreation of procollagen c-protease and promoting the reconstruction of extracellular matrix. High PCOLCE expression was associated with a negative prognosis of stomach cancer, ovarian cancer, and osteosarcoma. The goal of this work is to investigate the function of PCOLCE in glioma. Multiple bioinformatics techniques have been employed to investigate the roles of PCOLCE in glioma, consisting of the correlation between PCOLCE and prognosis, immune checkpoints, immune cell infiltrates, and tumor microenvironment (TME). The gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the potential function of PCOLCE in glioma. PCOLCE was found to be increased in glioma. We revealed that PCOLCE was a potential prognostic factor and related to tumor grade. Up-regulated PCOLCE was related to poor prognosis in lower-grade glioma (LGG), glioblastoma multiforme (GBM), and recurrent glioma. PCOLCE was correlated with immune cell infiltration, particularly B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LGG, and DCs infiltration in GBM. PCOLCE was co-expressed with many genes related to the immune and the immune checkpoint. In addition, glioma patients with low expression of PCOLCE had a higher response to the immunological checkpoint blockade (ICB). Additionally, PCOLCE may exert its roles via several immune-related biological processes or pathways, such as leukocyte migration, activation of T cells, adaptive immune response, neutrophil-mediated immunity, NF-κB, and TNF signaling pathways. In conclusion, PCOLCE may be a new immune-related gene and regulate tumor development through immunological pathways.

Abstract Hepatocellular carcinoma (HCC) is one of the deadliest malignancies worldwide, with late detection, ineffective treatment and poor overall survival. Immunotherapy, including immune checkpoint inhibitor (ICI) therapy, holds great potential for treatment of HCC. Although some patients respond well to ICIs, many fail to obtain a significant benefit. It is therefore of great interest to find appropriate markers to stratify patient responses to immunotherapy and to explore suitable targets for modulating the TME and immune cell infiltration. ATP6V1F encodes a constituent of vacuolar ATPase (V-ATPase). V-ATPase-mediated acidification of organelles is required for intracellular processes such as zymogen activation, receptor-mediated endocytosis, protein sorting and synaptic vesicle proton gradient generation. In this study, we confirmed for the first time that ATP6V1F is overexpressed in HCC and related to poor prognosis in these patients. We identified that overexpression of ATP6V1F is associated with infiltration of some immune cells and expression of several immune checkpoints. Furthermore, we explored the possible mechanisms of action of ATP6V1F. Finally, we conducted in vitro experiments, including wound healing, Transwell invasion, and apoptosis assays, to verify that ATP6V1F promotes development of HCC by promoting migration and invasion and inhibiting apoptosis of HCC cells. Our findings will contribute to providing precise immunotherapy to patients with HCC.

Abstract The gene expression profile of abdominal aortic aneurysm (AAA) neck is not fully understood. The etiology of AAA is considered to be related to atherosclerosis and the inflammatory response, involving congenital, genetic, metabolic, and other factors. The level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to those of cholesterol, oxidized low-density lipoprotein, and triglycerides. PCSK9 inhibitors have significant effects on lowering LDL-cholesterol, reversing atherosclerotic plaques, and reducing the risk of cardiovascular events and have been approved by several lipid-lowering guidelines. This work was aimed to investigate the potential role of PCSK9 in the neck of AAA. We extracted the expression dataset (GSE47472) containing 14 AAA patients and 8 donors and single-cell RNAseq (scRNA-seq) data (GSE164678) of CaCl2-induced (AAA) samples from the Gene Expression Omnibus dataset. Through bioinformatics methods, we found that PCSK9 was up-regulated in the proximal neck of human AAA. In AAA, PCSK9 was mainly expressed in fibroblasts. Additionally, immune check-point PDCD1LG2 was also expressed higher in AAA neck than donor, while CTLA4, PDCD1, and SIGLEC15 were down-regulated in AAA neck. The expression of PCSK was correlated with PDCD1LG2, LAG3, and CTLA4 in AAA neck. Additionally, some ferroptosis-related genes were also down-regulated in AAA neck. PCSK9 was also correlated with ferroptosis-related genes in AAA neck. In conclusion, PCSK9 was highly expressed in AAA neck, and may exert its role through interacting with immune check-points and ferroptosis-related genes.

Background: The survival rate of hepatocellular carcinoma (HCC) is low and the prognosis is poor. Metabolic reprogramming is still an emerging hallmark of cancer, and reprogramming of cholesterol metabolism plays a crucial action in tumor pathogenesis. Increasing evidence suggests that cholesterol metabolism affects the cell proliferation, invasion, migration, and resistance to chemotherapy of HCC. To date, no long noncoding RNA (lncRNA) signature associated with cholesterol metabolism has been developed to predict the outcome of patients with HCC. Methods: The RNA-seq data as well as the prognostic and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We conducted univariate and multivariate analyses to assess cholesterol metabolism-related lncRNAs correlated with the prognosis of patients with HCC in order to construct a prognostic signature. Functional differences between low- and high-risk groups were investigated using genomic enrichment analysis (GSEA). Kaplan-Meier (KM) curves were applied to explore the overall survival (OS) of the low- and high-risk groups. Single-sample genomic enrichment analysis (ssGSEA) was applied to investigate the association between this predictive signature and immune function. We subsequently examined how this signature relates to treatment response in HCC patients. Results: A prognostic signature comprising six lncRNAs related to cholesterol metabolism was constructed (AC124798.1, AL031985.3, AC103760.1, NRAV, WAC-AS1 and AC022613.1). We found that low-risk groups showed a better prognosis than high-risk groups. In HCC patients, the cholesterol metabolism-related lncRNA signature may be served as an independent prognostic factor. Cholesterol metabolism-related lncRNA signature had higher diagnostic efficiency compared to clinicopathologic variables. After stratifying patients according to different clinicopathological variables, patients with low-risk had a longer OS compared with high-risk patients. The ssGSEA demonstrated that this signature was closely related to the immune status of HCC patients. GSEA analysis demonstrated that immune- and tumor-related pathways were predominantly enriched in the high-risk group. High-risk patients were more responsive to immune checkpoint inhibitors (ICIs) and conventional chemotherapeutic agents. Conclusions: This cholesterol metabolism-related lncRNA signature can predict the prognosis of HCC patients and guide the clinical management of HCC patients, including immunotherapy.

BackgroundThe utilization of frozen-thawed embryo transfer (FET) cycles has been linked to heightened risks of adverse perinatal outcomes. However, the potential association between adverse perinatal outcomes and distinct endometrial preparation regimens remains unclear. Therefore, we aim to investigate the maternal and neonatal outcomes after hormone replacement treatment (HRT) cycles, natural cycles (NC) and HRT cycles with pretreatment using GnRHa (HRT + GnRHa) for ovulatory women undergoing FET cycles.MethodsA large sample retrospective cohort study was carried out from 2016 to 2020. The data included a total of 5316 women who had singleton deliveries undergoing FET cycles and which were divided into three groups based on different endometrial preparation protocols: 4399 patients in HRT groups, 621 in GnRHa+HRT groups, 296 in NC groups. The outcomes consisted of maternal outcomes (cesarean section, hypertensive disorders of pregnancy (HDP), placenta previa, gestational diabetes mellitus (GDM));and neonatal outcomes (preterm birth, newborn birthweight, low birthweight, small for gestational age (SGA), macrosomia, large for gestational age (LGA), fetal malformation).ResultsAfter adjusting for a series of confounding variables, we found an increased risk of HDP (aOR=3.362; 95%CI, 1.059-10.675) and cesarean section (aOR=1.838; 95%CI, 1.333-2.535) in HRT cycles compared with NC, especially for ovulatory women under 35 years old. However, in all three groups, newborn birth weight was not significantly different. Meanwhile, perinatal outcomes did not differ significantly in terms of perinatal outcomes in HRT +GnRHa cycles compared with HRT cycles solely.ConclusionDuring FET cycles, singletons from HRT were related to higher risks of HDP and cesarean section, particularly for young women. GnRHa pretreatment didn’t bring any benefit to perinatal outcomes compared with HRT cycles alone. Therefore, the natural cycle may be a more appropriate and safer option for young ovulatory women.

BackgroundThere is a higher risk of preterm delivery (PTD) in singleton live births conceived after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) compared with spontaneously conceived pregnancies. The objective of our study was to build a predictive nomogram model to suggest the possibility of PTD in singleton pregnancies after IVF/ICSI treatment.Method11513 IVF/ICSI cycles with singleton live births were enrolled retrospectively. These cycles were randomly allocated into a training group (80%) and a validation group (20%). We used the multivariate logistics regression analysis to determine prognostic factors for PTD in the training group. A nomogram based on the above factors was further established for predicting PTD. Receiver operating characteristic curves (ROC), areas under the ROC curves (AUC), concordance index (C-index), and calibration plots were analyzed for assessing the performance of this nomogram in the training and validation group.ResultsThere were fourteen risk factors significantly related to PTD in IVF/ICSI singleton live births, including maternal body mass index (BMI) > 24 kg/m2, smoking, uterine factors, cervical factors, ovulatory factors, double embryo transferred (DET), blastocyst transfer, FET, vanishing twin syndrome (VTS), obstetric complications (placenta previa, placenta abruption, hypertensive of pregnancies, and premature rupture of membrane), and a male fetus. These factors were further incorporated to construct a nomogram prediction model. The AUC, C-index, and calibration curves indicated that this nomogram exhibited fair performance and good calibration.ConclusionsWe found that the occurrence of PTD increased when women with obesity, smoking, uterine factors, cervical factors, ovulatory factors, DET, VTS, and obstetric complications, and a male fetus. Furthermore, a nomogram was constructed based on the above factors and it might have great value for clinic use.

Abstract Tubulin alpha-1c chain (TUBA1C), a subtype of α-tubulin, has been shown to be involved in cell proliferation and cell cycle progression in several cancers and to influence cancer development and prognosis. However, a pancancer analysis of TUBA1C to reveal its immunological and prognostic roles has not been performed. In this study, we first downloaded raw data on TUBA1C expression in cancers from The Cancer Genome Atlas (TCGA) database and multiple other databases and analysed these data with R software to investigate the prognostic and immunological value of TUBA1C in cancers. Immunohistochemical analysis was performed in gliomas to further validate our findings. Overall, TUBA1C was overexpressed in most cancers, and overexpression of TUBA1C was linked to poor prognosis and higher tumour grade in patients. In addition, TUBA1C expression was associated with tumour mutation burden (TMB), microsatellite instability (MSI), the tumour microenvironment (TME) and the infiltration of immune cells. TUBA1C was also coexpressed with most immune-related genes and influenced immune-related pathways. Immunohistochemical analysis showed that TUBA1C expression was highest in glioblastoma (GBM) tissues, second highest in low-grade glioma (LGG) tissues and lowest in normal tissues. Our study indicated that TUBA1C might be a biomarker for predicting the immune status and prognosis of cancers, offering new ideas for cancer treatment.

Abstract Background Currently, there is no universal criteria for the trigger time of controlled ovarian hyperstimulation (COH), especially with the emerging depot GnRH agonist protocol. It is challenging to explore an indicator that is representative of target follicle cohort development as an alternative to the conventional approach of determining the trigger time based on a few leading follicles. Methods This was a large-sample retrospective analysis. Between January 2016 and January 2020, 1,925 young normal ovarian responders who underwent their first in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycle using the depot GnRH agonist protocol were included. They were divided into three groups based on the dominant follicular proportion (DFP, defined as the ratio of ≥ 18 mm dominant follicles/ ≥ 14 mm large follicles on the human chorionic gonadotropin (HCG) day; Group A: < 30%; Group B: 30%−60%; and Group C: ≥ 60%). The binary logistic regression and multivariate linear regression were used to assess whether the DFP was associated with clinical pregnancy, the number of frozen blastocysts, the blastocyst formation rate, and the low number of frozen blastocysts. Results The logistic regression analysis showed that compared with Group A, the odds ratio (OR) for clinical pregnancy was 1.345 in Group B (P = 0.023), and there was no statistical difference between Group C and Group A (P = 0.216). The multivariate linear regression analysis showed that DFP was negatively associated with the number of frozen blastocysts (β ± SE: Group B vs. Group A = − 0.319 ± 0.115, P = 0.006; Group C vs. Group A = − 0.432 ± 0.154, P = 0.005) as well as the blastocyst formation rate (β ± SE: Group B vs. Group A = − 0.035 ± 0.016, P = 0.031; Group C vs. Group A = − 0.039 ± 0.021, P = 0.067). Furthermore, the OR for the low number of frozen blastocysts was 1.312 in Group B (P = 0.039) and 1.417 in Group C (P = 0.041) compared to Group A. Conclusions For young normal ovarian responders using the depot GnRH agonist protocol, increasing DFP might reduce the developmental potential of oocytes and reduce the number of available blastocysts, and this might result in a lower cumulative pregnancy rate. However, further confirmation using strict prospective randomised controlled studies is required.

ObjectiveThe aim of this study was to describe the cumulative live birth rates (CLBRs) of young women with or without low prognosis according to the POSEIDON criteria after IVF/ICSI cycles and to investigate whether the diagnosis of low prognosis increases the risk of abnormal birth outcomes.DesignRetrospective study.SettingA single reproductive medicine center.PopulationFrom January 2016 to October 2020, there were 17,893 patients (

Equid alphaherpesvirus type 8 (EqHV-8) is the causative agent of severe respiratory disease, abortions, and neurological syndromes in equines and has resulted in huge economic losses to the donkey industry. Currently, there exist no therapeutic molecules for controlling EqHV-8 infection. We evaluated the potential antiviral activity of cobalt protoporphyrin (CoPP) against EqHV-8 infection. Our results demonstrated that CoPP inhibited EqHV-8 infection in susceptible cells and mouse models. Furthermore, CoPP blocked the replication of EqHV-8 via HO-1 (heme oxygenase-1) mediated type I interferon (IFN) response. In conclusion, our data suggested that CoPP could serve as a novel potential molecule to develop an effective therapeutic strategy for EqHV-8 prevention and control.

The cloud condensation nuclei (CCN) activity and aerosol chemical composition were concurrently measured via a scanning mobility CCN analyzer (SMCA) and an Aerodyne Time-of-Flight Aerosol Chemical Speciation Monitor (ACSM), respectively, during wintertime 2022 in Beijing, China. During the observation period, the mean CCN number concentrations ranged from 1345 ± 1270 cm−3 at SS = 0.1% to 3267 ± 2325 cm−3 at SS = 0.3%. The mean critical activation diameters (D50) at SS = 0.1%, 0.2%, and 0.3% were 172 ± 13 nm, 102 ± 8 nm, and 84 ± 7 nm, corresponding to the average hygroscopicity parameters (κCCN) of 0.34, 0.33, and 0.26, respectively. The diurnal variations in D50 suggested that the local primary emissions significantly enhanced D50 at SS = 0.2% and 0.3%, but had less influence on D50 at SS = 0.1% due to the limited size (2.5 concentration increases, the dominant driver of CCN activity transitions from sulfate to nitrate. At a specific SS, D50 decreased with increases in the degree of internal mixing, implying that the elevated internal mixing degree during atmospheric aging was beneficial to CCN activation. In this study, the commonly used f44 (or O:C) was weakly correlated with κorg and failed to describe the variations in κorg. Instead, the variations in κorg can be well parameterized with the Org/BC ratio. The correlation between κ derived from bulk chemical compositions and CCN measurements was substantially improved when this κorg scheme was adopted, emphasizing the importance of considering κorg variations on deriving κchem from aerosol chemical composition.

Abstract Background Anti‐silencing function 1 (ASF1) is a conserved histone H3–H4 chaperone protein. ASF1B, a paralog of ASF1, acts by promoting cell proliferation and influencing cell cycle progression. Although there is some evidence demonstrating that ASF1B plays a key role in the development, progression, and prognosis of certain cancers, there are no pan‐cancer analyses of ASF1B. Methods We used a range of bioinformatics approaches to investigate the predictive role of ASF1B, including its correlation with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), and immune cell infiltration, in diverse cancer types. Results We found that ASF1B was highly expressed in 22 cancers and was negatively correlated with the prognosis of multiple major cancer types. Furthermore, ASF1B expression was correlated with TMB in 21 cancers and with MSI in 7 cancers. We found that ASF1B was coexpressed with genes encoding immune activators, immune suppressors, major histocompatibility complexes, chemokines, and chemokine receptors. We further found that the role of ASF1B in the infiltration of different types of immune cells varied across tumor types. ASF1B may potentially affect several key immune‐related pathways, such as those involved in antigen processing and presentation, natural killer cell‐mediated cytotoxicity, and autoimmune thyroid disease. Conclusions Our findings show that ASF1B may serve as a prognostic marker and potential immunotherapeutic target for several malignancies due to its role in tumorigenesis and immune infiltration.

ObjectiveThis study aims to analyze the gene expression profile of peripheral blood in different stages of myocardial infarction (MI) by transcriptome sequencing, and to study the gene expression characteristics of peripheral blood after MI.MethodsDifferentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify genes and modules associated with old myocardial infarction (OMI). Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation were applied to analyze the potential functions of genes. Hub genes were identified by Random Forest Classifier. CIBERSORT was used to provide an estimate of the abundance of 22 immune cells in peripheral blood. Quantitative polymerase chain reaction (qPCR) was used to detect gene expression levels in clinical samples. The cellular components (CC) of peripheral blood were counted by an automatic hematology analyzer.ResultsThrough differential gene analysis and co-expression network analysis, 11 candidate genes were obtained. A random forest classifier identified 10 hub genes. Immune cell distribution of peripheral blood was found that T cell CD4 memory resting, NK cells resting, Dendritic cells activated, Mast cells resting, Monocytes and Neutrophils were correlated with OMI. Spearman correlation analysis found that PFKFB2 is related to the above immune cells. Low expression of PFKFB2 in peripheral blood of OMI was detected in clinical samples, and the relationship between PFKFB2 and peripheral blood immune cell counts was analyzed, which showed monocytes were associated with PFKFB2 in our study.ConclusionPFKFB2 was low expressed in OMI, and related to the distribution of immune cells. PFKFB2 may play a key role in reflecting the transition from AMI to OMI, and predicting the distribution of immune cells, which provided a new perspective for improving myocardial fibrosis and adverse remodeling.

Liver hepatocellular carcinoma (LIHC) is a malignancy with a high mortality and morbidity rate worldwide. However, the pathogenesis of LIHC has still not been thoroughly studied. Transmembrane and coiled-coil domains 3 (TMCO3) encodes a monovalent cation, a member of the proton transducer 2 (CPA2) family of transporter proteins. In the present study, TMCO3 expression and its relationship with cancer prognosis, as well as its immunological role in LIHC were studied by bioinformatic analysis. We found the significant overexpression of TMCO3 in LIHC in the TCGA, HCCDB, and GEO databases. In LIHC patients, high TMCO3 expression was related to poorer overall survival (OS) and TMCO3 had good predictive accuracy for prognosis. Moreover, TMCO3 was linked to the infiltrates of certain immune cells in LIHC. The correlation of TMCO3 with immune checkpoints was also revealed. Moreover, patients with LIHC with low TMCO3 expression showed a better response to immune checkpoint blockade (ICB) than those with LIHC with high TMCO3 expression. GO and KEGG enrichment analyses indicated that TMCO3 was probably involved in the microtubule cytoskeleton organization involved in mitosis, small GTPase mediated signal transduction, and TGF-β pathway. In conclusion, TMCO3 may be a potential biomarker for LIHC prognosis and immunotherapy.

Glioma is the most common primary brain tumor in the human brain. The present study was designed to explore the expression of PIMREG in glioma and its relevance to the clinicopathological features and prognosis of glioma patients. The correlations of PIMREG with the infiltrating levels of immune cells and its relevance to the response to immunotherapy were also investigated. PIMREG expression in glioma was analyzed based on the GEO, TCGA, and HPA databases. Kaplan–Meier survival analysis was used to examine the predictive value of PIMREG for the prognosis of patients with glioma. The correlation between the infiltrating levels of immune cells in glioma and PIMREG was analyzed using the CIBERSORT algorithm and TIMRE database. The correlation between PIMREG and immune checkpoints and its correlation with the patients’ responses to immunotherapy were analyzed using R software and the GEPIA dataset. Cell experiments were conducted to verify the action of PIMREG in glioma cell migration and invasion. We found that PIMREG expression was upregulated in gliomas and positively associated with WHO grade. High PIMREG expression was correlated with poor prognosis of LGG, prognosis of all WHO grade gliomas, and prognosis of recurrent gliomas. PIMREG was related to the infiltration of several immune cell types, such as M1 and M2 macrophages, monocytes and CD8+ T cells. Moreover, PIMREG was correlated with immune checkpoints in glioma and correlated with patients’ responses to immunotherapy. KEGG pathway enrichment and GO functional analysis illustrated that PIMREG was related to multiple tumor- and immune-related pathways. In conclusion, PIMREG overexpression in gliomas is associated with poor prognosis of patients with glioma and is related to immune cell infiltrates and the responses to immunotherapy.

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of endometrium during the proliferative phase, which is orchestrated by complex cell–cell interactions and cytokine networks. However, the intercellular communication has not been fully delineated. In the present work, we studied the cell–cell interactome among cells of human proliferative phase endometrium using single-cell transcriptomics. The transcriptomes of 33,240 primary endometrial cells were profiled at single-cell resolution. CellChat was used to infer the cell–cell interactome by assessing the gene expression of receptor–ligand pairs across cell types. In total, nine cell types and 88 functionally related signaling pathways were found. Among them, growth factors and angiogenic factor signaling pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, and ANGPTL that are highly associated with endometrial growth, were further analyzed and verified. The results showed that stromal cells and proliferating stromal cells represented cell–cell interaction hubs with a large number of EGF, PDGF incoming signals, and FGF outgoing signals. Endothelial cells exhibited cell–cell interaction hubs with a plenty of VEGF, TGFb incoming signals, and ANGPT outgoing signals. Unciliated epithelial cells, ciliated epithelial cells, and macrophages exhibited cell–cell interaction hubs with substantial EGF outgoing signals. Ciliated epithelial cells represented cell–cell interaction hubs with a large number of IGF and TGFb incoming signals. Smooth muscle cells represented lots of PDGF incoming signals and ANGPT and ANGPTL outgoing signals. This study deconvoluted complex intercellular communications at the single-cell level and predicted meaningful biological discoveries, which deepened the understanding of communications among endometrial cells.

The equine herpesvirus type 8 (EHV-8) can cause significant economic losses in the global horses and donkey industry. The disease has been associated with abortion and respiratory symptoms. However, it is rare for a study to be reported about donkeys with neurological diseases induced by EHV-8 infection. In the present study, one 2-year-old male donkey, from a large-scale donkey farm in China, died with a severe neurological disorder. The causative agent, donkey/Shandong/10/2021 (GenBank accession: OL856098), was identified and isolated from the brain tissue of the dead donkey. Meanwhile, BALB/c mice were used as an animal model to evaluate the pathogenicity of the EHV-8 isolate. Our data showed that EHV-8 was positive in brains by PCR and immunohistochemistry, which induced typical viral encephalitis lesions in both donkey and mice consistent with clinical signs. For the first time, we reported that EHV-8 had been isolated from donkeys with a neurological illness in China, which is helpful to reveal the pathogenicity of EHV-8 in the donkey.

Ischemic stroke after cerebral artery occlusion is one of the major causes of chronic disability worldwide. Interleukins (ILs) play a bidirectional role in ischemic stroke through information transmission, activation and regulation of immune cells, mediating the activation, multiplication and differentiation of T and B cells and in the inflammatory reaction. Crosstalk between different ILs in different immune cells also impact the outcome of ischemic stroke. This overview is aimed to roughly discuss the multiple roles of ILs after ischemic stroke. The roles of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-16, IL-17, IL-18, IL-19, IL-21, IL-22, IL-23, IL-32, IL-33, IL-34, IL-37, and IL-38 in ischemic stroke were discussed in this review.

Restricted and repetitive behavior is a core symptom of autism spectrum disorder (ASD) characterized by features of restrictedness, repetition, rigidity, and invariance. Few studies have investigated how restrictedness is manifested in motor behavior. This study aimed to address this question by instructing participants to perform the utmost complex movement. Twenty children with ASD and 23 children with typical development (TD) performed one-dimensional, left-right arm oscillations by demonstrating varying amplitudes and frequencies. The entropy of amplitude and velocity was calculated as an index of kinematic complexity. Results showed that the velocity entropy, but not the amplitude entropy, was significantly lower in ASD than in TD (p < 0.01), suggesting restricted kinematics. Further analysis demonstrated that a significantly higher proportion of the velocity values was allocated at a low-speed level in the children with ASD (p < 0.01). A qualitative comparison of the complex movement with movement at preferred frequency suggested that the children with ASD might be less likely to shift away from the preferred movement. However, our study can be improved in terms of recruiting a larger sample of participants, measuring the level of motivation, and collecting both complex and preferred movements of the same participant.

MAX dimerization protein 3 (MXD3), a transcriptional regulator of the MXD3 superfamily, is a part of the MYC–MAX–MXD network. However, its role in tumors has been reported in several cancers, such as B-cell acute lymphoblastic leukemia, medulloblastoma, neuroblastoma, and glioblastoma. Based on TCGA and GEO data, our first pancancer study of MXD3 confirmed the high expression of MXD3 in cancer tissues. Our results revealed that patients suffering from cancers with higher MXD3 expression had poor OS, DSS, DFI, and PFI. We further explored the methylation status of the MXD3 gene body and gene promoter in cancer. Patients with a higher MXD3 gene body have better OS, while the prognosis of patients with a high MXD3 promoter is more complex. We also verified the differential expression of three clinical phenotypes of MXD3: age, sex, and tumor stage, in a variety of tumors, suggesting a correlation between MXD3 and clinical characteristics. We explored the negative relationship between MXD3 and TMB and MSI in most types of cancer, indicating the poor prognosis of patients with high MXD3 expression. We further investigated the relationship between MXD3 and immune infiltrating cells and identified the relationship between MXD3 and immune genes, immunosuppressive genes, and antigen-presenting genes. All of the above findings established a solid relationship between MXD3 and the immune environment and immune cells. These results demonstrated that MXD3 might also be a potential immune factor. We also found a higher expression of MXD3 and promoter according to the increasing glioma WHO grade or histologic types. Glioma patients with high MXD3 or MXD3 promoter expression had poor survival. Finally, we used IHC to verify the higher expression of MXD3 in glioma samples compared to normal samples. Our study shows that MXD3, as a poor prognostic factor, plays a significant role in many cancers, especially glioma. Although more clinical evidence for MXD3 as a clinical therapeutic target and an immunotherapy site is needed, MXD3 can play an important guiding role in multiple clinical treatments, including immunotherapy and demethylation therapy.

TUBA1C, a microtubule component, contributes to the development of several cancers. Our purpose was to study the expression of TUBA1C, its potential prognostic value, and its effects on the infiltration of immune cells of low-grade glioma (LGG). Through applying multiple bioinformatics analyses, we extracted and analyzed datasets from TCGA, TIMER, GTEx, GEPIA, and HPA to investigate the potential oncogenic mechanisms of TUBA1C, including the correlation between TUBA1C and prognosis, immune-checkpoints, tumor microenvironment (TME), and infiltration of immune cells in LGG. GO functional annotations and KEGG pathway analyses were further applied to investigate the potential action of TUBA1C in LGG. We revealed that the mRNA levels of TUBA1C were increased in LGG tumor tissues than in normal tissues. Additionally, TUBA1C was up-regulated in the grade III of LGG than in grade II. Moreover, we found that TUBA1C may be an independent prognostic factor of LGG, and high TUBA1C expression correlated to a poor prognosis of LGG. TUBA1C expression was positively associated with the infiltration of B cells, CD8 T+ cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils. TUBA1C was also verified to be co-expressed with immune-related genes and immune-checkpoints. GO and KEGG pathway analyses indicated that TUBA1C may potentially regulate the pathogenesis of LGG through immune-related pathways, including chemokine pathway; JAK-STAT pathway; natural killer cell mediated cytotoxicity; T cell receptor pathway; leukocyte migration; negative regulation of immune system process; regulation of lymphocyte activation; T cell activation and other pathways. In conclusion, TUBA1C expression is increased in LGG and high TUAB1C expression is related to a poor prognosis. TUBA1C may influence tumor development by regulating the tumor-infiltrating cells in the TME. TUBA1C may be a potential target for immunotherapy.

Chemoresistance remains as a major hindrance in the treatment of hepatocellular carcinoma (HCC). High mobility group box protein 1 (HMGB1) enhances autophagic flux and protects tumor cells from apoptosis, which results in acquired drug resistance. However, the exact mechanisms underlying HMGB1-modulated autophagy in HCC chemoresistance remain to be defined. In the present study, we found that administration of doxorubicin (DOX) significantly promoted HMGB1 expression and induced HMGB1 cytoplasmic translocation in human HCC cell lines BEL7402 and SMMC7721, which enhanced autophagy that contributes to protecting HCC cells from apoptosis and increasing drug resistance. Moreover, we observed HMGB1 translocation and elevation of autophagy in DOX-resistant BEL7402 and SMMC7721 cells. Additionally, inhibition of HMGB1 and autophagy increased the sensitivities of BEL-7402 and SMMC-7721 cells to DOX and re-sensitized their DOX-resistant cells. Subsequently, we confirmed with HMGB1 regulated autophagy by activating the 5ʹ adenosine monophosphate-activated protein kinase (AMPK)/mTOR pathway. In summary, our results indicate that HMGB1 promotes acquired DOX resistance in DOX-treated BEL7402 and SMMC7721 cells by enhancing autophagy through the AMPK/mTOR signaling pathway. These findings provide the proof-of-concept that HMGB1 inhibitors might be an important targeted treatment strategy for HCC.

Choriocarcinoma is a highly malignant trophoblastic tumor that occurs mostly in women of childbearing age. The main mode of metastasis is hematogenous metastasis. The most common sites of metastasis are the lung, vagina and brain, while splenic metastasis is rare. Because of its rapid development, extensive metastasis can occur in a short period, and some patients only show metastatic symptoms, which are often missed or misdiagnosed as ectopic pregnancy or other diseases. We describe a rare case of splenic metastatic choriocarcinoma with acute abdominal pain caused by nontraumatic splenic rupture. In addition, we review the previous literature on splenic metastasis of choriocarcinoma and summarize the clinical manifestations, management measures and prognoses. Our case and literature review indicate that splenic metastatic choriocarcinoma is rare and difficult to distinguish from splenic ectopic pregnancy and other diseases. Clinicians should strengthen their understanding of this disease and avoid misdiagnosis.

Whitecap formation is an important factor in the exchange of momentum, heat, and gas on the ocean surface. The long-term measurement of whitecaps is necessary to deepen our understanding of the mechanisms of ocean surface motion. However, traditional detection methods are highly sensitive to illumination. Under various illumination conditions, significant light pollution may be introduced into images. The poor performance caused by using images degraded with light pollution is not conducive to automated long-term whitecap measurement. In this study, we propose a two-step method for the detection of whitecaps under various illumination conditions. An abnormal detection method based on previous whitecap detection methods for the accurate detection of whitecaps in light-polluted areas is proposed as the first step. Using the detection results, we propose a post-processing method based on optical flow trajectories at two sampling rates to separate actual whitecap components in images containing false positives. Experiments show that the method proposed in this study can more accurately detect whitecaps in images with light pollution when compared to existing methods.

Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) localizes to the nucleus and can significantly elevate the nuclear localization of clathrin assembly lymphomedullary leukocythemia gene. Although there is some evidence to support an important action for PIMREG in the occurrence and development of certain cancers, currently no pan-cancer analysis of PIMREG is available. Therefore, we intended to estimate the prognostic predictive value of PIMREG and to explore its potential immune function in 33 cancer types. By using a series of bioinformatics approaches, we extracted and analyzed datasets from Oncomine, The Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia (CCLE) and the Human Protein Atlas (HPA), to explore the underlying carcinogenesis of PIMREG, including relevance of PIMREG to prognosis, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME) and infiltration of immune cells in various types of cancer. Our findings indicate that PIMREG is highly expressed in at least 24 types of cancer, and is negatively correlated with prognosis in major cancer types. In addition, PIMREG expression was correlated with TMB in 24 cancers and with MSI in 10 cancers. We revealed that PIMREG is co-expressed with genes encoding major histocompatibility complex, immune activation, immune suppression, chemokine and chemokine receptors. We also found that the different roles of PIMREG in the infiltration of different immune cell types in different tumors. PIMREG can potentially influence the etiology or pathogenesis of cancer by acting on immune-related pathways, chemokine signaling pathway, regulation of autophagy, RIG-I like receptor signaling pathway, antigen processing and presentation, FC epsilon RI pathway, complement and coagulation cascades, T cell receptor pathway, NK cell mediated cytotoxicity and other immune-related pathways. Our study suggests that PIMREG can be applied as a prognostic marker in a variety of malignancies because of its role in tumorigenesis and immune infiltration.

BackgroundPrevious studies have shown promising results in identifying individuals with autism spectrum disorder (ASD) by applying machine learning (ML) to eye-tracking data collected while participants viewed varying images (ie, pictures, videos, and web pages). Although gaze behavior is known to differ between face-to-face interaction and image-viewing tasks, no study has investigated whether eye-tracking data from face-to-face conversations can also accurately identify individuals with ASD. ObjectiveThe objective of this study was to examine whether eye-tracking data from face-to-face conversations could classify children with ASD and typical development (TD). We further investigated whether combining features on visual fixation and length of conversation would achieve better classification performance. MethodsEye tracking was performed on children with ASD and TD while they were engaged in face-to-face conversations (including 4 conversational sessions) with an interviewer. By implementing forward feature selection, four ML classifiers were used to determine the maximum classification accuracy and the corresponding features: support vector machine (SVM), linear discriminant analysis, decision tree, and random forest. ResultsA maximum classification accuracy of 92.31% was achieved with the SVM classifier by combining features on both visual fixation and session length. The classification accuracy of combined features was higher than that obtained using visual fixation features (maximum classification accuracy 84.62%) or session length (maximum classification accuracy 84.62%) alone. ConclusionsEye-tracking data from face-to-face conversations could accurately classify children with ASD and TD, suggesting that ASD might be objectively screened in everyday social interactions. However, these results will need to be validated with a larger sample of individuals with ASD (varying in severity and balanced sex ratio) using data collected from different modalities (eg, eye tracking, kinematic, electroencephalogram, and neuroimaging). In addition, individuals with other clinical conditions (eg, developmental delay and attention deficit hyperactivity disorder) should be included in similar ML studies for detecting ASD.

BackgroundInflammatory responses play a multiphase role in the pathogenesis of cerebral ischemic stroke (IS). Ruxolitinib (Rux), a selective oral JAK 1/2 inhibitor, reduces inflammatory responses via the JAK2/STAT3 pathway. Based on its anti-inflammatory and immunosuppressive effects, we hypothesized that it may have a protective effect against stroke. The aim of this study was to investigate whether inhibition of JAK2 has a neuroprotective effect on ischemic stroke and to explore the potential molecular mechanisms.MethodsRux, MCC950 or vehicle was applied to middle cerebral artery occlusion (MCAO) mice in vivo and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. After 3 days of reperfusion, neurological deficit scores, infarct volume and brain water content were assessed. Immunofluorescence staining and western blots were used to measure the expression of NLRP3 inflammasome components. The infiltrating cells were investigated by flow cytometry. Proinflammatory cytokines were assessed by RT-qPCR. The expression of the JAK2/STAT3 pathway was measured by western blots. Local STAT3 deficiency in brain tissue was established with a lentiviral vector carrying STAT3 shRNA, and chromatin immunoprecipitation (ChIP) assays were used to investigate the interplay between NLRP3 and STAT3 signaling.ResultsRux treatment improved neurological scores, decreased the infarct size and ameliorated cerebral edema 3 days after stroke. In addition, immunofluorescence staining and western blots showed that Rux application inhibited the expression of proteins related to the NLRP3 inflammasome and phosphorylated STAT3 (P-STAT3) in neurons and microglia/macrophages. Furthermore, Rux administration inhibited the expression of proinflammatory cytokines, including TNF-α, IFN-γ, HMGB1, IL-1β, IL-2, and IL-6, suggesting that Rux may alleviate IS injury by inhibiting proinflammatory reactions via JAK2/STAT3 signaling pathway regulation. Infiltrating macrophages, B, T, cells were also reduced by Rux. Local STAT3 deficiency in brain tissue decreased histone H3 and H4 acetylation on the NLRP3 promoter and NLRP3 inflammasome component expression, indicating that the NLRP3 inflammasome may be directly regulated by STAT3 signaling. Rux application suppressed lipopolysaccharide (LPS)-induced NLRP3 inflammasome secretion and JAK2/STAT3 pathway activation in the OGD/R model in vitro.ConclusionJAK2 inhibition by Rux in MCAO mice decreased STAT3 phosphorylation, thus inhibiting the expression of downstream proinflammatory cytokines and the acetylation of histones H3 and H4 on the NLRP3 promoter, resulting in the downregulation of NLRP3 inflammasome expression.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Sorafenib is approved by the U.S. Food and Drug Administration to be a first-line chemotherapy agent for patients with advanced HCC. A portion of advanced HCC patients can benefit from the treatment with sorafenib, but many patients ultimately develop sorafenib resistance, leading to a poor prognosis. The molecular mechanisms of sorafenib resistance are sophisticated and indefinite. Notably, non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are critically participated in the occurrence and progression of tumors. Moreover, growing evidence has suggested that ncRNAs are crucial regulators in the development of resistance to sorafenib. Herein, we integrally and systematically summarized the molecular mechanisms and vital role of ncRNAs impact sorafenib resistance of HCC, and ultimately explored the potential clinical administrations of ncRNAs as new prognostic biomarkers and therapeutic targets for HCC.

Malignant tumors are always a critical threat to human health, with complex pathogenesis, numerous causative factors, and poor prognosis. The features of cancers, such as gene mutations, epigenetic alterations, and the activation and inhibition of signaling pathways in the organism, play important roles in tumorigenesis and prognosis. MicroRNA (miRNA) enables the control of various molecular mechanisms and plays a variety of roles in human cancers, such as radiation sensitivity and tumor immunity, through the regulation of target genes. MiR-149-5p participates in the process and is closely related to lipogenesis, the migration of vascular endothelial cells, and the expression of stem-cell-related proteins. In recent years, its role in cancer has dramatically increased. In this review, we summarize the regular physiological roles of miRNAs, specifically miR-149-5p, in the organism and discuss the tumor-suppressive or oncogenic roles of miR-149-5p in different human cancers with respect to signaling pathways involved in regulation. Possible clinical applications of miR-149-5p in future targeted therapies and prognosis improvement in oncology are suggested.

Glioma is the common, most aggressive and poorest prognostic tumor type in the brain. More and more biomarkers associated with glioma treatment, prognosis, and immunity are being discovered. Here, we aimed to explore the underlying biological functions and prognostic predictive value of Apolipoprotein L4 (APOL4) in glioma. We downloaded the expression data of APOL4 and clinical information from several databases and used R software for preprocessing. The clinical significance of APOL4 in a glioma outcome was explored by the Cox regression analysis and Kaplan–Meier survival analysis. In addition, immune infiltrates and microenvironmental indicators were assessed by CIBERSORT and TIMER. GO and KEGG analyses were used to analyze the potential functions of APOL4 in gliomas. APOL4 expression was increased in glioma specimens compared to normal tissues and correlated dramatically with the WHO grade. A survival analysis showed a shorter overall survival (OS) in glioma patients with APOL4 overexpression, and a Cox regression analysis showed that APOL4 was an independent prognostic factor for the OS of glioma patients. GSEA, GO, and KEGG enrichment analyses showed remarkable enrichment in immune-related pathways. APOL4 expression was positively correlated with immune infiltration (including DC cells, neutrophils, CD8+ T cells, B cells, macrophages, CD4+ T cells, etc.) and microenvironmental parameters (including immune, stromal, and ESTIMATE scores) in gliomas. Glioma patients with a higher expression of APOL4 may be more sensitive to immune checkpoint inhibitors (ICI). In conclusion, these findings suggest that APOL4 is associated with the tumor grade and immune infiltrates; APOL4 may be a new and potential biomarker for therapeutic and prognostic evaluations that may further suggest the therapeutic efficacy of immunotherapy.

Stroke is the leading cause of disability and mortality in the world, but the pathogenesis of ischemic stroke (IS) is not completely clear and treatments are limited. Mounting evidence indicate that neovascularization is a critical defensive reaction to hypoxia that modulates the process of long-term neurologic recovery after IS. Angiogenesis is a complex process in which the original endothelial cells in blood vessels are differentiated, proliferated, migrated, and finally remolded into new blood vessels. Many immune cells and cytokines, as well as growth factors, are directly or indirectly involved in the regulation of angiogenesis. Inflammatory cells can affect endothelial cell proliferation, migration, and activation by secreting a variety of cytokines via various inflammation-relative signaling pathways and thus participate in the process of angiogenesis. However, the mechanism of inflammation-mediated angiogenesis has not been fully elucidated. Hence, this review aimed to discuss the mechanism of inflammation-mediated angiogenesis in IS and to provide new ideas for clinical treatment of IS.

Existing diagnosis of the autism spectrum disorder (ASD) heavily depends on the informant's evaluation of the patient's behavior, which is both time consuming and labor demanding. In order to develop a rapid diagnostic tool with high accuracy, machine learning (ML) approaches have been proposed to explore the feasibility of identifying ASD with a limited number of features extracted from behavioral evaluation, neuroimaging and kinematic data. Though restricted and repetitive behavior (RRB) is one of the cardinal symptoms of ASD, no study has been conducted to investigate whether restricted kinematic features (RKF) could be used to identify ASD. The present study aimed to address this question. Twenty children with high functioning autism and twenty-three children with typical development (TD) were recruited. They were instructed to perform a motor task that required the execution of the utmost variant movement. Entropy and 95% range of the movement amplitude, velocity and acceleration were computed as indices of RKF. Five ML classifiers were trained and tested including support vector machine (SVM), Linear Discriminant Analysis (LDA), Decision tree (DT), Random forest (RF), and K nearest neighbor (KNN). Results showed that the KNN algorithm (k = 1 ) yielded the highest classification accuracy with four kinematic features (accuracy: 88.37%, specificity: 91.3%, sensitivity: 85%, AUC: 0.8815). Our study demonstrated that RKF could help robustly identify ASD. It is inferred that the application of ML on genetic, neuroimaging, psychological and kinematic features might pose a considerable challenge to the current diagnostic criteria of ASD, and might potentially lead to an automated and objective diagnosis of ASD.

Wrist disability caused by a series of diseases or injuries hinders the patient’s capability to perform activities of daily living (ADL). Rehabilitation devices for the wrist motor function have gained popularity among clinics and researchers due to the convenience of self-rehabilitation. The inherent compliance of soft robots enabled safe human-robot interaction and light-weight characteristics, providing new possibilities to develop wearable devices. Compared with the conventional apparatus, soft robotic wearable rehabilitation devices showed advantages in flexibility, cost, and comfort. In this work, a compact and low-profile soft robotic wrist brace was proposed by directly integrating eight soft origami-patterned actuators on the commercially available wrist brace. The linear motion of the actuators was defined by their origami pattern. The extensions of the actuators were constrained by the brace fabrics, deriving the motions of the wrist joint, i.e., extension/flexion, ulnar/radial deviation. The soft actuators were made of ethylene-vinyl acetate by blow molding, achieving mass-production capability, low cost, and high repeatability. The design and fabrication of the soft robotic wrist brace are presented in this work. The experiments on the range of motion, output force, wearing position adaptivity, and performance under disturbance have been carried out with results analyzed. The modular soft actuator approach of design and fabrication of the soft robotic wrist brace has a wide application potential in wearable devices.

The prediction of visibility is an ongoing problem in air quality models, particularly that of low visibility during heavily polluted episodes. In this study, a new method of calculating visibility based on the particle mass concentration of PM2.5 (particles with diameter ≤ 2.5 μm) and relative humidity (RH), data for which are generally available in most regions of China, is developed. The method also considers the particle number size distribution (PNSD) and hygroscopic parameter (κ), and focuses on visibility below 10 km. First, the PNSD was re-constructed under dry condition (PNSDdry,rec) based on the relationship between PM2.5 and the particle volume size distribution modal parameters obtained in a previous study conducted in the North China Plain. Then, the ambient PNSD (PNSDamb,rec) was retrieved based on the PNSDdry,rec and κ, and the light extinction was calculated by applying the Mie code (σext,amb). Finally, the visibility was calculated based on the Koschmieder experimental equation, and denoted as Viscal. A parameterization scheme was proposed based on the σext,amb, PM2.5, and RH to simulate the visibility (Vissimu), which is more applicable than the theoretical calculation described above. This method was validated at different locations in different regions in China. The values calculated by the scheme showed agreed well with the observed data in general, especially for low visibility of ≤5 km, associated with severe haze. Although a large bias occurred at some sites, both the hourly and daily averages for almost every event with visibility lower than 5 km were captured. The method reported in this work exhibited smaller bias below 2 km than the other visibility parameterization scheme, and will be available for improving the prediction of visibility in air quality models.

Tubulin alpha 1b (TUBA1B) is an important microtubule isoform that is involved in the formation of the cytoskeleton. The objective of our study was to explore the potential of TUBA1B in predicting the prognosis of HCC and patients’ response to immunotherapy. Raw data was extracted from TCGA and GEO databases, and then HCCDB, TIMER, HPA, and GEPIA websites, as well as R software, were used to perform bioinformatics analysis to investigate the potential of TUBA1B as a prognostic and immunotherapeutic marker for hepatocellular carcinoma (HCC). We found that both TUBA1B mRNA and protein were highly expressed in HCC. TUBA1B was proved to be an independent prognostic predictor of HCC. Additionally, TUBA1B expression was associated with the infiltration of several immune cells in HCC. Moreover, TUBA1B was coexpressed with immune-related genes and immune checkpoints. Patients expressing high TUBA1B responded better to immune checkpoint inhibitor (ICI) therapy. GO and KEGG analyses revealed that TUBA1B may be involved in the processes of cell cycle, spliceosome, and DNA replication. In conclusion, TUBA1B is expected to be a prognostic and immunotherapeutic marker for HCC.

3' downstream inhibitory stem plays a crucial role in locking rpoS mRNA 5' untranslated region in a self-inhibitory state. Here, we used optical tweezers to study the unfolding/refolding of rpoS inhibitory stem in the absence and presence of Mg2+. We found adding Mg2+ decreased the free energy of the RNA junction without re-arranging its secondary structure, through confirming that this RNA formed a canonical RNA three-way junction. We suspected increased free energy might change the relative orientation of different stems of rpoS and confirmed this by small angle X-ray scattering. Such changed conformation may improve Hfq-bridged annealing between sRNA and rpoS RNA inhibitory stem. We established a convenient route to analyze the changes of RNA conformation and folding dynamics by combining optical tweezers with X-ray scattering methods. This route can be easily applied in the studies of other RNA structure and ligand-RNA.

Postural control is a complex skill based on the interaction of dynamic sensorimotor processes, and can be challenging for people with deficits in sensory functions. The foot plantar center of pressure (COP) has often been used for quantitative assessment of postural control. Previously, the foot plantar COP was mainly measured by force plates or complicated and expensive insole-based measurement systems. Although some low-cost instrumented insoles have been developed, their ability to accurately estimate the foot plantar COP trajectory was not robust. In this study, a novel individual-specific nonlinear model was proposed to estimate the foot plantar COP trajectories with an instrumented insole based on low-cost force sensitive resistors (FSRs). The model coefficients were determined by a least square error approximation algorithm. Model validation was carried out by comparing the estimated COP data with the reference data in a variety of postural control assessment tasks. We also compared our data with the COP trajectories estimated by the previously well accepted weighted mean approach. Comparing with the reference measurements, the average root mean square errors of the COP trajectories of both feet were 2.23 mm (±0.64) (left foot) and 2.72 mm (±0.83) (right foot) along the medial–lateral direction, and 9.17 mm (±1.98) (left foot) and 11.19 mm (±2.98) (right foot) along the anterior–posterior direction. The results are superior to those reported in previous relevant studies, and demonstrate that our proposed approach can be used for accurate foot plantar COP trajectory estimation. This study could provide an inexpensive solution to fall risk assessment in home settings or community healthcare center for the elderly. It has the potential to help prevent future falls in the elderly.