Search

Pancreatic cancer (PC) is an aggressive and metastatic gastrointestinal tumor with a poor prognosis. Persistent activation of the TGF-β/Smad signaling induces PC cell (PCC) invasion and infiltration via epithelial-to-mesenchymal transition (EMT). Hedgehog signaling is a crucial pathway for the development of PC via the transcription factors Gli1/2/3. This study aimed to investigate the underlying molecular mechanisms of action of hedgehog activation in TGF-β1-triggered EMT in PCCs (PANC-1 and BxPc-3). In addition, overexpression and shRNA techniques were used to evaluate the role of Smad4 in TGF-β1-treated PCCs. Our data showed that TGF-β1 promoted PCC invasion and infiltration via Smad2/3-dependent EMT. Hedgehog-Gli signaling axis in PCCs was activated upon TGF-β1 stimulation. Inhibition of hedgehog with cyclopamine effectively antagonized TGF-β1-induced EMT, thereby suggesting that the hedgehog signaling may act as a downstream cascade signaling of TGF-β1. As a key protein that assists the nuclear translocation of Smad2/3, Smad4 was highly expressed in PANC-1 cells, but not in BxPc-3 cells. Conversely, Gli1 expression was low in PANC-1 cells, but high in BxPc-3 cells. Furthermore, knockdown of Smad4 in PANC-1 cells by shRNA inhibited TGF-β1-mediated EMT and collagen deposition. Overexpression of Smad4 did not affect TGF-β1-mediated EMT due to the lack of significant increase in nuclear expression of Smad4. Importantly, Gli1 activity was upregulated by Smad4 knockdown in PANC-1 cells and downregulated by Smad4 overexpression in BxPc-3 cells, indicating that Gli1 may be a negative target protein downstream of Smad4. Thus, Smad4 regulates TGF-β1-mediated hedgehog activation to promote EMT in PCCs by suppressing Gli1 activity.

Abstract Objectives To explore whether monitored anesthesia care is more beneficial to the outcome of transcatheter aortic valve implantation. Methods The research methodology involved comprehensive searches across major databases, including the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. The aim was to identify trials comparing different anesthetic methods for transcatheter aortic valve implantation. The primary outcomes assessed were mortality and length of hospital stay, while secondary outcomes included common complications such as bleeding, stroke, paravalvular leakage, renal failure, and others. Data synthesis was conducted using risk ratios or standardized mean differences, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024507749). Results A total of 35 trials and 45,616 patients were included in this study. The results showed that monitored anesthesia care significantly reduced the patient's risk of death, shortened the patient's length of hospital stay, and also reduced the risk of common complications such as paravalvular leakage (RR, 0.80; 95% CI: 0.72 to 0.88; p

Abstract Background The estimated pulse wave velocity (ePWV) is a recently developed, simple and useful tool to measure arterial stiffness and to predict long-term cardiovascular mortality. However, the association of ePWV with mortality risk in patients with subarachnoid hemorrhage (SAH) is unclear. Herein, this study aims to assess the potential prediction value of ePWV on short- and long-term mortality of SAH patients. Methods Data of adult patients with no traumatic SAH were extracted from the Medical Information Mart for Intensive Care (MIMIC) III and IV database in this retrospective cohort study. Weighted univariate and multivariable Cox regression analyses were used to explore the associations of ePWV levels with 30-day mortality and 1-year mortality in SAH patients. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). In addition, subgroup analyses of age, the sequential organ failure assessment (SOFA) score, surgery, atrial fibrillation (AF), renal failure (RF), hepatic diseases, chronic obstructive pulmonary disease (COPD), sepsis, hypertension, and diabetes mellitus (DM) were also performed. Results Among 1,481 eligible patients, 339 died within 30 days and 435 died within 1 year. After adjusting for covariates, ePWV ≥ 12.10 was associated with higher risk of both 30-day mortality (HR = 1.77, 95%CI: 1.17–2.67) and 1-year mortality (HR = 1.97, 95%CI: 1.36–2.85), compared to ePWV

Abstract Background Thromboelastography (TEG) is a widely utilized clinical testing method for real‐time monitoring of platelet function and the thrombosis process. Lipid metabolism disorders are crucial risk factors for thrombosis. The lipid metabolism characteristics of hamsters resemble those of humans more closely than mice and rats, and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms. Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical procedures. TEG was employed to evaluate coagulation factor function, fibrinogen (Fib) function, platelet function, and the fibrinolytic system. Methods The whole blood from hamster or healthy human was isolated following the clinical procedure, and TEG was employed to evaluate the coagulation factor function, Fib function, platelet function, and fibrinolytic system. Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline. Blood routine testing used XN‐2000 automatic blood analyzer. Results TEG parameters revealed that hamsters exhibited stronger coagulation factor function than humans (reaction time [R], p = 0.0117), with stronger Fib function (alpha angle, p

Background: Neuromyelitis optica spectrum disorders (NMOSD) is characterized by inflammatory demyelinating events in the central nervous system (CNS), primarily affecting the spinal cord and optic nerve, with a significant influence of astrocytes. Longitudinal extensive transverse myelitis (LETM) is a distinct and relatively rare spinal cord syndrome, commonly associated with NMOSD. Case presentation: This report describes a unique case of myelitis in a patient diagnosed with NMOSD. The patient exhibited an uncommon manifestation of ultra- LETM (u-LETM), coexisting with connective tissue disorders including Sjögren's syndrome and autoimmune hepatitis-primary cholestatic cirrhosis. In the acute phase, high-dose methylprednisolone pulse therapy was administered in combination with intravenous human immunoglobulin, while prednisone was gradually tapered and discontinued upon stabilization of the patient's condition. Simultaneously, sequential disease-modifying therapy was initiated, starting with long-term oral administration of mycophenolate mofetil, followed by cyclophosphamide, telitacicept, and Inebilizumab. During follow-up visits conducted every three months, the patient showed gradual improvement, eventually achieving the ability to stand and walk independently. Conclusions: Early and comprehensive evaluation of autoimmune diseases is crucial in patients with NMOSD presenting with u-LETM as the initial symptom. Prompt treatment initiation, followed by disease-modifying therapy, is essential for improving patient prognosis.

BackgroundBreast cancer (BRCA) represents a substantial global health challenge marked by inadequate early detection rates. The complex interplay between the tumor immune microenvironment and fatty acid metabolism in BRCA requires further investigation to elucidate the specific role of lipid metabolism in this disease.MethodsWe systematically integrated nine machine learning algorithms into 184 unique combinations to develop a consensus model for lipid metabolism-related prognostic genes (LMPGS). Additionally, transcriptomics analysis provided a comprehensive understanding of this prognostic signature. Using the ESTIMATE method, we evaluated immune infiltration among different risk subgroups and assessed their responsiveness to immunotherapy. Tailored treatments were screened for specific risk subgroups. Finally, we verified the expression of key genes through in vitro experiments.ResultsWe identified 259 differentially expressed genes (DEGs) related to lipid metabolism through analysis of the cancer genome atlas program (TCGA) database. Subsequently, via univariate Cox regression analysis and C-index analysis, we developed an optimal machine learning algorithm to construct a 21-gene LMPGS model. We used optimal cutoff values to divide the lipid metabolism prognostic gene scores into two groups according to high and low scores. Our study revealed distinct biological functions and mutation landscapes between high-scoring and low-scoring patients. The low-scoring group presented a greater immune score, whereas the high-scoring group presented enhanced responses to both immunotherapy and chemotherapy drugs. Single-cell analysis highlighted significant upregulation of CPNE3 in epithelial cells. Moreover, by employing molecular docking, we identified niclosamide as a potential targeted therapeutic drug. Finally, our experiments demonstrated high expression of MTMR9 and CPNE3 in BRCA and their significant correlation with prognosis.ConclusionBy employing bioinformatics and diverse machine learning algorithms, we successfully identified genes associated with lipid metabolism in BRCA and uncovered potential therapeutic agents, thereby offering novel insights into the mechanisms and treatment strategies for BRCA.

Abstract Background Unintended (unwanted) pregnancy is a sexual and reproductive health issue with psychosocial consequences for the individual, their family, and society. However, the relationship between social support and related mental health issues, like depression and the effects of childhood adversity, is poorly studied. This study aims to explore the connections between childhood adversity, perceived social support, and depressive symptoms in pre-abortion women (women who have decided to have an abortion) in a clinical setting, based on the common risk factor approach and social support theory. Methods A total of 299 pre-abortion Chinese women 18–45 years were recruited in a hospital in Shantou, China. Hierarchical linear regression analyses were employed to examine the relative effects of childhood adversity and sources of social support on depressive symptoms, controlling for sociodemographic influences. Results The results show that 37.2 percent of participants reported at least one adverse experience in childhood. More than half of the respondents were at risk for depression. Results of regression analysis showed that childhood adversities were negatively associated with depressive symptoms before sources of social support were entered into the model. However, when the sources of perceived social support were added, the effect of childhood adversity was not significant. Perceived social support explained the additional 15 percent variance in depressive symptoms. Additionally, being married (β = -.12, p

Background This study aims to identify a novel gene signature for coronary artery disease (CAD), explore the role of immune cell infiltration in CAD pathogenesis, and assess the cell function of mast cell-expressed membrane protein 1 (MCEMP1) in human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL). Methods To identify differentially expressed genes (DEGs) of CAD, datasets GSE24519 and GSE61145 were downloaded from the Gene Expression Omnibus (GEO) database using the R “limma” package with p < 0.05 and |log2 FC| > 1. Gene ontology (GO) and pathway analyses were conducted to determine the biological functions of DEGs. Hub genes were identified using support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO). The expression levels of these hub genes in CAD were validated using the GSE113079 dataset. CIBERSORT program was used to quantify the proportion of immune cell infiltration. Western blot assay and qRT‐PCR were used to detect the expression of hub genes in ox-LDL-treated HUVECs to validate the bioinformatics results. Knockdown interference sequences for MCEMP1 were synthesized, and cell proliferation and apoptosis were examined using a CCK8 kit and Muse® Cell Analyzer, respectively. The concentrations of IL-1β, IL-6, and TNF-α were measured with respective enzyme-linked immunosorbent assay (ELISA) kits. Results A total of 73 DEGs (four down-regulated genes and 69 up-regulated genes) were identified in the metadata (GSE24519 and GSE61145) cohort. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that these DEGs might be associated with the regulation of platelet aggregation, defense response or response to bacterium, NF-kappa B signaling pathway, and lipid and atherosclerosis. Using SVM-RFE and LASSO, seven hub genes were obtained from the metadata. The upregulated expression of DIRC2 and MCEMP1 in CAD was confirmed in the GSE113079 dataset and in ox-LDL-treated HUVECs. The associations between the two hub genes (DIRC2 and MCEMP1) and the 22 types of immune cell infiltrates in CAD were found. MCEMP1 knockdown accelerated cell proliferation and suppressed cell apoptosis for ox-LDL-treated HUVECs. Additionally, MCEMP1 knockdown appeared to decrease the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Conclusions The results of this study indicate that MCEMP1 may play an important role in CAD pathophysiology.

Terrestrial dissolved organic matter (tDOM) holds great promise for controlling cyanobacteria blooms through watershed management. To identify tDOM that could inhibit the growth, photosynthesis and colony formation, unicellular Microcystis aeruginosa Kützing (FACHB-469) was cultivated and treated with varying concentrations of gallic acid, proline and tea polyphenols at different levels of iron. The results indicated that gallic acid and tea polyphenols could inhibit Microcystis growth by suppressing photosynthesis and colony formation by reducing extracellular polysaccharides (EPS) secretion. However, proline had no significant effect on the growth, photosynthesis, colony size and EPS content of Microcystis. Transcriptome analysis showed Microcystis may optimize the internal energy transfer mode of photosynthesis through the change of phycobilisome at different levels of iron. In addition, Microcystis adapted to different iron concentration environments by regulating the expression of genes associated with iron uptake and transport. These findings suggest that the effects of plant species on algal blooms should be considered in reforestation of watershed. This consideration necessitates finding a balance between the costs and benefits of controlling cyanobacteria blooms using tDOM.

Abstract Although engulfment is a hallmark of microglia function, fully validated platforms that facilitate high-throughput quantification of this process are lacking. Here, we present FEAST (Flow cytometric Engulfment Assay for Specific Target proteins), which enables interrogation of in vivo engulfment of synaptic material by brain resident macrophages at single-cell resolution. We optimize FEAST for two different analyses: quantification of fluorescent material inside live cells and of engulfed endogenous proteins within fixed cells. To overcome false-positive engulfment signals, we introduce an approach suitable for interrogating engulfment in microglia from perfusion-fixed tissue. As a proof-of-concept for the specificity and versatility of FEAST, we examine the engulfment of synaptic proteins after optic nerve crush and of myelin in two mouse models of demyelination (treatment with cuprizone and injections of lysolecithin). We find that microglia, but not brain-border associated macrophages, engulf in these contexts. Our work underscores how FEAST can be utilized to gain critical insight into functional neuro-immune interactions that shape development, homeostasis, and disease.

Abstract In order to comprehend the dynamic disaster mechanism induced by overburden rock caving during the advancement of a coal mining face, a physical simulation model is constructed basing on the geological condition of the 21221 mining face at Qianqiu coal mine in Henan Province, China. This study established, a comprehensive monitoring system to investigate the interrelations and evolutionary characteristics among multiple mechanical parameters, including mining-induced stress, displacement, temperature, and acoustic emission events during overburden rock caving. It is suggested that, despite the uniformity of the overburden rock caving interval, the main characteristic of overburden rock lies in its uneven caving strength. The mining-induced stress exhibits a reasonable interrelation with the displacement, temperature, and acoustic emission events of the rock strata. With the advancement of the coal seam, the mining-induced stress undergoes four successive stages: gentle stability, gradual accumulation, high-level mutation, and a return to stability. The variations in other mechanical parameters does not synchronize with the significant changes in mining-induced stress. Before the collapse of overburden rock occurs, rock strata temperature increment decreases and the acoustic emission ringing counts surges with the increase of rock strata displacement and mining-induced stress. Therefore, the collaborative characteristics of mining-induced stress, displacement, temperature, and acoustic emission ringing counts can be identified as the precursor information or overburden rock caving. These results are in good consistent with on-site situation in the coal mine.

IntroductionSpent mushroom substrate (SMS) is a solid waste in agricultural production that contains abundant lignocellulosic fibers. The indiscriminate disposal of SMS will lead to significant resource waste and pollution of the surrounding environment.The isolation and screening of microorganisms with high cellulase degradation capacity is the key to improving SMS utilization.MethodsThe cellulose-degrading microbial consortiums were constructed through antagonism and enzyme activity test. The effect of microbial consortiums on lignocellulose degradation was systematically evaluated by SMS liquid fermentation experiments.ResultsIn this study, four strains of cellulose-degrading bacteria were screened, and F16, F, and F7 were identified as B. amyloliquefaciens, PX1 identified as B. velezensis. At the same time, two groups of cellulose efficient degrading microbial consortiums (PX1 + F7 and F16 + F) were successfully constructed. When SMS was used as the sole carbon source, their carboxymethyl cellulase (CMCase) activities were 225.16 and 156.63 U/mL, respectively, and the filter paper enzyme (FPase) activities were 1.91 and 1.64 U/mL, respectively. PX1 + F7 had the highest degradation rate of hemicellulose and lignin, reaching 52.96% and 52.13%, respectively, and the degradation rate of F16 + F was as high as 56.30%. Field emission scanning electron microscopy (FESEM) analysis showed that the surface microstructure of SMS changed significantly after microbial consortiums treatment, and the change of absorption peak in Fourier transform infrared spectroscopy (FTIR) and the increase of crystallinity in X-ray diffraction (XRD) confirmed that the microbial consortiums had an actual degradation effect on SMS. The results showed that PX1 + F7 and F16 + F could effectively secrete cellulase and degrade cellulose, which had practical significance for the degradation of SMS.DiscussionIn this study, the constructed PX1 + F7 and F16 + F strains can effectively secrete cellulase and degrade cellulose, which holds practical significance in the degradation of SMS. The results can provide technical support for treating high-cellulose solid waste and for the comprehensive utilization of biomass resources.

BackgroundVisual field defect (VFD) refers to the phenomenon that the eye is unable to see a certain area within the normal range of vision, which may be caused by eye diseases, neurological diseases and other reasons. Transcranial direct current stimulation (tDCS) is expected to be an effective treatment for the recovery or partial recovery of VFD. This paper describes the potential for tDCS in combination with visual retraining strategies to have a positive impact on vision recovery, and the potential for neuroplasticity to play a key role in vision recovery.MethodsThis case report includes two patients. Patient 1 was diagnosed with a right occipital hemorrhage and homonymous hemianopia. Patient 2 had multiple facial fractures, a contusion of the right eye, and damage to the optic nerve of the right eye, which was diagnosed as a peripheral nerve injury (optic nerve injury). We administered a series of treatments to two patients, including transcranial direct current stimulation; visual field restoration rehabilitation: paracentric gaze training, upper and lower visual field training, VR rehabilitation, and perceptual training. One time per day, 5 days per week, total 6 weeks.ResultsAfter 6 weeks of visual rehabilitation and tDCS treatment, Patient 1 Humphrey visual field examination showed a significant improvement compared to the initial visit, with a reduction in the extent of visual field defects, increased visual acuity, and improvement in most visual functions. Patient 2 had an expanded visual field, improved visual sensitivity, and substantial improvement in visual function.ConclusionOur case reports support the feasibility and effectiveness of tDCS combined with visual rehabilitation training in the treatment of occipital stroke and optic nerve injury settings.

Abstract Background Many studies have found that engaging in activities, including physical exercise, social interaction, and cognitive training, is beneficial for preventing cognitive decline among older adults; however, the demographic differences in the association between activity engagement and cognitive functions remain understudied. This study investigates: (a) the influence of activity engagement on cognitive functions among Chinese older adults, and (b) the moderating roles of age and gender in these associations . Methods The data were derived from the China Health and Retirement Longitudinal Study in 2018, which included 9803 participants aged 60 or older. A multiple regression model was used to test the study hypotheses. Results Engaging in physical activity (b = 1.578, p

Abstract Background We investigated the influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of patients with acute ischemic stroke who received intravenous thrombolytic therapy (ITT) in Dalian, China, in 2020. Methods This retrospective descriptive study, conducted from February 1, 2020, to August 31, 2020, examined 13 hospitals in Dalian that participated in the “stroke emergency map”. To use this “stroke emergency map” of China, patients followed the official “Stroke Map” WeChat account and dialed 120 for emergency medical services. We analyzed the number of patients with acute ischemic stroke who underwent ITT. In particular, we examined the onset-to-door time (ODT), door-to-needle time (DNT), onset-to-needle time (ONT), mode of transportation to the hospital, and National Institutes of Health Stroke Scale (NIHSS) scores before and after ITT. Data were collected for the aforementioned period and compared with the 2021 baseline data from the same time of year. The Mann‒Whitney U test was performed for data analysis. Results Compared with the data from 2020, the number of patients with acute ischemic stroke who underwent ITT increased (from 735 to 1719 cases) in 2021, but the DNT decreased (from 59 to 45 min; P = 0.002). Moreover, 83.9% of patients in 2020 presented to the hospital without ambulance transport, compared to 81.1% of patients in the 2021 non-COVID-19 pandemic period. Patients with NIHSS scores of 6–14 were more likely to call an ambulance for transport to the hospital than to transport themselves to the emergency department. Conclusions During the 2020 COVID-19 pandemic, the DNT was prolonged as a result of strengthened fever surveillance. In 2021, the number of patients with acute ischemic stroke who underwent ITT increased compared to the previous year. Notably, the growth in the number of patients with acute ischemic stroke who underwent ITT benefited from both the “stroke emergency map” of China and the “green channel,” a novel treatment approach that focuses on the rational design of the rescue process. Trial registration. Our study was a retrospective descriptive study, not a clinical trial, thus we did not have to register for clinical trials.

Abstract Background Recent studies suggest that the incidence of small for gestational age (SGA) birth related to maternal depression, but the mechanism is unclear. The aim of this study was to explore the changes of promoter methylation in the placenta which may be involved in the relationship between prenatal depression and SGA. Methods Three hundred forty-five pregnant women were enrolled in this prospective cohort study. Perinatal emotion and sleep quality in the second and third trimesters were assessed using self-rating depression scale, self-rating anxiety scale, and Pittsburgh sleep quality index. According to the exposure (depressed emotion of mother) and outcome (SGA), the placentas were divided into four groups. Methylation of the promoter regions of the placental CRH, HSD11β2, SLA16A10, DIO3, and MTNR1B genes was determined using next generation sequencing based on bisulfite sequencing PCR. Results There were 97 (28.1%) and 95 (27.5%) pregnant women who had depression in the second trimester and third trimester, respectively. Thirty-five pregnant women had an SGA birth. The incidence of SGA births in this prospective cohort was 10.1%. The risk factors of SGA birth were low BMI of pregnancy women (RR = 0.71, 95%CI = 0.54 ~ 0.92), hypertensive disorder complicating pregnancy (HDCP, RR = 4.7, 95%CI = 1.18 ~ 18.72), and maternal depression in the second trimester (RR = 3.71, 95%CI = 1.31 ~ 12.16). We found that the CRH and HSD11β2 methylation levels were higher in the depression group than those in the non-depression group. Methylation levels of DIO3 were higher in SGA group than that in the non-SGA group. Higher methylation levels of CRH correlated with higher methylation levels of DIO3 in the placenta. Conclusions Maternal depression in the second trimester may lead to the changes of methylation levels in the promoter region of CRH and HSD11β2 gene, while the changes of methylation of DIO3 in subsequent could related to SGA. This study suggests that maternal depressed emotion during pregnancy may result in SGA due to the epigenetic changes of placenta.

Abstract Patients with pancreatic cancer (PC) show dismal prognosis and high mortality. The development of PC is associated with the overactivation of STAT3. Here, we have determined that the non-peptide small molecule Stattic inhibits PC development by targeting STAT3. In vitro, Stattic treatment time- and dose-dependently inhibited proliferation of pancreatic cancer cells (PCCs) by reducing c-Myc expression and enhancing p53 activity. Consequently, p-Rb, cyclin D1, Chk1, and p21 (cell cycle proteins) were downregulated, and PCCs were arrested at the G1 phase, which was also confirmed by decreased Ki67 expression and unaltered PCNA expression. In addition, Stattic-induced mitochondrial-dependent apoptosis by elevating cleaved caspase-3, and Bax, cytochrome C levels, while reducing expression of Bcl-2, which may be regulated by reduced survivin expression. Further studies showed that Stattic exerts its anti-tumor effect via inhibition of STAT3Y705 phosphorylation and nuclear localization in PCCs. In a nude mouse tumorigenesis model, Stattic inhibited PC growth by antagonizing STAT3Y705 phosphorylation. Interleukin-6 used as a molecule agonist to activate STAT3, as well as overexpression of STAT3, could partially reverse Stattic-mediated anti-proliferation and pro-apoptotic effects of PCCs. Thus, these findings indicate that inhibition of STAT3Y705 phosphorylation by Stattic suppresses PCC proliferation and promotes mitochondrial-mediated apoptosis.

The carotid web is commonly found in the carotid bulb or the beginning of the internal carotid artery. It presents as a thin layer of proliferative intimal tissue originating from the arterial wall and extending into the vessel lumen. A large body of research has proven that the carotid web is a risk factor for ischemic stroke. This review summarizes the current research status of the carotid web and focuses on its imaging presentation.

Daphnia galeata is a common and dominant species in warmer waters, and has a strong top-down effect on both phytoplankton and bacteria. The knowledge of its temporal and spatial patterns of genetic diversity is fundamental in understanding its population dynamics and potential ecological function in ecosystems. Its population genetics have been investigated at regional scales but few within regions or at smaller spatial scales. Here, we examined the fine-scale spatial genetic variation of D. galeata within four large, deep reservoirs in wet and dry seasons and the six-year variation of genetic diversity in one of the reservoirs by using cytochrome c oxidase subunit I and microsatellites (simple sequence repeat). Our study shows that fine-scale spatial genetic variation commonly occurred within the reservoirs, indicating strong environmental selection at least in the two of reservoirs with strong longitudinal gradients. Since the environmental gradients established in the dry season was largely reduced in the wet season, the fine-scale spatial genetic variation was much higher in the dry season. The dynamics of local genetic diversity did not follow the theoretical pattern of rapid erosion but peaked in mid or mid-late growth season. The local genetic diversity of D. galeata appears to be shaped and maintained not only by recruitment from resting egg banks but also by gene flow within reservoirs. The temporal and fine-scale genetic variation within a water body suggests that it is necessary to pay attention to sampling periods and locations of a given water body in regional studies.

Solution-processed scintillators hold great promise in fabrication of low-cost X-ray detectors. However, state of the art of these scintillators is still challenging in their environmental toxicity and instability. In this study, we develop a class of tetradecagonal CuI microcrystals as highly stable, eco-friendly, and low-cost scintillators that exhibit intense radioluminescence under X-ray irradiation. The red broadband emission is attributed to the recombination of self-trapped excitons in CuI microcrystals. We demonstrate the incorporation of such CuI microscintillator into a flexible polymer to fabricate an X-ray detector for high-resolution imaging with a spatial resolution up to 20 line pairs per millimeter (lp mm−1), which enables sharp image effects by attaching the flexible imaging detectors onto curved object surfaces.

Amylose content (AC) is an important indicator for rice quality grading. The rapid development of unmanned aerial vehicle (UAV) technology provides rich spectral and spatial information on observed objects, making non-destructive monitoring of crop quality possible. To test the potential of UAV-based hyperspectral images in AC estimation, in this study, observations on five rice cultivars were carried out in eastern China (Zhejiang province) for four consecutive years (from 2017 to 2020). The correlations between spectral and textural variables of UAV-based hyperspectral images at different growth stages (booting, heading, filling, and ripening) and AC (%) were analyzed, and the linear regression models based on spectral variables alone, textural variables alone, and combined spectral and textural variables were established. The results showed that the sensitive bands (P< 0.001) to AC were mainly centered in the green (536∽568 nm) and red regions (630∽660nm), with spectral and textural variables at the ripening stage giving the highest negative correlation coefficient of -0.868 and -0.824, respectively. Models based on combined spectral and textural variables give better estimation than those based on spectral or textural variables alone, characterized by less variables and higher accuracy. The best models using spectral or textural variables alone both involved three growth stages (heading, filling, and ripening), with root mean square error (RMSE) of 1.01% and 1.04%, respectively, while the models based on combined spectral and textural variables have RMSE of 1.04% 0.844% with only one (ripening stage) or two (ripening and filling stages) growth stages involved. The combination of spectral and textural variables of UAV-based hyperspectral images is expected to simplify data acquisition and enhance estimation accuracy in remote sensing of rice AC.

BackgroundMounting studies have investigated impairments in social cognitive domains (including theory of mind [ToM] and facial emotion recognition [FER] in adult patients with temporal lobe epilepsy (TLE). However, to date, inconsistent findings remain.MethodsA search of PubMed, Web of Science, and Embase databases was conducted until December 2021. Hedges g effect sizes were computed with a random-effects model. Meta-regressions were used to assess the potential confounding factors of between-study variability in effect sizes.ResultsThe meta-analysis included 41 studies, with a combined sample of 1,749 adult patients with TLE and 1,324 healthy controls (HCs). Relative to HCs, adult patients with TLE showed large impairments in ToM (g = −0.92) and cognitive ToM (g = −0.92), followed by medium impairments in affective ToM (g = −0.79) and FER (g = −0.77). Besides, no (statistically) significant differences were observed between the magnitude of social cognition impairment in adult with TLE who underwent and those who did not undergo epilepsy surgery. Meta-regressions exhibited that greater severity of executive functioning was associated with more severe ToM defects, and older age was associated with more severe FER defects.ConclusionsResults of this meta-analysis suggest that adult patients with TLE show differential impairments in the core aspects of social cognitive domains (including ToM and FER), which may help in planning individualized treatment with appropriate cognitive and behavioral interventions.

Many studies have investigated impairments in two key domains of social cognition (theory of mind [ToM] and facial emotion recognition [FER]) in children and adolescents with epilepsy. However, inconsistent conclusions were found. Our objective was to characterize social cognition performance of children and adolescents with epilepsy. A literature search was conducted using Web of Science, PubMed, and Embase databases. The article retrieval, screening, quality assessment (Newcastle-Ottawa-Scale), and data extraction were performed independently by two investigators. A random-effects model was used to examine estimates. The meta-analysis included 19 studies, with a combined sample of 623 children and adolescents with epilepsy (mean [SD] age, 12.13 [2.62] years; 46.1% female) and 677 healthy controls [HCs]) (mean [SD] age, 11.48 [2.71] years; 50.7% female). The results revealed that relative to HCs, children and adolescents with epilepsy exhibited deficits in ToM (g = −1.08, 95% CI [−1.38, −0.78], p < 0.001, the number of studies [k] = 13), FER (g = −0.98, 95% CI [−1.33, −0.64], p < 0.001, k = 12), and ToM subcomponents (cognitive ToM: g = −1.04, 95% CI [−1.35, −0.72], p < 0.001, k = 12] and affective ToM: g = −0.73, 95% CI [−1.12, −0.34], p < 0.001, k = 8). In addition, there were no statistically significant differences in social cognition deficits between children and adolescents with focal epilepsy and generalized epilepsy. Meta-regressions confirmed the robustness of the results. These quantitative results further deepen our understanding of the two core domains of social cognition in children and adolescents with epilepsy and may assist in the development of cognitive interventions for this patient population.Systematic review registration:https://inplasy.com/inplasy-2022-3-0011/, identifier INPLASY202230011.

This paper probed deep into a high-temperature resistant inorganic matrix: alkali-activated slag cement (AASC), which is a kind of cementitious material prepared by alkali-activator and pozzolanic or latent hydraulic material. Firstly, the mix ratio of the AASC was optimized to improve the wettability and mechanical properties. Then, the effects of the adhesive matrix and the type of fiber-reinforced polymer (FRP) were observed through FRP-to-concrete bond tests on 93 specimens. The test results, coupled with anchorage analysis, indicate that the AASC has comparable reinforcing effects as those of organic epoxy matrix; the anchorage length of FRP sheets has a significant influence on the failure behavior and failure mode of FRP-enhanced concrete structures. In addition, our tests prove that the AASC has favorable high-temperature resistance and bonding effects. The research results provide a good reference for the design and application of inorganic matrix for FRP-enhancement of concrete structures.

Inverse system method is effective for controlling permanent magnet synchronous motor (PMSM). A novel support vector regression(SVR) inverse system method is proposed to realize decoupling control of PMSM in the article. Firstly, kernel space feature of the inverse model is optimized by using the prior information provided by the mathematical model of analytical inverse system to build two accurate SVR inverse models, which can solve the unreasonable kernel space feature when conventional SVR algorithm is employed to model PMSM inverse system. Then, the inverse system composing of two inverse models is cascaded with the original system to decouple PMSM system into two pseudo-linear subsystems. Finally, PID controller is employed to form a closed-loop control system. The simulation and experiment results show that the proposed method improves the generalization ability of inverse model and achieves high-performance control of PMSM.

Paddy rice is one of the most widely planted crops in Asia. Yield estimation of paddy rice is crucial to food security. Gross primary productivity or net primary productivity (NPP) models are some of the most commonly used methods for crop yield estimation as they have a theoretical basis and are simple to use. The harvest index (HI) of paddy rice, one of the input parameters in yield estimation models, has been increasingly used with the improvement of paddy rice cultivars over the past four decades. However, in many previous researches, this parameter was arbitrarily determined to fit the observed yield data values, without considering its changing trend. In the present study, we developed an NPP-based rice yield estimation model with HI being a changing parameter. The accuracy of the proposed method is tested over the Jiangsu Province, Southeast China. The results showed that the rice HI increases linearly in study area. Compared with yield estimation with a fixed HI, yield estimations using a changing HI are greatly improved, with the average estimation accuracy greater than 96%, and the relative errors within ±5%. The results proved that the NPP-based yield estimation model with a changing HI can be a promising alternative for rice yield estimation.

The speedy development of UAV (Unmanned Aerial Vehicle) has provided more data choices for crop yield estimation. In most cases, spectral information derived from multispectral or hyperspectral images is used alone for yield estimation, while variables that contain spatial information such as textural measures were not considered. As UAV can acquire images with spatial resolution at centimeter-level, which contain rich spatial information of observed objects, the test of textural measures in improving yield estimation becomes possible. In this study, UAV-based hyperspectral images of rice in the east of China were acquired in 2017, 2018 and 2019 three consecutive year during rice growing seasons. Eight gray level co-occurrence matrix (GLCM) based texture measures were derived, and all two band combinations of these textural measures as well as spectral reflectance in three types (normalized type, differential type and simple ratio type) were calculated to developing textural and spectral index. Grain yield estimation models were established using spectral indices alone and spectral indices combining textural measures, respectively. The results show that models based on spectral indices combining textural measures all performed better than these using spectral indices alone, with coefficient of determination R2 of the best model greater than 0.8, RMSE (Root Mean Square Error) of 0.421 Mg ha−1 and MAPE (Mean Absolute Percentage Error) of 4.66% for calibration results, and 0.521 Mg ha−1 and 6.63% for validation results. Meanwhile, spectral indices combining textural measures can adjust the problems of overestimation and underestimation in models developed with spectral indices alone. This kind of improvement is especially obvious when grain yield is below 5.0 Mg ha−1 or above 8.0 Mg ha−1. Besides, the estimation accuracy of the model based on spectral index combining textural measure at the booting stage was equivalent to the model based on spectral indices at the booting and heading stages, indicating that textural measures may be helpful in monitoring grain yield at an earlier stage.

To analyze the effect of structural parameters on the damage potential ranking of ground motions, the effect of the yield strength coefficient (Cy) and natural vibration period (T) on the damage potential ranking of ground motions is analyzed based on the bilinear model and the modified Clough model, which are the most commonly used hysteretic models in structural dynamic analysis. The displacement response (Sd) spectrum under nonlinear conditions is taken as the damage potential intensity measure (IM) of ground motions, and the effect of the Cy and T on the Sd mean spectrum is also analyzed for comparative analysis. The results show that: (1) in the short-period range, Cy has a great effect on the displacement response ranking. On the other hand, in the medium- and long-period ranges, Cy has little effect on the Sd ranking; (2) with the change of T in medium- and long-period ranges, the variation of Sd values is obvious when the change of T is small, but the variation of Sd ranking is very small. This conclusion can provide a theoretical basis for evaluating the damage potential of ground motions and selecting input ground motions.

Abstract Background Embryonic Sertoli cells (eSCs) play an important role in sex determination and in male gonad development which makes them a very useful cell type for therapeutic applications. However, the deriving mechanism of Sertoli cells has been unclear and challenging to create a large number of quality eSCs. Therefore, this study aimed to create the eSCs induced from mouse embryonic stem (mES) cells by regulating defined factors and to explore the relevant regulatory mechanism. Methods Six inducing factors, Sry, Sox9, SF1, WT1, GATA4, and Dmrt1, were respectively transduced into mES cells by lentiviral infection according to the experimental design. The test groups were identified by development stage-specific markers, AMH, Emx2, SF1, and FasL, using flow cytometry. Induced eSCs were determined by FasL and AMH biomarkers under immunofluorescence, immunocytochemistry, and flow cytometry. Moreover, the pluripotency markers, gonad development-related markers, epithelial markers and mesenchymal markers in test groups were transcriptionally determined by qPCR. Results In this study, the co-overexpression of all the six factors effectively produced a large population of eSCs from mES cells in 35 days of culturing. These eSCs were capable of forming tubular-like and ring-like structures with functional performance. The results of flow cytometry indicated that the upregulation of GATA4 and WT1 contributed to the growth of somatic cells in the coelomic epithelium regarded as the main progenitor cells of eSCs. Whereas, SF1 facilitated the development of eSC precursor cells, and Sry and Sox9 promoted the determination of male development. Moreover, the overexpression of Dmrt1 was essential for the maintenance of eSCs and some of their specific surface biomarkers such as FasL. The cellular morphology, biomarker identification, and transcriptomic analysis aided in exploring the regulatory mechanism of deriving eSCs from mES cells. Conclusion Conclusively, we have elucidated a differentiation roadmap of eSCs derived from mES cells with a relevant regulatory mechanism. Through co-overexpression of all these six factors, a large population of eSCs was successfully induced occupying 24% of the whole cell population (1 × 105 cells/cm2). By adopting this approach, a mass of embryonic Sertoli cells can be generated for the purpose of co-culture technique, organ transplantation, gonadal developmental and sex determination researches.

Abstract Background Adipose-derived mesenchymal stem cells (ADMSCs) are considered an efficient and important candidate for male infertility treatment because they contain pluripotent stem cells, which can differentiate into all cells from three germ layers. However, the efficient generation of male germ-like cell (MGLCs) is one of the key issues, and little is known about the mechanisms underlying generation of MGLCs. Herein, we attempt to improve the efficient generation of MGLCs derived during co-culturing of rat ADMSCs with SCs under retinoic acid (RA) and testosterone (T) treatment. Methods ADMSCs isolated from male SD rat were induced into generation of MGLCs by using respective methods in vitro. Transwell insert system was used for co-culturing. Busulfan-induced non-obstructive azoospermia rat mode was used to evaluate spermatogenic recovery ability of treated ADMSCs. Besides, the relative gene expression level was detected by reverse transcription PCR, quantitative RT-PCR. The relative protein expression level was detected by western blot (WB) and immunostaining analysis. Results The results showed that ADMSCs co-cultured with TM4 cells under RA and T induction enhanced the formation of bigger and tightly packed MGLCs feature colonies in vitro. Moreover, the expression of male germ cell-related markers (Oct4, Stella, Ddx4, Dazl, PGP9.5, Stra8, and ITGα6) is significantly upregulated in TM4 cell-co-cultured ADMSCs in vitro and in busulfan-treated rat testis after injecting TM4 cell-treated ADMSCs for 2 months. Comparatively, the ADMSCs treated by TM4 cell with RA and T exhibited the highest expression of male germ cell-related markers. RA- and T-treated TM4 cell showed fewer dead cells and higher cytokine secretion than untreated groups. The protein expression level of TGFβ-SMAD2/3, JAK2-STAT3, and AKT pathways in ADMSCs co-cultured with TM4 cells under RA and T was higher than others. Whereas, downregulation of male germ cell-related marker expression subsequently inhibited the phosphorylation of SMAD2/3, JAK2, STAT3, and AKT. Conclusion These results suggested that TM4 cells could efficiently stimulate in vitro generation of MGLCs during co-culturing of ADMSCs under RA and T treatment. Conclusively, the ADMSCs co-cultured with TM4 cell under RA and T induction stimulate the efficient generation of MGLCs in vitro through activating TGFβ-SMAD2/3, JAK2-STAT3, and AKT pathways. Among them, JAK2-STAT3 and AKT pathways are being first reported to show involvement of in vitro generation of MGLCs during ADMSC co-culturing with SCs.

Rice is one of the most important food crops around the world. Remote sensing technology, as an effective and rapidly developing method, has been widely applied to precise rice management. To observe the current research status in the field of rice remote sensing (RRS), a bibliometric analysis was carried out based on 2680 papers of RRS published during 1980–2021, which were collected from the core collection of the Web of Science database. Quantitative analysis of the number of publications, top countries and institutions, popular keywords, etc. was conducted through the knowledge mapping software CiteSpace, and comprehensive discussions were carried out from the aspects of specific research objects, methods, spectral variables, and sensor platforms. The results revealed that an increasing number of countries and institutions have conducted research on RRS and a great number of articles have been published annually, among which, China, the United States of America, and Japan were the top three and the Chinese Academy of Sciences, Zhejiang University, and Nanjing Agricultural University were the first three research institutions with the largest publications. Abundant interest was paid to “reflectance”, followed by “vegetation index” and “yield” and the specific objects mainly focused on growth, yield, area, stress, and quality. From the perspective of spectral variables, reflectance, vegetation index, and back-scattering coefficient appeared the most frequently in the frontiers. In addition to satellite remote sensing data and empirical models, unmanned air vehicle (UAV) platforms and artificial intelligence models have gradually become hot topics. This study enriches the readers’ understanding and highlights the potential future research directions in RRS.

Detection of haloalkanes is of great industrial and scientific importance because some haloalkanes are found serious biological and atmospheric issues. The development of a flexible, wearable sensing device for haloalkane assays is highly desired. Here, we develop a paper-based microfluidic sensor to achieve low-cost, high-throughput, and convenient detection of haloalkanes using perovskite nanocrystals as a nanoprobe through anion exchanging. We demonstrate that the CsPbX3 (X = Cl, Br, or I) nanocrystals are selectively and sensitively in response to haloalkanes (CH2Cl2, CH2Br2), and their concentrations can be determined as a function of photoluminescence spectral shifts of perovskite nanocrystals. In particular, an addition of nucleophilic trialkyl phosphines (TOP) or a UV-photon-induced electron transfer from CsPbX3 nanocrystals is responsible for achieving fast sensing of haloalkanes. We further fabricate a paper-based multichannel microfluidic sensor to implement fast colorimetric assays of CH2Cl2 and CH2Br2. We also demonstrate a direct experimental observation on chemical kinetics of anion exchanging in lead-halide perovskite nanocrystals using a slow solvent diffusion strategy. Our studies may offer an opportunity to develop flexible, wearable microfluidic sensors for haloalkane sensing, and advance the in-depth fundamental understanding of the physical origin of anion-exchanged nanocrystals.

Embryonic Sertoli cells (eSCs) possess multiple supporting functions and research value in gonadal development and sex determination. However, the limitation of acquiring quality eSCs had hindered the further application. Herein, we successfully derived non-genetically modified (non-GM)-induced embryonic Sertoli-like cells (eSLCs) from mouse embryonic stem cells (ESCs) with a TM4 cell-derived conditioned medium containing recombinant endogenous protein factors Sry, Sox9, Sf1, Wt1, Gata4, and Dmrt1. These eSLCs were determined through morphology; transcriptional expression levels of stage-specific, epithelial, and mesenchymal marker genes; flow cytometry, immunofluorescence; and immunocytochemistry and functionally determined by coculture with spermatogonia stem cells. Results indicated that these eSLCs performed similarly to eSCs in specific biomarkers and expression of marker genes and supported the maturation of spermatogonia. The study induced eSLCs from mouse ESCs by defined protein factors. However, the inducing efficiency of the non-GM method was still lower than that of the lentiviral transduction method. Thus, this work established a foundation for future production of non-GM eSLCs for clinical applications and fundamental theory research.

X-ray imaging is a low-cost, powerful technology that has been extensively used in medical diagnosis and industrial nondestructive inspection. The ability of X-rays to penetrate through the body presents great advances for noninvasive imaging of its internal structure. In particular, the technological importance of X-ray imaging has led to the rapid development of high-performance X-ray detectors and the associated imaging applications. Here, we present an overview of the recent development of X-ray imaging-related technologies since the discovery of X-rays in the 1890s and discuss the fundamental mechanism of diverse X-ray imaging instruments, as well as their advantages and disadvantages on X-ray imaging performance. We also highlight various applications of advanced X-ray imaging in a diversity of fields. We further discuss future research directions and challenges in developing advanced next-generation materials that are crucial to the fabrication of flexible, low-dose, high-resolution X-ray imaging detectors.

To rank the pulse-like ground motions based on the damage potential to different structures, the internal relationship between the damage potential of pulse-like ground motions and engineering demand parameters (EDPs) is analyzed in this paper. First, a total of 240 pulse-like ground motions from the NGA-West2 database and 16 intensity measures (IMs) are selected. Moreover, four reinforced concrete frame structures with significantly different natural vibration periods are established for dynamic analysis. Second, the efficiency and sufficiency of the IMs of ground motion are analyzed, and the IMs that can be used to efficiently and sufficiently evaluate the EDPs are obtained. Then, based on the calculation results, the principal component analysis (PCA) method is employed to obtain a comprehensive IM for characterizing the damage potential of pulse-like ground motions for specific building structures and EDPs. Finally, the pulse-like ground motions are ranked based on the selected IM and the comprehensive IM for four structures and three EDPs. The results imply that the proposed method can be used to efficiently and sufficiently characterize the damage potential of pulse-like ground motions for building structures.

The accurate and rapid estimation of the aboveground biomass (AGB) of rice is crucial to food security. Unmanned aerial vehicles (UAVs) mounted with hyperspectral sensors can obtain images of high spectral and spatial resolution in a quick and effective manner. Integrating UAV-based spatial and spectral information has substantial potential for improving crop AGB estimation. Hyperspectral remote-sensing data with more continuous reflectance information on ground objects provide more possibilities for band selection. The use of band selection for the spectral vegetation index (VI) has been discussed in many studies, but few studies have paid attention to the band selection of texture features in rice AGB estimation. In this study, UAV-based hyperspectral images of four rice varieties in five nitrogen treatments (N0, N1, N2, N3, and N4) were obtained. First, multiple spectral bands were used to identify the optimal bands of the spectral vegetation indices, as well as the texture features; next, the vegetation index model (VI model), the vegetation index combined with the corresponding-band textures model (VI+CBT model), and the vegetation index combined with the full-band textures model (VI+FBT model) were established to compare their respective rice AGB estimation abilities. The results showed that the optimal bands of the spectral and textural information for AGB monitoring were inconsistent. The red-edge and near-infrared bands demonstrated a strong correlation with the rice AGB in the spectral dimension, while the green and red bands exhibited a high correlation with the rice AGB in the spatial dimension. The ranking of the monitoring accuracies of the three models, from highest to lowest, was: the VI+FBT model, then the VI+CBT model, and then the VI model. Compared with the VI model, the R2 of the VI+FBT model and the VI+CBT model increased by 1.319% and 9.763%, respectively. The RMSE decreased by 2.070% and 16.718%, respectively, while the rRMSE decreased by 2.166% and 16.606%, respectively. The results indicated that the integration of vegetation indices and textures can significantly improve the accuracy of rice AGB estimation. The full-band textures contained richer information that was highly related to rice AGB. The VI model at the tillering stage presented the greatest sensitivity to the integration of textures, and the models in the N3 treatment (1.5 times the normal nitrogen level) gave the best AGB estimation compared with the other nitrogen treatments. This research proposes a reliable modeling framework for monitoring rice AGB and provides scientific support for rice-field management.

This paper presents an experimental study on the seismic performance of a bidirectional self-centering reinforced concrete (RC) frame structure. In the structure, the column-base joints, which were installed with external mild steel (MS) dampers, could uplift freely and the beam-column joints could open effectively under earthquake excitations. Angle steels and MS dampers were installed at the beam-column joints in the structural X and Y directions, respectively. During the gap opening of the joints, unbonded posttensioned (PT) steel wires, which passed through the plastic ducts inserted in the RC beams and columns, provided the structure with the ability to return to pre-earthquake positions, and the yielding MS dampers and angle steels dissipated the seismic energy. A 1/2-scale two-story model structure was designed and constructed. Shaking table tests were performed on the structure under four different types of earthquake excitations with increasing seismic hazard levels. The test results indicated that the self-centering RC frames installed in both the directions showed satisfactory seismic performance, with only slight damage to the main structure after extreme earthquakes. The natural frequencies of the self-centering frames installed in both the directions degraded progressively, mainly because of the prestress loss of the PT steel wires and the yielding of the MS dampers. The structure showed desirable self-centering ability with very small residual deformation under ground motions of all hazard levels. The structural deformation was mainly concentrated at the column-base and beam-column joints, and hence, damage to the concrete beams and columns was considerably alleviated. In addition, the residual gap opening of the joints was minimal.

The constant-strength ductility spectrum is a nonlinear response spectrum that is commonly used to establish the demand curve of the seismic response during performance-based seismic design. It is affected by many factors. In this paper, to evaluate the effect of the major influencing factors, including the structural parameters and seismic factors, the constant-strength ductility spectrum is calculated under different conditions based on 5535 ground motion records. Conclusions are drawn based on the mean constant-strength ductility spectra. (1) With respect to the effects of structural factors, the variation trend of the ductility spectra is highly consistent with increasing T, and the ductility spectra are usually larger for larger ζ and smaller Cy and k2. (2) With respect to the seismic factors, the ductility spectra show obvious differences in different periods; however, some parameters, such as PGA, have no influence on the ductility spectra. The results of this study can provide a theoretical basis for the calculation of ductility demand in the seismic design of structures.

Abstract Purpose: To investigate the effect of oxymatrine on periodontitis in rats and related mechanism. Methods: Ninety SD rats were divided into control, model, 10, 20 and 40 mg/kg oxymatrine and tinidazole groups. The periodontitis model was established in later 5 groups. The 10, 20 and 40 mg/kg oxymatrine groups were intragastrically administrated with 10, 20 and 40 mg/kg oxymatrine, respectively. The tinidazole group was intragastrically administrated with 100 mg/kg tinidazole. The treatment duration was 4 weeks. The tooth mobility, gingival and plaque indexes, serum inflammatory factor levels and gingival tissue matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) protein levels were detected. Results: After treatment, compared with model group, in 40 mg/kg oxymatrine group the rat general conditions were obviously improved, the tooth mobility, gingival index and plaque index were significantly decreased (P

Rice floret number per unit area as one of the key yield structure parameters is directly related to the final yield of rice. Previous studies paid little attention to the effect of the variations in vegetation indices (VIs) caused by rice flowering on rice yield estimation. Unmanned aerial vehicles (UAV) equipped with hyperspectral cameras can provide high spatial and temporal resolution remote sensing data about the rice canopy, providing possibilities for flowering monitoring. In this study, two consecutive years of rice field experiments were conducted to explore the performance of florescence spectral information in improving the accuracy of VIs-based models for yield estimates. First, the florescence ratio reflectance and florescence difference reflectance, as well as their first derivative reflectance, were defined and then their correlations with rice yield were evaluated. It was found that the florescence spectral information at the seventh day of rice flowering showed the highest correlation with the yield. The sensitive bands to yield were centered at 590 nm, 690 nm and 736 nm–748 nm, 760 nm–768 nm for the first derivative florescence difference reflectance, and 704 nm–760 nm for the first derivative florescence ratio reflectance. The florescence ratio index (FRI) and florescence difference index (FDI) were developed and their abilities to improve the estimation accuracy of models basing on vegetation indices at single-, two- and three-growth stages were tested. With the introduction of florescence spectral information, the single-growth VI-based model produced the most obvious improvement in estimation accuracy, with the coefficient of determination (R2) increasing from 0.748 to 0.799, and the mean absolute percentage error (MAPE) and the root mean squared error (RMSE) decreasing by 11.8% and 10.7%, respectively. Optimized by flowering information, the two-growth stage VIs-based model gave the best performance (R2 = 0.869, MAPE = 3.98%, RMSE = 396.02 kg/ha). These results showed that introducing florescence spectral information at the flowering stage into conventional VIs-based yield estimation models is helpful in improving rice yield estimation accuracy. The usefulness of florescence spectral information for yield estimation provides a new idea for the further development and improvement of the crop yield estimation method.

Abstract Influenza virus uses a unique mechanism to initiate viral transcription named cap-snatching. The PB2 subunit of the viral heterotrimeric RNA polymerase binds the cap structure of cellular pre-mRNA to promote its cleavage by the PA subunit. The resulting 11–13 capped oligomer is used by the PB1 polymerase subunit to initiate transcription of viral proteins. VX-787 is an inhibitor of the influenza A virus pre-mRNA cap-binding protein PB2. This clinical stage compound was shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery. However, the binding of this molecule in the context of an extended form of the PB2 subunit has remained elusive. Here we generated a collection of PB2 truncations to identify a PB2 protein representative of its structure in the viral heterotrimeric protein. We present the crystal structure of VX-787 bound to a PB2 construct that recapitulates VX-787's biological antiviral activity in vitro. This co-structure reveals more extensive interactions than previously identified and provides insight into the observed resistance profile, affinity, binding kinetics, and conformational rearrangements induced by VX-787.

Summary: A hallmark of chronic hepatitis B (CHB) virus infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A small molecule, RG7834, has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase proteins 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identify additional factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients. : Hyrina et al. employ a non-biased functional CRISPR screening approach to identify host factors regulating HBsAg expression as well as those targeted by RG7834, a HBsAg inhibitor. The screen highlighted over 60 genes and identified a mechanism by which ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing. Keywords: HBV, HBsAg, CRISPR, genome-wide screen, RG7834, ZCCHC14, TENT4B, RNA tailing

Large landslides (volume greater than or equal to 106 m3) usually have disastrous consequences and clearly influence the evolution of the local landscape. In this study, a detailed investigation of large landslides, across 20 towns over an area of 5000 km2, was carried out on the northeastern margin of the Bayan Har Block, at the eastern margin of the Tibetan Plateau, China. The results show that there are 129 large landslides in this area. Among them, 79 landslides have volumes within 106–107 m3, 52 landslides have volumes within 107–108 m3 and 2 landslides have volumes larger than 108 m3. Most of these landslides are distributed along rivers, and more than 32% are densely concentrated in three small regions. The landslides mainly occur in high slopes and exhibit obvious sturzstrom characteristics. Analysis of the factors controlling landslide occurrence shows that elevation, slope angle, slope aspect, lithology, faults and rivers (valley) clearly influence landslide occurrence, while rainfall has no obvious influence. Earthquakes are considered an important trigger of and contributor to landslide occurrence.

The phenomenon of hospital functional interruption has been widely observed in the historical moderate-strong earthquakes, indicating that hospital functionality cannot be well considered in the current seismic design methods. The concept of seismic resilience pays enough attention to postearthquake functionality of buildings, and it is particularly significant for the urban hospitals which play critical role in the urban postearthquake rescue and recovery. This study proposes a framework to assess the seismic resilience of urban hospitals, by incorporating the fault tree analysis (FTA) to consider the interdependency between the damage of nonstructural components and the functionality of medical equipment, as well as the effect of external supplies on the functionality of hospital. The proposed framework is then applied to a case-study hospital, and the results indicate that this hospital needs 1.1 days to resume emergency functionality under REDi repair strategy after design basis earthquake (DBE), while it needs 28.8 days to resume emergency functionality under REDi repair strategy after maximum considered earthquake (MCE). It is found that the seismic resilience of this hospital after MCE cannot meet the community requirements on the recovery time, and necessary measures are needed to improve the seismic resilience. The proposed framework provides the quantitative results of seismic resilience assessment in the preearthquake environment and can further support emergency response planning and seismic retrofits strategies.

ABSTRACT Tight coordination of inner and outer membrane biosynthesis is very important in Gram-negative bacteria. Biosynthesis of the lipid A moiety of lipopolysaccharide, which comprises the outer leaflet of the outer membrane has garnered interest for Gram-negative antibacterial discovery. In particular, several potent inhibitors of LpxC (the first committed step of the lipid A pathway) are described. Here we show that serial passaging of Klebsiella pneumoniae in increasing levels of an LpxC inhibitor yielded mutants that grew only in the presence of the inhibitor. These strains had mutations in fabZ and lpxC occurring together (encoding either FabZR121L/LpxCV37G or FabZF51L/LpxCV37G). K. pneumoniae mutants having only LpxCV37G or LpxCV37A or various FabZ mutations alone were less susceptible to the LpxC inhibitor and did not require LpxC inhibition for growth. Western blotting revealed that LpxCV37G accumulated to high levels, and electron microscopy of cells harboring FabZR121L/LpxCV37G indicated an extreme accumulation of membrane in the periplasm when cells were subcultured without LpxC inhibitor. Significant accumulation of detergent-like lipid A pathway intermediates that occur downstream of LpxC (e.g., lipid X and disaccharide monophosphate [DSMP]) was also seen. Taken together, our results suggest that redirection of lipid A pathway substrate by less active FabZ variants, combined with increased activity from LpxCV37G was overdriving the lipid A pathway, necessitating LpxC chemical inhibition, since native cellular maintenance of membrane homeostasis was no longer functioning. IMPORTANCE Emergence of antibiotic resistance has prompted efforts to identify and optimize novel inhibitors of antibacterial targets such as LpxC. This enzyme catalyzes the first committed step of lipid A synthesis, which is necessary to generate lipopolysaccharide and ultimately the Gram-negative protective outer membrane. Investigation of this pathway and its interrelationship with inner membrane (phospholipid) biosynthesis or other pathways is therefore highly important to the fundamental understanding of Gram-negative bacteria and by extension to antibiotic discovery. Here we exploited the availability of a novel LpxC inhibitor to engender the generation of K. pneumoniae resistant mutants whose growth depends on chemical inhibition of LpxC. Inhibitor dependency resulted from the interaction of different resistance mutations and was based on loss of normal cellular mechanisms required to establish membrane homeostasis. This study provides new insights into the importance of this process in K. pneumoniae and how it may be linked to novel biosynthetic pathway inhibitors.

This paper introduces a method of improving the performance of reinforced concrete blocks and reveals the reinforcing effect of fibers. It is pointed out that the plant fibers treated by styrene-acrylic emulsion can effectively improve the interfacial bonding conditions, for the modified straw fibers which were treated by alkali processing and acrylic coating, their performance has been significantly improved, which is conducive to absorbing energy and improving the strength of the material. This paper focuses on introducing three types of reinforced concrete blocks, it’s known that the bridging effect can effectively prevent the development of micro cracks. The occurrence of cracks increases the macroscopic tensile strain of the material and increases the ductility and toughness of the matrix. Studying plant fiber reinforced blocks will help promote the application of this new wall materials.

Circular RNAs (circRNAs) own unique capabilities to communicate with nucleic acids and ribonucleoproteins and are emerging as indispensable compositions of the regulatory messages encoded in the genome. Due to lack of 3′ termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs. Moreover, circRNAs can act as microRNA (miRNA) sponge and affect messenger RNA (mRNA) splicing and transcription. By virtue of their great stability and elaborate regulatory mechanisms of gene expression, circRNAs play important roles in certain physiological activities. The development, homeostasis and stress response of the central nervous system (CNS) depend upon precise temporal and spatial regulation of gene networks. Moreover, emerging evidence has revealed that circRNAs are spatiotemporally regulated and dynamically expressed during brain development; therefore, they can exert significant influences on CNS development and diseases. In this review, we highlight the biogenesis of circRNAs and their central roles in regulation of CNS development and diseases.

We aim to identify levels of signal factors secreted by MSCs cultured in 2D monolayers (2D-MSCs), spheroids (spheroids MSCs), and cocultures of microvesicles (MVs) derived from 2D-MSCs or spheroid MSCs and retinal photoreceptor neurons. We seeded 2D-MSCs, spheroid MSCs, and cells derived from spheroids MSCs at equal numbers. MVs isolated from all 3 culture conditions were incubated with 661W cells. Levels of 51 signal factors in conditioned medium from those cultured conditions were quantified with bead-based assay. We found that IL-8, IL-6, and GROα were the top three most abundant signal factors. Moreover, compared to 2D-MSCs, levels of 11 cytokines and IL-2Rα were significantly increased in conditioned medium from spheroid MSCs. Finally, to test if enhanced expression of these factors reflects altered immunomodulating activities, we assessed the effect of 2D-MSC-MVs and 3D-MSC-MVs on CD14+ cell chemoattraction. Compared to 2D-MSC-MVs, 3D-MSC-MVs significantly decreased the chemotactic index of CD14+ cells. Our results suggest that spheroid culture conditions improve the ability of MSCs to selectively secrete signal factors. Moreover, 3D-MSC-MVs also possessed an enhanced capability to promote signal factors secretion compared to 2D-MSC-MVs and may possess enhanced immunomodulating activities and might be a better regenerative therapy for retinal degenerative diseases.