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Objective To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). Methods The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients’ clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. Results During a mean follow-up of 5.5 years (range, 5–7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. Conclusion Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.

Summary: Retinoic acid (RA), derived from retinol (ROL), is integral to cell growth, differentiation, and organogenesis. It is known that RA can inhibit herpes simplex virus (HSV) replication, but the interactions between alphaherpesviruses and RA metabolism are unclear. Our present study revealed that alphaherpesvirus (HSV-1 and Pseudorabies virus, PRV) infections suppressed RA synthesis from ROL by activating P53, which increased retinol reductase 3 (DHRS3) expression—an enzyme that converts retinaldehyde back to ROL. This process depended on the virus-triggered DNA damage response, the degradation of class I histone deacetylases, and the subsequent hyperacetylation of histones H3 and H4. Counteracting DHRS3 or P53 enabled higher RA synthesis and reduced viral growth. RA enhanced antiviral defenses by promoting ABCA1- and ABCG1-mediated lipid efflux. Treatment with the retinoic acid receptor (RAR) agonist palovarotene protected mice from HSV-1 infection, thus providing a potential therapeutic strategy against viral infections.

Literature on integrated coastal zonal management (ICZM) for coastal sustainability from a legal perspective provided significant measures. Recently, sustainable development goals (SDGs) have become a focus in ICZM literature, which establishes coastal goals and connects these goals with other goals. Although integrating coastal goals into ICZM under international law challenges the existing models presented in the literature, the comprehensive literature review (CLR) methodology is appropriate for observing the current literature and provides a way-forward for coastal goals. Therefore, through this research, a CLR on ICZM literature is conducted to observe how far SDGs are integrated for coastal sustainability. The CLR identified that coastal city governance is a pertinent part of ICZM, and the coastal goals are devised in the form of environmental goals of SDG – 14 (life below water). This CLR examines the anthropogenic connections of waste, sanitation, and emissions management and urban planning with coastal ecosystems under the ICZM system. For such purposes, governance tools of science-policy integration under international law and policy for sustainable development are utilized to form an obligatory framework. The CLR further provided coordination, adaptivity, monitoring, and capacity-building tools, which were utilized thoroughly throughout the literature and can be incorporated with the SDGs in a multilevel governance framework of ICZM. Throughout the study, international law formulating SDGs is pivotal to be transplanted successfully into the ICZM governance processes.

The Department of Medicinal Chemistry, together with the Institute for Structural Biology, Drug Discovery and Development, at Virginia Commonwealth University (VCU) has evolved, organically with quite a bit of bootstrapping, into a unique drug discovery ecosystem in response to the environment and culture of the university and the wider research enterprise. Each faculty member that joined the department and/or institute added a layer of expertise, technology and most importantly, innovation, that fertilized numerous collaborations within the University and with outside partners. Despite moderate institutional support with respect to a typical drug discovery enterprise, the VCU drug discovery ecosystem has built and maintained an impressive array of facilities and instrumentation for drug synthesis, drug characterization, biomolecular structural analysis and biophysical analysis, and pharmacological studies. Altogether, this ecosystem has had major impacts on numerous therapeutic areas, such as neurology, psychiatry, drugs of abuse, cancer, sickle cell disease, coagulopathy, inflammation, aging disorders and others. Novel tools and strategies for drug discovery, design and development have been developed at VCU in the last five decades; e.g., fundamental rational structure-activity relationship (SAR)-based drug design, structure-based drug design, orthosteric and allosteric drug design, design of multi-functional agents towards polypharmacy outcomes, principles on designing glycosaminoglycans as drugs, and computational tools and algorithms for quantitative SAR (QSAR) and understanding the roles of water and the hydrophobic effect.

Abstract Carbon nanomaterials are unique with excellent functionality and diverse structures. However, agglomerated structures are commonly formed because of small‐size effects and surface effects. Their hierarchical assembly into micro particles enables carbon nanomaterials to break the boundaries of classical Geldart particle classification before stable fluidization under gas‐solid interactions. Currently, there are few systematic reports regarding the structural evolution and fluidization mechanism of carbon nano agglomerations. Based on existing research on carbon nanomaterials, this article reviews the fluidized structure control and fluidization principles of prototypical carbon nanotubes (CNTs) as well as their nanocomposites. The controlled agglomerate fluidization technology leads to the successful mass production of agglomerated and aligned CNTs. In addition, the self‐similar agglomeration of individual ultralong CNTs and nanocomposites with silicon as model systems further exemplify the important role of surface structure and particle‐fluid interactions. These emerging nano agglomerations have endowed classical fluidization technology with more innovations in advanced applications like energy storage, biomedical, and electronics. This review aims to provide insights into the connections between fluidization and carbon nanomaterials by highlighting their hierarchical structural evolution and the principle of agglomerated fluidization, expecting to showcase the vitality and connotation of fluidization science and technology in the new era.

AbstractIntroduction The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients.Methods Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis.Results A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively).Conclusion The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.

Abstract Background Drug-drug interaction (DDI) information retrieval (IR) is an important natural language process (NLP) task from the PubMed literature. For the first time, active learning (AL) is studied in DDI IR analysis. DDI IR analysis from PubMed abstracts faces the challenges of relatively small positive DDI samples among overwhelmingly large negative samples. Random negative sampling and positive sampling are purposely designed to improve the efficiency of AL analysis. The consistency of random negative sampling and positive sampling is shown in the paper. Results PubMed abstracts are divided into two pools. Screened pool contains all abstracts that pass the DDI keywords query in PubMed, while unscreened pool includes all the other abstracts. At a prespecified recall rate of 0.95, DDI IR analysis precision is evaluated and compared. In screened pool IR analysis using supporting vector machine (SVM), similarity sampling plus uncertainty sampling improves the precision over uncertainty sampling, from 0.89 to 0.92 respectively. In the unscreened pool IR analysis, the integrated random negative sampling, positive sampling, and similarity sampling improve the precision over uncertainty sampling along, from 0.72 to 0.81 respectively. When we change the SVM to a deep learning method, all sampling schemes consistently improve DDI AL analysis in both screened pool and unscreened pool. Deep learning has significant improvement of precision over SVM, 0.96 vs. 0.92 in screened pool, and 0.90 vs. 0.81 in the unscreened pool, respectively. Conclusions By integrating various sampling schemes and deep learning algorithms into AL, the DDI IR analysis from literature is significantly improved. The random negative sampling and positive sampling are highly effective methods in improving AL analysis where the positive and negative samples are extremely imbalanced.

The accurate determination of the Diameter at Breast Height (DBH) of Moso bamboo is crucial for estimating biomass and carbon storage in Moso bamboo forests. In this research, we utilized handheld LiDAR point cloud data to extract the DBH of Moso bamboo and enhanced the accuracy of diameter fitting by optimizing denoising parameters. Specifically, we fine-tuned two denoising parameters, neighborhood point number and standard deviation multiplier, across five gradient levels for denoising. Subsequently, DBH fitting was conducted on data processed with varying denoising parameters, followed by a precision evaluation to investigate the key factors influencing the accuracy of Moso bamboo DBH fitting. The research results indicate that a handheld laser was used to scan six plots, from which 132 single Moso bamboo trees were selected. Out of these, 122 single trees were successfully segmented and identified, achieving an accuracy rate of 92.4% in identifying single Moso bamboo trees, with an average accuracy of 95.64% in extracting DBH for individual plants; the mean error was ±1.8 cm. Notably, setting the minimum neighborhood point to 10 resulted in the highest fitting accuracy for DBH. Moreover, the optimal standard deviation multiplier threshold was found to be 1 in high-density forest plots and 2 in low-density forest plots. Forest condition and slope were identified as the primary factors impacting the accuracy of Moso bamboo DBH fitting.

Orphaned colonies of Cryptotermes domesticus readily produce replacement reproductives and continue propagation. In this study, we aimed to investigate the production and fecundity of neotenic reproductives in 5-year-old colonies of C. domesticus after orphaning. All 15 experimental colonies were successfully re-established by the neotenic reproductive pair. Three types of neotenic reproductives with various wing-bud lengths were observed: type I with micro wing buds, type II with short wing buds, and type III with long wing buds. Four patterns of pairs made up of these neotenics, namely, type I + type II, type I + type III, type II + type II, and type II + type III, exhibited reproductive capacities similar to those of the primary reproductive pair. We speculated that these neotenic reproductives were derived from various nymphal instars. The 5-year-old colonies had three instars of nymphs, with the majority being in the second instar, followed by the first. Thus, the combination of neotenic reproductives with short wing buds and micro wing buds was the dominant differentiation pathway of the orphaned colonies. After the removal of the original primary reproductive pair, the nymphs matured into neotenic reproductives and took over reproduction in the colony in 107.40 ± 15.18 days. This study highlights the importance of quarantine and routine inspection of wood, as well as the significance of early prevention and control of C. domesticus infestation in wood. Moreover, this study confirms the high differentiation and reproductive capacities of C. domesticus.

BackgroundAdvanced perfusion modalities are increasingly popular for various diseases. However, few studies have focused on contrasting perfusion patterns.ObjectiveThis study aimed to compare the time efficiency and clinical outcomes of patients with acute ischemic stroke (AIS) who underwent endovascular treatment (EVT) before one-stop arterial spin labeling (ASL) and computed tomography perfusion (CTP) protocols.MethodsThis study retrospectively included 326 patients with AIS who had accepted EVT within 24 h of onset from four comprehensive stroke centers between October 2017 and September 2022. After 1:1 matching of the propensity scores, 202 patients were separated into two groups: the ASL group (n = 101) and the CTP group (n = 101).ResultsFunctional independence at 90 days (modified Rankin Scale [mRS] 0–2; p = 0.574), onset-to-puncture time (p = 0.231), door-to-puncture time (p = 0.136), and door-to-perfusion time (p = 0.646) were not significantly different between the two groups. The proportion of EVT complications (31.7% in the ASL group vs. 14.9% in the CTP group, p = 0.005) and symptomatic intracranial hemorrhage (sICH) at 24 h (23.8% in the ASL group vs. 9.9% in the CTP group, p = 0.008) in the CTP group were lower than the ASL group. The ischemic core volume was a common predictor of favorable outcomes in both ASL (p

Background: Hepatocellular Carcinoma (HCC) is a common lethal digestive system tumor. The oxidative stress mechanism is crucial in the HCC genesis and progression.Methods: Our study analyzed single-cell and bulk sequencing data to compare the microenvironment of non-tumor liver tissues and HCC tissues. Through these analyses, we aimed to investigate the effect of oxidative stress on cells in the HCC microenvironment and identify critical oxidative stress response-related genes that impact the survival of HCC patients.Results: Our results showed increased oxidative stress in HCC tissue compared to non-tumor tissue. Immune cells in the HCC microenvironment exhibited higher oxidative detoxification capacity, and oxidative stress-induced cell death of dendritic cells was attenuated. HCC cells demonstrated enhanced communication with immune cells through the MIF pathway in a highly oxidative hepatoma microenvironment. Meanwhile, using machine learning and Cox regression screening, we identified PRDX1 as a predictor of early occurrence and prognosis in patients with HCC. The expression level of PRDX1 in HCC was related to dysregulated ribosome biogenesis and positively correlated with the expression of immunological checkpoints (PDCD1LG2, CTLA4, TIGIT, LAIR1). High PRDX1 expression in HCC patients correlated with better sensitivity to immunotherapy agents such as sorafenib, IGF-1R inhibitor, and JAK inhibitor.Conclusion: In conclusion, our study unveiled variations in oxidative stress levels between non-tumor liver and HCC tissues. And we identified oxidative stress gene markers associated with hepatocarcinogenesis development, offering novel insights into the oxidative stress response mechanism in HCC.

Abstract Background Liver carcinoma generally presents as an immunosuppressive microenvironment that promotes tumor evasion. The intercellular crosstalk of immune cells significantly influences the construction of an immunosuppressive microenvironment. This study aimed to investigate the important interactions between immune cells and their targeting drugs in liver carcinoma, by using single-cell and bulk transcriptomic data. Methods Single-cell and bulk transcriptomic data were retrieved from Gene Expression Omnibus (GSE159977, GSE136103, and GSE125449) and The Cancer Genome Atlas (TGCA-LIHC), respectively. Quality control, dimension reduction, clustering, and annotation were performed according to the Scanpy workflow based on Python. Cell–cell interactions were explored using the CellPhone database and CellChat. Trajectory analysis was executed using a partition-based graph abstraction method. The transcriptomic factors (TFs) were predicted using single-cell regulatory network inference and clustering (SCENIC). The target genes from TFs were used to establish a related score based on the TCGA cohort; this score was subsequently validated by survival, gene set enrichment, and immune cell infiltration analyses. Drug prediction was performed based on the Cancer Therapeutics Response Portal and PRISM Repurposing datasets. Results Thirty-one patients at four different states, including health, hepatitis, cirrhosis, and cancer, were enrolled in this study. After dimension reduction and clustering, twenty-two clusters were identified. Cell–cell interaction analyses indicated that macrophage-naive CD4 + T cell interaction significantly affect cancerous state. In brief, macrophages interact with naive CD4 + T cells via different pathways in different states. The results of SCENIC indicated that macrophages present in cancer cells were similar to those present during cirrhosis. A macrophage-naive CD4 + T cell (MNT) score was generated by the SCENIC-derived target genes. Based on the MNT score, five relevant drugs (inhibitor of polo-like kinase 1, inhibitor of kinesin family member 11, dabrafenib, ispinesib, and epothilone-b) were predicted. Conclusions This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma. Tumor-associated macrophages may be derived from cirrhosis and can initiate liver carcinoma. Predictive drugs that target the macrophage-naive CD4 + T cell interaction may help to improve the immunosuppressive microenvironment and prevent immune evasion. The relevant mechanisms need to be further validated in experiments and cohort studies. Graphical Abstract

We assessed the generalizability of machine learning methods using natural language processing (NLP) techniques to detect adverse drug events (ADEs) from clinical narratives in electronic medical records (EMRs). We constructed a new corpus correlating drugs with adverse drug events using 1,394 clinical notes of 47 randomly selected patients who received immune checkpoint inhibitors (ICIs) from 2011 to 2018 at The Ohio State University James Cancer Hospital, annotating 189 drug-ADE relations in single sentences within the medical records. We also used data from Harvard’s publicly available 2018 National Clinical Challenge (n2c2), which includes 505 discharge summaries with annotations of 1,355 single-sentence drug-ADE relations. We applied classical machine learning (support vector machine (SVM)), deep learning (convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM)), and state-of-the-art transformer-based (bidirectional encoder representations from transformers (BERT) and ClinicalBERT) methods trained and tested in the two different corpora and compared performance among them to detect drug–ADE relationships. ClinicalBERT detected drug–ADE relationships better than the other methods when trained using our dataset and tested in n2c2 (ClinicalBERT F-score, 0.78; other methods, F-scores, 0.61–0.73) and when trained using the n2c2 dataset and tested in ours (ClinicalBERT F-score, 0.74; other methods, F-scores, 0.55–0.72). Comparison among several machine learning methods demonstrated the superior performance and, therefore, the greatest generalizability of findings of ClinicalBERT for the detection of drug–ADE relations from clinical narratives in electronic medical records.

Abstract Background The ecology and evolution of phoretic mites and termites have not been well studied. In particular, it is unknown whether the specific relationship between mites and termites is commensal or parasitic. High phoretic mite densities have often been found to occur in weak termite colonies, suggesting that the relationship is closer to that of parasitism than commensalism. Results To examine this, Coptotermes formosanus was used as a carrier, and Acarus farris as the phoretic mite. We used video recordings to observe termite social immunity behaviors and bioassay to examine termite fitness. Our results showed that the attachment of the mite on the termite can enhance termite social immunity behaviors like alarm vibration and grooming frequency while decreasing the duration of individual grooming episodes in phoretic mites. Further, A. farris phoresy led to a 22.91% reduction in termite abdomen volume and a 3.31-fold increase in termite mortality. Conclusions When termites groom more frequently, the consequence is short duration of grooming bouts. This may be indicative of a trade-off which provides suggestive evidence that frequent social behaviors may cost termites energy. And this caused phoretic behavior hastened termites’ death, and helped propagate the population of mites feeding on dead termites. So, it provides a case for phoresy being a precursor to parasitism, and the specific relationship between A. farris and C. formosanus is closer to parasitism than to commensalism.

Abstract Background Adverse events induced by drug-drug interactions are a major concern in the United States. Current research is moving toward using electronic health record (EHR) data, including for adverse drug events discovery. One of the first steps in EHR-based studies is to define a phenotype for establishing a cohort of patients. However, phenotype definitions are not readily available for all phenotypes. One of the first steps of developing automated text mining tools is building a corpus. Therefore, this study aimed to develop annotation guidelines and a gold standard corpus to facilitate building future automated approaches for mining phenotype definitions contained in the literature. Furthermore, our aim is to improve the understanding of how these published phenotype definitions are presented in the literature and how we annotate them for future text mining tasks. Results Two annotators manually annotated the corpus on a sentence-level for the presence of evidence for phenotype definitions. Three major categories (inclusion, intermediate, and exclusion) with a total of ten dimensions were proposed characterizing major contextual patterns and cues for presenting phenotype definitions in published literature. The developed annotation guidelines were used to annotate the corpus that contained 3971 sentences: 1923 out of 3971 (48.4%) for the inclusion category, 1851 out of 3971 (46.6%) for the intermediate category, and 2273 out of 3971 (57.2%) for exclusion category. The highest number of annotated sentences was 1449 out of 3971 (36.5%) for the “Biomedical & Procedure” dimension. The lowest number of annotated sentences was 49 out of 3971 (1.2%) for “The use of NLP”. The overall percent inter-annotator agreement was 97.8%. Percent and Kappa statistics also showed high inter-annotator agreement across all dimensions. Conclusions The corpus and annotation guidelines can serve as a foundational informatics approach for annotating and mining phenotype definitions in literature, and can be used later for text mining applications.

‘Maritime Community with a Shared Future’ is the broad vision through which China aims to lead the global fisheries governance. This research has been motivated by China's ambition of equating its maritime development goals with sustainable development goal – 14 (Life Below Water). Through this research, the influential role of China in ‘global fisheries governance' has been put through an 'ocean governance mechanism at various levels (national, regional, and international). Therefore, China's role in 'global ocean and fisheries' are discussed side-by-side, focusing on and supporting a better understanding of China's potential challenges and opportunities in world fisheries. The role of China in global and regional fisheries governance has been critically analysed throughout the discussion. It is also discussed how China plays its part in Regional Fisheries Management Organisations (RFMOs) and how this role-playing can be utilised through the Belt and Road initiative (BRI) for effective governance, conservation and preservation of marine fisheries. The scope of China's national ocean and fisheries legislation is framed to support China's stance in leading global fisheries governance. The conclusion followed the discussion in descending order suggesting ocean and fisheries governance improvement and appropriate advocacy options available to China.

This work investigated the mechanical response of engineered cementitious composites (ECC) with high content fly ash by four-point bending tests, and a suitable method was recommended for the flexural toughness evaluation of ECC. The test variables were fiber volume fraction (for polyvinyl alcohol (PVA) fiber), fiber type (PVA and polyethylene (PE)), curing age (56d, 28d and 7d), water-to-binder ratio, sand-to-binder ratio and fly ash content. The results of the tests showed that the crack pattern, deflection-hardening behavior and energy dissipation capacity of ECC were mainly affected by fiber volume fraction, fiber type and curing age. The larger the proportion of fiber pulling out during crack bridging was, the higher the deflection and energy dissipation of ECC exhibited. The commonly used JSCE-SF4 method, ASTM C1609 method and post crack strength (PCS) method for evaluating the flexural toughness of fiber reinforced concrete were not applicable to evaluate the toughness of ECC, because the significant deflection-hardening behavior of ECC could not be considered. An improved method was proposed for flexural toughness evaluation of ECC materials, which included two modified indexes (equivalent initial flexural and post-peak flexural toughness index) and a new index (initial energy factor). The large deformation of ECC was taken into account and the determining the first crack point was eliminated in this new method.

Insulin resistance and progressive decline in functional β-cell mass are two key factors for developing type 2 diabetes (T2D), which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and act on multiple pathophysiological components could be more effective for treating T2D. Here, we report that elenolic acid (EA), a phytochemical, is such a dual-action agent. we show that EA dose-dependently stimulates GLP-1 secretion in mouse clonal L-cells and isolated mouse ileum crypts. In addition, EA induces L-cells to secrete peptide YY (PYY). EA induces a rapid increase in intracellular [Ca2+]i and the production of inositol trisphosphate in L-cells, indicating that EA activates phospholipase C (PLC)-mediated signaling. Consistently, inhibition of (PLC) or Gαq ablates EA-stimulated increase of [Ca2+]i and GLP-1 secretion. In vivo, a single dose of EA acutely stimulates GLP-1 and PYY secretion in mice, accompanied with an improved glucose tolerance and insulin levels. Oral administration of EA at a dose of 50 mg/kg/day for 2 weeks normalized the fasting blood glucose and restored glucose tolerance in high-fat diet-induced obese (DIO) mice to levels that were comparable to chow-fed mice. In addition, EA suppresses appetite, reduces food intake, promotes weight loss, and reverses perturbated metabolic variables in obese mice. These results suggest that EA could be a dual-action agent as an alternative or adjuvant treatment for both T2D and obesity.

ObjectiveTo evaluate the radiologic parameters of degenerative lumbar spondylolisthesis (DLS) and determine the radiographic risk factors for DLS by making comparisons with healthy control subjects.MethodsSeventy-five patients with L4/5 DLS (Meyerding grade I) and 53 healthy control subjects were analyzed. The L1-S1 disc height index (DHI), L4/5 facet joint angle (FJA), and relative cross-sectional area (RCSA) of paravertebral muscles were measured in both groups. The initial L4/5 DHI (iDHI) before the onset of DLS were estimated based on the L3/4 DHI of the DLS group and DHI of the control group. The sagittal parameters of DLS were also included in this study.ResultsThe DHI of L4/5 was lower in the DLS group than in the control group (P

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both in vitro and in vivo on a patient derived tumor xenograft of HCC (PDXHCC). TP/Ce6-LP significantly reduced the side effects of TP. Furthermore, TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway. Overall, TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.

Termites possess a mighty social immune system, serving as one of the key obstacles to controlling them biologically. However, the dynamic mechanism coordinating the social immunologic defense and caste distribution of the termites remains elusive. This study used the Coptotermes formosanus Shiraki and an entomopathogenic fungus as a host–pathogen system and experimentally manipulated a series of groups with different caste compositions of workers and soldiers. Then, the impact of demography on the behavior and innate immunity of termites was explored by analyzing the fungus susceptibility of the respective caste, efficiencies, and caste preferences of sanitary care, as well as the expression of the immune genes and phenoloxidase activity. Overall, to ensure the general health and survival of a group, the infected workers were found to sacrifice their survivorship for maintaining the soldier proportion of the group. If soldier proportion was limited within a threshold, both the survivorship of the workers and soldiers were not significantly affected by the infection. Correspondingly, the infected group with a higher proportion of soldiers stimulated the higher efficiency of a non-caste-biased sanitary care of the workers to the nestmate workers and soldiers. Moreover, the innate immunities of the infected workers were found to be more intensely upregulated in the group with higher soldier proportions. This suggested that the adjustable non-caste-biased sanitary care and innate immunity of the workers would contribute to the flexibility of the worker–soldier caste ratio in C. formosanus. This study, therefore, enhanced our understanding of the functional adaptation mechanism between pathogen-driven social immunity and the demography of the termites.

The NLRP3 inflammasome is a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by PAMPs and DAMPs, NLRP3 oligomerizes and activates caspase-1 which initiates the processing and release of pro-inflammatory cytokines IL-1β and IL-18. NLRP3 is the most extensively studied inflammasome to date due to its array of activators and aberrant activation in several inflammatory diseases. Studies using small molecules and biologics targeting the NLRP3 inflammasome pathway have shown positive outcomes in treating various disease pathologies by blocking chronic inflammation. In this review, we discuss the recent advances in understanding the NLRP3 mechanism, its role in disease pathology, and provide a broad review of therapeutics discovered to target the NLRP3 pathway and their challenges.

Biochar has attracted worldwide attention owing to its potential for mitigating greenhouse gas emissions, improving soil properties, increasing plant growth and so on. While, the assessment of a substantial amount of security is required to determine before biochar is more extensively applied. Our goal was to evaluate the security of biochar by determining the effect of biochar on the preference of soil arthropods for microhabitats. In this study, we examined the effect of varying amounts of biochar on the preference of the Formosan subterranean termite (Coptotermes formosanus) to microhabitats. In addition, we analyzed key soil characteristics to explore their relevance to the termite preferences. Our results found that when compared with 0% (control soil), there was no preference when 2.5% and 5% of biochar were applied. The application of >5% biochar repelled the termites, which then left these soils. Their fresh weight and rates of survival also decreased. The soil pH increased, but the humidity decreased when >5% of biochar was applied. Soil bacteria composition when biochar was amended at 20% also differed from 0% and 2.5% applications. The relative abundance of Cellvibrio and Flavisolibacter in 20% were significantly higher than 0% and 2.5%, while the relative abundance of Burkholderia, Candidatus_Solibacter, Dyella, Edaphobacter, Fulvimonas and Occallatibacter were significantly lower than them. And the functional results predicted by Bugbase suggested that biochar application can cause an increase in the soil potentially pathogen phenotype. In conclusion, our research indicated that biochar can affect the preference of termites for microhabitats and changes in the characteristics of soil might cause changes in these preferences. In addition, our results suggest that soil that has been amended with >10% biochar has the potential to control termites.

[This corrects the article DOI: 10.1371/journal.pone.0091834.].

Objective: Hepatocellular carcinoma (HCC) is a genetically and phenotypically heterogeneous tumor, and the prediction of its prognosis remains a challenge. In the past decade, studies elucidating the mechanisms that induce tumor cell pyroptosis has rapidly increased. The elucidation of their mechanisms is essential for the clinical development optimal application of anti-hepatocellular carcinoma therapeutics.Methods: Based on the different expression profiles of pyroptosis-related genes in HCC, we constructed a LASSO Cox regression pyroptosis-related genes signature that could more accurately predict the prognosis of HCC patients.Results: We identified seven pyroptosis-related genes signature (BAK1, CHMP4B, GSDMC, NLRP6, NOD2, PLCG1, SCAF11) in predicting the prognosis of HCC patients. Kaplan Meier survival analysis showed that the pyroptosis-related high-risk gene signature was associated with poor prognosis HCC patients. Moreover, the pyroptosis-related genes signature performed well in the survival analysis and ICGC validation group. The hybrid nomogram and calibration curve further demonstrated their feasibility and accuracy for predicting the prognosis of HCC patients. Meanwhile, the evaluation revealed that our novel signature predicted the prognosis of HCC patients more accurately than traditional clinicopathological features. GSEA analysis further revealed the novel signature associated mechanisms of immunity response in high-risk groups. Moreover, analysis of immune cell subsets with relevant functions revealed significant differences in aDCs, APC co-stimulation, CCR, check-point, iDCs, Macrophages, MHC class-I, Treg, and type II INF response between high- and low-risk groups. Finally, the expression of Immune checkpoints was enhanced in high-risk group, and m6A-related modifications were expressed differently between low- and high-risk groups.Conclusion: The novel pyroptosis-related genes signature can predict the prognosis of patients with HCC and insight into new cell death targeted therapies.

Graphene conductive inks have attracted significant attention in recent years due to their high conductivity, corrosion resistance, and environmentally friendly nature. However, the dispersion of graphene in aqueous solution is still challenging. In this work, we synthesized an amphiphilic graft copolymer, polyvinyl alcohol-g-polyaniline (PVA-g-PANI), and studied the graphene dispersion prepared with the graft copolymer by high-speed shear dispersion. The amphiphilic graft copolymer can be used as a stabilizer and adhesive agent in graphene dispersion. Given the steric hindrance of the graft copolymer, the stability of graphene dispersion is improved by decreasing the probability of π–π stacking. PVA-g-PANI has a better stability on graphene dispersion than carboxymethylcellulose sodium (CMC-Na) and a mixture of PVA and PANI. The graft copolymer has only a slight effect on the conductivity of graphene dispersion due to the existence of conductive PANI, which is beneficial for preparing the graphene dispersion with good conductivity and adhesion. Graphene dispersion is well-adapted to screen printing and is very stable with regard to the sheet resistance bending cycle.

The mobile manipulator is a floating base structure with wide space operability. An integrated mechanical device for mobile operation is formed through the organic combination of the mobile platform and multi-axis manipulator. This paper presents a general kinematic modeling method for mobile manipulators and gives the relevant derivation of the dynamic model. Secondly, the null-space composition of the mobile manipulator is analyzed, the task space is divided, and a variety of task-switching criteria are designed. Finally, a hybrid control model combining dynamic feedback and synovial control based on dynamic parameter identification is designed, and stability proof is given. The theoretical method is also verified by the experimental platform. The proposed method can effectively improve the control accuracy of the mobile manipulator, and the hybrid control method can effectively control the output torque to reach the ideal state.

Hepatocellular carcinoma (HCC) is one of the most common primary cancers, and its pathogenesis is complicated and difficult to screen. Currently, there is no effective treatment. In traditional Chinese medicine, a large proportion of patients with HCC have been diagnosed with spleen deficiency (SD) syndrome and treated with tonifying traditional Chinese medicine, which has significant clinical efficacy. However, the role and molecular mechanism of SD in HCC remain unclear. In this study, 40 mice were randomly divided into four groups: control, SD, HCC, and SD-HCC groups. The liver cancer model of SD was established by reserpine induction and orthotopic transplantation. The effects of SD on the proliferation, apoptosis, invasion, and metastasis of HCC cells were studied by cell proliferation, cell apoptosis, cell scratch, and transwell assay. We found that compared with the HCC group, the protein expressions of cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), phosphatase and tensin homolog (PTEN), and AKT (also known as protein kinase B or PKB) in the exosomes of the SD-HCC group were upregulated. In addition, the metastases and self-renewal of exosomes in the SD-HCC group were more aggressive than those in the HCC group, which could be partially reversed with the addition of CTLA-4 inhibitors. Further studies showed that in the internal environment of SD, CTLA-4 promoted tumor invasion and metastasis by regulating the PTEN/CD44 pathway. In conclusion, our findings suggest that during SD in the internal environment, exosome CTLA-4 regulates the PTEN/CD44 signal pathway to promote the proliferation, self-renewal, and metastasis of liver cancer.

BackgroundPrevious studies have reported the potential of aryl hydrocarbon receptor (AhR) in cancer immunotherapy. However, the mechanisms underpinning its therapeutic value have yet to be comprehensively investigated. Thus, this research aimed to explore the underlying association between AhR and cancer immunotherapy in 33 human cancers.MethodsThe gene expression data and clinical characteristics of 33 cancers were retrieved from The Cancer Genome Atlas database. The immunotherapeutic cohorts included GSE67501 and GSE78220 as well as IMvigor210, which were obtained from the Gene Expression Omnibus database and included in a previously published study respectively. Clinical parameters, including patient age, gender, survival, and tumor stage were analyzed to assess the prognostic value of AhR. The activity of AhR was generated by single sample gene set enrichment analysis and used to evaluate the difference between the AhR transcriptome and protein expression level. To better understand the role of AhR in cancer immunotherapy, the correlation between AhR and tumor microenvironment, as well as its relation to immune processes/elements, such as immune cell infiltration, immune inhibitors and stimulators, and the major histocompatibility complex were analyzed. The relevant underlying pathways associated with AhR signaling in cancer were also explored. Furthermore, the correlation between AhR and two immunotherapeutic biomarkers (tumor mutational burden and microsatellite instability) was investigated. Finally, the relationship between AhR and immunotherapeutic response was explored using three independent immunotherapeutic cohorts.ResultsAlthough AhR was not closely associated with age (5/33), gender (3/33), or tumor stage (3/21) in any of the studied human cancers, it exhibited potential prognostic value for predicting patient survival. Consistency has been observed between AhR activity and expression in some cancers (7/33). Generally, AhR presented a robust correlation with immune cell infiltration, immune modulators, and immunotherapeutic markers. Moreover, high AhR expression was significantly related to immune-relevant pathways. However, no significant correlation was observed between AhR and the immunotherapeutic response.ConclusionsThis research investigated the immunotherapeutic value of AhR in 33 human cancers, providing evidence regarding the function of AhR and its role in clinical treatment. However, considering that a bioinformatics approach was adopted, the current results are preliminary and require further validation.

Abstract Background Neuroinflammation is an essential player in many neurological diseases including traumatic brain injury (TBI). Recent studies have identified that inflammasome complexes are responsible for inflammatory responses in many pathological conditions. Inflammasomes are intracellular multiprotein complexes which regulate the innate immune response, activation of caspase-1, production of pro-inflammatory cytokines IL-1β and IL-18, and induction of cell death (pyroptosis). Among inflammasome family members, the nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3) is the most extensively studied and its activation is induced following TBI. As a novel target, drug development targeting the formation and activation of NLRP3 inflammasome is a prospective therapy for TBI. We have recently developed a small molecule JC124 with specificity on NLRP3 inflammasome. In this study, we explored the therapeutic value of JC124 for TBI treatment. Methods Adult male Sprague-Dawley rats were subjected to a moderate cortical impact injury. Following TBI, animals received 4 doses of JC124 treatment with the first dose starting at 30 min, the second dose at 6 h after TBI, the third and fourth doses at 24 or 30 h following TBI, respectively. Animals were sacrificed at 2 days post-injury. Brain tissues were processed either for ELISA and western blotting analysis for inflammatory response, or for histological examination to assess degenerative neurons, acute inflammatory cell response and lesion volume. Results We found that post-injury treatment with JC124 significantly decreased the number of injury-induced degenerating neurons, inflammatory cell response in the injured brain, and cortical lesion volume. Injured animals treated with JC124 also had significantly reduced protein expression levels of NLRP3, ASC, IL-1 beta, TNFα, iNOS, and caspase-1. Conclusion Our data suggest that our novel NLRP3 inhibitor has a specific anti-inflammatory effect to protect the injured brain following TBI.

Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC.Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score.Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts.Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.

Background5-methylcytosine (5mC) has been reported in the prognosis of a variety of cancers, however, its role in hepatocellular carcinoma (HCC) has not been investigated yet. This study aimed at identifying the molecular subtypes associated with 5mC and establishing a relevant score to predict its prognosis in HCC.MethodsSomatic gene mutation data and gene expression data were retrieved from The Cancer Genome Atlas database. Molecular subtypes were identified by unsupervised clustering based on the expression of 5mC regulators, and the molecular features of each subtype were investigated by survival, mutation, gene set variation, and immune cell infiltration analyses. Next, we performed a differentially expressed analysis based on the new subtypes and selected the overlapping genes for further analysis. We undertook univariate Cox analysis to analyze these genes and constructed a prognostic model by lasso regression analysis. Meanwhile, survival and gene set enrichment analyses were used to explore the prognosis and the relevant pathways, respectively. The LIRI cohort from the International Cancer Genome Consortium database was used as a reference to validate the 5mC subtypes and 5mC score.ResultsTwenty-one types of 5mC regulators were employed in this study, and three 5mC-associated molecular subtypes were identified. These three subtypes presented significant differences in prognosis, immune cell infiltration, immune checkpoint inhibitors, signaling pathways, and mutational features. Compared with cluster 3, cluster 2 exhibited significantly increased expression of PD-L1, TIM3, Galectin9, CTLA4, and CD80, while PD-L1, TIM3, and CD80 were higher in cluster 2 than in cluster 1. Furthermore, a 5mC-related score, composed of seven genes (SGPP2, SALL4, B3GNT7, ROR1, MYBL2, SLC7A1, and CAND2), was proven to be significantly associated with prognosis. The established subtypes and scores were thus successfully verified by the validated cohort.ConclusionTo the best of our knowledge, this is the first study to identify a novel molecular subtype based on 5mC regulators. The identification of the 5mC-associated subtype may help reveal the potential relation between 5mC and immunity and provide novel insights for the development of individualized therapy for HCC.

Objective: Regular consumption of n-3 polyunsaturated fatty acids is associated with decreased cardiovascular morbidity and mortality. This study assessed the therapeutic effect of docosahexaenoic acid (DHA) in palmitic acid (PA)-induced cytotoxicity in vitro and in rats fed a high-fat diet (HFD). Methods: H9C2 cells and rat primary cardiomyoblasts were exposed to PA or PA + DHA for 24 h. PA-induced lipotoxicity and mitochondrial dysfunction were evaluated by immunostaining, real-time PCR, cardiomyocyte contraction and transmission electron microscopy. The effects of dietary DHA on diabetic cardiomyopathy were evaluated in male Sprague-Dawley rats fed a reference diet rich in DHA, an HFD, or an HFD with added DHA for 16 weeks. Oxidative stress and lipotoxicity in rat heart tissue were assayed by Masson staining, immunohistochemistry, and TUNEL. Results: In vitro studies showed that dietary DHA reduced the occurrence of cardiomyopathy and improved cardiac responses to PA. In the rat model, dietary DHA reduced mitochondrial oxidative stress in HFD-induced diabetic cardiomyopathy. Conclusion: Dietary DHA reduced mitochondrial oxidative stress and ameliorated PA-induced lipid toxicity. DHA consumption may have had direct effects on cardiovascular risk via myocardial protection.

BackgroundA hypoxia microenvironment plays a role in the initiation and progression of many cancer types, but its involvement in lung adenocarcinoma is still unclear. This study aimed to explore the potential correlation between hypoxia and lung adenocarcinoma and establish the hypoxia-associated gene signature in lung adenocarcinoma.MethodsLung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The genes to be included in the hypoxia-associated signature were selected by performing univariate Cox regression analysis and lasso regression analysis. Then, the gene signature was verified by performing a survival analysis and constructing the multiple receiver operating characteristic (ROC) curve. The CIBERSORT tool was then used to investigate the potential correlation between the gene signature and immune cells. Moreover, a nomogram was constructed and evaluated by calculating the C-index.ResultsFour genes (XPNPEP1, ANGPTL4, SLC2A1, and PFKP) were included in the final signature. The results showed that patients in the high-risk group showed worse survival than those in the low-risk group. Moreover, we found two types of immune cells (memory activated CD4+ T cell and M0 macrophages) which showed a significant infiltration in the tissues of the high-risk group patients.ConclusionThe hypoxia-associated gene signature established and validated in this study could be used as a potential prognostic factor in lung adenocarcinoma and may guide the immunotherapy choice.

Background: Tumor mutational burden (TMB) was verified to be closely associated with immune checkpoint inhibitors, but it is unclear whether gene mutation has an effect on immunotherapy of hepatocellular carcinoma (HCC). This research aimed to investigate the underlying correlation between gene mutation and immunotherapy in HCC.Methods: The somatic gene mutation data and gene expression data were retrieved from International Cancer Genome Consortium database and The Cancer Genome Atlas (TCGA) database. The mutational genes were selected by the intersection of three cohorts and further identified using survival analysis and TMB correlation analysis. After the identification of key mutational gene, we explored the correlation between gene mutation and both the immune cell infiltration and immune inhibitors. The signaling pathways associated with gene mutation were confirmed through gene set enrichment analysis. Furthermore, the survival analysis and mutational analysis based on TCGA cohort were performed for the validation of included gene.Results: As one of the frequently mutational genes in HCC, CTNNB1 was finally included in our research, for which it showed the significant result in survival analysis and the positive association with TMB of the three cohorts. Meanwhile, the validation of TCGA showed the significant results. Furthermore, natural killer (NK) cells and neutrophil were found to significantly infiltrate CTNNB1 mutation group from two cohorts. Besides, further analysis demonstrated that four types of immune inhibitors (CD96, HAVCR2, LGALS9, and TGFB1) were downregulated in CTNNB1 mutation group.Conclusion: Our research firstly revealed the underlying association between CTNNB1 mutation and immunotherapy, and we speculated that CTNNB1 mutation may modulate NK cells by affecting CD96. However, more functional experiments should be performed for verification.

Ethnopharmacological relevance: The root of Averrhoa carambola L. (Oxalidaceae), a traditional Chinese medicine, was mainly used in ancient times in the treatment of urinary calculi, recurrent headache and joint pain. Aim of the study: Our aims were to explore the potential therapeutic effect of the extract of Averrhoa carambola L. (Oxalidaceae) roots (EACR) against hepatic fibrosis in CCl4-treated rats and to understand the underlying molecular mechanism. Materials and methods: Six groups of male Sprague Dawley rats were treated as follows: vehicle (olive oil), CCl4 alone, CCl4+colchicine, CCl4+EACR 1.0 g/kg, CCl4+EACR 0.5 g/kg and CCl4+EACR 0.25 g/kg. At the end of the 12th week, biomarkers of liver function, liver fibrosis, hepatic oxidative stress and antioxidant status were assayed, and histopathological and immunohistochemical evaluation of liver tissue were conducted to investigate the liver damage and fibrosis degree. Furthermore, expressions of COL-1a1, α-SMA, TGF-β1, Smad2, smad3, Smad4 and TIMP2 were examined by qPCR and/or western blot. The expressions of apoptosis-related proteins were also detected using western blot analysis. Results: EACR treatment markedly reduced the CCl4-induced elevation of serum aminotransferase activities, liver fibrosis indexes, and the extent of oxidative stress. EACR treatment also significantly reduced the accumulation of collagen and the immunostaining of α-SMA, TGF-β1 and Smad2, 4 and 7 in the liver of CCl4 treated rats. In addition, EACR treatment markedly reversed the CCl4-induced increase in mRNA expression of COL-1a1, α-SMA, TIMP2, TGF-β1, Smad2 and Smad4 and suppressed the expressions of α-SMA, TIMP2, TGF-β1, smad2, 3 and 4, BAX and cleaved caspase-3 proteins. Meanwhile, EACR treatment also significantly elevated the mRNA expression of Smad7 and the protein expression of Smad7 and Bcl-2. Conclusion: These results suggest that EACR has protective activity against liver fibrosis. The anti-fibrotic activity of EACR in vivo is associated with enhanced antioxidant, apoptosis-inhibition and increased MMP-2/TIMP-2 expression ratio, and with modulation of TGF-β1/Smad signaling pathway.

Abstract Background The aim of this study is to assess the value of contrast-enhanced ultrasound (CEUS) as a new non-invasive approach to locate the testicular area in which spermatogenesis is most likely to be found in non-obstructive azoospermic testes and to evaluate the accuracy of CEUS as a predictor of successful sperm retrieval. Methods CEUS was performed in 120 nonobstructive azoospermia (NOA) patients. Microdissection testicular sperm extraction (M-TESE) was performed on the best and poorest perfusion areas selected by CEUS and on conventional areas. Results In the 187 testicles that underwent M-TESE, the sperm retrieval rates (SRRs) in the best perfusion area and poorest perfusion area over the maximal longitudinal section and conventional area were 63.1, 34.7 and 47.1%. According to receiver operating characteristic (ROC) analysis, the arrival times (AT) ≤27 s, time-to-peak intensity (TTP) ≤45 s, and peak intensity (PI) ≥11 dB were the best predictors of positive sperm retrieval. The location of the best perfusion area was able to guide M-TESE to improve the success rates. Conclusions Testicle CEUS is suggested to be performed in all patients with NOA. If AT≤27 s, TTP ≤ 45 s or PI≥11 dB are found in the best perfusion area, M-TESE is strongly recommended.

Effective approaches to exploiting the biomass of the abundant invasive weed Mikania micrantha Kunth are limited. Termites have been a focus of significant attention as mediators of biomass-processing owing to their ability to digest lignocellulose. Here, the GC/TOF-MS approach was employed to assess the effects of a diet composed of M. micrantha leaves on Coptotermes formosanus workers, with the growth performance of these workers also being assessed. The workers increased their dietary intake when fed M. micrantha leaves, with a concomitant gradual increase in mortality rate. A total of 62 differentially abundant metabolites and nine significantly affected pathways were found when comparing termites fed M. micrantha leaves to pinewood. Key metabolites, including carbohydrates, polyols, 4-hydroxyphenylacetic acid, and their related metabolic pathways, suggested that termites can digest and utilize M. micrantha-derived lignocellulose. However, changes in the tryptophan metabolism, tyrosine metabolism, and sphingolipid metabolism suggest an adverse effect of M. micrantha leaves on antioxidant activity and signal transduction in termites. Overall, this study identified the key metabolites and pathways associated with the response of these termites to dietary changes and the effect of M. micrantha on termites.

The internet of things (IoT) has been widely concerned and developed in the world,and its security has been paid more and more attention.However,due to the characteristics of the IoT itself,a lot of security measures in the internet field can’t be applied directly.The current security strategy mainly provide solutions according to the threat of the IoT one by one.In face of increasingly intelligent,systematic,integrated security threats,a trusted IoT architecture of two layers and tri-elements,which brought about a whole trusted security mechanism according to the function of IoT.Starting with the integrity and safety inspection of hardware and software of sensor devices,the trusted chain was transmitted until the application layer,and data was processed according to behavior trusted value in application layer.At the same time,the control function and the data function were separated,and the security strategies cooperated and verified with each other,therefore improving the ability of the IoT to deal with security threats effectively.

Disturbing the lignocellulose digestive system of termites is considered to be a promising approach for termite control. The research on the tolerance mechanism of the termite lignocellulose digestive system to harmful environment conditions is limited. In this study, we keep Coptotermes formosanus Skiraki under a non-lethal toxic condition by feeding the termites with filter paper containing the kojic acid (a low toxic insecticide). The effects of low toxic stress on the activities and gene expressions of host/symbiotic originated lignocellulases, and on the symbiotic microbial community structure of C. formosanus were explored. Our result showed that the low toxic stress would lead to the synchronous decrease of cellulase and hemicellulase activities, and supplementary increase of corresponding gene expressions. The symbiotic community maintained its role as the main force in the lignocellulolytic system of C. formosanus. Meanwhile, a large number of rare taxa were significantly enriched by kojic acid treatment. These numerically inconspicuous bacterial populations might be responsible for the functions similar to phenoloxidase or insecticide detoxification and enable C. formosanus to tolerate the harmful environment. Overall, our data suggested that the digestive adaptation of C. formosanus to physiotoxic feeding is closely related to the triple collaboration of termites–flagellates–bacteria.

Low-temperature environments can strongly affect the normal growth and health of livestock. In winter, cold weather can be accompanied by strong winds that aggravate the effects of cold on livestock. In this study, two experiments were conducted to investigate the effect of low temperature and/or wind speed on physiological indices, rumen microbiota, immune responses and oxidative stress in sheep. When sheep were exposed to cold temperature and/or stronger wind speeds, the average daily gain (ADG) decreased (p < 0.05), and the abundance of Lachnospiraceae was significantly higher (p < 0.05). The acetate and propionate contents and the proportion of propionate in the rumen also significantly reduced (p < 0.05). The immunoglobulin G (IgG) and TH1-related cytokines in the blood were significantly lower (p < 0.05). However, antioxidant enzyme contents were significantly increased and the concentration of malondialdehyde (MDA) was reduced (p < 0.05). In a cold environment, the abundance of Lachnospiraceae in the rumen of sheep was highly enriched, and the decreasing of propionate might be one of the factors affecting the immunity of the animals, the sheep did not suffer from oxidative damage during the experiment.

Background/Aims: Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD), isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Methods: Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA)-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. Conclusions: DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway.

As the improvement of the enterprise’s informationalization level and the increasing management requirement of enterprise refinement，the demand of data management of enterprise is becoming greater and greater，how to improve the data quality of the enterprise is the key problem needed to be solved. Aiming at the challenges of data quality management that the power enterprise faces，some solutions for distributed data quality management were proposed. After researching the system features of data quality，some foreign and domestic cases of big data were analyzed as reference，and a solution based on Hadoop distributed processing framework was given to solve the performance bottleneck of centralized data quality system. Hadoop clustering could dissociate defect data from Oracle and the data would be stored separately on multiple servers of the clustering，which could improve the I/O performance and data analysis performance of the magnetic disk effectively.

The outbreak of pseudorabies in China, caused by more virulent pseudorabies virus (PRV) than the classical strains, has led to considerable economic losses. In this study, PRV strain HNXY was isolated from the Henan province of China in 2015 from the pig farm with severe reproductive failure in sows and a high mortality in piglets. The 50% tissue culture infectious doses (TCID50) of HNXY in Vero cells were examined to be 106.5/mL, and the neutralisation titer against Bartha-K61 was significantly higher than against HNXY when tested with the serum from Bartha-K61 vaccinated pigs. The 50% lethal doses (LD50) of HNXY to six-week-old BALB/c mice and two-month-old PRV-free pigs were both 102.3 TCID50. HNXY was classified as genotype II, and numerous amino acid variations were found in gB, gE, gC, gD, TK, and RR1 proteins, compared with PRV from other countries or those prevalent in China before 2012. The attenuated rHNXY-∆TK/∆gE was further constructed, which presented significantly smaller plaques than HNXY, as well as the similar growth kinetics. rHNXY-∆TK/∆gE was confirmed to be non-pathogenic to six-week-old BALB/c mice and zero-day-old piglets. This study isolated updated PRV promising to develop into a new vaccine candidate.

Aim: The primary objective of this study was to study the effects of 17-methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC) on pressure overload-induced cardiac remodeling in rats, as well as the endothelial mechanisms based on PGI2. Methods: Six weeks following surgery, rats were divided randomly into the following groups: a sham group, a model group, an MHBFC 12 mg/kg/day group (MHBFC 12), an indomethacin 2 mg/kg/day group (Indo 2), and an Indo 2+ MHBFC 12 group. The MS 4000 organism signal system was used to record the rats' hemodynamic indices. Additionally, the heart weight was determined, and the cardiac remodeling index was calculated. HE and Masson's stains were utilized to perform histological analyses; the immunofluorescence was used to observe the microvessel density of myocardial tissue; the colorimetric method was used to determine the hydroxyproline content of cardiac tissue; the ELISA method was used to measure the plasma PGI2 content; and transmission electron microscopy was used to observe the ultrastructure of the myocardium. Results: A hyperdynamic circulation state, cardiac remodeling, decreased microvessel density and decreased plasma PGI2 content were each observed in the model group compared with the sham group, in which any changes in the above parameters were effectively reversed by MHBFC. Single-use Indo administration resulted in the progression of these pathophysiological changes; however, MHBFC prevented the worsening of these parameters. Conclusion: MHBFC significantly reverses pressure overload-induced cardiac remodeling, and its mechanism may partially contribute to the amelioration of endothelial cell function and the augmentation of PGI2 synthesis and secretion.

Aims: Effect and mechanism of Yulangsan flavonoid (YLSF) on rat myocardial ischemia/reperfusion injury (MI/RI) has been investigated. Methods: Sprague-Dawley (SD) rats were randomly divided into seven groups (sham group, model group and NS group: 2 mL of normal saline/kg body weight was administered; diltiazem group: 5 mg of diltiazem hydrochloride/kg body weight was administered; YLSFL, YLSFM and YLSFH groups: 20, 40 and 80 mg of YLSF/kg body weight was administered) and the MI/RI model was established. Myocardial infarct area, levels of myocardial enzymes and nitric oxide synthase (NOS) were measured. Caspase-3 and adenine nucleotide translocator-1 (ANT1) mRNA expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Pathological structure and cardiocyte ultrastructure were also analysed. Results: Compared with the MI/RI group, pretreatment with YLSF or diltiazem hydrochloride decreased the infarct area, levels of inducible nitric oxide synthase (iNOS), caspase-3 as well as the leakage of myocardial enzyme and increased activities of total nitric oxide synthase (tNOS) as well as constitutive nitric oxide synthase (cNOS). Cellular edema and the infiltration of inflammatory cells were alleviated. Conclusions: The experiment showed that YLSF protected the heart against MI/RI, possibly by reducing lipid peroxidation damage, regulating NOS activity and modulating the apoptosis genes expression.

Background Carbon dioxide (CO2) is a pervasive chemical stimulus that plays a critical role in insect life, eliciting behavioral and physiological responses across different species. High CO2 concentration is a major feature of termite nests, which may be used as a cue for locating their nests. Termites also survive under an elevated CO2 concentration. However, the mechanism by which elevated CO2 concentration influences gene expression in termites is poorly understood. Methods To gain a better understanding of the molecular basis involved in the adaptation to CO2 concentration, a transcriptome of Coptotermes formosanus Shiraki was constructed to assemble the reference genes, followed by comparative transcriptomic analyses across different CO2 concentration (0.04%, 0.4%, 4% and 40%) treatments. Results (1) Based on a high throughput sequencing platform, we obtained approximately 20 GB of clean data and revealed 189,421 unigenes, with a mean length and an N50 length of 629 bp and 974 bp, respectively. (2) The transcriptomic response of C. formosanus to elevated CO2 levels presented discontinuous changes. Comparative analysis of the transcriptomes revealed 2,936 genes regulated among 0.04%, 0.4%, 4% and 40% CO2 concentration treatments, 909 genes derived from termites and 2,027 from gut symbionts. Genes derived from termites appears selectively activated under 4% CO2 level. In 40% CO2 level, most of the down-regulated genes were derived from symbionts. (3) Through similarity searches to data from other species, a number of protein sequences putatively involved in chemosensory reception were identified and characterized in C. formosanus, including odorant receptors, gustatory receptors, ionotropic receptors, odorant binding proteins, and chemosensory proteins. Discussion We found that most genes associated with carbohydrate metabolism, energy metabolism, and genetic information processing were regulated under different CO2 concentrations. Results suggested that termites adapt to ∼4% CO2 level and their gut symbionts may be killed under high CO2 level. We anticipate that our findings provide insights into the transcriptome dynamics of CO2 responses in termites and form the basis to gain a better understanding of regulatory networks.

FXIa is suggested as a major target for anticoagulant drug discovery because of reduced risk of bleeding. In this paper, we defined 5-phenyl-1H-pyrazole-3-carboxylic acid derivatives as privileged fragments for FXIa inhibitors’ lead discovery. After replacing the (E)-3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylamide moiety in compound 3 with 5-(3-chlorophenyl)-1H-pyrazole-3-carboxamide, we traveled from FXIa inhibitor 3 to a scaffold that fused the privileged fragments into a pharmacophore for FXIa inhibitors. Subsequently, we synthesized and assessed the FXIa inhibitory potency of a series of 5-phenyl-1H-pyrazole-3-carboxamide derivatives with different P1, P1′ and P2′moiety. Finally, the SAR of them was systematically investigated to afford the lead compound 7za (FXIa Ki = 90.37 nM, 1.5× aPTT in rabbit plasma = 43.33 μM) which exhibited good in vitro inhibitory potency against FXIa and excellent in vitro coagulation activities. Furthermore, the binding mode of 7za with FXIa was studied and the results suggest that the 2-methylcyclopropanecarboxamide group of 7za makes 2 direct hydrogen bonds with Tyr58B and Thr35 in the FXIa backbone, making 7za binds to FXIa in a highly efficient manner.

BACKGROUND: Most studies about aquaporin 3 (AQP3) in the gastrointestinal tract were carried out on both in vivo and in vitro. The role of AQP3-mediated water transport in human gastrointestinal tract is still unclear. Our aim in this study was to explore the expression of AQP3 gene in chronic atrophic gastritis (CAG) and chronic superficial gastritis (CSG) atients and to determine its possible function in the development of gastritis. METHODS: Twenty-two outpatients diagnosed as CSG and 12 outpatients diagnosed as CAG were selected randomly. Ten cases of healthy individuals were selected as normal control group. In all cases, AQP3 gene expression of gastric mucosa was detected by fluorescence quantitative polymerase chain reaction (FQ-PCR). RESULTS: The AQP3 gene expression was significantly higher in gastric mucosa of CSG and healthy individuals than that in CAG (P0.05). CONCLUSIONS: AQP3 expression might play certain role in the occurrence and development of gastritis. KEY WORDS: Aquaporin 3, chronic superficial gastritis, chronic atrophic gastritis.