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IntroductionAnkle fractures require temporary fixation to allow swelling to subside prior to surgery; this is typically achieved using calcaneal distraction or cast immobilization. We compared the results of these methods in the treatment of Danis–Weber type C ankle fractures.MethodsThis retrospective study analyzed the data of 86 patients with Danis–Weber type C ankle fractures, of whom 40 underwent calcaneal distraction and 46 underwent cast immobilization. Clinical measures including preoperative detumescence time, daily swelling value, skin condition, and pain, SF-36 Health Survey (SF-36) score and ankle scores were compared between the two groups.ResultsBaseline characteristics did not differ significantly between the groups. Calcaneal distraction resulted in a lower preoperative detumescence time (6.22 ± 0.64 vs. 8.94 ± 0.82 days) and lower daily swelling values compared with cast immobilization, leading to a lower skin necrosis rate. Resting pain scores were significantly lower in the calcaneal distraction group than in the cast immobilization group at various postoperative time points (P

BackgroundSarcopenia can lead to significant personal, social, and economic burdens. The diagnosis of sarcopenia heavily relies on the identification of Low Skeletal Muscle Mass (LSMM), which is an independent predictor of frailty, disability, and increased risk of death among seniors. Women have physiologically lower levels of skeletal muscle mass than men, and female sarcopenia appears to be more influenced by menopause. They also tend to have higher body fat levels than man, which increases the risk of sarcopenia obesity. On another front, it’s also recognized that humans are largely prone to Helicobacter pylori (H. pylori) infection, with global prevalence rates often surpassing 50%. Nevertheless, the interconnection between H. pylori infection and LSMM remains relatively unexplored. Hence, our study specifically targeted women as the research population and sought to explore several risk factors for LSMM. Additionally, we delved into the potential correlation between LSMM and H. pylori infection in women, hoping to gain insights into potential preventative measures or treatment options that may enhance the quality of life for women affected by sarcopenia.MethodsWe conducted a cross-sectional study among women aged over 18 years undergoing physical examination. We performed 13C-urea breath test (UBT) for diagnosis of H. pylori infection and Bioelectrical impedance analysis (BIA) for the assessment of LSMM. Logistic regression models were used to analyze the associations of H. pylori infection with LSMM.ResultsThis study enrolled 1984 Chinese women who were undergoing health check-ups. A univariate logistic regression analysis did not reveal a direct correlation between H. pylori infection and LSMM among this female population (OR=1.149, 95% CI 0.904-1.459, p=0.257). Yet, upon dividing the participants into age-based subgroups, an evident link was observed between H. pylori infection and LSMM in women aged 40 or above (OR=1.381, 95%CI 1.032-1.848, p= 0.030). After adjusting for variables including Age, BMI, TP, ALK, Cre, this relationship remained statistically relevant (OR=1.514, 95%CI 1.085-2.113, p= 0.015).ConclusionsWomen who are over 40 years old and currently infected with H. pylori have an increased risk of developing LSMM. Therefore, timely treatment for H. pylori eradication is recommended for this group of women to reduce the occurrence of LSMM.

Background: Echocardiographic data investigating the association between left ventricular (LV) function and gout is still limited.Purpose: To analyze the association of echocardiographic parameters based on two-dimentional speckle tracking analysis with clinically related indicators in patients with gout, and to provide a clinical basis for the early diagnosis and treatment of cardiovascular disease in patients with gout.Methods: This study collected gout patients who visited the outpatient and inpatient departments of the first affiliated hospital of chengdu medical college from November 2019 to December 2020. Spearman correlation test was performed to analyze the correlation coefficients between the laboratorial indicators with echocardiographic parameters. And the logistic regression analysis was performed to evaluate the independent effects.Results: The results of multivariate logistic regression showed that fasting plasma glucose (FPG) was a risk factor for the decrease in absolute value of global longitudinal strain [GLS (OR = 2.34; 95% CI, 1.01–5.39; p = 0.04)], Urea was a risk factor for absolute reduction in GCS (OR = 1.40; 95% CI, 1.07–1.85; p = 0.02), age (OR = 1.09, 95% CI, 1.04–1.16; p = 0.001), and hypertension (OR = 8.35; 95% CI, 1.83–38.02; p = 0.006) were risk factors for increased E/Em. High urea levels were significantly related with high risks of LVH (OR = 1.59, 95% CI, 1.04–2.43; p = 0.03) and enlargement of LAVI (OR = 1.68, 95% CI, 1.01–2.80; p = 0.04).Conclusion: Our study found that elevated urea and FPG were risk factors for subclinical LV myocardial dysfunction in patients with gout, which might provide a theoretical basis for the early diagnosis and treatment of heart disease in clinical practice.

Sepia esculenta is a cephalopod widely distributed in the Western Pacific Ocean, and there has been growing research interest due to its high economic and nutritional value. The limited anti-stress capacity of larvae renders challenges for their adaptation to high ambient temperatures. Exposure to high temperatures produces intense stress responses, thereby affecting survival, metabolism, immunity, and other life activities. Notably, the molecular mechanisms by which larval cuttlefish cope with high temperatures are not well understood. As such, in the present study, transcriptome sequencing of S. esculenta larvae was performed and 1,927 differentially expressed genes (DEGs) were identified. DEGs were subjected to functional enrichment analyses using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The top 20 terms of biological processes in GO and 20 high-temperature stress-related pathways in KEGG functional enrichment analysis were identified. A protein-protein interaction network was constructed to investigate the interaction between temperature stress-related genes. A total of 30 key genes with a high degree of participation in KEGG signaling pathways or protein-protein interactions were identified and subsequently validated using quantitative RT-PCR. Through a comprehensive analysis of the protein-protein interaction network and KEGG signaling pathway, the functions of three hub genes (HSP90AA1, PSMD6, and PSMA5), which belong to the heat shock protein family and proteasome, were explored. The present results can facilitate further understanding of the mechanism of high temperature resistance in invertebrates and provide a reference for the S. esculenta industry in the context of global warming.

The virtual inertia technology of DGs (Distributed Generations) can provide inertia and damping support for the power system by imitating the traditional synchronous machine. However, the inherent delay problems around the communication and process links of the virtual inertia control will make an impact on the fast support effect. In this paper, the virtual inertia based hierarchical control scheme considering communication delay for distributed generations integration systems is proposed. The hierarchical control architecture including the PQ primary control and the virtual inertia based secondary control method which can realize the optimal power utilization and certain frequency support under the situation of communication signal delay at the same time. Firstly, the basic hierarchical control scheme for distributed generations and corresponding small signal modeling considering communication delay are presented. Then to enhance the inertia support ability of the distributed generation integration system, an improved hierarchical control strategy considering communication delay is designed based on the robust passivity method to compensate the equivalent delay disturbance. Finally, the effectiveness verification of the proposed control is carried out with the simulation cases in PSCAD platform.

As many schools remain closed during the COVID-19 pandemic, various courses have to be migrated online. Previous studies have showed that students’ satisfaction of the courses could reflect the quality of online learning, which is determined by students’ perception of online courses. Although the community of inquiry (CoI) framework provided an effective tool for measuring students’ perception in online learning, the mechanisms between the CoI and satisfaction, especially the role of academic emotion and self-regulation, still need to be investigated in the online context. The present study aimed to (1) explore the relationships among three elements of the CoI framework; and (2) explore the relationships between the CoI and satisfaction, as well as the mediating role of academic emotion and self-regulation. The data was collected from 461 university students who were taking online courses in China. The results of Structural Equation Modeling showed that teaching presence significantly and positively predicted social presence and cognitive presence; both positive and negative academic emotions played the mediating roles between teaching presence, social presence and satisfaction; self-regulation played the mediating role between teaching presence, cognitive presence and satisfaction. The present study provided empirical evidence for the dynamics among the CoI framework as well as mechanisms between CoI and satisfaction in the online education environment.

As a biological sound source widely distributed in temperate and tropical coastal waters, snapping shrimp produce strong pulses which can serve as honest signals to indicate habitat-specific soundscape. The past decade has witnessed the growing interest in investigating the acoustical activity of snapping shrimp across many shallow waters including the coastal line of the west Pacific Ocean. It was extended to the Southeast China coastal area where snapping sounds and the associated soundscape were recorded at four sites. Customized codes incorporating bandwidth and amplitude threshold operations were developed to detect snaps from the ambient noise to estimate snap rate and extract snaps individually. The subsequent analysis suggested that snaps recorded at different sites were unanimously stronger than background noise. Sound pressure level of the snaps ranged from 150 dB to 190 dB (re 1 μPa). The characteristics of snaps, including sound pressure level, duration, peak frequency, -3dB bandwidth from different sites are examined to evaluate the variability across the sites. Though snapping pulses had peak frequencies and the -3 dB bandwidth consistently below 10 kHz, snaps had considerable energy extending to the high frequency range over 200 kHz. The analysis of the acoustic data received for 7 consecutive days at one site indicated that the snap rate corresponded to tidal level periodicity. A high tide was accompanied with a local high snap rate regardless of light but this local snap rate peak was much higher at night. The mean rate fluctuated between 2000 and 4000 snaps per minute and more snaps were recorded after sunset suggesting that snapping shrimp living in the area snapped in response to light. These data may indicate that snaps are important communication means in light-limited condition and deepen our understanding on the correlation of snapping behavior and ecological environments.

IntroductionNumerous studies have reported the modification of particulate matters (PMs) on the association between cold temperature and health. However, it remains uncertain whether the modification effect may vary by size of PMs, especially in Shandong Province, China where the disease burdens associated with cold temperature and PMs are both substantial. This study aimed to examine various interactive effects of cold exposure and ambient PMs with diameters ≤1/2.5 μm (PM1 and PM2.5) on premature deaths in Shandong Province, China.MethodsIn the 2013-2018 cold seasons, data on daily mortality, PM1 and PM2.5, and weather conditions were collected from the 1822 sub-districts of Shandong Province. A time-stratified case-crossover study design was performed to quantify the cumulative association between ambient cold and mortality over lag 0-12 days, with a linear interactive term between temperature and PM1 and PM2.5 additionally added into the model.ResultsThe mortality risk increased with temperature decline, with the cumulative OR of extreme cold (−16.9°C, the 1st percentile of temperature range) being 1.83 (95% CI: 1.66, 2.02), compared with the minimum mortality temperature. The cold-related mortality risk was 2.20 (95%CI: 1.83, 2.64) and 2.24 (95%CI: 1.78, 2.81) on high PM1 and PM2.5 days, which dropped to 1.60 (95%CI: 1.39, 1.84) and 1.60 (95%CI: 1.37, 1.88) on low PM1 and PM2.5 days. PM1 showed greater modification effect for per unit concentration increase than PM2.5. For example, for each 10?g/m3 increase in PM1 and PM2.5, the mortality risk associated with extreme cold temperature increased by 7.6% (95% CI: 1.3%, 14.2%) and 2.6% (95% CI: −0.7%, 5.9%), respectively.DiscussionThe increment of smaller PMs' modification effect varied by population subgroups, which was particularly strong in the elderly aged over 75 years and individuals with middle school education and below. Specific health promotion strategies should be developed towards the greater modification effect of smaller PMs on cold effect.

Semicarbazide (SMC), also known as carbamoyl hydrazide, is a key intermediate for the organic synthesis of drugs, pesticides, and a panoply of other applications. It is also regarded as a landmark metabolite of nitrofurazone, a banned veterinary drug. SMC produced in different ways will eventually enter the ocean and become an emerging marine pollutant, affecting the physiological metabolism, behavioral activities, and even survival of aquatic organisms. Sea cucumbers are sediment-feeding organisms, and their risk of exposure to pollutants has attracted increasing attention. In this study, an integrated proteomic and metabolomic approach was used to investigate the responses of Apostichopus japonicus treated with SMC (3.72 g/L) for 72 h. After SMC treatment, the proteins and metabolites of A. japonicus intestine changed significantly. The results showed that 342 differentially expressed proteins were identified, of which 174 were upregulated, 168 were downregulated, and 74 differentially expressed metabolites, of which 62 were upregulated and 12 were downregulated. These differential proteins and metabolites were primarily involved in energy metabolism, lipid metabolism, signal transduction, immune regulation, autophagy, and apoptosis. On the basis of a combination of proteomic and metabolomic data, a hypothetical network of proteins, metabolites, and pathways in sea cucumbers was also described; the resulting network indicated several significant biological activities in response to SMC. This work offers a thorough analysis of the intricate mechanisms by which sea cucumbers respond to SMC stress and indicates numerous possible indicators for further research on creatures exposed to SMC. Further, our results provide scientific guidance for pollution control of Apostichopus japonicus culture to ensure healthy breeding.

BackgroundThe tibial-eminence fracture (TEF) is an anterior cruciate-ligament avulsion fracture with a low incidence. Many surgical techniques have been described, but none of them allow early functional exercise, and there are many postoperative complications.PurposesThis study aimed to evaluate the early clinical efficacy and complications of day case arthroscopic-surgery treatment of adult TEF with button plates.MethodsWe retrospectively analyzed patients with TEF treated with arthroscopic surgery. Clinical subjective evaluation included International Knee Documentation Committee (IKDC) subjective score, Lysholm Knee Score, and Visual Analog Scale (VAS) score. Knee joint scores were evaluated by Lysholm score. Clinical objective assessment included the Lachman test, anterior-drawer test (ADT), IKDC, and range of motion. We assessed patient quality of life using a life summary table. Assessment of fracture healing and internal fixation was based on lateral x-rays of the knee joint. We measured and evaluated patient satisfaction at the last follow-up in accordance with Marsh criteria.ResultsAt final follow-up (average follow-up time, 28.23 ± 3.14 months), we evaluated results from 22 patients (22 knees). Average patient age during surgery was 33.64 ± 6.96 years. Average time from injury to surgery was 6.59 ± 1.47 h. Postoperative function was better than pre-operative function in all patients. IKDC subjective score, Lysholm score, and VAS score were better at final follow-up than before surgery. Differences in Lachman test and ADT scores before and after surgery were statistically significant. According to Intra-articular button position classification, 6 patients (6 knees) showed ideal position (A), 16 patients (16 knees) showed nearly ideal position (B), and none of the patients had nonideal position (C). The fractures of 22 patients healed completely; 2 patients had a 5°–10° knee joint dysfunction, and 1 had an abnormal knee sound. According to intra-articular button position classification, the rate of ideal position was 100%. Patient satisfaction rate was 81.8%.ConclusionDay surgery using double-button plates to treat TEF could achieve anatomical reduction, power and stability, as well as good clinical efficacy.

Sepia esculenta is a popular economic cephalopod with high yield, delicious meat, and rich nutrition. With the rapid development of heavy industry and medical industry, a large amount of waste has been released into the ocean recklessly in recent years, inducing a significant increase in the content of heavy metals, especially cadmium (Cd) and copper (Cu), in the ocean. This phenomenon significantly affects the growth and development of S. esculenta, causing a serious blow to its artificial breeding. In this study, transcriptome analysis is used to initially explore immune response mechanisms of Cd and Cu co-exposed juvenile S. esculenta. The results show that 1,088 differentially expressed genes (DEGs) are identified. And DEGs functional enrichment analysis results suggests that co-exposure may promote inflammatory and innate immune responses in juvenile S. esculenta. Fifteen key genes that might regulate the immunity of S. esculenta are identified using protein-protein interaction (PPI) network and KEGG enrichment analyses, of which the three genes with the highest number of interactions or involve in more KEGG pathways are identified as hub genes that might significantly affect the immune response processes. Comprehensive analysis of PPI network and KEGG signaling pathway is used for the first time to explore co-exposed S. esculenta juvenile immune response processes. Our results preliminarily reveal immune response mechanisms of cephalopods exposed to heavy metals and provide a valuable resource for further understanding of mollusk immunity.

BackgroundThis study sought to develop and validate a dynamic nomogram chart to assess the risk of acute kidney injury (AKI) in patients with acute ischemic stroke (AIS).MethodsThese data were drawn from the Medical Information Mart for Intensive Care III (MIMIC-III) database, which collects 47 clinical indicators of patients after admission to the hospital. The primary outcome indicator was the occurrence of AKI within 48 h of intensive care unit (ICU) admission. Independent risk factors for AKI were screened from the training set using univariate and multifactorial logistic regression analyses. Multiple logistic regression models were developed, and nomograms were plotted and validated in an internal validation set. Based on the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) to estimate the performance of this nomogram.ResultsNomogram indicators include blood urea nitrogen (BUN), creatinine, red blood cell distribution width (RDW), heart rate (HR), Oxford Acute Severity of Illness Score (OASIS), the history of congestive heart failure (CHF), the use of vancomycin, contrast agent, and mannitol. The predictive model displayed well discrimination with the area under the ROC curve values of 0.8529 and 0.8598 for the training set and the validator, respectively. Calibration curves revealed favorable concordance between the actual and predicted incidence of AKI (p > 0.05). DCA indicates the excellent net clinical benefit of nomogram in predicting AKI.ConclusionIn summary, we explored the incidence of AKI in patients with AIS during ICU stay and developed a predictive model to help clinical decision-making.

Periodontitis is highly prevalent worldwide. It is characterized by periodontal attachment and alveolar bone destruction, which not only leads to tooth loss but also results in the exacerbation of systematic diseases. As such, periodontitis has a significant negative impact on the daily lives of patients. Detailed exploration of the molecular mechanisms underlying the physiopathology of periodontitis may contribute to the development of new therapeutic strategies for periodontitis and the associated systematic diseases. Pyroptosis, as one of the inflammatory programmed cell death pathways, is implicated in the pathogenesis of periodontitis. Progress in the field of pyroptosis has greatly enhanced our understanding of its role in inflammatory diseases. This review first summarizes the mechanisms underlying the activation of pyroptosis in periodontitis and the pathological role of pyroptosis in the progression of periodontitis. Then, the crosstalk between pyroptosis with apoptosis, necroptosis, and NETosis in periodontitis is discussed. Moreover, pyroptosis, as a novel link that connects periodontitis with systemic disease, is also reviewed. Finally, the current challenges associated with pyroptosis as a potential therapeutic target for periodontitis are highlighted.

Background and purposeThis study aimed to explore the association between triglyceride–glucose (TyG) index and stroke recurrence in elderly patients with ischemic stroke in China.MethodsWe enrolled ischemic stroke patients aged ≥ 65 years from the Nanjing Stroke Registry Program. The primary endpoint was defined as recurrent stroke within one year after the index stroke. We used multivariable Cox proportional hazards regression models to investigate the association between TyG index and stroke recurrence. We assessed the discriminative ability of TyG index with the receiver operative characteristic and the area under the curve.ResultsA total of 955 patients (median age, 70.0 [67.0, 75.0]; male sex, 67.2%) from the Nanjing Stroke Registry Program were enrolled. During one year follow-up, 97 (10.2%) elderly patients experienced stroke recurrence. In multivariable analyses, the association between TyG index and stroke recurrence remained significant after adjusting for confounders (quartile 4 versus quartile 1; hazard ratio, 2.073, 95% confidence interval, 1.158-3.711; P = 0.014). The restricted cubic spline showed an increasing trend for TyG index and stroke recurrence (P for non-linearity = 0.072). The area under the curve to predict stroke recurrence with TyG index was 0.719 (95% confidence interval, 0.666-0.772). Besides, TyG index slightly improved the prediction for stroke recurrence.ConclusionElevated TyG index was associated with stroke recurrence in elderly patients with ischemic stroke. Further studies are warranted to assess the role of TyG index in the development of stroke recurrence in the elderly.

MicroRNAs (miRNAs) play a pivotal role in regulating a number of physiologic and pathologic processes including bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, making them a candidate used to promote osteogenesis. However, due to intrinsic structure and characteristics, “naked” miRNAs are unstable in serum and could not pass across the cellular membrane. Nano delivery systems seem to be a solution to these issues. Recently, graphene oxide (GO)-based nanomaterials are considered to be promising for gene delivery due to their unique physiochemical characteristics such as high surface area, biocompatibility, and easy modification. In this work, a GO-based nanocomplex functionalized by polyethyleneglycol (PEG) and polyethylenimine (PEI) was prepared for loading and delivering miR-29b, which participates in multiple steps of bone formation. The nanocomplex revealed good biocompatibility, miRNA loading capacity, and transfection efficiency. The miR-29b/GO-PEG-PEI nanocomplex was capsulated into chitosan (CS) hydrogel for osteogenesis. In vitro and in vivo evaluation indicated that miR-29b/GO-PEG-PEI@CS composite hydrogel was able to promote BMSC osteogenic differentiation and bone regeneration. All these results indicate that PEG/PEI functionalized GO could serve as a promising candidate for miRNA cellular delivery, and the miR-29b/GO-PEG-PEI@CS hydrogel has the potential for repairing bone defects in vivo.

BackgroundTranssphenoidal surgery (TSS) is first-line treatment for giant pituitary adenomas (PAs). Although PA is a benign neuroendocrine tumor that originates from adenohypophysial cells, the surgical outcomes and prognosis of giant PAs differ significantly due to multiple factors such as tumor morphology, invasion site, pathological characteristics and so on. The aim of this study was to evaluate surgical outcomes of giant PAs in a single-center cohort.MethodsThe clinical features and outcomes of 239 patients with giant PA who underwent sphenoidal surgery at the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2021 were collected from medical records. The basic clinical information (age, gender, function etc.), surgical procedure, imaging features (maximum diameter, invasion characteristics, tumor shape etc.) and histopathological characteristics (pathological results, Ki-67, P53 etc.) were retrospectively reviewed. SPSS 25.0 and Stata 12.0 software were used for statistical analysis.ResultsA total of 239 patients with giant PAs underwent TSS, of which 168 surgeries (70.29%) were endoscopic endonasal transsphenoidal (EETS) and 71 (29.71%) were microscopic transsphenoidal (MTS). The mean preoperative maximum diameter in the cohort was 45.64 mm. Gross-total resection was achieved in 46 patients (19.25%), near-total in 56 (23.43%), subtotal in 68 (28.45%), and partial in 69 (28.87%) patients. The maximum tumor diameter and Knosp grade were the significant factors that limited the extent of the resection of giant PAs. A total of 193 patients (80.75%) experienced surgical complications, and the most common complications were postoperative diabetes insipidus (DI) (91, 38.08%), intracranial infection (36, 15.06%) and cerebrospinal fluid (CSF) leaks (37, 15.48%). In addition, there was a significant difference in the incidence of CSF leaks between the neuroendoscopy group and the microscopic group (P < 0.05).ConclusionThe management of giant PAs remains a therapeutic challenge due to their large size and postoperative complications. The maximum diameter and Knosp grade of giant PAs significantly limited the extent of resection, which warrants a reasonable surgical plan.

PurposeWe previously found that Hu antigen R (HuR) can regulate the proliferation and metastasis of esophageal cancer cells. This study aims to explore the effects of HuR on the radiosensitivity of esophageal cancer.Materials and MethodAnalyses of CCK-8, colony formation assay, Western blot, immunofluorescence, flow cytometry, reactive oxygen species (ROS), and mitochondrial membrane potential were conducted to characterize the esophageal cancer cells. Nude mouse models were used to detect the effects of HuR in a combination of X-ray treatment on the subcutaneous xenografts of esophageal cancer. In addition, a luciferase assay was used to detect the direct interaction of HuR with Snail mRNA 3’-UTR.ResultsThe down-regulation of HuR combined with X-ray can significantly inhibit the proliferation and colony formation of esophageal cancer cells. Flow cytometry data showed that the down-regulation of HuR could induce a G1 phase cell cycle block in esophageal cancer cells, and aggravate X-ray-induced apoptosis, indicated by the increases of apoptosis-related proteins Bax, caspase-3 and caspase-9. Moreover, the down-regulation of HuR could significantly impair the mitochondrial membrane potential and increase the ROS production and DNA double-strand break marker γH2AX expression in esophageal cancer cells that were exposed to X-rays. In vivo data showed that the down-regulation of HuR combined with radiation significantly decreased the growth of subcutaneous xenograft tumors. Furthermore, HuR could interact with Snail. Up-regulation of Snail can reverse the EMT inhibitory effects caused by HuR down-regulation, and attenuate the tumor-inhibiting and radiosensitizing effects caused by HuR down-regulation.ConclusionIn summary, our data demonstrate that HuR effectively regulates the radiosensitivity of esophageal cancer, which may be achieved by stabilizing Snail. Thus, HuR/Snail axis is a potentially therapeutic target for the treatment of esophageal cancer.

Feather performs important physiological functions in birds, and it is also one of the economic productions in goose farming. Understanding and modulating feather follicle development during embryogenesis are essential for bird biology and the poultry industry. CHIR-99021 is a potent Wnt/β-catenin signaling pathway activator associated with feather follicle development. In this study, goose embryos (Anser cygnoides) received an in ovo injection of CHIR-9902, which was conducted at the beginning of feather follicle development (E9). The results showed that feather growth and feather follicle development were promoted. The Wnt signaling pathway was activated by the inhibition of GSK-3β. Transcriptomic analyses showed that the transcription changes were related to translation, metabolism, energy transport, and stress in dorsal tissue of embryos that received CHIR-99021, which might be to adapt and coordinate the promoting effects of CHIR-99021 on feather follicle development. This study suggests that in ovo injection of CHIR-99021 is a potential strategy to improve feather follicle development and feather-related traits for goose farming and provides profiling of the Wnt signaling pathway and transcriptome in dorsal tissue of goose embryos for further understanding of feather follicle development.

ObjectivesCervical radiotherapy can lead to accelerated carotid artery stenosis, increased incidence of stroke, and a higher rate of in-stent restenosis in irradiated patients. Our objective was to reveal the morphological characteristics of radiation-induced carotid stenosis (RICS) and the stent–vessel interactions in patients with previous cervical radiotherapy by optical coherence tomography (OCT).Materials and MethodsBetween November 2017 and March 2019, five patients with a history of cervical radiotherapy were diagnosed with severe carotid artery stenosis and underwent carotid artery stenting (CAS). OCT was conducted before and immediately after the carotid stent implantation. Two patients received OCT evaluation of carotid stenting at 6- or 13-month follow-up.ResultsThe tumor types indicating cervical radiotherapy were nasopharyngeal carcinoma (n = 3), cervical esophageal carcinoma (n = 1), and cervical lymphoma (n = 1). The median interval from the radiotherapy to the diagnosis of RICS was 8 years (range 4–36 years). Lesion characteristics of RICS were detected with heterogeneous signal-rich tissue, dissection, and advanced atherosclerosis upon OCT evaluation. Post-interventional OCT revealed 18.2–57.1% tissue protrusion and 3.3–13.8% stent strut malapposition. Follow-up OCT detected homogeneous signal-rich neointima and signal-poor regions around stent struts. In the patient with high rates of tissue protrusion and stent strut malapposition, the 6-month neointima burden reached 48.9% and microvessels were detected.ConclusionThe morphological features of RICS were heterogeneous, including heterogeneous signal-rich tissue, dissection, and advanced atherosclerosis. Stenting was successful in all 5 patients with severe RICS. One patient, with high rates of tissue protrusion and stent strut malapposition immediately after stenting, received in-stent neointimal hyperplasia at a 6-month follow-up.

Hepatocellular carcinoma (HCC) is one of the most common fatal malignancies and the main cause of cancer-related deaths. The multitarget tyrosine kinase inhibitors (TKIs) sorafenib and regorafenib are systemic therapeutic drugs approved for the treatment of HCC. Here, we found that sorafenib and regorafenib injured mitochondria by inducing mitochondrial Ca2+ (mtCa2+) overload and mitochondrial permeability transition pore (mPTP) opening, resulting in mitochondria-mediated cell death, which was alleviated by cyclosporin A (CsA), an inhibitor of mPTP. Meanwhile, mPTP opening caused PINK1 accumulation on damaged mitochondria, which recruited Parkin to mitochondria to induce mitophagy. Inhibition of autophagy by the lysosomal inhibitor chloroquine (CQ) or inhibition of mitochondrial fission by mdivi-1 aggravated sorafenib- and regorafenib-induced cell death. Moreover, knockdown of PINK1 also promotes sorafenib- and regorafenib-induced cell death. An in vivo study showed that sorafenib and regorafenib inhibited HepG2 cell growth more effectively in PINK1 knockdown cells than in shNTC cells in null mice. Thus, our data demonstrate that PINK1-Parkin-mediated mitophagy alleviates sorafenib and regorafenib antitumor effects in vitro and in vivo.

Earthworms are known to accumulate inorganic contaminants from the soil; they are also used as a traditional Chinese medicine (TCM) called Pheretima, which might cause safety problems with long-term exposure. Here, this study was conducted to determine and analyze the level of heavy metal contamination such as arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), and lead (Pb) in Pheretima and then explore the probabilistic health risks caused by 8 heavy metals in 98 batches of Pheretima using Monte Carlo simulation. A risk assessment strategy was conducted to assess heavy metal–associated health risk of Pheretima based on consumption data. For random consumption sampling, the results found that the non-carcinogenic risk of As is higher than the acceptable level, and the carcinogenic risk levels of As and Cr exceeded the acceptable risk recommended by the USEPA. Cr and As were regarded as the priority metals for risk control in the present study. Finally, it was recommended that the dosing frequency should be less than 24 d/y. In general, this study conducted a probabilistic risk assessment of heavy metals in Pheretima, which would be of significance for policy makers to take effective strategies to improve the quality and safety of Pheretima.

The metabolic processes of organisms are very complex. Each process is crucial and affects the growth, development, and reproduction of organisms. Metabolism-related mechanisms in Octopus ocellatus behaviors have not been widely studied. Brood-care is a common behavior in most organisms, which can improve the survival rate and constitution of larvae. Octopus ocellatus carried out this behavior, but it was rarely noticed by researchers before. In our study, 3,486 differentially expressed genes (DEGs) were identified based on transcriptome analysis of O. ocellatus. We identify metabolism-related DEGs using GO and KEGG enrichment analyses. Then, we construct protein–protein interaction networks to search the functional relationships between metabolism-related DEGs. Finally, we identified 10 hub genes related to multiple gene functions or involved in multiple signal pathways and verified them using quantitative real-time polymerase chain reaction (qRT-PCR). Protein–protein interaction networks were first used to study the effects of brood-care behavior on metabolism in the process of growing of O. ocellatus larvae, and the results provide us valuable genetic resources for understanding the metabolic processes of invertebrate larvae. The data lay a foundation for further study the brood-care behavior and metabolic mechanisms of invertebrates.

Neurocognitive impairment (NCI) and gut microbiota dysbiosis are prevalent in patients with HIV infection. Docosahexanoic acid (DHA) supplementation may alleviate multiple neurocognitive diseases symptoms and plays important role in regulating gut microbiota. However, it is not known whether DHA algae oil supplements can alleviate neurocognitive impairment (NCI) and regulate gut microbiota and fecal metabolites. A randomized, double-blind, placebo-controlled trial was performed on 68 HIV-infected patients with NCI. Participants were randomized to receive a 3.15 g daily DHA algae oil supplement or placebo for 6 months. We collected blood and fecal samples from these patients before and after the trial. Mini mental state examination (MMSE) and neuropsychological tests (NP tests) were administered to assess the cognitive status of participants. The influence of DHA algae oil on the gut microbiota, fecal metabolomics, plasma proinflammatory, and oxidative stress factors was also investigated. There were no significant changes in NCI according to global diagnosis score (GDS) and MMSE score within the two groups, while patients receiving DHA had improvement in several blood lipids, pro-inflammatory and oxidative stress factors. The DHA supplement increased α-diversity indexes, increased abundances of Blautia, Bifidobacterium, Dorea, Lactobacillus, Faecalibacterium, Fusobacterium, and Agathobacter, and decreased abundances of Bacteroides and Prevotella_9. Furthermore, DHA supplement was correlated with improved fecal lipid metabolites as indicated by ceramides, bile acids, glycerophospholipids. In addition, the DHA supplement was associated with altered cholesterol metabolism and purine metabolism pathways. A daily supplement of DHA algae oil for 6 months has been shown to promote favorable transformations in gut microbiota, profiles of fecal metabolomic, and factors responsible for proinflammatory and oxidative stress, which might be beneficial for the prognosis of HIV-infected patients with NCI in the long-term.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04242004, identifier: NCT04242004.

Introduction: Symptomatic carotid disease conveys a high risk of recurrent stroke. Plaque morphology and specific plaque characteristics are associated with the risk of stroke. This study aimed to evaluate the detailed plaque features by optical coherence tomography (OCT) and develop a simple scale combining clinical indicators, digital subtraction angiography (DSA), and OCT imaging markers to identify symptomatic carotid plaque.Methods: Carotid plaques from consecutive patients who underwent carotid OCT imaging between June 2017 and June 2021 were evaluated. Clinical characteristics, DSA, and OCT data were compared between the symptomatic and asymptomatic groups. Logistic regression was performed to identify the factors associated with symptomatic carotid plaque and to develop a scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the scale.Results: A total of 90 carotid plaques from 90 patients were included (symptomatic 35.6%, asymptomatic 64.4%). Three main factors were found to be associated with symptomatic carotid plaque: high-density lipoprotein cholesterol (HDL-C)

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.

Gut microbiota dysbiosis has been associated with many neurological diseases. However, how microbiota composition and metabolism relate to neurocognitive impairment (NCI) in HIV-infected individuals is largely unknown. In this study, a total of 102 HIV infected participants were classified into two groups—those with NCI and those without—using the global deficit score (GDS). Fecal samples were collected from the participants for 16S rRNA gene sequencing and untargeted metabolomics. The plasma level of 25 hydroxy-vitamin D (25(OH)D) was also evaluated. Although α-diversity and β-diversity were comparable, the HIV patients with NCI were significantly different from those without NCI in terms of abundance of several gut microbiota. The decreased abundance of butyrate-producing bacteria (BPB) and increased abundance of Klebsiella were related with NCI and carotid intima-media thickness (CIMT). Significant differences in fecal metabolites were also found between individuals with versus without NCI, including increased bile acids and bioactive lipids, decreased vitamin D, terpenoids, and resolvin D1 in the NCI group. Furthermore, the perturbed metabolic profile was closely related to BPB and Klebsiella. In addition, a low level of vitamin D was associated with NCI and CIMT. Both fecal and plasma vitamin D were positively correlated with BPB. Our results show that BPB and Klebsiella and the associated metabolites are associated with NCI in people with HIV. In addition, vitamin D, both in feces and blood, was associated with NCI and BPB, suggesting a protective effect of vitamin D on NCI.

Glycogen content is a quantitative trait, its phenotype differences are found between individual oysters due to genetic effects and environmental factors which were including food, water temperature, salinity, and so on. In this study, a full sibling family of Pacific oyster Crassostrea gigas showed different phenotypes with high and low glycogen content between South Huanghai Sea (Rizhao offshore area, RZ) and North Huanghai Sea (Kongtong Dao area, KTD), respectively. At the same time, the content of 11 glucogenic amino acids and 13 fatty acids were also significant differences between RZ and KTD. RNA-seq and small RNA-seq technologies were used for transcriptome sequencing and functional enrichment analysis of differentially expressed RNA were used by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A total of 2,084 mRNAs, 1,080 long non-coding RNAs (lncRNAs), 34 circular RNAs (circRNAs), and 7 microRNAs (miRNAs) were differentially expressed. Based on these differentially expressed genes (DEGs), miRNA target interactions (lncRNA/circRNA–miRNA pairs and miRNA–mRNA pairs) were predicted using the miRanda software. The differentially expressed mRNAs in this network were mainly shown to be involved in calcium signaling pathway and insulin signaling pathway. These findings could help to speculate that environmental factors may be epigenetically regulated by non-coding RNA in C. gigas, thereby further affecting glycogen content.

Improvement of understanding of the safety profile and biological significance of antidiabetic agents in breast cancer (BC) progression may shed new light on minimizing the unexpected side effect of antidiabetic reagents in diabetic patients with BC. Our recent finding showed that Saxagliptin (Sax) and Sitagliptin (Sit), two common antidiabetic dipeptidyl peptidase-4 inhibitors (DPP-4i) compounds, promoted murine BC 4T1 metastasis via a ROS–NRF2–HO-1 axis in nonobese diabetic–severe combined immunodeficiency (NOD-SCID) mice. However, the potential role of DPP-4i in BC progression under immune-competent status remains largely unknown. Herein, we extended our investigation and revealed that Sax and Sit also accelerated murine BC 4T1 metastasis in orthotopic, syngeneic, and immune-competent BALB/c mice. Mechanically, we found that DPP-4i not only activated ROS–NRF2–HO-1 axis but also triggered reactive oxygen species (ROS)-dependent nuclear factor kappa B (NF-κB) activation and its downstream metastasis-associated gene levels in vitro and in vivo, while NF-кB inhibition significantly abrogated DPP-4i-driven BC metastasis in vitro. Meanwhile, inhibition of NRF2–HO-1 activation attenuated DPP-4i-driven NF-кB activation, while NRF2 activator ALA enhanced NF-кB activation, indicating an essential role of ROS–NRF2–HO-1 axis in DPP-4i-driven NF-кB activation. Furthermore, we also found that DPP-4i increased tumor-infiltrating CD45, MPO, F4/80, CD4, and Foxp3-positive cells and myeloid-derived suppressor cells (MDSCs), and decreased CD8-positive lymphocytes in metastatic sites, but did not significantly alter cell viability, apoptosis, differentiation, and suppressive activation of 4T1-induced splenic MDSCs. Moreover, we revealed that DPP-4i triggered ROS-NF-κB-dependent NLRP3 inflammasome activation in BC cells, leading to increase in inflammation cytokines such as interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), IL-1β and IL-33, and MDSCs inductors granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, and M-CSF, which play a crucial role in the remodeling of tumor immune-suppressive microenvironment. Thus, our findings suggest that antidiabetic DPP-4i reprograms tumor microenvironment that facilitates murine BC metastasis by interaction with BC cells via a ROS–NRF2–HO-1–NF-κB–NLRP3 axis. This finding not only provides a mechanistic insight into the oncogenic ROS–NRF2–HO-1 in DPP-4i-driven BC progression but also offers novel insights relevant for the improvement of tumor microenvironment to alleviate DPP-4i-induced BC metastasis.

Immune defense systems are indispensable for living organisms. Within an immune network, problems with any given link can impact the normal life activities of an organism. Amphioctopus fangsiao is a cephalopod that exists widely throughout the world’s oceans. Because of its nervous system and locomotive organs, it has become increasingly studied in recent years. Vibrio anguillarum is one of the most common pathogenic bacteria in aquaculture organisms. It is highly infectious and can infect almost all aquaculture organisms. V. anguillarum infection can cause many adverse biological phenomena, including tissue bleeding. Study the immune response after V. anguillarum infection would help us to understand the molecular mechanisms of immune response in aquaculture organisms. In this research, we infected the primary incubation A. fangsiao with V. anguillarum for 24 h. We analyzed gene expression in A. fangsiao larvae via transcriptome profiles at 0, 4, 12, and 24 h after hatching, and 1,385, 734, and 6,109 differentially expressed genes (DEGs) were identified at these three time points. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify immune-related DEGs. Protein–protein interaction networks were constructed to examine interactions between immune-related genes. Twenty hub genes involved in multiple KEGG signaling pathways or with multiple protein–protein interaction relationships were identified, and their differential expression verified by quantitative RT-PCR. We first studied V. anguillarum infection of A. fangsiao larvae by means of protein–protein interaction networks. The results provide valuable genetic resources for understanding immunity in molluscan larvae. These data serve as a theoretical basis for the artificial breeding of A. fangsiao.

Cancer has been as one of common comorbidities of diabetes. Long-term antidiabetic treatment may potentially exert uncertain impacts on diabetic patients with cancer including breast cancer (BC). Dipeptidyl peptidase-4 inhibitors (DPP-4i) are currently recommended by the AACE as first-line hypoglycemic drugs in type 2 diabetes mellitus (T2DM). Although the safety of DPP-4i has been widely evaluated, the potential side-effects of DPP-4i in cancer metastasis were also reported and remain controversial. Here, we revealed that Saxagliptin (Sax) and Sitagliptin (Sit), two common DPP-4i compounds, potentially promoted murine BC 4T1 metastasis in vitro and in vivo under immune-deficient status. Mechanically, we observed that DPP-4i treatment induced aberrant oxidative stress by triggering ROS overproduction, as well as ROS-dependent NRF2 and HO-1 activations in BC cells, while specific inhibition of ROS, NRF2 or HO-1 activations abrogated DPP-4i-driven BC metastasis and metastasis-associated gene expression in vitro. Furthermore, ALA, a NRF2 activator significantly promoted BC metastasis in vitro and in vivo, which can be abrogated by specific HO-1 inhibition in vitro. Moreover, specific HO-1 inhibition not only reversed DPP-4i-induced NRF2 activation but also abrogated ALA-induced NRF2 activation, resulting in a decrease of metastasis-associated genes, indicating a positive-feedback NRF2-HO-1 loop. Our findings suggest that DPP-4i accelerates murine BC metastasis through an oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into an oncogenic role of DPP-4i in BC progression but also provides new strategies to alleviate the dark side of DPP-4i by targeting HO-1.

Angle is an important concept in geometry. Young children have difficulty separating angle size from other dimensions such as the length of angle sides, perhaps due to whole-object bias in word learning. The present study used the pre-test–training–post-test design to investigate the effectiveness of two ways of separating angle from angle size in 3–6-year-old Chinese preschoolers. A total of 228 children were given a pre-test and 219 of them failed the crucial test. 168 of the 219 children were present at school during the training phase and were randomly assigned to three groups: the “toma” group (n = 57), which received training to call the whole angle figure as “toma” and angle size as angle size; the “angle/angle size” group (n = 56), which received the training of separating “angle” from “angle size”; and the control group (n = 55), which used “angle size” alone to represent both the overall angle figure and angle size. Results showed that the “toma” group improved significantly more than the other two groups, the latter of which did not differ from each other. These results suggest that it is insufficient to have two separate words/phrases (angle and angle size) for children to learn to differentiate angle from angle size, perhaps due to their shared usage of the word angle. Instead, the use of a novel term is necessary and sufficient to improve learning. Implications for preschool education are discussed.

Block building is a popular play activity among young children and is also used by psychologists to assess their intelligence. However, little research has attempted to systematically explore the cognitive bases of block-building ability. The current study (N = 66 Chinese preschoolers, 32 boys and 34 girls; mean age = 4.7 years, SD = 0.29, range = 3.4 to 5.2 years) investigated the relationships between six measures of spatial skills (shape naming, shape recognition, shape composition, solid figure naming, cube transformation, and mental rotation, with the former four representing form perception and the latter two representing visualization) and block-building complexity. Correlation results showed that three of the four measures of form perception (shape naming, shape recognition, and shape composition) were significantly and positively correlated with block-building complexity, whereas the two measures of visualization were not. Results from regression models indicated that shape recognition and shape composition, as well as shape-recognition-by-gender interaction, were unique predictors of children’s block-building complexity. These findings provide preliminary evidence for the basic spatial skills underlying children’s block-building complexity and have implications for classroom instructions aimed at improving preschoolers’ block-building complexity.

Background: Plaque rupture is an important etiology for symptomatic carotid stenosis. The role of calcification in the plaque vulnerability has been controversial. We aimed to detect the geometric features of calcifications in carotid plaque and to examine its association with plaque rupture.Methods: Optical coherence tomography assessment of carotid plaque was performed in 88 patients. Calcification shape was evaluated through quantitative measurements of the long and short axis, area size, circumference, calcification arc, and longitudinal length. Calcification location was analyzed through the distance to the lumen. Furthermore, we developed idealized fluid-structure interaction models to investigate the association of calcification shape and plaque stress.Results: A total of 33 ruptured plaques and 30 non-ruptured plaques were recognized. Ruptured plaques had more multiple calcifications and protruded calcifications. The calcifications in the ruptured plaques displayed a remarkably lower long-axis/short-axis (L/S) ratio than in the non-ruptured plaques (p = 0.001). We classified calcification shape into crescentic calcification (L/S > 2.5) and rotund calcification (L/S ≤ 2.5). Rotund-shaped calcifications were more common in ruptured plaques than in non-ruptured plaques (p = 0.02). Superficial calcifications with minimal distance to the lumen ≤ 50 μm accounted for 79.4% of all calcifications in the ruptured plaques, and only 7.7% in the non-ruptured plaques (p < 0.001). Biomechanical analysis showed that the plaque with rotund-shaped calcification developed 7.91-fold higher von Mises stress than the plaque with crescentic calcification.Conclusions: Superficial calcifications and rotund-shaped calcifications are associated with carotid plaque rupture, suggesting that calcification location and shape may play a key role in plaque vulnerability.

In vitro studies had shown that C-Phycocyanin (C-PC) inhibited cervical cancer HeLa cells growth. We constructed C-PC/CMC-CD55sp nanospheres using C-PC, Carboxymethyl Chitosan (CMC), and CD55 ligand peptide (CD55sp) to allow for targeted antitumor effects against HeLa cells in vitro and in vivo. The characteristics of the nanospheres were determined using FTIR, electron microscopy, and laser particle size analysis. Flow cytometry, laser confocal microscopy and small animal imaging system showed the targeting of C-PC/CMC-CD55sp nanospheres on HeLa cells. Subsequently, the proliferation and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), flow cytometry, TUNEL assay and electron microscopy. The expression of the apoptosis-related protein was determined using western blot. The stainings of Hematoxylin and Eosin (HE) were employed to evaluate the cell condition of tumor tissue sections. The cytokines in the blood in tumor-bearing nude mice was determined using ELISA. These results showed that C-PC/CMC-CD55sp nanospheres were successfully constructed and targeted HeLa cells. The constructed nanospheres were more effective than C-PC alone in inhibiting the proliferation and inducing apoptosis in HeLa cells. We also found that C-PC/CMC-CD55sp nanospheres had a significant inhibitory effect on the expression of antiapoptotic protein Bcl-2 and a promotion on the transformation of caspase 3 to cleaved caspase 3. C-PC/CMC-CD55sp nanospheres played an important role in tumor suppression, reduced the expression TGF-β, and increased IL-6 and TNF-α. This study demonstrates that the constructed new C-PC/CMC-CD55sp nanospheres exerted targeted antitumor effects in vivo and in vitro which provided a novel idea for application of C-PC, and provided experimental basis for comprehensive targeted treatment of tumors.

Oxidized-low density lipoprotein (ox-LDL) can induce injury of endothelial cells, causing atherosclerosis, which is an important initial event in several cardiovascular diseases. Long non-coding RNAs (lncRNAs) have emerged as regulators of diverse biological processes, but their specific biological functions and biochemical mechanisms in ox-LDL-induced endothelial cell injury have not been well investigated. Here, we describe the initial functional analysis of a poorly characterized human lncRNA ZEB1 antisense 1 (ZEB1-AS1). We found that ox-LDL treatment could induce a decreased cell viability and an increased cell apoptosis in endothelial cells, and knockdown of ZEB1-AS1 significantly reversed this effect. Mechanistically, ox-LDL treatment could sequester p53 from binding to ZEB1-AS1 promoter region, causing transcriptional activation and upregulation of ZEB1-AS1. Moreover, enhanced ZEB1-AS1 could upregulate Nucleotide-Binding Oligomerization Domain 2 (NOD2) expression through recruiting leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) to stabilize NOD2 mRNA. Experimental data showed that knockdown of NOD2 or LRPPRC dramatically abrogated the functional role of ZEB1-AS1 in ox-LDL-induced endothelial cell injury. In summary, we demonstrated that lncRNA ZEB1-AS1 regulates the ox-LDL-induced endothelial cell injury via an LRPPRC-dependent mRNA stabilization mechanism. Therefore, ZEB1-AS1 may serve as a multi-potency target to overcome endothelial cell injury, atherosclerosis and other cardiovascular diseases.

Childhood maltreatment is associated with error hypersensitivity. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA) interaction on functional brain connectivity during error processing in medication/drug-free adolescents. Functional connectivity was compared, using generalized psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 22 age- and gender-matched medication-naïve and substance abuse-free adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed an individually adjusted tracking stop-signal task, designed to elicit 50% inhibition failures. During inhibition failures, abused participants relative to healthy controls exhibited reduced connectivity between right and left putamen, bilateral caudate and anterior cingulate cortex (ACC), and between right supplementary motor area (SMA) and right inferior and dorsolateral prefrontal cortex. Abuse-related connectivity abnormalities were associated with longer abuse duration. No group differences in connectivity were observed for successful inhibition. The findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-cingulo-striatal networks during error processing. Furthermore that the severity of connectivity abnormalities increases with abuse duration. Reduced connectivity of error detection networks in maltreated individuals may be linked to constant monitoring of errors in order to avoid mistakes which, in abusive contexts, are often associated with harsh punishment.

BackgroundUnderstanding the experience of Hispanic parents of children diagnosed with asthma can be useful in the delivery of effective and meaningful asthma education. In order to assess the needs of Hispanic families with asthmatic children in South Texas, investigators utilized a combination of qualitative and quantitative research methods.ObjectivesThis study aimed (1) to assess the impact of asthma in the quality of life of Hispanic children and their families and (2) to identify barriers and challenges to asthma management as perceived by parents of children diagnosed with asthma.MethodsA mixed-methods study included a quality-of-life survey and focus group discussions. The Children’s Health Survey for Asthma (CHSA) was completed by 90 parents of children with asthma. Three focus groups were conducted with 15 low-income, Hispanic parents of asthmatic children to assess their needs and experience in managing the disease.ResultsResults from the CHSA showed that asthma significantly affects the quality of life of children with asthma and their families, particularly the emotional dimensions and the child’s physical health. Fifty-three percent of the children had visited the emergency room, and 51% had been hospitalized due to asthma. One out of five parents had missed work, and 27% of children had missed school in the past 2 weeks due to the child’s asthma. In the focus group discussions, the key themes emerging included lack of asthma knowledge, the burden of disease for asthmatic children and their families, and the importance of asthma education and self-management behaviors for asthma control.ConclusionOne of the main challenges faced by Hispanic families with asthmatic children is the lack of asthma-related knowledge to help understand and control their children’s disease. Lack of knowledge and self-management skills lead to significant stress and anxiety among children with asthma and their parents. Results highlight that while asthma has an effect on the quality of life of children and their families, particularly on the emotional health domain, a wide dissemination of asthma management education in different settings might help prevent asthma attacks and improve symptom control among those suffering from this disease along the US–Mexico border.

There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including: improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology.

Background: Echocardiographic data investigating the association between left ventricular (LV) function and gout is still limited. Purpose: To analyze the association of echocardiographic parameters based on two-dimentional speckle tracking analysis with clinically related indicators in patients with gout, and to provide a clinical basis for the early diagnosis and treatment of cardiovascular disease in patients with gout. Methods: This study collected gout patients who visited the outpatient and inpatient departments of the first affiliated hospital of chengdu medical college from November 2019 to December 2020. Spearman correlation test was performed to analyze the correlation coefficients between the laboratorial indicators with echocardiographic parameters. And the logistic regression analysis was performed to evaluate the independent effects. Results: The results of multivariate logistic regression showed that fasting plasma glucose (FPG) was a risk factor for the decrease in absolute value of global longitudinal strain [GLS (OR = 2.34; 95% CI, 1.01-5.39; p = 0.04)], Urea was a risk factor for absolute reduction in GCS (OR = 1.40; 95% CI, 1.07-1.85; p = 0.02), age (OR = 1.09, 95% CI, 1.04-1.16; p = 0.001), and hypertension (OR = 8.35; 95% CI, 1.83-38.02; p = 0.006) were risk factors for increased E/Em. High urea levels were significantly related with high risks of LVH (OR = 1.59, 95% CI, 1.04-2.43; p = 0.03) and enlargement of LAVI (OR = 1.68, 95% CI, 1.01-2.80; p = 0.04). Conclusion: Our study found that elevated urea and FPG were risk factors for subclinical LV myocardial dysfunction in patients with gout, which might provide a theoretical basis for the early diagnosis and treatment of heart disease in clinical practice. [ABSTRACT FROM AUTHOR]

The Taihongcun landslide, which was a remarkable geological disaster triggered by the 2008 Wenchuan earthquake, had a volume of about 2 × 106 m3 and killed about 23 people. Through detailed field investigations, basic information of topography, geological structure and stratigraphy for the landslide were acquired and key kinetic characteristics of the landslide were identified. On the basis of filed investigations, 2D numerical models with discrete element method (DEM) were established to simulate the kinematics and failure process of the landslide. To ensure the validity of the dynamic calculations, the free-field boundary condition was developed and introduced intro the DEM models. According to filed investigations and DEM simulations, the dynamic processes of the Taihongcun landslide can be divided into four phases: fragmentation, projection motion, scraping, and granular debris flow and accumulation. In addition, the parameter analysis showed that the particle bond strength had a significant influence on the runout distance and landslide debris morphology. Finally, the possible mechanism of the Taihongcun landslide was determined: a rock mass of poor quality provided the lithological basis for this landslide formation; a joint set J1 in the back scarp and a weak interlayer of carbonaceous slate and shale between the upper sliding mass and the bedrock formed the rupture boundaries of the upper source area; a strong seismic ground motion was the external excitation that triggered the destructive landslide event; additionally, hypermobility was caused by the high elevation and topographical conditions of the landslide.

Objective:We examined two potential biomarkers of brain damage in hypoxic-ischemic encephalopathy (HIE) neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis) and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury).We hypothesized that the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. We further hypothesized that higher levels would be detected in serum samples of HIE neonates and would correlate with brain damage on magnetic resonance imaging (MRI) and later developmental outcomes.? Study Design: Serum UCH-L1 and GFAP concentrations from HIE neonates (n D16) were compared to controls (nD11). The relationship between biomarker concentrations of HIE neonates and brain damage (MRI) and developmental outcomes (Bayley-III) was examined using Pearson correlation coefficients and a mixed model design. Result: Both biomarkers were detectable in cord blood from control subjects. UCH-L1 concentrations were higher in HIE neonates (p <0.001), and associated with cortical injury (p <0.055) and later motor and cognitive developmental outcomes (p <0.05). The temporal change in GFAP concentrations during (from birth to 96 h of age) predicted motor developmental outcomes (p <0.05) and injury to the basal ganglia and white matter. Conclusion: Ubiquitin C-terminal hydrolase L1 and GFAP should be explored further as promising serum biomarkers of brain damage and later neurodevelopmental outcomes in neonates with HIE. [ABSTRACT FROM AUTHOR]

Background: Failure to account for the etiological diversity that typically occurs in psychiatric cohorts may increase the potential for confounding as a proportion of genetic variance will be specific to exposures that have varying distributions in cases.This study investigated whether minimizing the potential for such confounding strengthened the evidence for a genetic candidate currently unsupported at the genome-wide level. Methods: Two hundred and ninety-one first-episode psychosis cases from South London, UK and 218 unaffected controls were evaluated for a functional polymorphism at the rs1360780 locus in FKBP5. The relationship between FKBP5 and psychosis was modeled using logistic regression. Cannabis use (Cannabis Experiences Questionnaire) and parental separation (Childhood Experience of Care and Abuse Questionnaire) were included as confounders in the analysis. Results: Association at rs1360780 was not detected until the effects of the two environmental factors had been adjusted for in the model (OR=2.81, 95% Cl 1.23-6.43, p=0.02). A statistical interaction between rs1360780 and parental separation was confirmed by stratified tests (OR=2.8, p=0.02 vs. OR=0.89, p=0.80). The genetic main effect was directionally consistent with findings in other (stress-related) clinical phenotypes. Moreover, the variation in effect magnitude was explained by the level of power associated with different cannabis constructs used in the model (r=0.95). Conclusion: Our results suggest that the extent to which genetic variants in FKBP5 can influence susceptibility to psychosis may depend on other etiological factors. This finding requires further validation in large independent cohorts. Potentially this work could have translational implications; the ability to discriminate between genetic etiologies based on a case-by-case understanding of previous environmental exposures would confer an important clinical advantage that would benefit the delivery of personalizable treatment strategies. [ABSTRACT FROM AUTHOR]