Search

Nano-selenium (Se) has attracted growing attention due to its high bioavailability, low toxicity and its possible applications in the prevention of oxidative damage in animal tissues. Recent research works have conveyed that the use of nano-seleniumas food additive could have positive effects on the nutrition of aquatic animals.In this study, the intestinal bacterial communities associated with low and high concentrations of nano-selenium in the diet of Chinese tongue sole were characterized, through 16S rRNA V3–V4 sequencing.Samples were derived from fish fed with diet containing different nano-selenium level, 0 mg/kg for the control group, 1.6 mg/kg for low dose group, and 2.4 mg/kg for high dose group The intestinal microbial community structure showed a low overall diversity, among which the vibro genus occupied the most important position with more than 90% relative abundance in all three group. Significant differences in specie diversity occurred between the nano-selenium treated (both low dose [IL] and high dose [LH]) groups and the control group(IC). Acinetobacter, Arthrobacter, and Streptophytes were the top three enriched genera after the treatment with nano-selenium compared to IC. Meantime, the weight gain rate of the LH group was 9% higher than control. The results revealed the effect of nano-selenium on microbial community structure of gut and growth performance of C.semilaevis, Future research exploring the interaction mechanism between micronutrients and the microbial communities would increase our understanding of the fish nutrition.

Understanding mechanisms of coexistence is a central topic in ecology. Mathematical analysis of models of competition between two identical species moving at different rates of symmetric diffusion in heterogeneous environments show that the slower mover excludes the faster one. The models have not been tested empirically and lack inclusions of a component of directed movement toward favourable areas. To address these gaps, we extended previous theory by explicitly including exploitable resource dynamics and directed movement. We tested the mathematical results experimentally using laboratory populations of the nematode worm, Caenorhabditis elegans. Our results not only support the previous theory that the species diffusing at a slower rate prevails in heterogeneous environments but also reveal that moderate levels of a directed movement component on top of the diffusive movement allow species to coexist. Our results broaden the theory of species coexistence in heterogeneous space and provide empirical confirmation of the mathematical predictions.

Background Endoscopic thyroidectomy is widely performed as it does not result in neck scar. However, there is a paucity of reports pertaining to completely endoscopic lateral neck dissection (LND). In this study, we introduce our step-wise approach for performing endoscopic selective LND via the chest–breast approach. We refer to this approach as Qin’s seven steps. Methods The Qin’s seven steps are: (1) establishment of working space range; (2) dissection of lymph nodes between the SCM and the sternohyoid muscle (level IV) and exposure of omohyoid; (3) dissection of lymph nodes at level IV; (4) dissection of lymph nodes at level III; (5) dissection of lymph nodes at carotid triangle (level III); (6) exposure of accessory nerve and dissection of lymph nodes at level II a; (7) dissection of lymph nodes at level II b. We reviewed the clinical data of 35 patients with papillary thyroid cancer (PTC) who were operated using the Qin’s seven steps. Results All 35 patients successfully underwent LND; bilateral LND was performed in 5 patients. The mean tumor size was 1.8 ± 1.0 cm; seven patients had multiple lesions. The mean number of retrieved lymph nodes in level II, III and IV were 8.8 ± 5.6, 6.1 ± 4.0 and 9.3 ± 5.1, respectively. As for complications, there were 3 cases of accessory nerve injury and 1 case of hypoglossal nerve injury. Internal jugular vein injury, cervical plexus injury and lymphatic leakage occurred in 2, 7, and 1 patients, respectively. Conclusion The Qin’s seven steps for performing endoscopic selective LND could be safely used in PTC patients with lateral lymph node metastasis. Satisfactory results were achieved in the short-term follow-up period. We recommend the use of Qin’s seven steps for PTC patients who are not desirous of neck scar.

Purpose To investigate the associations of sociodemographic characteristics and PROMIS domain scores with patient activation among patients presenting for spine surgery at a university-affiliated spine center. Methods Patients completed a survey collecting demographic and social information. Patients also completed the Patient-Reported Outcomes Measurement Information System (PROMIS) and Patient Activation Measure questionnaires. The associations of PROMIS scores and sociodemographic characteristics with patient activation were assessed using linear and ordinal logistic regression (patient activation stage as ordinal). Results A total of 1018 patients were included. Most respondents were white (84%), married (73%), and female (52%). Patients were distributed among the 4 activation stages as follows: stage I, 7.7%; stage II, 12%; stage III, 26%; and stage IV, 55%. Mean (±standard deviation) patient activation score was 70 ± 17 points. Female sex (adjusted coefficient [AC] = 4.3; 95% confidence interval [CI] 2.1, 6.4) and annual household income >$80,000 (OR = 3.7; 95% CI 0.54, 6.9) were associated with higher patient activation scores. Lower patient activation scores were associated with worse PROMIS Depression (AC = −0.31; 95% CI −0.48, −0.14), Fatigue (OR = −0.19; 95% CI −0.33, −0.05), Pain (OR = 0.22; 95% CI 0.01, 0.43), and Social Satisfaction (OR = 0.33; 95% CI 0.14, 0.51) scores. Conclusion Depression and socioeconomic status, along with PROMIS Pain, Fatigue, and Social Satisfaction domains, were associated with patient activation. Patients with a greater burden of depressive symptoms had lower patient activation; conversely, women and those with higher income had greater patient activation. Level of evidence Level 1.

The surgical approaches and resection extent for rectal gastrointestinal stromal tumors (GISTs) are controversial due to the low incidence of this disease. A multicenter retrospective cohort study was conducted to compare the postoperative and oncologic outcomes of local excision (LE) and radical resection (RR) in patients with low rectal GIST.The medical records of rectal GIST patients from 11 large-scale medical centers in China (January 2000-December 2019) were reviewed. All patients were divided into either the LE group or the RR group. Propensity score matching (PSM) was conducted to reduce confounders.A total of 280 patients with low rectal GIST were enrolled. After PSM, 144 patients were included (72 in each group). The LE group showed a higher anal preservation rate (100.0% vs. 76.4%, P 0.001), shorter operation time (77.1 ± 68.4 min vs. 159.1 ± 83.6 min, P 0.001), fewer complications (8.3% vs. 22.2%, P = 0.021) and shorter postoperative hospital stay (4.9 ± 4.1 d vs. 10.7 ± 8.1 d, P 0.001) than the RR group. There was no significant difference in recurrence-free survival (RFS) between the RR and LE groups among patients with tumors ≤2 cm (P = 0.220), and the RR group had a superior RFS than the LE group in patients with tumors2 cm (P = 0.046).LE resulted in improved postoperative outcomes and comparable oncological safety with a low rectal GIST of ≤2 cm. However, for patients with a low rectal GIST of2 cm, RR might be a more appropriate option with better RFS.

Background: Malignant transformation of gastrointestinal stromal tumors (GISTs) is correlated with poor prognosis; however, the underlying biological mechanism is not well understood. Methods: In the present study, low-risk (LR) GISTs, GISTs categorized as high-risk based on tumor size (HBS), and on mitotic rate (HBM) were collected for RNA sequencing. Candidate hub lncRNAs were selected by Oncomine analysis. Expression of a selected hub lncRNA, DNM3OS, and its correlation with patients’ prognosis were analyzed using FISH staining, followed with the determination of function and underlying mechanism. Results: Our results revealed a series of key pathways and hub lncRNAs involved in the malignant transformation of GISTs. Oncomine analysis revealed a tight association between clinical signatures and DNM3OS and suggested that DNM3OS is a hub lncRNA that is involved in the Hippo signaling pathway. In addition, DNM3OS was upregulated in HBS, HBM, and HBS/M GIST and correlated with worse prognosis in patients with GISTs. In addition, DNM3OS promoted GIST cell proliferation and mitosis by regulating the expression of GLUT4 and CD36. Conclusions: These results improve our understanding of the malignant transformation of GISTs and unveil a series of hub lncRNAs in GISTs.

Background Copy number variants (CNVs) linked to genes involved in nervous system development or function are often associated with neuropsychiatric disease. While CNVs involving deletions generally cause severe and highly penetrant patient phenotypes, CNVs leading to duplications tend instead to exhibit widely variable and less penetrant phenotypic expressivity among affected individuals. CNVs located on chromosome 15q13.3 affecting the alpha-7 nicotinic acetylcholine receptor subunit (CHRNA7) gene contribute to multiple neuropsychiatric disorders with highly variable penetrance. However, the basis of such differential penetrance remains uncharacterized. Here, we generated induced pluripotent stem cell (iPSC) models from first-degree relatives with a 15q13.3 duplication and analyzed their cellular phenotypes to uncover a basis for the dissimilar phenotypic expressivity. Results The first-degree relatives studied included a boy with autism and emotional dysregulation (the affected proband-AP) and his clinically unaffected mother (UM), with comparison to unrelated control models lacking this duplication. Potential contributors to neuropsychiatric impairment were modeled in iPSC-derived cortical excitatory and inhibitory neurons. The AP-derived model uniquely exhibited disruptions of cellular physiology and neurodevelopment not observed in either the UM or unrelated controls. These included enhanced neural progenitor proliferation but impaired neuronal differentiation, maturation, and migration, and increased endoplasmic reticulum (ER) stress. Both the neuronal migration deficit and elevated ER stress could be selectively rescued by different pharmacologic agents. Neuronal gene expression was also dysregulated in the AP, including reduced expression of genes related to behavior, psychological disorders, neuritogenesis, neuronal migration, and Wnt, axonal guidance, and GABA receptor signaling. The UM model instead exhibited upregulated expression of genes in many of these same pathways, suggesting that molecular compensation could have contributed to the lack of neurodevelopmental phenotypes in this model. However, both AP- and UM-derived neurons exhibited shared alterations of neuronal function, including increased action potential firing and elevated cholinergic activity, consistent with increased homomeric CHRNA7 channel activity. Conclusions These data define both diagnosis-associated cellular phenotypes and shared functional anomalies related to CHRNA7 duplication that may contribute to variable phenotypic penetrance in individuals with 15q13.3 duplication. The capacity for pharmacological agents to rescue some neurodevelopmental anomalies associated with diagnosis suggests avenues for intervention for carriers of this duplication and other CNVs that cause related disorders.

BACKGROUND Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported. CASE SUMMARY A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d. CONCLUSION COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.

Iron-based alloy coatings were deposited on grey cast iron through plasma transfer arc welding. Results showed that the iron-based alloy coatings are composed of pearlite, martensite, austenite, an...

Lead (Pb) exposure can cause central nervous system (CNS) damage. The process of Pb neurotoxicity is accompanied by the microglia activation. In addition, microglia activation was observed under the intervention of high-fat diets (HFD). This study was designed to investigate the effect of Pb on the cognitive function of mice with HFD, with focus on the microglia activation in brain. Male C57BL/6J mice, 8 weeks of age, were randomly divided into control, HFD, Pb, and HFD + Pb groups. The results showed that HFD following Pb exposure could exacerbate the learning and memory impairment in mice. Pb exposure could promote microglia activation and increase the expression of M1 microglia marker and decrease the expression of M2 microglia marker in the hippocampus of mice with HFD. Our finding suggested that Pb exposure may aggravate CNS damage by promoting M1 polarization and inhibiting M2 polarization of hippocampal microglia in HFD mice.

TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) is a newly defined multisystemic disease with its pathophysiology largely unknown. Here, we report the whole-genome sequencing (WGS) analysis on the tumor-normal paired cells from a patient with TEMPI syndrome. WGS revealed somatic nonsynonymous single-nucleotide variants, including SLC7A8, NRP2, and AQP7. Complex structural variants of chromosome 2 were found, particularly within regions where some putative oncogenes reside. Of potential clinical relevance, duplication of 22q11.23 was identified, and the expression of the located gene macrophage migration inhibitory factor (MIF) was significantly upregulated in 3 patients with TEMPI syndrome. Importantly, the level of serum MIF in one patient with TEMPI syndrome was significantly decreased in accordance with the downtrend of plasma cells, M-protein, hemoglobin, and erythropoietin and the improvement of telangiectasias, perinephric fluid collections, and intrapulmonary shunting after treatment with plasma cell–directed therapy. In conclusion, our study provides insights into the genomic landscape and suggests a role of MIF in the pathophysiology of TEMPI syndrome.

The current study aimed to assess the dietary salt intake in patients with CKD in Jiangsu province and investigate the relationship of urinary sodium excretion with blood pressure. A total of 800 patients with CKD stages 1–4 were recruited. All enrolled patients were asked to collect complete 24‐h urine specimen. At the same time, patient's demographic and laboratory data were recorded. The mean age was 47.45 ± 15.25 years old, including 423 men and 377 women. There was no significant difference in urinary sodium excretion among different stages of CKD (p = .748). This study revealed that the median urinary sodium excretion of all patients was 127.20 mmol/d (IQR 91.03–172.06), corresponding to a salt intake of 7.4 g/d. Among them, only 167 (20.9%) cases had salt intake

Background. To assess the association of metformin monotherapy with the risk of all-cause deaths and cardiovascular deaths and events in type 2 diabetes patients in real clinical practice. Methods. This retrospective, observational study comprised patients with type 2 diabetes initially treated with metformin or nonmetformin monotherapy over 2011-2016. Data were extracted from the National Healthcare Big Data database in Fuzhou, China. Propensity score matching (PSM) was performed, matching each patient on metformin to one on nonmetformin in terms of a set of covariates. The primary endpoint was all-cause death, and secondary endpoints were cardiovascular death, heart failure, and heart failure hospitalization. Covariate-adjusted associations of metformin use with all the endpoints were assessed by Cox proportional hazards models. Results. Among 24,099 patients, 5491 were initially treated with metformin and 18,608 with nonmetformin. PSM yielded 5482 patients in each cohort. During a median follow-up of 2.02 years, we observed 110 and 211 deaths in the metformin and nonmetformin groups, respectively. Metformin was significantly associated with reduced risk of all-cause death (adjusted hazard ratio (aHR) 0.52, 95% confidence interval (CI) 0.39-0.69), cardiovascular death (aHR 0.63, 95% CI 0.43-0.91), and heart failure (aHR 0.61, 95% CI 0.52-0.73), whereas the reduced risk in heart failure hospitalization was not statistically significant (aHR 0.70, 95% CI 0.47-1.02). Conclusions. In this analysis of electronic health record data from a large database in China, metformin as first-line monotherapy greatly reduced the risk of all-cause death, cardiovascular death, and heart failure in diabetes patients as compared with nonmetformin medications.

Summary Linalool is one of the common flavour‐related volatiles across the plant kingdom and plays an essential role in determining consumer liking of plant foods. Although great process has been made in identifying terpene synthase (TPS) genes associated with linalool synthesis, much less is known about regulation of this pathway. We initiated study by identifying PpTPS3 encoding protein catalysing enantiomer (S)‐(+)‐linalool synthesis, which is a major linalool component (˜70%) observed in ripe peach fruit. Overexpression of PpTPS3 led to linalool accumulation, while virus‐induced gene silencing of PpTPS3 led to a 66.5% reduction in linalool content in peach fruit. We next identified transcription factor (TF) PpbHLH1 directly binds to E‐box (CACATG) in the PpTPS3 promoter and activates its expression based on yeast one‐hybrid assay and EMSA analysis. Significantly positive correlation was also observed between PpbHLH1 expression and linalool production across peach cultivars. Peach fruit accumulated more linalool after overexpressing PpbHLH1 in peach fruit and reduced approximately 54.4% linalool production after silencing this TF. DNA methylation analysis showed increased PpTPS3 expression was associated with decreased 5 mC level in its promoter during peach fruit ripening, but no reverse pattern was observed for PpbHLH1. Arabidopsis and tomato fruits transgenic for peach PpbHLH1 synthesize and accumulate higher levels of linalool compared with wild‐type controls. Taken together, these results would greatly facilitate efforts to enhance linalool production and thus improve flavour of fruits.

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics sequencing, is a powerful tool to decipher the cellular and molecular landscape at a single-cell resolution, unlike bulk sequencing, which provides averaged data. The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. In this review, we summarize emerging single-cell sequencing technologies and recent cancer research progress obtained by single-cell sequencing, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and the underlying mechanisms of tumor biological behaviors. Overall, the prospects of single-cell sequencing in facilitating diagnosis, targeted therapy and prognostic prediction among a spectrum of tumors are bright. In the near future, advances in single-cell sequencing will undoubtedly improve our understanding of the biological characteristics of tumors and highlight potential precise therapeutic targets for patients.

Objective To identify spine patients' barriers to appropriate postoperative opioid use, comfort with naloxone, knowledge of safe opioid disposal practices, and associated factors. Methods We preoperatively surveyed 174 spine patients about psychobehavioral barriers to appropriate opioid use, comfort with naloxone, and knowledge about opioid disposal. Multivariable logistic regression identified factors associated with barriers and knowledge (α = 0.05). Results Common barriers were fear of addiction (71%) and concern about disease progression (43%). Most patients (78%) had neutral/low confidence in the ability of nonopioid medications to control pain; most (57%) felt neutral or uncomfortable with using naloxone; and most (86%) were familiar with safe disposal. Anxiety was associated with fear of distracting the physician (adjusted odds ratio [aOR], 3.8; 95% confidence interval [CI], 1.1–14) and with lower odds of knowing safe disposal methods (aOR, 0.18; 95% CI, 0.04–0.72). Opioid use during the preceding month was associated with comfort with naloxone (aOR, 4.9; 95% CI, 2.1–12). Patients with a higher educational level had lower odds of reporting fear of distracting the physician (aOR, 0.30; 95% CI, 0.09–0.97), and those with previous postoperative opioid use had lower odds of concern about disease progression (aOR, 0.25; 95% CI, 0.09–0.63) and with a belief in tolerating pain (aOR, 0.34; 95% CI, 0.12–0.95). Conclusions Many spine patients report barriers to appropriate postoperative opioid use and are neutral or uncomfortable with naloxone. Some are unfamiliar with safe disposal. Associated factors include anxiety, lack of recent opioid use, and no previous postoperative use.

A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model. Here we characterize four transcript types (lncRNAs, TUCPs, miRNAs, and circRNAs) and protein-coding genes in 31 adult pig tissues and two cell lines. We uncover the transcriptomic variability among 47 skeletal muscles, and six adipose depots linked to their different origins, metabolism, cell composition, physical activity, and mitochondrial pathways. We perform comparative analysis of the transcriptomes of seven tissues from pigs and nine other vertebrates to reveal that evolutionary divergence in transcription potentially contributes to lineage-specific biology. Long-range promoter–enhancer interaction analysis in subcutaneous adipose tissues across species suggests evolutionarily stable transcription patterns likely attributable to redundant enhancers buffering gene expression patterns against perturbations, thereby conferring robustness during speciation. This study can facilitate adoption of the pig as a biomedical model for human biology and disease and uncovers the molecular bases of valuable traits., A comprehensive transcriptomic survey of the pig could enable mechanistic understanding of tissue specialization and accelerate its use as a biomedical model. Here the authors characterize four distinct transcript types in 31 adult pig tissues to dissect their distinct structural and transcriptional features and uncover transcriptomic variability related to tissue physiology.

There is growing interest in expanding the production of soybean oils (mainly triacylglycerol, or TAG) to meet rising feed demand and address global energy concerns. We report that a plastid-localized glycerol-3-phosphate dehydrogenase (GPDH), encoded by GmGPDHp1 gene, catalyzes the formation of glycerol-3-phosphate (G3P), an obligate substrate required for TAG biosynthesis. Overexpression of GmGPDHp1 increases soybean seed oil content with high levels of unsaturated fatty acids (FAs), especially oleic acid (C18:1), without detectably affecting growth or seed protein content or seed weight. Based on the lipidomic analyses, we found that the increase in G3P content led to an elevated diacylglycerol (DAG) pool, in which the Kennedy pathway-derived DAG was mostly increased, followed by PC-derived DAG, thereby promoting the synthesis of TAG containing relatively high proportion of C18:1. The increased G3P levels induced several transcriptional alterations of genes involved in the glycerolipid pathways. In particular, genes encoding the enzymes responsible for de novo glycerolipid synthesis were largely upregulated in the transgenic lines, in-line with the identified biochemical phenotype. These results reveal a key role for GmGPDHp1-mediated G3P metabolism in enhancing TAG synthesis and demonstrate a strategy to modify the FA compositions of soybean oils for improved nutrition and biofuel.

Coronary artery bypass graft (CABG) surgery is the most widely performed cardiac surgery in the United States. Transesophageal echocardiography (TEE) is frequently used in a variety of cardiac surgical procedures, but its clinical benefit in isolated CABG surgery is unclear, and guidelines remain indeterminate. The aim of this study was to compare clinical outcomes among patients undergoing isolated CABG surgery with versus without TEE in order to test the hypothesis that TEE would be associated with improved clinical outcomes after CABG surgery.A matched retrospective cohort study was conducted among Medicare beneficiaries undergoing isolated CABG surgery with versus without intraoperative monitoring using TEE in the United States. The primary analysis was a near/far instrumental variable match that paired hospitals with similar characteristics and patient populations but with opposing probabilities for using TEE in CABG surgery. Outcomes included 30-day mortality, a composite outcome of stroke or 30-day mortality, length of hospitalization, and incidence of esophageal perforation.Of 114,871 patients undergoing isolated CABG surgery, 65,471 (57%) underwent TEE and 49,400 (43%) did not. Hospital-level instrumental variable matched analysis demonstrated that among the subset of 968 matched hospitals, TEE receipt was associated with lower 30-day mortality (3.7% vs 4.9%, P .001), a lower incidence of the composite outcome of stroke or 30-day mortality (4.5% vs 5.6%, P .001), no difference in length of hospitalization (10.32 vs 10.52 days, P = .26), and no difference in the incidence of esophageal perforation (0.01% vs 0.01%, P = .63). These results were replicated in surgeon-level and patient-level matched-pair instrumental variable analyses, and all analyses were robust to sensitivity analyses that tested for biases introduced by unmeasured confounding.The findings from this study suggest that TEE may offer a clinical benefit to cardiac surgical patients undergoing isolated CABG surgery.

Photoperiod (Ppd) genes play an important role in the adaptation of wheat to the ecological environment. However, the transcriptional regulation mechanism of photoperiodic genes has remained elusive. This study isolated a full-length promoter of Ppd-D1b (2518 bp) from the common wheat genome. Several essential core cis-acting elements and numerous light-responsive cis-acting regulatory elements were identified in Ppd-D1b promoter by the in-silico analysis. Ten 5'-deleted length fragments of the Ppd-D1b promoter fused with GUS were constructed and named D0 ~ D9, then transferred them into Arabidopsis thaliana. GUS gene driven by full-length (D0) in transgenic Arabidopsis thaliana showed the same rhythm with Ppd-D1b in wheat under short-day conditions (SDs, 8-h light/16-h dark). The expression of GUS gene in D0 reached its peak at 3 h after dawn, then decreased to the lowest and remained stable. Analysis of the series of 5'-deleted fragments showed that at 3 h after dawn, GUS gene expression activity decreased significantly in D7a due to removal of CHEBS (CCA1 HIKING EXPEDITION binding site). Moreover, yeast one-hybrid (Y1H) and dual-luciferase (dual-LUC) assays revealed that TaTCP20 could bind to the Ppd-D1b promoter to increase its transcriptional activity. This study revealed a transcription factor, TaTCP20, which activated Ppd-D1b by binding to CHEBS, provided a foundation for the theoretical research on wheat's photoperiodic response mechanism.

Kava, the rhizomes and roots of Piper methysticum Forst, is a popular edible medicinal herb traditionally used to prepare beverages for anxiety reduction. Since the German kava ban has been lifted by the court, the quality evaluation is particularly important for its application, especially the flavokawains which were believed to be responsible for hepatotoxicity. Now, by employing two different standard references and four different methods to calculate the relative correction factors, eight different quantitative analyses of multicomponents by single-marker methods have been developed for the simultaneous determination of eight major kavalactones and flavokawains in kava. The low standard method difference on quantitative measurement of the compounds among the external standard method and ours confirmed the reliability of the mentioned methods. A radar plot clearly illustrated that the contents of dihydrokavain and kavain were higher, whereas flavokawains A and B were lower in different kava samples. Only one of eight samples did not detect flavokawains that may be related to hepatotoxicity. In summary, by using different agents as an internal standard reference, the developed methods were believed as a powerful analytical tool not only for the qualitative and quantitative of kava constituents but also for the other multicomponents when authentic standard substances were unavailable.

Background The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. Aim To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. Methods We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. Results In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR)PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HRos = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). Conclusion There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line systemic treatment should be selected based on individualized treatment goals.

Background The cylindromatosis (CYLD) tumor suppressor is a microtubule‐associated deubiquitinase that plays a critical role in the regulation of cell signaling and contributes to a variety of physiological and pathological processes. However, the functions of CYLD in zebrafish are less well known, particularly with regard to their development and physiology. In this context, we investigated the loss of function of CYLD in zebrafish via transcription activator‐like effector nuclease (TALEN)‐based gene deletion. Methods Semi‐quantitative RT‐PCR was used to quantify CYLD mRNA expression in zebrafish embryos at various developmental stages. We also performed whole‐mount in situ hybridization to further assess the dynamic expression and distribution of CYLD in the entire zebrafish embryos at different stages. In addition, we deleted CYLD in zebrafish with TALENs to investigate its potential impact on embryonic development. Results The expression of CYLD mRNA varied during early embryonic development. The CYLD mRNA localized to the brain and notochord of developing zebrafish embryos. Homozygous deletion of CYLD resulted in embryonic death before 8 h post‐fertilization. Conclusions CYLD appears to play an important role in central nervous system development in zebrafish. Although severe embryonic death restricted analysis of homozygous mutants, further research into the role of CYLD in central nervous system development is warranted., Cylindromatosis (CYLD) has important pathophysiological roles in humans. More than just a tumor suppressor, CYLD has many potential functions. We exploited the zebrafish model to investigate dynamic changes in CYLD expression during embryonic development. In doing so, we discovered a potential role for CYLD in brain and notochord development, providing experimental evidence for a novel pathophysiological role in central nervous system development.

Diabetes mellitus (DM) is defined as a group of metabolic diseases characterized by hyperglycemia, which results from a deficiency in insulin secretion and/or insulin action. In diabetic patients, type 2 diabetes mellitus (T2DM) is in the majority. We explored the effects of circANKRD36 on streptozotocin (STZ)-induced insulin resistance and inflammation in diabetic rats with the aim of uncovering the underlying mechanism. STZ was used to induce the in vivo T2DM rat model. After circANKRD36 interference, blood glucose, insulin and adiponectin were respectively detected. Hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) were conducted to examine inflammation and apoptosis in T2DM rats, and western blot was used for detecting apoptosis-related proteins. The binding relationships among circANKRD36, miR-145 and XBP1 were examined by luciferase reporter assay. Results showed that circANKRD36 was expressed at a high level in T2DM rats, while silencing circANKRD36 led to decreased blood glucose and insulin, accompanied by increased adiponectin level, and ameliorating insulin resistance. Silencing circANKRD36 alleviated the inflammation and suppressed cell apoptosis in the pancreatic tissues of T2DM rats, which was abated by miR-145 inhibitor. The binding of miR-145 to XBP1 was then confirmed. Additionally, miR-145 inhibitor increased the level of XBP1 in T2DM rats, which was decreased in the presence of circANKRD36 silencing. This study is the first to prove that silencing circANKRD36 inhibits STZ-induced insulin resistance and inflammation in diabetic rats by targeting miR- 145 via XBP1. The results warrant the importance of circRNAs as drug target and thereby pave way for the development of newer therapeutic measures for T2DM.

Purpose Numerous studies have applied a variety of methods to assess paraspinal muscle degeneration. However, the methodological differences in imaging evaluation may lead to imprecise or inconsistent results. This article aimed to provide a pragmatic summary review of the current imaging modalities, measurement protocols, and imaging parameters in the evaluation of paraspinal muscle fat infiltration (FI) in MRI studies. Methods Web of Science, EMBASE, and PubMed were searched from January 2005 to March 2020 to identify studies that examined the FI of paraspinal muscles on MRI among patients with lumbar degenerative diseases. Results Intramyocellular lipids measured by magnetic resonance spectroscopy and FI measured by chemical‐shift MRI were both correlated to low back pain and several degenerative lumbar diseases, whereas results on the relationship between FI and degenerative lumbar pathologies using conventional MRI were conflicting. Multi‐segment measurement of FI at the lesion segment and adjacent segments could be a prognostic indicator for lumbar surgery. Most studies adopted the center of the intervertebral disc or endplate as the level of slice to evaluate the FI. Compared with visual semiquantitative assessment, quantitative parameters appeared to be precise for eliminating individual or modality differences. It has been demonstrated that fat CSA/total CSA (based on area) and muscle–fat index (based on signal intensity) as quantitative FI parameters are associated with multiple lumbar diseases and clinical outcomes after surgery. Conclusion Having a good command of the methodology of paraspinal muscle FI on MRI was effective for diagnosis and prognosis in clinical practice., Heterogeneity in assessing the paraspinal muscle fat infiltration exists in imaging modalities, measurement protocols (including measured level and slices, region of interest definition, and fat detection methods), and imaging parameters (semiquantitative and quantitative parameters).

Background Bipolar disorder (BD) is predominantly treated with medication, and previous studies have shown that psychotropic drugs have an effect on the neuroendocrine system. And the objectives of this study were: 1) to assess changes in neuroendocrine hormones of HPA axis and HPT axis in patients with BD after psychotropic drug treatment; 2) to determine differences in the above neuroendocrine hormones between psychotropic drug monotherapy and polytherapy treated patients. Methods This study was a retrospective study that included 188 subjects. Results After psychotropic drugs treatment, TSH levels increased significantly from baseline (p Conclusion Although the incidence of significant HPT axis and HPA axis dysfunction after psychotropic drug treatment is low in patients with BD who have normal baseline neuroendocrine hormone levels, psychotropic drug treatment does suppress HPT axis and HPA axis function irrespective of the use of psychotropic drugs alone or in combination, and duration of psychotropic drug treatment. Therefore, even patients with BD who have normal baseline levels of neuroendocrine hormones should have their neuroendocrine hormone levels regularly monitored after psychotropic drug medication. But, the interval of monitoring can be slightly longer, which can be once every six months after taking psychotropic drugs.

BackgroundHypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction.MethodsIn the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (H2O2), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.ResultsHypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (H2O2) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects.ConclusionThe findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine H2O2into the pulmonary vascular microenvironment.

Background Tigecycline, eravacycline, and omadacycline are recently developed tetracyclines. Susceptibility of microbes to these tetracyclines and their molecular mechanisms have not been well elucidated. We investigated the susceptibility of Moraxella catarrhalis to tigecycline, eravacycline, and omadacycline and its resistance mechanisms against these tetracyclines. Methods A total of 207 non-duplicate M. catarrhalis isolates were collected from different inpatients. The minimum inhibitory concentrations (MICs) of the tetracyclines were determined by broth microdilution. Tigecycline-, eravacycline-, or omadacycline-resistant isolates were induced under in vitro pressure. The tet genes and mutations in the 16S rRNA was detected by PCR and sequencing. Results Eravacycline had a lower MIC50 (0.06 mg/L) than tigecycline (0.125 mg/L) or omadacycline (0.125 mg/L) against M. catarrhalis isolates. We found that 136 isolates (65.7%) had the tetB gene, and 15 (7.2%) isolates were positive for tetL; however, their presence was not correlated with high tigecycline, eravacycline, or omadacycline (≥1 mg/L) MICs. Compared with the initial MIC after 160 days of induction, the MICs of tigecycline or eravacycline against three M. catarrhalis isolates increased ≥eight-fold, while those of omadacycline against two M. catarrhalis isolates increased 64-fold. Mutations in the 16S rRNA genes (C1036T and/or G460A) were observed in omadacycline-induced resistant isolates, and increased RR (the genes encoding 16SrRNA (four copies, RR1-RR4) copy number of 16S rRNA genes with mutations was associated with increased resistance to omadacycline. Conclusions Tigecycline, eravacycline, and omadacycline exhibited robust antimicrobial effects against M. catarrhalis. Mutations in the 16S rRNA genes contributed to omadacycline resistance in M. catarrhalis.

Objective Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been shown to be a safe and effective alternative therapy for ameliorating medically refractory primary Meige syndrome. However, the associations between DBS target position and surrounding electrophysiological properties as well as patients’ clinical outcomes remains largely unknown. In a large number of patients, we investigated electrophysiological features around stimulation targets and explored their roles in predicting clinical outcomes following bilateral GPi-DBS. Methods The locations of DBS active contacts along the long axis of the GPi in a standard space were calculated and compared among three groups with different clinical outcomes. The firing rates of individual neurons within the GPi were calculated for each patient and compared across the three groups. Results Compared with the bad group (poor clinical outcome), active contacts in the good group (good clinical outcome) and the best group (best clinical outcome) were located in the more posterior GPi. The average firing rates in the good and best groups were significantly higher than in the bad group, and this difference was pronounced within the ventral GPi. For the bad group, the average firing rates were significantly lower in the ventral than in the dorsal GPi. Conclusions This study suggests that DBS of the posterior GPi may produce better clinical outcomes during primary Meige syndrome treatment and that higher GPi neuronal activity, particularly within the ventral part, can be used as a biomarker to guide DBS electrode implantation during surgery.

Background:. Single-nucleotide polymorphisms (SNPs)-associated genes and long non-coding RNAs (lncRNAs) can contribute to human disease. To comprehensively investigate the contribution of lncRNAs to breast cancer, we performed the first genome-wide lncRNA association study on Han Chinese women. Methods:. We designed an lncRNA array containing >800,000 SNPs, which was incorporated into a 96-array plate by Affymetrix (CapitalBio Technology, China). Subsequently, we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals (5634 breast cancer patients and 6308 healthy controls). Additionally, in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene. Results:. We identified a novel breast cancer-associated susceptibility SNP, rs11066150 (Pmeta = 2.34 × 10−8), and a previously reported SNP, rs9397435 (Pmeta = 4.32 × 10−38), in Han Chinese women. rs11066150 is located in NONHSAT164009.1 (lncHSAT164), which is highly expressed in breast cancer tissues and cell lines. lncHSAT164 overexpression promoted colony formation, whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle. Conclusions:. Based on our lncRNA array, we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle. These findings suggest a potential therapeutic target in breast cancer.

There is now a relatively large body of evidence suggesting a relationship between dysfunction of myelin and oligodendrocytes and the etiology of several neuropsychiatric disorders, including depression and schizophrenia, and also suggesting that ultrasound methods may alleviate some of the symptoms of depression. We have applied low-intensity pulsed ultrasound (LIPUS) to the brains of mice treated with the demyelinating drug cuprizone, a drug that has been used as the basis for a rodent model relevant to a number of psychiatric and neurologic disorders including depression, schizophrenia, and multiple sclerosis. Prior to conducting the studies in mice, preliminary studies were carried out on the effects of LIPUS in vitro in neuron-like SH-SY5Y cells and primary glial cells. In subsequent studies in mice, female C57BL/6 mice were restrained in plastic tubes for 20 min daily with the ultrasound transducer near the end of the tube directly above the mouse's head. LIPUS was used at an intensity of 25 mW/cm2 once daily for 22 days in control mice and in mice undergoing daily repetitive restraint stress (RRS). Behavioral or neurochemical studies were done on the mice or the brain tissue obtained from them. The studies in vitro indicated that LIPUS stimulation at an intensity of 15 mW/cm2 delivered for 5 min daily for 3 days in an enclosed sterile cell culture plate in an incubator increased the viability of SH-SY5Y and primary glial cells. In the studies in mice, LIPUS elevated levels of doublecortin, a marker for neurogenesis, in the cortex compared to levels in the RRS mice and caused a trend in elevation of brain levels of brain-derived neurotrophic factor in the hippocampus relative to control levels. LIPUS also increased sucrose preference (a measure of the attenuation of anhedonia, a common symptom of several psychiatric disorders) in the RRS model in mice. The ability of LIPUS administered daily to rescue damaged myelin and oligodendrocytes was studied in mice treated chronically with cuprizone for 35 days. LIPUS increased cortex and corpus callosum levels of myelin basic protein, a protein marker for mature oligodendrocytes, and neural/glial antigen 2, a protein marker for oligodendrocyte precursor cells, relative to levels in the cuprizone + sham animals. These results of this exploratory study suggest that future comprehensive time-related studies with LIPUS on brain chemistry and behavior related to neuropsychiatric disorders are warranted. Exploratory Study on Neurochemical Effects of Low Intensity Pulsed Ultrasound in Brains of Mice. Upper part of figure: LIPUS device and in-vitro cell experimental set-up. The center image is the LIPUS generating box; the image in the upper left shows the cell experiment set-up; the image in the upper right shows a zoomed-in sketch for the cell experiment; the image in the lower left shows the set-up of repetitive restraint stress (RRS) with a mouse; the image in the lower middle shows the set-up of LIPUS treatment of a mouse; the image in the lower right shows a zoomed-in sketch for the LIPUS treatment of a mouse.

Objective The aim of this study was to determine the clinical outcomes and long-term stability of individualized titanium mesh combined with free flap for orbital floor reconstruction after maxillectomy and to identify the risk factors for titanium mesh exposure. Material and methods The data of 66 patients who underwent maxillectomy and orbital floor defect reconstruction by individualized titanium mesh in Peking University School and Hospital of Stomatology between 2011 and 2019 were retrospectively reviewed. Postoperative ophthalmic function and success of aesthetic restoration were assessed. Titanium mesh exposure was recorded and the risk factors were identified. Results Mean follow-up was for 24.8 months (range, 6-92 months). Ophthalmic function was successfully restored in 63/66 patients. Aesthetic restoration was not considered satisfactory by 10 patients. Titanium mesh exposure occurred in six patients (exposure rate, 9.1%). Preoperative radiotherapy was identified as an independent risk factor for mesh exposure (OR = 28.8, P = 0.006). Previous surgery, postoperative radiotherapy, pathological type of the primary lesion, the type of tissue flap applied, and the use of intraoperative navigation were not significant risk factors. Six patients with titanium mesh exposure underwent second surgery, but mesh exposure recurred in two patients due to insufficient soft tissue coverage. Conclusion Individualized titanium mesh with free flap can effectively restore maxilla-orbital defects. Preoperative radiotherapy is an independent predictor of postoperative titanium mesh exposure. Adequate soft tissue coverage of the mesh may reduce the risk of mesh exposure. Level of evidence Level 4 (case-control study) Laryngoscope, 2021.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00376-w.

Si Shen Wan is a classic traditional Chinese medicine formula, which has been used to treat chronic colitis for thousands of years. Many research and experience show that Si Shen Wan was developed by the combination of two sets of "Herb Pairs," Er Shen Wan and Fructus Schisandrae Chinensis Powder. This research aimed to revealing the effective substances, guide the clinical treatment, and represent the synergy effects from the view of pharmacokinetics. An ultra high performance liquid chromatography with tandem mass spectrometry method was established and validated for simultaneous quantification of 26 main bioactive compounds in normal and colitis rat plasma after oral administration of Si Shen Wan and its "Herb Pairs" extract. The method validation results illustrated that the experimental method was reliable and reproducible for quantitative determination of the biological samples. The pharmacokinetic behaviors in different groups were compared and discussed comprehensively, which indicated that the treatment of Si Shen Wan has a superiority in synthetic action of the "Herb Pairs" for the higher peak concentrations and bioavailability of some mainly components. Furthermore, the synergy effect was still existing backed up again for the longer eliminate time and a better bioavailability in colitis groups. The pharmacokinetics research of multiple components in Si Shen Wan and its "Herb Pairs" supplied a significant basis for better understanding the metabolic mechanism of these formulas in both normal and pathological state.

BACKGROUND Mechanical thrombectomy (MT) has been demonstrated to be useful for the treatment of ischemic stroke in patients with large vessel occlusions. However, recanalization by MT is not recommended for distal vessels such as second-order branches of the middle cerebral artery and posterior inferior cerebellar artery (PICA). Because of the small size and tortuosity of these arteries, the risks of using the available endovascular devices outweigh the benefits of treatment. However, MT appears to be effective in patients with primary distal vessel occlusion in eloquent areas, those with a high National Institutes of Health Stroke Scale score, and those ineligible for recombinant tissue plasminogen activator therapy. Here, we report the use of MT for treating acute occlusion of the PICA using a direct-aspiration first-pass technique (ADAPT). CASE SUMMARY In this case, the patient received acute occlusion of the PICA with ADAPT when right internal carotid artery stenting was performed. CONCLUSION With the introduction of advanced endovascular devices, MT may now be a feasible treatment for acute occlusion of the PICA.

Background To determine if trigeminal nerve electrical stimulation (TNS) would be an effective arousal treatment for loss of consciousness (LOC), we applied neuroscientific methods to investigate the role of potential brain circuit and neuropeptide pathway in regulating level of consciousness. Methods Consciousness behavioral analysis, Electroencephalogram (EEG) recording, Chemogenetics, Microarray analysis, Milliplex MAP rat peptide assay, Chromatin immune-precipitation (ChIP), Dual-luciferase reporter experiment, Western blot, PCR and Fluorescence in situ hybridization (FISH). Results TNS can markedly activate the neuronal activities of the lateral hypothalamus (LH) and the spinal trigeminal nucleus (Sp5), as well as improve rat consciousness level and EEG activities. Then we proved that LH activation and upregulated neuropeptide hypocretin are beneficial for promotion of consciousness recovery. We then applied gene microarray experiment and found hypocretin might be mediated by a well-known transcription factor Early growth response gene 1 (EGR1), and the results were confirmed by ChIP and Dual-luciferase reporter experiment. Conclusion This study illustrates that TNS is an effective arousal strategy Treatment for LOC state via the activation of Sp5 and LH neurons and upregulation of hypocretin expression.

Extracellular vesicles play a regulatory role in intracellular and intercellular transmission through a variety of biological information molecules, including mRNA, small RNAs and proteins. piRNAs are one kind of regulatory small RNAs in the vesicles at the post transcriptional level. Hereby, we isolated the extracellular vesicles from skin mucus and screened the piRNA profiles of these vesicles, aiming at developing biomarkers related to bacterial infections in Cynoglossus semilaevis. The different profilings of piRNAs in mucous extracellular vesicles of C. semilaevis were compared through small RNA sequencing, between fish infected with Vibrio harveyi and healthy ones. The number of clean reads on the alignment of exosome sick (ES) group was 105, 345 and that of exosome control (EC) group was 455, 144. GO and KEGG pathway enrichment analysis showed that most of the target genes were involved in cellular process, response to stimulus, biological regulation, immune system process and signal transduction, signal molecular and interaction, transport and catabolism. The 45 final candidate piRNAs related to immunity or infectious diseases included 20 piRNAs with high expression in the ES group and 25 piRNAs with a low expression in the ES group. After verification by qRT-PCR, there was significant difference of five piRNAs expression level between infected fish and healthy fish, in line with the sequencing. The expression level of piR-mmu-16401212, piR-mmu-26829319 and piR-gga-244092 in infected fish were significantly lower than that of control group, while piR-gga-71717 and piR-gga-99034 were higher, which implying that these piRNAs in mucous extracellular vesicles can be used to identify diseased fish from normal ones. This work supplied a novel class of biomarker for infection diagnosis in fish, and it will be benefit for screening disease resistant breeding of C. semilaevis.

The growth of the well-known fungus Ganoderma lucidum is influenced by temperature, which has an impact on the associated microbial structure in the substrate. In this study, we analyzed the bacterial diversity of the substrate at different temperatures using next-generation sequencing technology. A total of 513 733 sequences from 15 samples were assigned to 19 bacterial phyla. The samples were dominated by Proteobacteria, followed by Firmicutes; the 2 phyla exhibited opposite changes with elevated temperature. Bacterial genera showed different abundances at different temperatures, in which Sediminibacterium maintained a stable abundance below 40 °C, while Ochrobactrum and Rhodococcus were enriched with elevated temperature and both showed their highest abundances at 40 °C. Functional prediction uncovered 39 identified KEGG pathways, and bacterial genes involved in the membrane transport pathway exhibited the highest abundance subject to heat (40 °C) during the growth of G. lucidum. In general, our findings illustrated the influence of temperatures on G. lucidum mycelial morphology and the bacterial community in the substrate, and the results will facilitate cultivation of this fungus.

The emergence of the global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic underscores the importance of the rapid development of a non-invasive vaccine that can be easily administered. A vaccine administered by nasal delivery is endowed with such characteristics against respiratory viruses. In this study, we generated a recombinant SARS-CoV-2 receptor-binding domain (RBD)-based subunit vaccine. Mice were immunized via intranasal inoculation, microneedle-intradermal injection, or intramuscular injection, after which the RBD-specific immune responses were compared. Results showed that when administrated intranasally, the vaccine elicited a robust systemic humoral immunity with high titers of IgG antibodies and neutralizing antibodies as well as a significant mucosal immunity. Besides, antigen-specific T cell responses were also analyzed. These results indicated that the non-invasive intranasal administration should be explored for the future SARS-CoV-2 vaccine design.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm(2) respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm(3); p = .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm(3)) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p

INTRODUCTION Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD. METHODS Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively. RESULTS Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD health-related quality of life (P = 0.028) and improved nutrient drink-induced fullness (P < 0.001) and belching (P < 0.001) in patients with GERD. Although only acute TEA significantly enhanced LES pressure (P < 0.05), both acute and chronic TEA remarkedly increased DCI (P < 0.05) and reduced the incidence of ineffective esophageal contractions during wet swallows (P = 0.02). In addition, chronic TEA significantly increased gastric accommodation and the percentage of postprandial normal GSW compared with sham-TEA and baseline. Concurrently, TEA-enhanced vagal activity (P = 0.02) and the vagal activity positively correlated with LES pressure (r = 0.528; P = 0.003) and DCI (r = 0.522; P = 0.003). DISCUSSION The TEA treatment performed in this study improves reflux-related symptoms, increases DCI, reduces the incidence of ineffective esophageal contractions during wet swallows, and improves gastric accommodation and slow waves. The improvement in GERD symptoms might be attributed to the integrative effects of TEA on these gastroesophageal functions mediated via the vagal mechanism.

Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR: 1.08; 95% CI: 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR: 1.08; 95% CI: 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.

Background Distant metastasis is the leading cause of death for esophageal squamous cell carcinoma (ESCC) with limited treatment options and unsatisfactory effectiveness. Bromodomain (BRD) containing proteins are emerging targets for cancer therapy with promising effects. As a unique member of BRD family, the function and molecular mechanism of ATAD2 in cancer development is seldomly investigated. Methods The clinical impact of ATAD2 was assessed both at RNA and protein level in 75 and 112 ESCC patients separately. The biological function of ATAD2 was investigated in vitro and in vivo. Signaling pathway and downstream effectors of ATAD2 were identified by RNA sequencing, luciferase reporter, co-immunoprecipitation, chromatin immunoprecipitation, immunofluorescence and western blot assay. Results We found that elevated ATAD2 expression was significantly associated with lymph node metastasis, advanced clinical stage as well as poor survival of ESCC patients. Silencing ATAD2 significantly suppressed ESCC cell migration and invasion in vitro, and inhibited tumor growth and lung metastasis in vivo. Mechanically, we identified a new cofactor, C/EBPβ. ATAD2 directly interacted with C/EBPβ and promoted its nuclear translocation, which directly bound to the promoter region of TGF-β1 and activated its expression. Further, we demonstrated that TGF-β1 activated its downstream effectors in a Smad3 dependent manner. In addition, we further found that ATAD2 promoted ESCC metastasis through TGF-β signaling induced Snail expression and the subsequent epithelial-mesenchymal transition. Conclusion Our findings demonstrated the pro-metastatic function of ATAD2 and uncovered the new molecular mechanism by regulating C/EBPβ/TGF-β1/Smad3/Snail signaling pathway, thus providing a potential target for the treatment of ESCC metastasis.

Background This study aimed at investigating: 1) the relationship between self-care agency and depression and anxiety; 2) the sociodemographic and clinical factors associated with depression and anxiety in patients with diabetic retinopathy (DR) in China. Methods A cross-sectional study was conducted. One-hundred and five patients with DR were recruited. Self-care agency was assessed by the exercise of self-care agency (ESCA) scale. Depression and anxiety were assessed by the hospital anxiety and depression scale (HADS-D and HADS-A). Pearson or Spearman correlations were performed to assess the association between self-care agency and depression and anxiety. Stepwise multivariate linear regression analyses were conducted to assess the contribution of the sociodemographic and clinical factors to depression and anxiety. Results Thirty-six (34.3%) and 43 (41.1%) patients exhibited depressive and anxiety symptoms, respectively. Only 24 (22.9%) patients showed a high self-care agency. The ESCA total and subscale scores were negatively correlated depressive symptoms (P Conclusions Self-care agency negatively correlates with depression and anxiety in patients with DR. Special attention should be paid to patients living in rural areas and/or those having a history of hypertension when assessing depression and anxiety in patients with DR. Future studies are needed to clarify the causal relationship between self-care agency and depression and anxiety.

High pathogenicity island (HPI), which is widely distributed in Escherichia coli (E. coli), can enhance the pathogenicity of E. coli. Thus the HPI positive E. coli could pose a threat to human and animal health. It remains to be elucidated how HPI affects the virulence of pathogenic E. coli. Autophagy is an important mechanism to maintain cellular homeostasis and an innate immunity responses of organisms against pathogens. The interaction between pathogenic E. coli possessing HPI (E. coli HPI) and host autophagy system has not been reported. In this study, it was demonstrated that pathogenic E. coli induced autophagy in 3D4/21 macrophages and HPI was associated with enhanced autophagy through transmission electron microscopy, immunofluorescence and real-time PCR. The PI3K/Akt/mTOR pathway is an important negative regulatory pathway for autophagy. Through detecting the expression of key genes of PI3K/Akt/mTOR pathway, it was speculated that HPI enhanced the inhibition of the signaling pathway stimulated by pathogenic E. coli. Furthermore, HPI inhibited the secretion of IFN-γ, while the presence of HPI did not significantly affect the secretion of IL-1β. This work is the first attempt to explore the interplay between HPI carried by pathogenic E. coli and host cell autophagy. The findings might enable better understanding of the contribution of HPI to pathogenicity.

Background Previous studies have suggested that sensory loss is linked to depression. However, most of these studies have been conducted in developed countries and the results are mixed. Objectives The current study aims to examine the longitudinal relationship between hearing loss, vision loss, dual sensory loss, and depression among Chinese older adults over four years. Methods The data were obtained from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 6353 Chinese older adults aged 60 years and over were included at baseline in this study. Self-reported hearing and vision status was used, and dual sensory loss was a combined variable of hearing loss and vision loss. Depressive symptoms were assessed by The Center for Epidemiologic Studies Depression Scale (CESD-10). The baseline relationship between sensory loss and depression was explored by logistic regression analyses. A logistic mixed model was used to assess whether baseline sensory loss was associated with incident depression for older adults with no depressive symptoms at baseline over four years. Results At baseline, vision loss (OR=1.46, 95%CI: 1.19-1.79) and dual sensory loss (OR=2.14, 95%CI: 1.77-2.58) were associated with depression, while hearing loss was not. After four years, vision loss (OR=1.60, 95%CI: 1.16-2.22) and dual sensory loss (OR=1.78, 95%CI: 1.32-2.41) were associated with incident depression. Limitations Not all potential confounding factors are measured and adjusted in the analysis. Apart from that, all measurements of interest are self-reported scales. Conclusion Vision loss and dual sensory loss are significantly associated with both onset and increased depressive symptoms over time, while hearing loss is not associated with depression. Interactions between all types of sensory loss and social activities are not significant. Our results suggest that target mental health intervention programs should be delivered to vision loss or dual sensory loss populations.

Aims/Introduction To investigate the differential effects of maternal versus paternal history of diabetes on the risks for diabetes and prediabetes, as well as on insulin secretion and resistance in Chinese individuals. Materials and Methods From the 2007 to 2008 China National Diabetes and Metabolism Disorders Study, 39,244 participants were included and divided into four categories: negative parental history, paternal history only (PH), maternal history only (MH), and both paternal and maternal history. Results The age‐ and sex‐standardized prevalence rates of diabetes in the negative parental history, PH, MH, and both paternal and maternal history groups were 8.59, 12.56, 15.86 and 29.81%, respectively. The prevalence rates of impaired glucose metabolism were 24.13, 25.41, 31.13 and 50.80%, with the prevalence in the MH group being significantly higher than that in the PH group. Compared with that in the FH0 group, the risks of diabetes in the PH, MH, and both paternal and maternal history groups were 2.01‐, 2.67‐ and 6.37‐fold greater, and the risks of impaired glucose metabolism were 1.28‐, 1.65‐ and 3.45‐fold greater. In addition, MH had a significantly greater impact on impaired glucose metabolism than PH (P MHvsPH = 0.0292). Regression analyses suggested MH was associated with homeostatic model assessment for β‐cell function (β[SE] = −0.0910[0.0334], P = 0.0065), insulinogenic index (−0.1866[0.0550], P = 0.0007), homeostatic model assessment for insulin resistance (0.0662[0.0227], P = 0.0036) and Matsuda Index [−0.0716(0.0203), P = 0.0004]. PH was specifically associated with homeostatic model assessment for insulin resistance (0.1343[0.0267], P, Impaired glucose metabolism was significantly more prevalent among participants with a maternal history of diabetes than among those with a paternal history. Maternal history had significantly greater influences on the elevated disease risk for impaired glucose metabolism than paternal history. Maternal history could contribute to the diseases through its impact on both insulin secretion impairment and insulin resistance, whereas the contribution of paternal history could rely on its specific impact on insulin resistance.

Background: Oncolytic adenovirus-mediated gene therapy is an emerging strategy for cancer treatment. However, oncolytic adenoviruses are mainly administered locally at tumor site. Intravenous administration of oncolytic adenovirus for cancer gene therapy is a problem that needs to be solved urgently. Methods: We constructed recombinant oncolytic adenovirus KGHV500 carrying anti-p21Ras scFv and employed CIK cells to deliver KGHV500. TUNEL, wound healing, MTT, and Transwell invasion assays were used to determine the anti-tumor efficacy of KGHV500 on liver cancer cells in vitro. Nude mouse xenograft model was used to examine the anti-tumor efficacy of CIK cells combined with KGHV500 in vivo. Furthermore, KGHV500 accumulation in different organs was detected to assess the safety. Results: KGHV500 inhibited the migration, proliferation, invasion, and induced the apoptosis of liver cancer cells. CIK cells carrying KGHV500 reached tumor site and exerted much better anti-tumor efficacy than CIK cells or KGHV500 alone in nude mouse xenograft model. Moreover, we detected KGHV500 and anti-p21Ras scFv in different organs of nude mice, with little effects on the organs. Conclusions: We develop a novel strategy for the treatment of Ras-driven liver cancer by combining CIK cells with oncolytic adenovirus expressing anti-p21Ras scFv. Intravenous injection of CIK cells carrying KGHV500 in vivo significantly inhibits tumor growth, has little effect on normal organs, and is relatively safe.

Introduction Pediatric myasthenia encompasses juvenile myasthenia gravis (JMG) and congenital myasthenic syndrome (CMS), which are chronic disorders with fluctuating symptoms amenable to medical therapy. Disease activity and treatment response may be difficult to assess, but, unlike adults, outcome measures have not been developed in children. Methods The study was performed in children (0-18 years of age) at the neuromuscular center of a pediatric hospital over a 3-year period. Patients were recruited prospectively as part of their routine clinical care. Demographic data, diagnosis (JMG/CMS), and the following scales were recorded at each visit: Myasthenia Gravis Foundation of America (MGFA) class, Myasthenia Gravis Composite (MGC), and Pediatric Myasthenia-Quality of Life 15 (PM-QOL15). Results Thirty-three patients (24 JMG, 9 CMS) were included in the study, 22 had two or more visits. We established known-groups validity of the MGC and PM-QOL15 scores as compared with the MGFA class. To establish concurrent validity, we constructed a receiver-operating characteristic curve and calculated threshold values of MGC and PM-QOL15 with optimal sensitivity and specificity for identifying a patient with more severe (MGFA III or higher) disease. Finally, we demonstrated the concordance between the MGC and PM-QOL15 by their statistically significant positive Pearson and Spearman correlations. Discussion Our study suggests that MGC and PM-QOL15 are important disease outcome measures in pediatric myasthenia that are easy to administer and provide reliable assessment of disease activity in the clinic setting. Further studies are needed to validate their use for pediatric clinical research trials.

Titanium (Ti) and Ti alloys are widely used biomaterials, but they lack osteogenic capability for rapid bone integration. To improve osseointegration of Ti implants, TiO2 nanotubes were prepared using the anodizing oxidation technique, and strontium (Sr) combined with icariin (ICA) was loaded on TiO2 nanotube coatings. Cell adhesion and proliferation of MC3T3-E1 cells, alkaline phosphatase (ALP) activity, mineralization of extracellular matrix, and bone formation around titanium implants in ovariectomized rats, were examined separately. The results showed that compared with pure Ti, TiO2 and Sr-loaded TiO2 coatings, the coatings loaded with both Sr and ICA showed better effect on cell adhesion and proliferation, higher ALP activity and more red-stained mineralized nodules. Furthermore, more bone was formed around implants loaded with both Sr and ICA in osteoporotic rats. Therefore, coating with Sr and ICA is valuable for clinical application to strengthen the osseointegration of titanium implants, especially in osteoporotic patients.