Effect of geographic isolation on genetic variation and population structure of Euphrasia nankotaizanensis, a threatened endemic alpine herb in Taiwan.

Euphrasia nankotaizanensis (Orobanchaceae) is a rare alpine herb that is endemic to Taiwan. Only four small populations remain in Xue, Nanhu, and Cilai Mountains of Taiwan. The distribution of alpine herbs is severely threatened by climate change, which influences genetic variation and population structure. In this study, we investigated the effects of the natural isolation of alpine habitats on the genetic diversity and geographic structure of populations of E. nankotaizanensis using chloroplast (cp) and nuclear DNA (nrDNA) markers. We found lower levels of genetic diversity in E. nankotaizanensis than in other alpine plants and little to no genetic variation within populations, which could be mainly attributed to the small population size and genetic drift. Only one nrDNA haplotype was present in each population. The lack of monophyly of the four populations in cpDNA probably resulted from lineage sorting or occasional long-distance seed dispersal. Phylogeographic analysis suggested that Nanhu Mountain was probably a refugium over the glacial maxima, agreeing with the potential refugia in central Taiwan. The STRUCTURE and AMOVA analyses revealed significant genetic differentiation in nrDNA among the mountains, which resulted from geographical isolation among these mountains. Estimates of the effective population size (Ne) and demography reflected lower Ne values and a recent population decline, probably implying a greater extinction risk for E. nankotaizanensis. We observed genetic depletion and considerable genetic differentiation among mountain populations, which should be considered in future conservation efforts for this species. In addition, this study provides important insights into the long-term potential of alpine herbs in Taiwan, which are useful for a better prediction of their responses to future climate change.

NOTCH2NLC GGC Repeat Expansion in Patients With Vascular Leukoencephalopathy.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID), caused by GGC (guanine-guanine-cytosine) repeat expansion in NOTCH2NLC, has several clinical and radiological features akin to cerebral small vessel disease (cSVD). The present study tested the hypothesis that NOTCH2NLC GGC expansion may contribute to cSVD. METHODS: One hundred and ninety-seven unrelated patients with genetically unsolved vascular leukoencephalopathy without NOTCH3, HTRA1, and mitochondrial m.3243A>G mutations and 730 healthy individuals were screened for NOTCH2NLC GGC repeat expansion using repeat-primed polymerase chain reaction, fragment analysis, Southern blot analysis, or nanopore sequencing with Cas9 (CRISPR associated protein 9)-mediated enrichment. The clinical and neuroimaging features of the patients were compared between individuals with and without NOTCH2NLC GGC repeat expansion. RESULTS: Six of the 197 (3.0%) patients with unsolved vascular leukoencephalopathy and none of the controls carried the GGC repeat expansion (P=0.00009). Skin biopsy of 1 patient revealed eosinophilic, ubiquitin-positive, and p62-positive intranuclear inclusions in the cells of sweat gland and capillary, providing pathologic evidence for the involvement of small vessels in NIID. For the 6 patients, gait disturbance and cognitive decline were common manifestations with a median onset age of 65 (59-69) years. They all had multiple neuroimaging features suggestive of cSVD, including diffuse white matter hyperintensities, lacunes, and enlarged perivascular space in all 6 patients, cerebral microbleeds in 5, and old intracerebral hemorrhage in 4. Four patients had linear hyperintensity in the corticomedullary junction on diffusion-weighted imaging-the characteristic neuroimaging feature of NIID. There was no difference in the severity of cSVD imaging features between the patients with and without the GGC expansion but more pronounced brain atrophy in the patients with the GGC expansion. CONCLUSIONS: NOTCH2NLC GGC repeat expansion accounted for 3% of genetically unsolved Taiwanese vascular leukoencephalopathy cases after excluding participants with cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). NIID should be considered in patients manifesting cSVD, especially in those with characteristic neuroimaging feature of NIID.

Arboviruses and symbiotic viruses cooperatively hijack insect sperm-specific proteins for paternal transmission.

Arboviruses and symbiotic viruses can be paternally transmitted by male insects to their offspring for long-term viral persistence in nature, but the mechanism remains largely unknown. Here, we identify the sperm-specific serpin protein HongrES1 of leafhopper Recilia dorsalis as a mediator of paternal transmission of the reovirus Rice gall dwarf virus (RGDV) and a previously undescribed symbiotic virus of the Virgaviridae family, Recilia dorsalis filamentous virus (RdFV). We show that HongrES1 mediates the direct binding of virions to leafhopper sperm surfaces and subsequent paternal transmission via interaction with both viral capsid proteins. Direct interaction of viral capsid proteins mediates simultaneously invasion of two viruses into male reproductive organs. Moreover, arbovirus activates HongrES1 expression to suppress the conversion of prophenoloxidase to active phenoloxidase, potentially producing a mild antiviral melanization defense. Paternal virus transmission scarcely affects offspring fitness. These findings provide insights into how different viruses cooperatively hijack insect sperm-specific proteins for paternal transmission without disturbing sperm functions.

AFP Response to Locoregional Therapy Can Stratify the Risk of Tumor Recurrence in HCC Patients after Living Donor Liver Transplantation.

(1) Background: Alpha-fetoprotein (AFP) has been incorporated into the selection criteria of liver transplantation and been used to predict the outcome of hepatocellular carcinoma (HCC) recurrence. Locoregional therapy (LRT) is recommended for bridging or downstaging in HCC patients listed for liver transplantation. The aim of this study was to evaluate the effect of the AFP response to LRT on the outcomes of hepatocellular carcinoma patients after living donor liver transplantation (LDLT). (2) Methods: This retrospective study included 370 HCC LDLT recipients with pretransplant LRT from 2000 to 2016. The patients were divided into four groups according to AFP response to LRT. (3) Results: The nonresponse group had the worst 5-year cumulative recurrence rates whereas the complete-response group (patients with abnormal AFP before LRT and with normal AFP after LRT) had the best 5-year cumulative recurrence rate among the four groups. The 5-year cumulative recurrence rate of the partial-response group (AFP response was over 15% lower) was comparable to the control group. (4) Conclusions: AFP response to LRT can be used to stratify the risk of HCC recurrence after LDLT. If a partial AFP response of over 15% declineis achieved, a comparable result to the control can be expected.

Zinc Finger Protein 90 Knockdown Promotes Cisplatin Sensitivity via Nrf2/HO-1 Pathway in Ovarian Cancer Cell.

Our study discussed the role of Zfp90 in ovarian cancer (OC) cell lines' sensitivity to cisplatin. We used two OC cell lines, SK-OV-3 and ES-2, to evaluate their role in cisplatin sensitization. The protein levels of p-Akt, ERK, caspase 3, Bcl-2, Bax, E-cadherin, MMP-2, MMP-9 and other drug resistance-related molecules, including Nrf2/HO-1, were discovered in the SK-OV-3 and ES-2 cells. We also used a human ovarian surface epithelial cell to compare the effect of Zfp90. Our outcomes indicated that cisplatin treatment generates reactive oxygen species (ROS) that modulate apoptotic protein expression. The anti-oxidative signal was also stimulated, which could hinder cell migration. The intervention of Zfp90 could greatly improve the apoptosis pathway and block the migrative pathway to regulate the cisplatin sensitivity in the OC cells. This study implies that the loss of function of Zfp90 might promote cisplatin sensitization in OC cells via regulating the Nrf2/HO-1 pathway to enhance cell apoptosis and inhibit the migrative effect in both SK-OV-3 and ES-2 cells.

Factors associated with viral rebound among COVID-19 patients receiving oral antivirals.

BACKGROUND: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. METHODS: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units). RESULTS: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 109/L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered. CONCLUSION: Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.

A systems approach points to a therapeutic role for retinoids in asparaginase-associated pancreatitis.

Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.

Decreased hospital readmissions after programmatic strengthening of an outpatient parenteral antimicrobial therapy (OPAT) program.

Objective: To determine whether a structured OPAT program supervised by an infectious disease physician and led by an OPAT nurse decreased hospital readmission rates and OPAT-related complications and whether it affected clinical cure. We also evaluated predictors of readmission while receiving OPAT. Patients: A convenience sample of 428 patients admitted to a tertiary-care hospital in Chicago, Illinois, with infections requiring intravenous antibiotic therapy after hospital discharge. Methods: In this retrospective, quasi-experimental study, we compared patients discharged on intravenous antimicrobials from an OPAT program before and after implementation of a structured ID physician and nurse-led OPAT program. The preintervention group consisted of patients discharged on OPAT managed by individual physicians without central program oversight or nurse care coordination. All-cause and OPAT-related readmissions were compared using the χ2 test. Factors associated with readmission for OPAT-related problems at a significance level of P < .10 in univariate analysis were eligible for testing in a forward, stepwise, multinomial, logistic regression to identify independent predictors of readmission. Results: In total, 428 patients were included in the study. Unplanned OPAT-related hospital readmissions decreased significantly after implementation of the structured OPAT program (17.8% vs 7%; P = .003). OPAT-related readmission reasons included infection recurrence or progression (53%), adverse drug reaction (26%), or line-associated issues (21%). Independent predictors of hospital readmission due to OPAT-related events included vancomycin administration and longer length of outpatient therapy. Clinical cure increased from 69.8% before the intervention to 94.9% after the intervention (P < .001). Conclusion: A structured ID physician and nurse-led OPAT program was associated with a decrease in OPAT-related readmissions and improved clinical cure.

Screening the risk of obstructive sleep apnea by utilizing supervised learning techniques based on anthropometric features and snoring events.

Objectives: Obstructive sleep apnea (OSA) is typically diagnosed by polysomnography (PSG). However, PSG is time-consuming and has some clinical limitations. This study thus aimed to establish machine learning models to screen for the risk of having moderate-to-severe and severe OSA based on easily acquired features. Methods: We collected PSG data on 3529 patients from Taiwan and further derived the number of snoring events. Their baseline characteristics and anthropometric measures were obtained, and correlations among the collected variables were investigated. Next, six common supervised machine learning techniques were utilized, including random forest (RF), extreme gradient boosting (XGBoost), k-nearest neighbor (kNN), support vector machine (SVM), logistic regression (LR), and naïve Bayes (NB). First, data were independently separated into a training and validation dataset (80%) and a test dataset (20%). The approach with the highest accuracy in the training and validation phase was employed to classify the test dataset. Next, feature importance was investigated by calculating the Shapley value of every factor, which represented the impact on OSA risk screening. Results: The RF produced the highest accuracy (of >70%) in the training and validation phase in screening for both OSA severities. Hence, we employed the RF to classify the test dataset, and results showed a 79.32% accuracy for moderate-to-severe OSA and 74.37% accuracy for severe OSA. Snoring events and the visceral fat level were the most and second most essential features of screening for OSA risk. Conclusions: The established model can be considered for screening for the risk of having moderate-to-severe or severe OSA.

Synergistic effects of pH shift and heat treatment on solubility, physicochemical and structural properties, and lysinoalanine formation in silkworm pupa protein isolates.

The application of silkworm pupa protein isolates (SPPI) in food industry was limited because SPPI's solubility is poor and it contains a potential harmful component of lysinoalanine (LAL) which formed during protein extraction. In this study, combined treatments of pH shift and heating were performed to improve the solubility of SPPI and to reduce the content of LAL. The experimental results showed that the promoting effect on SPPI's solubility by alkaline pH shift + heat treatment was greater than that by acidic pH shift + heat. And an 8.62 times increase of solubility was observed after pH 12.5 + 80 â„ƒ treatment compared to the control SPPI sample which was extracted at pH 9.0 without pH shift treatment. Very strong positive correlation was found between alkali dosage and SPPI solubility (Pearson's correlation coefficient r = 0.938). SPPI with pH 12.5 shift treatment showed the highest thermal stability. Alkaline pH shift combined with heat treatment altered the micromorphology of SPPI and destroyed the disulfide bonds between macromolecular subunits (72 and 95 kDa), resulting in reduced particle size and increased zeta potential and free sulfhydryl content of the isolates. The fluorescence spectra analysis showed red shifts phenomena with pH increasing and fluorescence intensity increase with temperature increasing, implying the alterations in the tertiary structure of protein. Compared to the control SPPI sample, the amount of LAL reduced by 47.40 %, 50.36 % and 52.39 % using pH 12.5 + 70 â„ƒ, pH 12.5 + 80 â„ƒ and pH 12.5 + 90 â„ƒ treatment, respectively. These findings provide fundamental information for the development and application of SPPI in food industry.

Modeling of land subsidence using GIS-based artificial neural network in Yunlin County, Taiwan.

In this study, the land subsidence in Yunlin County, Taiwan, was modeled using an artificial neural network (ANN). Maps of the fine-grained soil percentage, average maximum drainage path length, agricultural land use percentage, electricity consumption of wells, and accumulated land subsidence depth were produced through geographic information system spatial analysis for 5607 cells in the study area. An ANN model based on a backpropagation neural network was developed to predict the accumulated land subsidence depth. A comparison of the model predictions with ground-truth leveling survey data indicated that the developed model had high accuracy. Moreover, the developed model was used to investigate the relationship of electricity consumption reduction with reductions in the total area of land with severe subsidence (> 4 cm per year); the relationship was approximately linear. In particular, the optimal results were obtained when decreasing the electricity consumption from 80 to 70% of the current value, with the area of severe land subsidence decreasing by 13.66%.

Ethane groups modified DNA nanopores to prolong the dwell time on live cell membranes for transmembrane transport.

Transmembrane transport, mostly relying on biological channels, is crucial for the metabolic processes of live cells including sensing, signaling, cellular communicating and molecular transport. Artificial biomimetic channels offer excellent opportunities for studying the mechanisms of the metabolic processes of live cells and promote the applications of gene transfection, drug delivery, and regulations of cellular communications. DNA nanopores can be designed flexibly and operated easily while maintaining good biocompatibility, offering a good candidate for applications in basic research. However, because of the small size and good biocompatibility of DNA nanopores, it is still difficult to form stable channels on the plasma membrane of live cells by DNA nanopores. As a result, it significantly limits the applications of DNA nanopores in vivo. Thus, in this work, we have constructed ethane-phosphorothioate (PPT) groups modified DNA nanopores (E-DNA nanopores) to simulate biological channels for the transmembrane transport of small molecules. The E-DNA nanopores were found to be more hydrophobic and stable to anchor at the plasma membrane of live cells for a longer time window for subsequent transmembrane transport after the modification of ethane-PPT groups. The membrane-spanning E-DNA nanopores with a longer dwell time window could inspire the design of new DNA nanostructures and expand their biological applications including biosensing and sequencing, construction of artificial cells and regulation of transmembrane transport.

Age-dependent changes in the anatomical and histological characteristics of the aggregated lymphoid nodules in the stomach of Dromedary camels (Camelus Dromedarius).

Gastrointestinal associated lymphoid tissue (GALT) is an important component of the mucosal immune system. It is the largest mass of lymphoid tissues in the body and makes up more than 70% immune cells of entire body. GALT is considered to be the origin of systemic mucosal immunity and consists of solitary lymphoid nodules, aggregated lymphoid nodules (Peyer's patches, PPs), scattered lymphoid tissues, and follicular associated epithelia. PPs play important roles as antigen inductive sites of the mucosal immune system, which are mainly distributed in the intestine of animals and humans (especially ileum and appendix). However, a special area of well-developed aggregated lymphoid nodules in the abomasum of Dromedary camel was found in our laboratory. Its existence was rarely described in the stomach before. In the present study, we investigated this special structure with the dromedary camels of different ages (young, 0.5-2 years; pubertal, 3-5 years; middle-aged, 6-16 years; old, 17-20 years), by the anatomical, histological and immunohistochemical approaches. The results showed that the special structure was mainly distributed in the cardiac glandular area of the abomasum, forming a triangular area. The mucosal folds in this area were significantly thicker than those in the surrounding region. These mucosal folds had two different forms, namely reticular mucosal folds (RMF) and longitudinal mucosal folds (LMF). There were abundant lymphoid nodules in the submucosa of RMF and LMF, which were arranged in one or multiple rows. The statistical analysis of the height and thickness of RMF and LMF showed that the structure was most developed in pubertal dromedary camels. The histological characteristics of the structure were the same as PPs in the intestine of the Dromedary camel, while anatomical appearance showed some difference. The immunohistochemical examination revealed that both immunoglobulin A (IgA) and G (IgG) antibodies-producing cells (APCs) were extensively distributed in the gastric lamina propria (LP) in all age group. Our finding suggest that camel stomach not only performs digestive functions, but also involves parts of body immunity.

High-dose dual therapy versus bismuth-containing quadruple therapy for the treatment of helicobacter pylori infection: A meta-analysis of randomized controlled trials.

Background: Helicobacter pylori (H. pylori) infection is one of the most important public health issues, and bismuth-containing quadruple therapy (BQT) is the first-line therapeutic option. This study aimed to compare the efficacy and safety of high-dose dual therapy (HDDT) and BQT in eradicating H. pylori. Methods: Randomized controlled trials (RCTs) were retrieved from Pubmed, Embase, and Cochrane Library to evaluate the effects of HDDT and BQT on H. pylori infection from 2002 to August 31, 2022 (last 20 years). A meta-analysis was conducted using Review Manager 5.4 and dichotomous data were estimated by the risk ratio (RR) and the 100% confidence interval (CI). A heterogeneity test and publication bias adjustment were carried out using Stata 12.0. Results: 5604 participants from 14 RCTs were included in this meta-analysis. The eradication rates of H. pylori in the HDDT group and the BQT group were 87.46% and 85.70%, respectively. There was a bordered significant difference (RR = 1.02, 95% CI: 1.00 ~ 1.04, P = 0.03) in the intention-to-treat (ITT) analysis. Inconsistently, in per-protocol (PP) analysis, HDDT showed similar efficacy to BQT (89.97% vs 89.82%, RR = 1.00, 95% CI: 0.99 ~ 1.02, P = 0.67). HDDT showed fewer frequent adverse events than BQT (13.00% vs 31.05%, RR = 0.41, 95% CI: 0.33 ~0.50, P < 0.00001). After adjusting for publication bias, the tendency did not change (RR = 0.49, 95% CI: 0.44 ~ 0.55, P < 0.00001). The compliance of the HDDT group has no significant difference compared with the BQT group (95.88% vs 93.84%, RR = 1.01, 95% CI: 1.00 ~ 1.03, P = 0.14). Conclusion: HDDT achieved a non-inferiority eradication rate, fewer side effects, and similar compliance compared with BQT.

Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study.

Background and aims: The efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients. Methods: This multicenter prospective study included patients with ePVTT treated with IMRT combined with atezo/bev from March to September 2021 in three centers in China. The outcomes of this study included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and association between response and tumor mutational burden (TMB). Treatment-related adverse events (TRAEs) were analyzed to assess safety. Results: Of 30 patients in this study, the median follow-up was 7.4 months. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the ORR was 76.6%, the median OS for the entire cohort was 9.8 months, the median PFS was 8.0 months, and the median TTP was not reached. This study failed to establish a significant correlation between TMB with any of the following outcomes, including ORR, OS, PFS or TTP. The most common TRAEs at all levels were neutropenia (46.7%), and the most common grade 3/4 TRAE was hypertension (16.7%). There was no treatment-related deaths. Conclusions: IMRT combined with atezo/bev showed encouraging treatment efficacy with an acceptable safety profile, making this treatment to be a promising option for HCC patients with ePVTT. Further studies are required to support the findings of this preliminary study. Clinical trial registration: http://www.chictr.org.cn, Identifier ChiCTR2200061793.

Low-energy production of a monolithic catalyst with MnCu-synergetic enhancement for catalytic oxidation of volatile organic compounds.

Producing a low-cost catalyst by a low-cost method is one of the hottest topics in the field of catalytic oxidization of volatile organic compounds (VOCs). In this work, a catalyst formula with a low-energy requirement was optimized in the powdered state, and verified in the monolithic state. An effective MnCu catalyst was synthesized at a temperature as low as 200 °C. Removals were all bigger than 88% for toluene, ethyl acetate, hexane, formaldehyde, and cyclohexanone at a low temperature of 240 °C. The MnCu catalyst was then loaded on a honeycomb cordierite, which was also effective for toluene removal at 240 °C. After characterizations, active phases were Mn3O4/CuMn2O4 in both the powdered and monolithic catalysts. The enhanced activity was attributed to balanced distributions of low-valence Mn and Cu, as well as abundant surface oxygen vacancies. The obtained catalyst is produced by low energy and effective at low temperature, which suggests a perspective application.

Gossypium purpurascens genome provides insight into the origin and domestication of upland cotton.

INTRODUCTION: Allotetraploid upland cotton (Gossypium hirsutum L.) is native to the Mesoamerican and Caribbean regions, had been improved in the southern United States by the mid-eighteenth century, was then dispersed worldwide. However, a Hainan Island native cotton (HIC) has long been grown extensively on Hainan Island, China. OBJECTIVES: Explore HIC's evolutionary relationship and genomic diversity with other tetraploid cottons, its origin and whether it was used for YAZHOUBU (Yazhou cloth, World Intangible Cultural Heritage) weaving, and the role of structural variations (SVs) in upland cotton domestication. METHODS: We assembled a high-quality genome of one HIC plant. We performed phylogenetic analysis, divergence time estimation, principal component analysis and population differentiation estimation using cotton assemblies and/or resequencing data. SVs were detected by whole-genome comparison. A F2 population was used for linkage analysis and to study effects of SVs. Buoyancy and salt water tolerance tests for seeds were conducted. RESULTS: We found that the HIC belongs to G. purpurascens. G. purpurascens is best classified as a primitive race of G. hirsutum. The potential for long range transoceanic dispersal of G. purpurascens seeds was proved. A set of SVs, selective sweep regions between G. hirsutum races and cultivars, and quantitative trait loci (QTLs) of eleven agronomic traits were obtained. SVs, especially large-scale SVs, were found to have important effects on cotton domestication and improvement. Of them, eight large-scale inversions strongly associated with yield and fiber quality have probably undergone artificial selection in domestication. CONCLUSION: G. purpurascens including HIC is a primitive race of G. hirsutum, probably disperse to Hainan from Central America by floating on ocean currents, may have been partly domesticated, planted and was likely used for YAZHOUBU weaving in Hainan much earlier than the Pre-Columbian period. SV play an important role in cotton domestication and improvement.

Transcriptomic Analyses of Exercise Training in Alzheimer's Disease Cerebral Cortex.

BACKGROUND: Research reported exercise could reduce Alzheimer's disease (AD) symptoms in human and animals. However, the molecular mechanism of exercise training via transcriptomic analysis was unclear especially in AD in the cortex area. OBJECTIVE: Investigate potential significant pathways in the cortex area that were affected by exercise during AD. METHODS: RNA-seq analysis, differential expressed genes, functional enrichment analysis, and GSOAP clustering analysis were performed in the isolated cerebral cortex from eight 3xTg AD mice (12 weeks old) randomly and equally divided into control (AD) and exercise training (AD-EX) group. Swimming exercise training in AD-EX group was conducted 30 min/day for 1 month. RESULTS: There were 412 genes significant differentially expressed in AD-EX group compared to AD group. Top 10 upregulated genes in AD-EX group against AD group mostly correlated with neuroinflammation, while top 10 downregulated genes mostly had connection with vascularization, membrane transport, learning memory, and chemokine signal. Pathway analysis revealed the upregulated interferon alpha beta signaling in AD-EX had association with cytokines delivery in microglia cells compared to AD and top 10 upregulated genes involved in interferon alpha beta were Usp18, Isg15, Mx1, Mx2, Stat1, Oas1a, and Irf9; The downregulated extracellular matrix organization in AD-EX had correlation with Aß and neuron cells interaction and Vtn was one of the top 10 downregulated genes involved in this pathway. CONCLUSION: Exercise training influenced 3xTg mice cortex through interferon alpha beta signaling upregulation and extracellular matrix organization downregulation based on transcriptomics analysis.

Cyclization of Vinyl Diazo Compounds with Benzofuran-Derived Azadienes Enabled by NaBArF4.

An unprecedented cycloaddition of vinyl diazo compounds with benzofuran-derived azadienes catalyzed by rarely independently used NaBArF4 has been established. Benzofuran-fused hydropyridines were constructed with excellent yields and high diastereoselectivity via a Na+-catalyzed inverse-electron-demand aza-Diels-Alder reaction. Notably, this transformation also features good compatibility with a one-pot protocol to deliver the spiro[benzofuran-cyclopentene] skeleton, as well as perfect atom economy and simple reaction conditions.

Skin sympathetic nerve activity as a potential biomarker for overactive bladder.

PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.