HortGenome Search Engine, a universal genomic search engine for horticultural crops.

Horticultural crops comprising fruit, vegetable, ornamental, beverage, medicinal and aromatic plants play essential roles in food security and human health, as well as landscaping. With the advances of sequencing technologies, genomes for hundreds of horticultural crops have been deciphered in recent years, providing a basis for understanding gene functions and regulatory networks and for the improvement of horticultural crops. However, these valuable genomic data are scattered in warehouses with various complex searching and displaying strategies, which increases learning and usage costs and makes comparative and functional genomic analyses across different horticultural crops very challenging. To this end, we have developed a lightweight universal search engine, HortGenome Search Engine (HSE; http://hort.moilab.net), which allows for the querying of genes, functional annotations, protein domains, homologs, and other gene-related functional information of more than 500 horticultural crops. In addition, four commonly used tools, including 'BLAST', 'Batch Query', 'Enrichment analysis', and 'Synteny Viewer' have been developed for efficient mining and analysis of these genomic data.

Not only baseline but cumulative exposure of remnant cholesterol predicts the development of nonalcoholic fatty liver disease: a cohort study.

BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION: Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.

Synthesis and biological evaluation of structurally diverse 6-aryl-3-aroyl-indole analogues as inhibitors of tubulin polymerization.

The synthesis and evaluation of small-molecule inhibitors of tubulin polymerization remains a promising approach for the development of new therapeutic agents for cancer treatment. The natural products colchicine and combretastatin A-4 (CA4) inspired significant drug discovery campaigns targeting the colchicine site located on the beta-subunit of the tubulin heterodimer, but so far these efforts have not yielded an approved drug for cancer treatment in human patients. Interest in the colchicine site was enhanced by the discovery that a subset of colchicine site agents demonstrated dual functionality as both potent antiproliferative agents and effective vascular disrupting agents (VDAs). Our previous studies led to the discovery and development of a 2-aryl-3-aroyl-indole analogue (OXi8006) that inhibited tubulin polymerization and demonstrated low nM IC50 values against a variety of human cancer cell lines. A water-soluble phosphate prodrug salt (OXi8007), synthesized from OXi8006, displayed promising vascular disrupting activity in mouse models of cancer. To further extend structure-activity relationship correlations, a series of 6-aryl-3-aroyl-indole analogues was synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity against human cancer cell lines. Several structurally diverse molecules in this small library were strong inhibitors of tubulin polymerization and of MCF-7 and MDA-MB-231 human breast cancer cells. One of the most promising analogues (KGP591) caused significant G2/M arrest of MDA-MB-231 cells, disrupted microtubule structure and cell morphology in MDA-MB-231 cells, and demonstrated significant inhibition of MDA-MB-231 cell migration in a wound healing (scratch) assay. A phosphate prodrug salt, KGP618, synthesized from its parent phenolic precursor, KGP591, demonstrated significant reduction in bioluminescence signal when evaluated in vivo against an orthotopic model of kidney cancer (RENCA-luc) in BALB/c mice, indicative of VDA efficacy. The most active compounds from this series offer promise as anticancer therapeutic agents.

Metabolic health phenotype better predicts subclinical atherosclerosis than body mass index-based obesity phenotype in the non-alcoholic fatty liver disease population.

Background: Non-alcoholic fatty liver disease (NAFLD), especially lean NAFLD is associated with an increased risk of atherosclerotic cardiovascular disease (CVD). It is not currently known which clinical phenotypes of NAFLD contribute most to individual subclinical atherosclerosis risk. We examined the relationship between body mass index (BMI), the metabolically healthy status, and subclinical atherosclerosis in the NAFLD population. Methods: Data from asymptomatic NAFLD subjects who participated in a routine health check-up examination were collected. Participants were stratified by BMI (cutoff values: 24.0-27.9 kg/m2 for overweight and ≥28.0 kg/m2 for obesity) and metabolic status, which was defined by Adult Treatment Panel III criteria. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity (baPWV) in 27,738 participants and by carotid plaque in 14,323 participants. Results: Within each BMI strata, metabolically unhealthy subjects had a significantly higher prevalence of subclinical atherosclerosis than metabolically healthy subjects, whereas fewer differences were observed across subjects within the same metabolic category. When BMI and metabolic status were assessed together, a metabolically unhealthy status was the main contributor to the association of clinical phenotypes with the subclinical atherosclerosis burden (all p < 0.001). When BMI and metabolic abnormalities were assessed separately, the incidence of subclinical disease did not increase across BMI categories; however, it increased with an increase in the number of metabolic abnormalities (0, 1, 2 and ≥3). Conclusion: A metabolically healthy status in NAFLD patients was closely correlated with subclinical atherosclerosis, beyond that of the BMI-based obesity phenotype. The application of metabolic phenotyping strategies could enable more precise classification in evaluating cardiovascular risk in NAFLD.

Structure Guided Design, Synthesis, and Biological Evaluation of Oxetane-Containing Indole Analogues.

The oxetane functional group offers a variety of potential advantages when incorporated within appropriate therapeutic agents as a ketone surrogate. OXi8006, a 2-aryl-3-aroyl-indole analogue, functions as a small-molecule inhibitor of tubulin polymerization that has a dual mechanism of action as both an antiproliferative agent and a tumor-selective vascular disrupting agent. Replacement of the bridging ketone moiety in OXi8006 with an oxetane functional group has expanded structure activity relationship (SAR) knowledge and provided insights regarding oxetane incorporation within this class of molecules. A new synthetic method using an oxetane-containing tertiary alcohol subjected to Lewis acid catalyzed conditions led to successful Friedel-Crafts alkylation and yielded fourteen new oxetane-containing indole-based molecules. This synthetic approach represents the first method to successfully install an oxetane ring at the 3-position of a 2-aryl-indole system. Several analogues showed potent cytotoxicity (micromolar GI50 values) against human breast cancer cell lines (MCF-7 and MDA-MB-231) and a pancreatic cancer cell line (PANC-1), although they proved to be ineffective as inhibitors of tubulin polymerization. Molecular docking studies comparing colchicine with the OXi8006-oxetane analogue 5m provided a rationale for the differential interaction of these molecules with the colchicine site on the tubulin heterodimer.

Transition patterns of metabolic dysfunction-associated fatty liver disease status in relation to arterial stiffness progression: a health check-up cohort study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new diagnostic criterion based on hepatic steatosis and metabolic dysfunction. However, a comprehensive evaluation of the association of MAFLD dynamic transitions with arterial stiffness progression has yet to be conducted. This cohort study included 8807 Chinese health check-up participants (median follow-up = 50.2 months). Participants were categorized into four groups according to MAFLD status at baseline and follow-up (none, persistent, developed and regressed). Arterial stiffness progression was assessed by the annual brachial-ankle pulse wave velocity (ba-PWV) increase and arterial stiffness incidence. Compared with the non-MAFLD group, the annual increase in ba-PWV was highest in the persistent-MAFLD group [6.75 cm/s/year, (95% CI 4.03-9.33)], followed by the developed-[6.35 cm/s/year, (95% CI 3.80-8.91)] and the regressed-[1.27 cm/s/year, (95% CI - 2.18 to 4.72)] MAFLD groups. Similarly, compared with the non-MAFLD group, the persistent-MAFLD group had a 1.31-fold increased arterial stiffness risk [OR 1.31; 95% CI 1.03-1.66]. The associations of MAFLD transition patterns with arterial stiffness incidence did not differ across any clinically specific subgroups evaluated. Furthermore, the potential effect of dynamic changes in cardiometabolic risk factors on arterial stiffness incidence among persistent-MAFLD participants was mostly driven by annual fasting glucose and triglyceride increases. In conclusion, persistent MAFLD was associated with an increased risk of arterial stiffness development. Moreover, in persistent-MAFLD subjects, elevated blood glucose and triglyceride levels might facilitate the arterial stiffness incidence.

Spectrophotometric Detection of the BRCA1 Gene via Exponential Isothermal Amplification and Hybridization Chain Reaction of Surface-Bound Probes.

In this work, we demonstrated an ultrasensitive approach with a dual-amplification strategy for DNA assay based on isothermal exponential amplification (EXPAR) and the hybridization chain reaction (HCR). In the presence of target DNA, the hairpin probe DNA (HP1) recognized and partially hybridized with the target DNA to form double-stranded structures containing the full recognition sequences for nicking endonuclease and then initiated EXPAR. Under the reaction of EXPAR, a large number of single-stranded DNA (ssDNA) was produced in the circle of nicking, polymerization, and strand displacement. The resulting ssDNA can bind to the surface-bound probe on the well of the microplate and trigger the hybridization chain reaction, resulting in the production of numerous double-stranded DNA concatamers with biotin labeling. In the presence of streptavidin-conjugated horseradish peroxidase (HRP), the amplified signal can be detected by a spectrophotometer via HRP-catalyzed substrate 3,3'5,5'-tetramethylbenzidine (TMB). This proposed dual-amplification method provides a detection limit of 74.48 aM, which also exhibits good linearity ranging from 0.1 fM to 100 pM.

A Study on the Relationship Between Consumer Motivations and Subjective Well-Being: A Latent Profile Analysis.

Consumer motivation plays an important role in their purchase decisions and well-being. Previous studies have investigated the relationship between certain consumer motivations and well-being separately. We aim to employ latent profile analysis (LPA) to explore subgroups of participants who display similar patterns of consumer multiple motivations and to examine differences in subjective well-being across these subtypes. The final group of (N = 1,023, ages 18-58) completed the Consumer Motivation scale online, assessing seven dimensions of consumer motivation. Results of LPA identified four subpopulations of participants: the enthusiastic group has high expectations in all aspects; the balanced group values each aspect of the product but has lower expectations; the rational group emphasizes aspects such as value for money, comfort, and quality; the apathetic group has no strong motivation for consumption, and they are relatively concerned with the dimensions of security, social acceptance, and stimulation. Consumers' subjective well-being (life satisfaction, positive affect, and negative affect) differed significantly across the four profiles. Specifically, scores for positive affect and life satisfaction were highest in the enthusiastic group, medium in the balanced group, and lowest in the rational and apathetic groups. Scores for negative affect were significantly higher in the enthusiastic and apathetic groups than in the rational group. These findings enable marketers to develop customized marketing strategies for different motivation profiles and contribute to helping consumers with varying motivation profiles to consciously pay attention to their well-being.

Association of umbilical cord blood miR-375 with neonatal respiratory distress syndrome and adverse neonatal outcomes in premature infants.

BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is a common respiratory disorder occurring in premature infants, and some microRNAs (miRNAs) have been demonstrated to play critical roles in NRDS progression. This study aimed to measure relative expression of miR-375 in infants with NRDS, and further evaluate the clinical significance of miR-375 in predicting the onset and clinical prognosis of NRDS in infants. METHODS: This study collected umbilical cord blood from 180 premature neonates, including 90 neonates with NRDS and 90 non-NRDS neonates. Quantitative real-time PCR was used to detect relative expression level of miR-375. The diagnostic value of miR-375 in screening NRDS neonates from control neonates and its predictive accuracy for clinical prognosis were evaluated by receiver operating characteristic analysis. The relationship of miR-475 with disease onset and clinical outcomes in NRDS infants was assessed by univariate and multivariate logistic regression analyses. RESULTS: Relative miR-375 expression was upregulated in NRDS neonates, and high levels of miR-375 were observed in NRDS grade III-IV cases compared to those early-stage neonates. miR-375 had relatively high diagnostic accuracy to screen NRDS neonates and was independently associated with NRDS onset in infants. Moreover, relative miR-375 expression was upregulated in NRDS neonates with poor prognosis and could independently predict the clinical outcomes of NRDS neonates with considerable predictive accuracy. CONCLUSION: Umbilical cord serum miR-375 is elevated and associated with NRDS onset and clinical outcomes in NRDS neonates. Thus, miR-375 may serve as a biomarker for the diagnosis and prognosis of infants with NRDS.

Universal point-of-care detection of proteins based on proximity hybridization-mediated isothermal exponential amplification.

We have developed a point-of-care (POC) lateral flow biosensor (LFB) for universal protein detection based on a proximity hybridization-mediated protein-to-DNA signal transducer, isothermal exponential amplification (EXPAR) and catalytic hairpin assembly (CHA) with high sensitivity and specificity. In this assay, a protein signal transducer was employed to convert the input protein to the output DNA signal. Antibody conjugated DNA1 was firstly hybridized with the output DNA (DNA3). The binding of antibody conjugated DNA1 and DNA2 to the same protein was able to increase the local concentrations, resulting in strand displacement between DNA3 and DNA2. DNA3 with nicking endonuclease recognition sequences at the 5' end then hybridized with hairpin probe 1 to mediate EXPAR in the presence of nicking endonuclease and polymerase. A large number of single strand DNA were produced in the circle of nicking, polymerization and strand displacement. The resulting ssDNA products were further amplified by CHA to generate double-stranded DNA products. The double-stranded DNA products were detected with a lateral flow biosensor within 5 min. This proposed assay has very high sensitivity and selectivity with a dynamic response ranging from 1 fM to 100 nM, and the detection limit was 0.74 fM. This work provides a universal and simple method for protein detection.

The small molecule chemical compound cinobufotalin attenuates resistance to DDP by inducing ENKUR expression to suppress MYH9-mediated c-Myc deubiquitination in lung adenocarcinoma.

The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to ß-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.

Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing's syndrome.

Objective: Chronic hypercortisolism leads to a phenotype resembling metabolic syndrome. We aimed to investigate the association between gut microbiota and metabolic abnormalities in endogenous hypercortisolism (Cushing's syndrome). Methods: A total of 23 patients with Cushing's syndrome (18 female and 5 men, aged 47.24 ± 12.99 years) and 30 age-, sex-and BMI-matched healthy controls (18 female and 12 men, aged 45.03 ± 6.69 years) were consecutively recruited. Differences in gut microbiota and plasma short-chain fatty acid (SCFAs) concentrations between the Cushing's syndrome patients and controls were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Results: Compared to the controls, the Simpson and Pielou indices of α diversity were dramatically decreased in Cushing's syndrome (P < 0.05). The gut microbiota community structure differed significantly between Cushing's syndrome patients and controls. Compared to controls, the bacterial communities of the Cushing's syndrome patients were enriched in Proteobacteria and Escherichia-Shigella, and depleted in Firmicutes, including Agathobacter, Blautia, Anaerostipes, Eubacterium_eligens_group, and Lachnospira. Spearman analysis demonstrated that HbA1c, SBP, DBP, and cortisol levels were significantly positively correlated with Proteobacteria and Escherichia-Shigella, whereas negatively correlated with Agathobacter, Blautia, Anaerostipes, Eubacterium_hallii_group, and Lachnospira, etc. Cushing's syndrome patients also had a lower propionic acid concentration (0.151±0.054 vs. 0.205±0.032 µg/mL, P=0.039) than controls. Furthermore, the level of propionic acid was negatively correlated with systolic pressure and cortisol levels (P<0.05). Conclusion: Gut microbiota dysbiosis and decreased propionic acid levels were observed in patients with Cushing's, suggesting that the gut microbiota may be a potential therapeutic intervention target to improve hypercortisolism-related metabolic abnormalities.

[Therapeutic effects of "kidney three-needle" therapy plus fire needling therapy in treatment of post-stroke urinary incontinence].

OBJECTIVE: To observe the efficacy of "kidney three-needle" therapy［Qugu（CV2） and 1 cun to the left and right of CV2］ and the pricking technique of fire needing therapy on urinary frequency and maximal bladder volume in potients with post-stroke urinary incontinence. METHODS: A total of 60 patients with post-stroke urinary incontinence were collected according to the inclusion and exclusion criteria and were randomized into an observation group (30 cases) and a control group (30 cases). On the base of the routine medication and rehabilitation treatment, acupuncture was applied to the general acupoints for motor impairment and speech disorder in the two groups. Additionally, the combination of "kidney three-needle" therapy and the pricking technique of fire needling therapy was used for urinary incontinence in the observation group and the common acupuncture was applied in the control group. Needles were retained for 30 min and acupuncture was provided once daily, 5 days a weeks, 2 weeks of treatment as one course. Both groups were treated for 3 courses. Before and after treatment, the rank of daytime urinary frequency was compared in the patients of the two groups. Ultrasound B was adopted to determine the maximal bladder volume. The total effective rate was compared between the two groups. RESULTS: After treatment, the rank of daytime urinary frequency all reduced significantly as compared with that before treatment in the patients of the two groups (P<0.01)， and the observation group was lower than the control group (P<0.05). After the treatment, the maximal bladder volume increased significantly as compared with that before treatment in the self-comparison of each group (P<0.01) and the volume in the observation group was significantly higher than that in the control group (P<0.01). The total effective rate was 93.3% (28/30) in the observation group and was 66.7% (20/30) in the control group. The total effective rate in the observation group was higher obviously than that in the control group (P<0.05). CONCLUSION: The combination of "kidney three-needle" therapy and the pricking technique of fire needling therapy significantly reduces the rank of daytime urinary frequency and increases maximal bladder volume in the patients with post-stroke urinary incontinence. The therapeutic effect of such combined acupuncture treatment is better than the common acupuncture therapy.

Fabrication of Few-Layered Porous Graphite for Removing Fluorosurfactant from Aqueous Solution.

Due to the persistence, toxicity, and widespread occurrence of fluorosurfactants in the blood of general population, it is very important to develop recyclable and highly effective adsorbent material for their removal from aqueous solution. Herein, a new type of few-layered porous graphite (FPG) was fabricated as an adsorbent, and the adsorption characteristics of FPG toward potassium perfluorobutane sulfonate (PFBS), potassium perfluorohexane sulfonate (PFHxS), and potassium perfluorooctane sulfonate (PFOS) in environmental cleanup were evaluated under laboratory condition. The results indicated that the as-prepared FPG had sorption capacities of 1.22, 1.52, and 2.48 mmol g-1 for PFBS, PFHxS, and PFOS, respectively, which were the highest adsorption values of PFHxS, PFBS, and PFOS on different kinds of today's carbon materials. The efficiency of FPG remained almost constant during the first five cycles of the adsorption-desorption process after heating. The outstanding adsorption performance of FPG was attributed to its unique physical properties, such as high porosity, high hydrophobicity, low density, and excellent heat stability. The findings presented herein indicated that FPG could serve as a promising adsorbent for the removal of fluorosurfactant in waste water.

A systematic review of clinical studies on electrical stimulation therapy for patients with neurogenic bowel dysfunction after spinal cord injury.

BACKGROUND: This study aimed to perform a systematic literature review of the clinical trial evidence on electrical stimulation for the treatment of neurogenic bowel dysfunction (NBD) after spinal cord injury (SCI). METHODS: Systematic electronic searches were carried out in the PubMed/Medline, EMBASE, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure databases, along with the reference lists in the include studies. Studies were eligible for inclusion if they adopted a controlled clinical design based on human population, the patients suffered from spinal cord injury, the main outcomes were the disorders of bowel function and the intervention was electrical stimulation. Also, the language was limited to English and Chinese. RESULTS: Eleven studies were included in this systematic review, comprising transcutaneous electrical stimulation, transrectal bowel stimulation, sacral nerve stimulation, intravesical electrical stimulation, etc. Of the 11 studies, 3 were randomized controlled trials, 8 were controlled before-and-after trials. The quality of the included studies was moderate bias risk. Most studies revealed that the electrical stimulation was beneficial for the patient with NBD after SCI. CONCLUSIONS: Only 11 small clinical studies with 298 participants have evaluated the efficacy of electrical stimulation for NBD after SCI. Although some studies showed electrical stimulation was benefit for the patient with NBD after SCI, there was currently not enough evidence to support the use of electrical stimulation could improve the clinical symptoms of those patients. Thus, well-designed randomized controlled trials with larger patient population are warranted to establish its benefit in clinical practice in the future.