Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.

Establishment and Reliability Evaluation of Prognostic Models in Diabetic Foot.

Purpose: To study the risk factors affecting amputation and survival in patients with diabetic foot (DF) and to construct a predictive model using the machine learning technique for DF foot amputation and survival and evaluate its effectiveness. Materials and Methods: A total of 200 patients with DF hospitalized in the First Affiliated Hospital of Shantou University Medical College in China were selected via cluster analysis screening, Kaplan-Meier survival calculation, amputation rate and Cox proportional hazards model investigation of risk factors associated with amputation and death. In addition, we constructed various models, including Cox proportional hazards regression analysis, the deep learning method convolution neural network (CNN) model, backpropagation (BP) neural network model, and backpropagation neural network prediction model after optimizing the genetic algorithm. The accuracy of the 4 prediction models for survival and amputation was assessed, and we evaluated the reliability of these computational models based on the size of the area under the ROC curve (AUC), sensitivity and specificity. Results: We found that the 1-year survival rate in patients with DF was 88.5%, and the 1-year amputation rate was 12.5%. Wagner's Classification of Diabetic Foot Ulcers grade, ankle-brachial index (ABI), low-density lipoprotein (LDL), and percutaneous oxygen partial pressure (TcPO2) were independent risk factors for amputation in patients with DF, while cerebrovascular disease, Sudoscan sweat gland function score, glycated hemoglobin (HbA1c) and peripheral artery disease (PAD) were independent risk factors for death in patients with DF. In addition, our results showed that in the case of amputation, the COX regression predictive model revealed an AUC of 0.788, sensitivity of 74.1% and specificity of 83.6%. The BP neural network predictive model identified an AUC of 0.874, sensitivity of 87.0% and specificity of 87.7%. An AUC of 0.909, sensitivity of 90.7% and specificity of 91.1% were found after optimizing the BP neural network prediction model via genetic algorithm. In the deep learning CNN model, the AUC, sensitivity and specificity were 0.939, 92.6%, and 95.2%, respectively. In the analysis of risk factors for death, the COX regression predictive model identified the AUC, sensitivity and specificity as 0.800, 74.1% and 85.9%, respectively. The BP neural network predictive model revealed an AUC, sensitivity and specificity of 0.937, 93.1% and 94.4%, respectively. Genetic algorithm-based optimization of the BP neural network predictive model identified an AUC, sensitivity and specificity of 0.932, 91.4% and 95.1%, respectively. The deep learning CNN model found the AUC, sensitivity and specificity to be 0.861, 82.8% and 89.4%, respectively. Conclusion: To identify risk factors for death, the BP neural network predictive model and genetic algorithm-based optimizing BP neural network predictive model have higher sensitivity and specificity than the deep learning method CNN predictive model and COX regression analysis.

A chromosome-scale Rhubarb (Rheum tanguticum) genome assembly provides insights into the evolution of anthraquinone biosynthesis.

Rhubarb is the collective name for various perennial plants from the genus Rheum L. and the Polygonaceae family. They are one of the most ancient, commonly used, and important herbs in traditional Chinese medicine. Rhubarb is a major source of anthraquinones, but how they are synthesized remains largely unknown. Here, we generate a genome sequence assembly of one important medicinal rhubarb R. tanguticum at the chromosome level, with 2.76 Gb assembled into 11 chromosomes. The genome is shaped by two recent whole-genome duplication events and recent bursts of retrotransposons. Metabolic analyses show that the major anthraquinones are mainly synthesized in its roots. Transcriptomic analysis reveals a co-expression module with a high correlation to anthraquinone biosynthesis that includes key chalcone synthase genes. One CHS, four CYP450 and two BGL genes involved in secondary metabolism show significantly upregulated expression levels in roots compared with other tissues and clustered in the co-expression module, which implies that they may also act as candidate genes for anthraquinone biosynthesis. This study provides valuable insights into the genetic bases of anthraquinone biosynthesis that will facilitate improved breeding practices and agronomic properties for rhubarb in the future.

Feasibility of anterior lobe-preserving transurethral enucleation and resection of prostate on improving urinary incontinence in patients with benign prostatic hyperplasia: A retrospective cohort study.

Transurethral enucleation and resection of prostate (TUERP), as one of the conventional surgical methods for patients with benign prostatic hyperplasia (BPH), usually resulted in pseudo urinary incontinence after surgery. The present study was thereby conducted to evaluate the feasibility of anterior lobe-preserving transurethral enucleation and resection of prostate (ALP-TUERP) on reducing the incidence rate of urinary incontinence after surgery in patients with BPH. Patients diagnosed with BPH underwent surgical treatment were enrolled in the present study within the inclusion criteria. Characteristics including age, prostate volume (before surgery), PSA level, maximum free flow rate, international prostate symptom score, and quality of life were reviewed and compared between the groups of ALP-TUERP and TUERP. Incidence rate of urinary incontinence on 24 hours, 3 days, 7 days, and 14 days after catheter drawing was deemed as main outcome, which was compared between the groups. In addition, secondary outcomes including surgery time, difference value of hemoglobin before and after surgery (∆Hemoglobin), catheter retaining time, catheter flushing time, and incidence rate of recurrent bleeding were also compared between the groups. There were 81 patients included in the present study within the inclusion criteria. There was no statistical difference on the baseline characteristics including age, prostate volume (before surgery), PSA level, maximum free flow rate (before surgery), international prostate symptom score, or quality of life between the 2 groups. Statistical superiority was observed on the incidence rate of urinary incontinence on day 1 (χ2 = 9.375, P = .002), and day 3 (χ2 = 4.046, P = .044) in the group ALP-TUERP, when comparing to group TUERP. However, the difference was not observed anymore after 7 days after catheter drawing (P = .241 for day 7, P = .494 for day 14) between them. In addition, no statistical differences were observed on surgery time, difference value of hemoglobin before and after surgery (∆Hemoglobin), catheter retaining time, or catheter flushing time between the group ALP-TUERP and TUERP (all P > .05). Results of the present study demonstrated a potentially statistical superiority of ALP-TUERP on the reduction of incidence rate of urinary incontinence comparing to conventionally TUERP.

[Identification, biological characterization, and fungicide screening of pathogens causing leaf spot of Belamcanda chinensis].

The leaf spot of Belamcanda chinensis often appears in May to June and spreads rapidly during the flowering stage(July to September) in the cultivation fields, seriously affecting the yield and quality of B. chinensis. To identify and characterize the pathogens of the leaf spot, we isolated two species of Alternaria, identified them according to Koch's postulates, and tested their pathogenicity and biological characteristics. Furthermore, we determined the inhibitory effects of 6 chemical fungicides, 1 plant fungicide, and 3 microbial fungicides on the pathogens by using mycelial growth rate and plate confrontation method to select the appropriate control agents. The results showed that the two pathogens causing B. chinensis leaf spot were Alternaria tenuissima and A. alternata. The conidia of A. tenuissima often formed long chains with no or a few branches, while those of A. alternata often formed short branched chains. The optimum growth temperature of both A. tenuissima and A. alternata was 25 ℃. The two pathogens grew well in alkaline environment. The indoor fungicide screening experiments showed that 40% flusilazole had good inhibitory effects on the two pathogens, with the EC_(50) values of 12.42 mg·L~(-1) and 12.78 mg·L~(-1) for A. tenuissima and A. alternata, respectively. The results of this study provide a theoretical basis for the subsequent theoretical research and field control of B. chinensis leaf spot.

[Identification, biological characteristics, and control of pathogen causing southern blight of Pinellia ternata].

In summer in 2020, Pinellia ternata in many planting areas in Hubei suffered from serious southern blight, as manifested by the yellowing and wilted leaves and rotten tubers. This study aims to identify the pathogen, clarify the biological characteristics of the pathogen, and screen fungicides. To be specific, the pathogen was isolated, purified, and identified, and the pathogenicity was detected according to the Koch's postulates. Moreover, the biological characteristics of the pathogen were analyzed. Furthermore, PDA plates and seedlings were used to determine the most effective fungicides. The results showed that the mycelia of the pathogen were white and villous with silk luster, which produced a large number of white to black brown sclerotia. The pathogen was identified as Athelia rolfsii by morphological observation and molecular identification based on LSU and TEF gene sequences. The optimum growth conditions for A. rolfsii were 30 ℃ and pH 5-8, and the optimum conditions for the germination of sclerotia were 25 ℃ and pH 7-9. Bacillus subtilis, difenoconazole, and flusilazole were identified as effective fungicides with PDA, and their half maximal effective concentration(EC_(50)) was all less than 5 mg·L~(-1). The effective fungicides screened with the seedlings were hymexazol and difenoconazole. Based on the screening experiments, difenoconazole can be used as the main agent for the prevention and treatment of southern blight.

Variation in Sediment Available-Phosphorus in Dianchi Lake and Its Impacts on Algal Growth.

Sediment phosphorus (P) is an active component of the P cycle in lakes and its availability and movement could play an important role in eutrophication. Sediments from different depths in five representative sites of Dianchi Lake China, i.e., Haigeng, Dounan, Luojiacun, Xinjie, and Kunyang, were studied from January to December to evaluate the spatial and temporal dynamics in available-P and soluble-P and their impacts on algal growth. The results showed that the average sediment available-P and soluble-P were 41.2 mg kg-1 and 0.27 mg kg-1, respectively. Sediment available-P and soluble-P concentrations varied significantly among seasons, sites, and layers, with the following order: surface (0-5 cm) > middle (5-10 cm) > bottom (10-20 cm). The release and transformation characteristics of available-P and soluble-P at the sediment-water interface varied among sites. The Haigeng site, with the most severe algae blooms, had significantly higher average available-P and soluble-P in sediment than other sites. This indicated that phosphorus release and availability were associated with algal growth, and that the sediment surface (0-5 cm) is an important internal source that supports algal growth in Dianchi Lake.

Post-Diagnosis Vitamin D Supplement Use and Survival among Cancer Patients: A Meta-Analysis.

Vitamin D administered pre-diagnostically has been shown to reduce mortality. Emerging evidence suggests a role of post-diagnosis vitamin D supplement intake for survival among cancer patients. Thus, we conducted a meta-analysis to evaluate the relationship. PubMed and Embase were searched for relevant observational cohort studies and randomized trials published through April 2022. Summary relative risk (SRR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The SRR for post-diagnosis vitamin D supplement use vs. non-use, pooling cohort studies and randomized trials, was 0.87 (95% CI, 0.78-0.98; p = 0.02; I2 = 0%) for overall survival, 0.81 (95% CI, 0.62-1.06; p = 0.12; I2 = 51%) for progression-free survival, 0.86 (95% CI, 0.72-1.03; p = 0.10; I2 = 0%) for cancer-specific survival, and 0.86 (95% CI, 0.64-1.14; p = 0.29; I2 = 0%) for relapse. Albeit not significantly heterogeneous by variables tested, a significant inverse association was limited to cohort studies and supplement use during cancer treatment for overall survival, and to studies with ≤3 years of follow-up for progression-free survival. Post-diagnosis vitamin D supplement use was associated with improved overall survival, but not progression-free or cancer-specific survival or relapse. Our findings require confirmation, as randomized trial evidence was insufficient to establish cause-and-effect relationships.

Current Research on Complementary and Alternative Medicine in the Treatment of Premature Ovarian Failure: An Update Review.

Complementary and alternative medicine (CAM) encompasses a wide range of different non-mainstream therapies that have been increasingly used for the treatment or adjunct treatment of various ailments, with premature ovarian failure (POF) being one of the most common conditions treated with CAM. This review updates the progress of CAM in the treatment of POF, and we focus specifically on reviewing the evidence for the efficacy and mechanisms of a range of CAM treatments in POF, including single herbal medicines and their active ingredients, compound Chinese medicines, acupuncture and moxibustion, psychotherapy, exercise, vitamins, massage, and dietary supplements. According to the literature, CAM is very helpful for improving POF symptoms, and we hope to provide some instructive suggestions for clinical treatment and experimental research in the future. However, more clinical trials are needed to prove the safety of CAM.

Oily sludge treatment in subcritical and supercritical water: A review.

Oily sludge, an inherent byproduct of the petroleum industry, presents dual characteristics of petroleum resources and hazardous waste. Owing to the unique physicochemical properties of sub-/supercritical water, hydrothermal technologies have been increasingly used for oily sludge treatment. This review is the first to focus on oily sludge treatment using sub-/supercritical water. Eight hydrothermal technologies used for different purposes are summarized herein: pressurized hot water extraction (PHWE) for hydrocarbon separation, thermal hydrolysis (TH) for dewaterability improvement, hydrothermal carbonization (HTC) for hydrochar production, wet air oxidation (WAO) for biodegradability improvement, hydrothermal liquefaction (HTL) for bio-oil production, supercritical water upgrading (SCWU) for light oil production, supercritical water oxidation (SCWO) for complete degradation, and supercritical water gasification (SCWG) for H2-rich syngas production. Moreover, a general reaction pathway for sub-/supercritical water treatment of oily sludge is presented, with a particular focus on the chemical mechanism at temperatures above 350 °C. Lastly, two reaction maps are included to illustrate the reaction pathways of two groups of identifiable model compounds in oily sludge: aliphatic and aromatic hydrocarbons. This review provides detailed information that can promote a better understanding of various hydrothermal technologies, a guideline for selecting the suitable hydrothermal process for a particular oily sludge, and recommendations for further researches.

Programmed Stimuli-Responsive Carbon Dot-Nanogel Hybrids for Imaging-Guided Enhanced Tumor Phototherapy.

For harmonizing the contradiction of nanotheranostic agents between enhanced tumor accumulation and penetration, efficient cell internalization and fast elimination are key tactics for promoting their clinical applications. Herein, programmed stimuli-responsive poly(N-isopropylacrylamide)-carbon dot (PNIPAM-CD) hybrid nanogels are designed to address the abovementioned conflicts. The enlarged particle size of PNIPAM-CDs enables one to effectively improve their accumulation at tumor sites. Once the hybrid nanogels are docked in tumors and exposed to deep-red-light (660 nm) irradiation, heat and reactive oxygen species (ROS) are generated from the CDs, consequently activating photothermal therapy (PTT) and photodynamic therapy (PDT) effects and meanwhile inducing partial degradation of PNIPAM-CDs for deep tissue penetration. Further, enhanced cellular internalization of the functional components can be achieved owing to the pH-responsive charge reversal and temperature-dependent hydrophilic/hydrophobic conversion characteristics of PNIPAM-CDs. Finally, the overexpressed glutathione (GSH) in tumor cells would trigger further cleavage of the partially degraded hybrid nanogels, which is beneficial for their rapid clearance from the body. This work not only proposed a novel strategy to fabricate nanotheranostic agents using just a single functional component (i.e., the versatile CDs) to simplify the preparation process but also achieved effective delivery of agents into tumor cells by overcoming the multiple biological barriers to enhance therapeutic efficacy and decrease side effects.

Impact of growth hormone supplementation on improving oocyte competence in unexplained poor embryonic development patients of various ages.

OBJECTIVES: To evaluate the effectiveness of Growth hormone (GH) co-treatment during in vitro fertilization (IVF) cycles in women of different ages who manifest unexplained poor embryonic development. METHOD: This cohort study included a total of 2647 patients with unexplained poor embryonic development in their previous IVF procedures: 872 women received GH co-treatment and 1775 untreated women served as a control group. Patients were divided into 6 groups according to treatment and stratified by age (<35 years of age, A-GH group and A-control group; 35-40 years, B-GH group and B-control group; and ≥40 years, C-GH group and C-control group). The primary outcome was the oocyte-cleavage rate and the clinical pregnancy rate (CPR). RESULTS: The oocyte-cleavage rates among the three age groups were significantly higher in the GH group compared to the same-aged control group. In both group A and group B, there was no significant difference in clinical pregnancy rate between the GH group and controls. However, in patients ≥40 years of age, the clinical pregnancy rate in the GH group was significantly higher than in the control group (31.8% vs. 13.7%, p = 0.019). In the three age groups, there was no significant difference in the live birth rate between the GH group and controls. In the multivariate logistic regression analysis model, in both group A and group B, the number of cleaved embryos was independent predictors for CPR (OR = 1.464, 95% CI: 1.311-1.634; respectively, OR = 1.336, 95% CI: 1.126-1.586); Besides, in both group B and group C, age was independent predictors for CPR (OR = 0.657, 95%CI: 0.555-0.778; respectively, OR = 0.622, 95%CI: 0.391-0.989). However, only in group C, supplementation GH increased CPR as compared with not supplementation GH (OR = 2.339, 95%CI: 1.182-6.670). CONCLUSIONS: For patients with unexplained poor embryonic development, supplementation with GH increased the oocyte-cleavage rates in all three age groups, and the clinical pregnancy rate gradually improved commensurate with increasing age. There was no difference in the clinical pregnancy rate in group A and group B, but group C improved significantly. Therefore, compared with patients under 40 years of age, patients ≥40 may benefit more from GH supplementation.

Quinones contained in wastewater as redox mediators for the synergistic removal of azo dye in microbial fuel cells.

The present paper aimed to investigate the roles of quinones contained in wastewater and the enhanced effects on microbial fuel cells (MFCs) under different redox conditions. The feasibility of using wastewater rich in quinones to act as co-substrate and redox mediators (RMs) library to strengthen the synergistic removal of azo dye in MFCs was evaluated. The results demonstrated that quinones achieved enhanced effects on electricity generation and COD removal of MFC better at higher current intensity. The addition of pure quinone decreased electron transfer resistance (Rct) of MFCs from 4.76 Ω to 2.13 Ω under 1000 Ω resistance and 1.16 Ω-0.75 Ω under 50 Ω resistance. Meanwhile, higher coulombic efficiency was achieved. Compared with sodium acetate, using quinone-rich traditional Chinese medicine (TCM) wastewater as the co-substrate enhanced the synergistic removal of reactive red 2 (RR2) in MFCs from 79.58% to 92.45% during 24 h. RR2 was also degraded more thoroughly due to the accelerated electron transfer process mediated by RMs. Microbial community analysis demonstrated that the presence of quinone in TCM wastewater can enrich different exoelectrogens under varied redox conditions and thus influenced the enhanced effects on MFC. Metagenomic functional prediction results further indicated that the abundance of functional genes involved in carbohydrate metabolism, membrane transport metabolism, biofilm formation, and stress tolerance increased significantly in presence of RMs. Redundancy analyses revealed that RMs addition was the more important factor driving the variation of the microorganism community. This study revealed the potential effect of quinones as redox mediators on the bioelectrochemical system for pollutants removal.

Effect of Er-Xian decoction on autoimmune premature ovarian failure in mice.

OBJECTIVE: To investigate the therapeutic effect of Er-Xian decoction on the autoimmune premature ovarian failure (POF) in mice, and its regulatory mechanisms. METHODS: Female BALB mice were treated with a single intraperitoneal injection of zona pellucida 3 (ZP3). One week later, mice received low (5 g/kg), moderate (10 g/kg) and high (20g/kg) doses of EXD by gastrogavage once daily for 90 d. Premarin (0.03 mg/kg) served as the positive control group. Serum levels of estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by enzyme-linked immunosorbent assay, lymphocyte subtypes were analyzed, and follicular structure differences were observed by hematoxylin and eosin staining. The main mechanisms of POF was investigated by immunohistochemical analysis. RESULTS: Serum E2 levels in POF model mice were decreased, whereas FSH and LH levels were dramatically increased. Serum levels of LH and FSH were reduced in POF model mice treated with EXD (moderate and high doses) and premarin, while serum level of E2 were increased after POF model mice had been treated with EXD and premarin. The CD3+ T, CD4+ T, CD4+ T/CD8+ T ratio of mice in the positive control group and high and medium dose groups of EXD increased (P < 0.05), and the number of CD8 + T cells decreased significantly (P < 0.05) when compared with the model group. Bone morphogenetic protein 15 (BMP15) and Akt were repressed in autoimmune POF model mice, whereas high expression was observed in control mice and those treated with EXD (moderate and high doses) and premarin. CONCLUSION: EXD is effective in treating ZP3-induced POF in mice and increased expression of BMP-15, and Akt is represented in the mechanism accounting for this therapeutic effect.

[Identification,biological characteristics and fungicide screening of pathogen of southern blight in Cynanchum stauntonii].

During the high-temperature and rainy season from June to October in 2017-2019,serious southern blight broke out in the Cynanchum stauntonii planting area in Tuanfeng county,Hubei province,which had a great impact on the yield and quality of medicinal materials. In this study,the pathogen of C. stauntonii was isolated,purified,and identified,and the pathogenicity was tested according to Koch's postulates. Meanwhile,the biological characteristics of the pathogen were analyzed. On this basis,the effective fungicides were screened in laboratory. Finally,the pathogen( BQ-1) was identified as Athelia rolfsii( Deuteromycotina,Basidiomycota,anamorph: Sclerotium rolfsii). The optimum growth conditions for BQ-1 were 25-30 ℃,p H 5-8,and alternating light and dark.The effective chemical fungicides were lime-sulphur-synthelic-solution( LSSS) and flusilazole,and the effective botanical fungicide was osthole. BQ-1 was highly homologous to the pathogen HS-1 of peanut southern blight,with the similarity of 18 S r DNA and TEF sequences at 99. 09%. The southern blight in C. stauntonii might be resulted from that in peanut. In the production of C. stauntonii,the following measures should be taken: avoiding rotation or neighboring with peanut,draining water from June to October to reduce humidity,and reasonably applying fungicides.

L-arginine supplementation to mitigate cardiovascular effects of walking outside in the context of traffic-related air pollution in participants with elevated blood pressure: A randomized, double-blind, placebo-controlled trial.

Exposure to traffic-related air pollution (TRAP) increases blood pressure (BP) and cardiovascular morbidity and mortality. We aimed to evaluate the potential efficacy of L-arginine supplementation in mitigating the adverse cardiovascular effects of adults with elevated BP walking outside under TRAP using a randomized, double-blind and placebo-controlled trial. 118 adults with elevated BP were recruited and were randomly assigned to either the placebo group or the intervention group with 9 g/day L-arginine supplementation for 2 weeks. On the 14th day, paired participants from the two groups walked along a traffic road for 2 h. Resting BP, L-arginine-nitric oxide metabolites and inflammatory biomarkers were measured before, during and after the 2 h exposure scenario, and ambulatory BP and Holter were measured during the 2 h outdoor walk. Participants in the intervention group had significantly elevated plasma L-arginine levels compared to the placebo group after supplementation. The two groups had similar exposures to traffic-related air pollutants. However, participants in the intervention group showed significant reductions of 5.3 mmHg (95% CI: -9.9, -0.7) in resting systolic BP (SBP), 4.3 mmHg (95% CI: -7.2, -1.3) in resting diastolic BP (DBP) and 4.6 mmHg (95% CI: -7.9, -1.3) in resting mean arterial pressure (MAP) at 30 min after the 2 h outdoor walk compared with the placebo group. There were also significant decreases in ambulatory SBP, DBP and MAP (7.5-9.9 mmHg, 5.3-7.6 mmHg and 4.7-7.9 mmHg, respectively) during the walk in the intervention group compared with the placebo group. There were no substantial changes in ST-segment level, L-arginine-NO metabolites and inflammatory biomarkers, and no significant associations were found between specific traffic-related air pollutants and cardiovascular health indicators. Specifically, our study shows that oral L-arginine supplementation was safe and well-tolerated, and could improve BP levels in adults with elevated BP during outside walk under TRAP.

Effects of short-term personal exposure to air pollution on platelet mitochondrial DNA methylation levels and the potential mitigation by L-arginine supplementation.

The potential effect of short-term exposure to air pollution on mitochondrial DNA (mtDNA) methylation remains to be explored. This study adopted an experimental exposure protocol nested with an intervention study on L-arginine (L-Arg) supplementation among 118 participants. Participants walked along a traffic road for 2 hours in the last day of a 14-day intervention to investigate the effects of short-term personal exposure to air pollution on platelet mtDNA methylation and the possible modifying effects of L-Arg supplementation. Results showed that short-term personal exposure to air pollutants was associated with hypomethylation in platelet mtDNA in 110 participants who completed the study protocol. Specifically, 2-h fine particulate matter (PM2.5) exposure during the outdoor walk was significantly associated with hypomethylation in mt12sRNA; 24-h PM2.5 and black carbon (BC) exposures from the start of the walk till next morning were both significantly associated with hypomethylation in the D-loop region; 24-h BC exposure was also significantly associated with hypomethylation in ATP8_P1. Supplementation with L-Arg could mitigate the air pollution effects on platelet mtDNA methylation, especially the D-loop region. These findings suggest that platelet mtDNA methylation may be sensitive effect biomarker for short-term exposure to air pollution and may help deepen the understanding of the epigenetic mechanisms of adverse cardiovascular effects of air pollution.

[Identification and biological characteristics of southern blight causing root rot on three medicine plants of Iridaceae in Dabie Mountains].

In order to identify the species and biological characteristics of the pathogen of southern blight from three kinds of Chinese medicine of Iridaceae(Belamcanda chinensis, Iris tectorum and I. japonica) in Dabie Mountains, the isolation, identification, pathogenicity and biological characteristics of the pathogens were studied according to Koch's postulates. In addition, 9 chemical fungicides, 3 botanical fungicides and 5 microbial fungicides were used to evaluate their inhibition to the isolates in vitro. The results showed that all the strains(SG-Q, YW-Q, and HDH-Q) isolated and purified from the diseased plants of B. chinensis, I. tectorum and I. japonica, respectively, were identified as Sclerotium rolfsii through morphological observation and sequence aligement of 18 S rDNA, rDNA-ITS and TEF. Field observations showed that the intensity of the disease incidence of three Iridaceae plants was B. chinensis>I. japonica> I. tectorum, and the pathogenicity of the strains was SG-Q>YW-Q>HDH-Q. For biological characteristics, SG-Q strain was suitable for growth under the 12 h light/12 h dark cycle, with the optimal growth temperature of 30 ℃ and pH of 5. Among the 9 tested chemical fungicides, 29% lime sulphure and 10% flusilazole had stronger inhibitory effect on mycelia growth of SG-Q. For 3 botanical fungicides, 1% osthol, 20% eugenol and 0.5% berberine could effectively inhibt the mycelial growth of SG-Q and cause the morphological variation of the pathogen. For 5 microbial fungicides, Trichoderma harzianum and Bacillus subtilis had better inhibition on the mycelium growth of SG-Q.

Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA.

The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.

1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel.

Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that it decreased the cell survival and colony formation of MDA-MB-231 and MDA-MB-468 cells. An increase in mitochondrial reactive oxygen species was also observed in TNBC cells exposed to KY-20-22. Furthermore, KY-20-22 decreased epithelial-mesenchymal formation (EMT) as evidenced by the modulation of the EMT markers E-cadherin and N-cadherin. Based on the fact that KY-20-22 regulates interleukin-6, a cytokine involved in chemotherapy resistance, we combined it with paclitaxel and found that it synergistically induced anti-proliferative action in TNBC cells. The results from this study suggested that 1-chromonyl-5-imidazolylpentadienone KY-20-22 exhibited anti-cancer action in MDA-MB-231 and MDA-MB-468 cells. Future studies are required to evaluate the anti-cancer ability and bioavailability of KY-20-22 in the TNBC animal model.