Sustainability assessment on paddy-upland crop rotations by carbon, nitrogen and water footprint integrated analysis: A field scale investigation.

Nutrients of carbon, nitrogen and water of farmland ecosystem are essential foundation to guarantee crop production, but also environmental flows associated greenhouse gas (GHG), reactive nitrogen (Nr) releases, and water consumption. Their flow characteristics serve as a crucial starting point for creating efficient management practices and mitigation measures. Therefore, the objectives of this study are to quantify the carbon footprint (CF), nitrogen footprint (NF), water footprint (WF), and comprehensive environmental footprint (ComF) of six paddy-upland rotation systems, including fallow-paddy rice (FA-PR), Chinese milk vetch-paddy rice (CMV-PR), wheat-paddy rice (WH-PR), rapeseed-paddy rice (RA-PR), green forage wheat-paddy rice (WF-PR), and vicia faba bean-paddy rice (FB-PR), as well as to analysis their relationships and define driving factors. Results showed that the lowest area-scaled CF of 3.74 t CO2-eq ha-1 were observed in the CMV-PR rotation, which were 41% lower than that for WH-PR (the highest CF, 9.13 t CO2-eq ha-1) when soil carbon change was taken into account. It is of importance that soil carbon sequestration in CMV-PR rotation could offset up to around 57% of its CF, while the WH-PR rotation only offset 25%. The RA-PR rotation had the highest area-scaled NF and WF, which was 1.8 and 1.9 times greater than those of the lowest rotation in FA-PR. In terms of comprehensive environmental effects, the six rotation systems showed the order of FA-PR < CMV-PR < FB-PR < RA-PR < WF-PR < WH-PR, with NH3 volatilization accounting 60.7%-66.7% and blue-green WF for 17.5%-26.6% of the total. Therefore, priority should be given to optimizing N fertilizer application and water consumption for paddy-upland rotation systems. The study also suggested that appropriate inter-annual adjustment of rotation system could contribute to achieving GHG mitigations and Nr losses.

Impacts of Chemical and Organic Fertilizers on the Bacterial Communities, Sulfonamides and Sulfonamide Resistance Genes in Paddy Soil Under Rice-Wheat Rotation.

The responses of sulfonamides, sulfonamide-resistance genes (sul) and soil bacterial communities to different fertilization regimes were investigated by performing a field experiment using paddy soil with no fertilizer applied, chemical fertilizer applied, organic fertilizer applied, and combination of chemical and organic fertilizer applied. Applying organic fertilizer increased the bacterial community diversity and affected the bacterial community composition. Eutrophic bacteria (Bacteroidetes, Gemmatimonadetes, and Proteobacteria) were significantly enriched by applying organic fertilizer. It was also found organic fertilizer application increased sulfamethazine content and the relative abundances of sul1 and sul2 in the soil. In contrast, applying chemical fertilizer significantly increased the abundance of Nitrospirae, Parcubacteria, and Verrucomicrobia and caused no obvious changes on sul. Correlation analysis indicated that sul enrichment was associated with the increases in sulfamethazine content and potential hosts (e.g., Novosphingobium and Rhodoplanes) population. The potential ecological risks of antibiotics in paddy soil with organic fertilizer applied cannot be ignored.

Bilateral adrenal hemorrhage after hip arthroplasty: an initially misdiagnosed case.

BACKGROUND: Bilateral adrenal hemorrhage (BAH) is a rare but potentially catastrophic condition. Its clinical manifestation is often non-specific and sometimes difficult to be diagnosed in time. A 57-year-old woman, who presented with severe fatigue, nausea and vomiting after left hip arthroplasty due to her femoral neck fracture in a local hospital, was transferred to our medical center. Laboratory results revealed significant hyponatremia, low serum cortisol and elevated serum ACTH. Computed tomography (CT) showed a bilateral adrenal mass, measured 3.6 × 2.7 cm on the left and 3.4 × 2.3 cm on the right. Further magnetic resonance imaging (MRI) confirmed the diagnosis of BAH. The patient was prescribed with oral prednisolone acetate, 5 mg, tid, and her condition improved gradually. Nine months after, the patient was in good condition with 5 mg prednisolone acetate per day. CT revealed a clearly shrunken adrenal mass compared with 9 months ago. CONCLUSIONS: This case illustrates the difficulty in making the diagnosis of BAH with atypical presentation. Such cases necessitate greater alertness on the part of the clinician and require rapid diagnosis and prompt glucocorticoid replacement for better clinical outcomes.

Discovery of potent and selective urea-based ROCK inhibitors: Exploring the inhibitor's potency and ROCK2/PKA selectivity by 3D-QSAR, molecular docking and molecular dynamics simulations.

An activity model and a selectivity model from 3D-QSAR studies were established by CoMFA and CoMSIA to explore the SAR. Then docking was used to study the binding modes between ligand and kinases (ROCK2 and PKA), and the molecular docking results were further validated by MD simulations. Computational results suggested that substitution containing positive charge attached to the middle phenyl ring, or electropositive group in urea linker was favored for both activity and ROCK2/PKA selectivity. Finally, three compounds were designed, and biological evaluation demonstrated that these molecular models were effective for guiding the design of potent and selective ROCK inhibitors.

Discovery of bis-aryl urea derivatives as potent and selective Limk inhibitors: Exploring Limk1 activity and Limk1/ROCK2 selectivity through a combined computational study.

Lim kinase (Limk), a proline/serine-rich sequence, can regulate the polymerization of the actin filaments by phosphorylating, and it is found to be highly involved in various human diseases. In this paper, 47 reported Limk1 inhibitors with bis-aryl urea scaffold were used to design potent and selective Limk inhibitors by computational approaches. Firstly, the structure-Limk1 activity relationship models (3D-QSAR) and structure-Limk1/ROCK2 selectivity relationship models (3D-QSSR) were developed and both 3D-QSAR and 3D-QSSR models showed good correlative and predictive abilities. Then, the molecular docking and molecular dynamics (MD) simulations were employed to validate the optimal docking conformation and explore the binding affinities. Finally, five new compounds were designed and all of them exhibited good Limk1 inhibition and Limk1/ROCK2 selectivity after synthesis and biological evaluation, which demonstrated that the obtained information from computational studies were valuable to guide Limk inhibitors' design.

Left ventricular diastolic dysfunction in nonhuman primate model of dysmetabolism and diabetes.

BACKGROUND: Diabetes is one of the major risk factors for cardiomyopathy and heart failure with reduced ejection fraction (EF) and highly associated with left ventricular (LV) dysfunction in human. This study aimed 1) to noninvasively assess cardiac function using echocardiography; 2) to test the hypothesis that like diabetic human, cardiac function may also be compromised; in spontaneously developed obese, dysmetabolic and diabetic nonhuman primates (NHPs). METHODS: Cardiovascular functions were measured by noninvasive echocardiography in 28 control, 20 dysmetabolic/pre-diabetic and 41 diabetic cynomolgus monkeys based on fasting blood glucose and other metabolic status. RESULTS: The LV end-systolic volume (ESV) was higher while end-diastolic volume (EDV, 12 ± 5.7 mL) and EF (63 ± 12.8 %) significantly lower in the diabetic compared to control (14 ± 7 mL and 68 ± 9.8 %) group, respectively. The E/A ratio of LV trans-mitral peak flow rate during early (E) over late (A) diastole was significantly lower in the diabetic (1.19 ± 0.45) than control (1.44 ± 0.48) group. E-wave deceleration time (E DT) was prolonged in the diabetic (89 ± 41 ms) compared to control (78 ± 26 ms) group. Left atrial (LA) maximal dimension (LADmax) was significantly greater in the diabetic (1.3 ± 0.17 cm) than control (1.1 ± 0.16 cm) group. Biochemical tests showed that total cholesterol and LDL were significant higher in the diabetic (167 ± 63 and 69 ± 37 mg/dL) than both pre-diabetic (113 ± 37 and 41 ± 23 mg/dL) and control (120 ± 28 and 41 ± 17 mg/dL) groups, respectively. Multivariable logistic regression analysis demonstrated that LV systolic (reduced EF) and diastolic (abnormal E/A ratio) dysfunctions are significantly correlated with aging and hyperglycemia. Histopathology examination of the necropsy heart revealed inflammatory infiltration, cardiomyocyte hypertrophy and fragmentation, indicating the myocardial ischemia and remodeling which is consistent with the LV dysfunction phenotype. CONCLUSIONS: Using noninvasive echocardiography, the present study demonstrated for the first time that dysmetabolic and diabetic NHPs are associated with LV systolic (increased ESV, decreased EF, etc.) and diastolic (decreased EDV and E/A ratio, prolonged E DT, etc.) dysfunctions, accompanied by LA hypertrophic remodeling (increased LADmax), the phenotypes similarly to those found in diabetic patients. Thus, spontaneously developed dysmetabolic and diabetic NHPs is a highly translatable model to human diseases not only in the pathogenic mechanisms but also can be used for testing novel therapies for cardiometabolic disorders.

Identification of hub genes related to metastasis and prognosis of osteosarcoma and establishment of a prognostic model with bioinformatic methods.

Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and adolescents. Improvements in our understanding of the OS pathogenesis and metastatic mechanism on the molecular level might lead to notable advances in the treatment and prognosis of OS. Biomarkers related to OS metastasis and prognosis were analyzed and identified, and a prognostic model was established through the integration of bioinformatics tools and datasets in multiple databases. 2 OS datasets were downloaded from the Gene Expression Omnibus database for data consolidation, standardization, batch effect correction, and identification of differentially expressed genes (DEGs); following that, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs; the STRING database was subsequently used for protein-protein interaction (PPI) network construction and identification of hub genes; hub gene expression was validated, and survival analysis was conducted through the employment of the TARGET database; finally, a prognostic model was established and evaluated subsequent to the screening of survival-related genes. A total of 701 DEGs were identified; by gene ontology and KEGG pathway enrichment analyses, the overlapping DEGs were enriched for 249 biological process terms, 13 cellular component terms, 35 molecular function terms, and 4 KEGG pathways; 13 hub genes were selected from the PPI network; 6 survival-related genes were identified by the survival analysis; the prognostic model suggested that 4 genes were strongly associated with the prognosis of OS. DEGs related to OS metastasis and survival were identified through bioinformatics analysis, and hub genes were further selected to establish an ideal prognostic model for OS patients. On this basis, 4 protective genes including TPM1, TPM2, TPM3, and TPM4 were yielded by the prognostic model.

B-cell maturation antigen chimeric antigen receptor-T therapy alleviated heart failure in patients with multiple myeloma.

Patients with multiple myeloma (MM) are likely to achieve poor therapeutic response when organs are involved. We produced anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells, which are in a trial for patients with relapsed/refractory MM. One enrolled patient developed severe heart failure, highly suspected as light chain cardiac amyloidosis. He exhibited increased N-terminal pro-brain natriuretic peptide with a peak of 32 299 ng/mL and heart failure with an ejection fraction of 30%. Anti-BCMA CAR-T cells were administered following lymphodepletion. The patient achieved cardiac response within 1 week with a decrease in N-terminal pro-brain natriuretic peptide by 80%, an increase in ejection fraction from 30% to 56%, and a haematological response with negative minimal residual disease at 1 month and a complete response at 1 year. To date, this patient has maintained good health without heart failure or haematological relapse. Herein, we show the efficacy of anti-BCMA CAR-T cells in patients with MM and severe heart failure.

Population diversity analyses provide insights into key horticultural traits of Chinese native thymes.

Chinese native thymes (CNTs) in the genus Thymus (family Lamiaceae) are rich in bioactive terpenes, which exert antiviral, anti-inflammatory, antioxidation, immunological, and antimicrobial effects. Plants exhibit morphological variation, including erect-type and creeping-type growth forms; however, the molecular mechanisms underlying important horticultural traits have not been determined. Here, we collected 39 CNTs providing strategic plant resources for studies of lignin, terpenoids, and glandular trichomes of thymes. Using resequencing data as well as phenotypic, metabonomic, phylogenetic, population genetic, and transcriptomic analyses, we identified and characterized key genes involved in lignin biosynthesis, terpenoid biosynthesis, and glandular trichome formation. We found many regulatory genes or transcription factors related to these three important horticultural traits, including genes encoding caffeic acid O-methyltransferase (COMT), terpene synthase (TPS), v-myb avian myeloblastosis viral oncogene homolog (MYB), and homeodomain-leucine zipper (HD-ZIP). Population diversity analyses provided insights into growth form, terpenoid, and glandular trichome evolution in CNTs. Furthermore, our results revealed that T. mongolicus accessions might be wild ancestors, and T. quinquecostatus, T. quinquecostatus var. asiaticus, and T. quinquecostatus var. przewalskii might be transitional accessions that derived from T. mongolicus accessions. Finally, T. nervulosus, T. inaequalis, T. mandschuricus, T. curtus, T. amurensis, T. proximus, T. altaicus, T. roseus, and T. marschallianus showed high divergence. We found evidence for introgression between erect-type European cultivated thymes and CNTs. These findings improve our understanding of the determinants of variation in horticultural traits and provide candidate loci for research and breeding.

Anti­BCMA CAR­T cell immunotherapy for relapsed or refractory multiple myeloma.

The present study aimed to study the efficacy and adverse effects of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in relapsed or refractory multiple myeloma. Patients were divided into three dose groups based on cell therapy concentration. After CAR-T cell therapy for 10 patients with recurrent or refractory multiple myeloma, the patients were monitored and evaluated regularly to observe the efficacy and adverse reactions of CAR-T cell therapy. At a median follow-up of 337 (253-504) days, one patient succumbed 24 days due to rapidly progressing disease. The overall response rate of nine patients was 88.9%, including 77.8% (7/9) with minimal residual disease negative complete remission (CR) and 11.1% (1/9) with partial remission. A total of three patients were maintained in remission state for more than a year and eight were maintained for more than six months. Among the three patients with extramedullary invasion, two extramedullary lesions disappeared and one was stable. The highest copy number of CAR-T cells in seven patients with CR was >1x105 copies/µl gDNA, and the best therapeutic effect can be achieved within 30 (7-30) days after the copy number of CAR-T cells reached 1x105 copies/µl genomic DNA. The median onset time in the nine patients was 43 (22-169) days, and the median progression-free survival was 337 (253-504). Among the 10 patients, nine (90%) had cytokine release syndrome, all of which were below grade II. There were nine (90%) patients with hematological adverse reactions, six (60%) patients with severe anemia, five (50%) patients with grade III and above leukopenia, five (50%) patients with granulocytopenia, four (40%) patients with grade III and above thrombocytopenia, and three (30%) patients with grade III and above pancytopenia. It was concluded that anti-BCMA CAR-T cell therapy is a promising treatment method for relapsed or refractory multiple myeloma and extramedullary invasion, with stable efficacy and controllable adverse effects.

CO oxidation catalyzed by silver nanoclusters: mechanism and effects of charge.

The mechanism of the CO oxidation promoted by a neutral Ag(55) cluster was investigated extensively, using density functional theory calculations. The CO oxidation process catalyzed by anionic and cationic Ag(55) clusters was also studied, to clarify the effects of the charge state. The Eley-Rideal (ER) and Langmuir-Hinshelwood (LH) mechanisms were discussed in detail. Six reaction pathways were found for the Ag(55)-mediated CO oxidation. It was found that the ER mechanism competed with the LH mechanism. The rate-limiting step of the CO oxidation was the reaction of CO with the Ag(55)O species. All of the anionic, neutral, and cationic Ag(55) clusters were able to promote CO oxidation at low temperatures. The present results enrich our understanding of the catalytic oxidation of CO by nano-sized Ag-based catalysts.

[Maximal androgen blockade little influences bone mineral density in prostate cancer patients].

OBJECTIVE: To determine the influence of maximal androgen blockade (MAB) on bone mineral density (BMD) in men with prostate cancer. METHODS: We enrolled 40 men with prostate cancer treated by MAB for 7 to 12 months. We obtained the laboratory results of PSA, testosterone, serum calcium and phosphorus, 24-h urine calcium and phosphorus, alkaline phosphatase, and parathyroid hormone, measured the BMD of the lumbar spine and femoral neck by dual energy X-ray absorptiometry, recorded pain scores, and compared the results before and after the treatment. RESULTS: Before MAB treatment, 5 (12.5%) of the patients met the BMD criteria of lumbar spine (L2-4) osteopenia, 8 (20%) lumbar spine (L2-4) osteoporosis, 13 (32.5%) left femoral neck osteopenia, and 15 (37.5%) left femoral neck osteoporosis. The PSA and testosterone levels were decreased from (52.9 +/- 69.9) microg/L and (18.9 +/- 6.5) nmol/L before MAB to (1.5 +/- 1.6) microg/L and (1.9 +/- 1.3) nmol/L after it (P<0.05). There were no statistically significant differences before and after MAB in the levels of serum calcium and phosphorus, 24-h urine calcium and phosphorus, alkaline phosphatase, and parathyroid hormone (P>0.05), nor in the BMD levels of the lumbar spine ([1.1 +/- 0.1] vs [1.1 +/- 0.2] g/cm2) and femoral neck ([0.8 +/- 0.2] vs [0.8 +/- 0.1] g/cm2), nor in the pain score ([0.6 +/- 0.2] vs [0.7 +/- 0.1], P>0.05). CONCLUSION: MAB treatment (range from 7 to 12 months) has no significant influence on BMD in men with prostate cancer, but BMD should be measured before MAB.

[Face and content validation of the virtual reality transurethral prostatic resection simulator].

OBJECTIVE: To evaluate the face and content validation of the virtual reality transurethral resection of the prostate simulator (TURPSim(TM)). METHODS: The 60 urology doctor aged 26 - 50 years old all over the country were enrolled for virtual reality training of TURP from September 2010 to June 2011. Participants classified as experts (more than 50 procedures performed) and novices (50 or fewer procedures performed) performed TURPs on TURPSim(TM) involving resection of 25 - 80 g prostate. They completed questionnaires regarding utility for residency training, realism and overall score of the TURPSim(TM). Performances of two groups were evaluated after 2-day training. RESULTS: were recorded and analyzed. RESULTS: Mean utility for residency training, realism and overall score were (8.8 ± 1.1) and (8.5 ± 1.4), (8.0 ± 1.2) and (8.4 ± 1.1), (8.7 ± 0.9) and (8.6 ± 0.8) in experts and novices respectively. There was no significant difference between two groups (P > 0.05). Spearman's correlation coefficients analysis showed an significant positive correlation between utility for residency training and realism (r = 0.625, P = 0.000), utility for residency training and overall score (r = 0.691, P = 0.000) in experts, utility for residency training and realism (r = 0.702, P = 0.000), utility for residency training and overall score (r = 0.664, P = 0.001) in novices. Prostate resection rate (87.3% ± 7.7%), bleeding control rate (94.4% ± 6.6%) and safety (95.2% ± 5.5%) in novices increased after training (t = -3.689, -2.274, -2.507, all P < 0.05). CONCLUSIONS: The face and content validation of transurethral resection of the prostate simulator is good, virtual reality training of TURP may improve the skills necessary to perform TURP. Transurethral resection of the prostate simulator can be used to train urology residents.

[Value of laparoscopic virtual reality simulator in laparoscopic suture ability training of catechumen].

OBJECTIVE: To investigate the value of laparoscopic virtual reality simulator in laparoscopic suture ability training of catechumen. METHODS: After finishing the virtual reality training of basic laparoscopic skills, 26 catechumen were divided randomly into 2 groups, one group undertook advanced laparoscopic skill (suture technique) training with laparoscopic virtual reality simulator (virtual group), another used laparoscopic box trainer (box group). Using our homemade simulations, before grouping and after training, every trainee performed nephropyeloureterostomy under laparoscopy, the running time, anastomosis quality and proficiency were recorded and assessed. RESULTS: For virtual group, the running time, anastomosis quality and proficiency scores before grouping were (98 ± 11) minutes, 3.20 ± 0.41, 3.47 ± 0.64, respectively, after training were (53 ± 8) minutes, 6.87 ± 0.74, 6.33 ± 0.82, respectively, all the differences were statistically significant (all P < 0.01). In box group, before grouping were (98 ± 10) minutes, 3.17 ± 0.39, 3.42 ± 0.67, respectively, after training were (52 ± 9) minutes, 6.08 ± 0.90, 6.33 ± 0.78, respectively, all the differences also were statistically significant (all P < 0.01). After training, the running time and proficiency scores of virtual group were similar to box group (all P > 0.05), however, anstomosis quality scores in virtual group were higher than in box group (P = 0.02). CONCLUSION: The laparoscopic virtual reality simulator is better than traditional box trainer in advanced laparoscopic suture ability training of catechumen.

Chromosome-level assembly and analysis of the Thymus genome provide insights into glandular secretory trichome formation and monoterpenoid biosynthesis in thyme.

Thyme has medicinal and aromatic value because of its potent antimicrobial and antioxidant properties. However, the absence of a fully sequenced thyme genome limits functional genomic studies of Chinese native thymes. Thymus quinquecostatus Celak., which contains large amounts of bioactive monoterpenes such as thymol and carvacrol, is an important wild medicinal and aromatic plant in China. Monoterpenoids are abundant in glandular secretory trichomes. Here, high-fidelity and chromatin conformation capture technologies were used to assemble and annotate the T. quinquecostatus genome at the chromosome level. The 13 chromosomes of T. quinquecostatus had a total length of 528.66 Mb, a contig N50 of 8.06 Mb, and a BUSCO score of 97.34%. We found that T. quinquecostatus had experienced two whole-genome duplications, with the most recent event occurring ∼4.34 million years ago. Deep analyses of the genome, in conjunction with comparative genomic, phylogenetic, transcriptomic, and metabonomic studies, uncovered many regulatory factors and genes related to monoterpenoids and glandular secretory trichome development. Genes encoding terpene synthase (TPS), cytochrome P450 monooxygenases (CYPs), short-chain dehydrogenase/reductase (SDR), R2R3-MYB, and homeodomain-leucine zipper (HD-ZIP) IV were among those present in the T. quinquecostatus genome. Notably, Tq02G002290.1 (TqTPS1) was shown to encode the terpene synthase responsible for catalyzing production of the main monoterpene product γ-terpinene from geranyl diphosphate (GPP). Our study provides significant insight into the mechanisms of glandular secretory trichome formation and monoterpenoid biosynthesis in thyme. This work will facilitate the development of molecular breeding tools to enhance the production of bioactive secondary metabolites in Lamiaceae.

Yeast-induced formation of graphene hydrogels anode for efficient xylose-fueled microbial fuel cells.

Microbial fuel cells (MFCs) are of great interest due to their capability to directly convert organic compounds to electric energy. In particular, MFCs technology showed great potential to directly harness the energy from xylose in the form of bioelectricity and biohydrogen simultaneously. Herein, we report a yeast strain of Cystobasidium slooffiae JSUX1 enabled the reduction and assembly of graphene oxide (GO) nanosheets into three-dimensional reduced GO (3D rGO) hydrogels on the surface of carbon felt (CF) anode. The autonomously self-modified 3D rGO hydrogel anode entitled the yeast-based MFCs with two times enhancement on bioelectricity and biohydrogen production from xylose. Further analysis demonstrated that the 3D rGO hydrogel attracted more yeast cells and reduced the interfacial charge transfer resistance, which was the underlying mechanism for the improvement of MFCs performance. This work offers a new strategy to reinforce the performance of yeast-based MFCs and provides a new opportunity to efficiently harvest energy from xylose.

1,4-Bis(1H-benzimidazol-1-yl)benzene.

In the title compound, C(20)H(14)N(4), the dihedral angles between the central benzene ring and the pendant benzimidazole ring systems are 46.60 (15) and 47.89 (16)°. The dihedral angle between the benzimidazole ring systems is 85.62 (12)° and the N atoms lie to the same side of the mol-ecule. In the crystal, mol-ecules are linked by C-H⋯N inter-actions and weak aromatic π-π stacking [shortest centroid-centroid separation = 3.770 (2) Å] is observed.

[Association of the serum testosterone level with metabolic syndrome in men].

OBJECTIVE: To investigate the association of the serum testosterone (T) level with metabolic syndrome (MS). METHODS: We enrolled in this investigation 1,006 men aged 30-60 years in Beijing and obtained the data on their blood pressure (BP), waist circumference (WC), fasting blood glucose (FBG), serum triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) and serum testosterone (T). The men were divided into an MS group and a non-MS (NMS) group based on The Chinese Adult Dyslipidemia Prevention Guide 2007. The results were compared and analyzed. RESULTS: There was no statistically significant difference between the ages of the two groups (P >0.05). Systolic BP (SBP), diastolic BP (DBP), WC, FBG and TG were significantly higher, while serum T and HDL-C remarkably lower in the MS than in the NMS group (P <0.001). The serum T level was markedly decreased with the increase of MS components (P <0.01). Both Pearson's correlation coefficients and multiple linear regression analyses showed that the serum T level was negatively correlated with age, WC, SBP and TG (P < 0.05). CONCLUSION: Low serum T level may predict the development of MS in men.

Pharmacodynamic and pharmacokinetic effects of S086, a novel angiotensin receptor neprilysin inhibitor.

BACKGROUND AND PURPOSE: Angiotensin receptor-NEP inhibitor (ARNi), which includes an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has been proven safe and effective for treating heart failure with reduced ejection fraction (HF-REF). S086 is a novel single-molecule ARNi that includes the molecular moieties of EXP3174 (the active metabolite of the ARB losartan) and sacubitril (a NEP inhibitor prodrug) in a 1:1 M ratio. We performed preclinical animal model studies to evaluate the efficacy of S086 in treating HF. EXPERIMENTAL APPROACH: Rat and dog models of myocardial ischemia-induced chronic heart failure were used in this research. PRINCIPAL RESULTS: The oral administration of S086 dose-dependently lowered the heart weight index, attenuated cardiac fibrosis, and improved left ventricular ejection fraction, shortening fraction, and cardiac output, without effects on hemodynamics in animal models of myocardial ischemia-induced chronic heart failure. A comparable protective effect to LCZ696 was observed for S086 at an equal molar dose in dog models. In addition, S086 was superior to LCZ696 since it significantly reversed the decrease in left ventricular posterior wall end-systolic thickness. CONCLUSION: This animal study suggests that S086 is effective in treating myocardial ischemia-induced chronic heart failure.

Changes in the androgen levels in the ventral prostate of spontaneously hypertensive rats after castration.

OBJECTIVE: To characterize the changes in androgen levels in the prostate after castration, as androgens are critical in the progression of prostate cancer after castration, but the time at which the androgen remaining in the prostatic cancer tissue after castration exerts its effects is poorly understood. MATERIALS AND METHODS: The ventral prostate (VP) in adult male spontaneously hypertensive rats was excised at 2, 4 and 8 h, 1, 2, 4 and 7 days, and 2, 4 and 8 weeks after castration. The dihydrotestosterone (DHT), testosterone, dehydroepiandrosterone (DHEA) and androstenedione (4-dione) levels in the VP were measured simultaneously using gas chromatography/tandem mass spectrometry. RESULTS: Within 2 days of castration, the DHT and testosterone levels in the VP decreased sharply, while there were no significant changes in the DHEA or 4-dione levels. From 2 days to 2 weeks after castration (2-7 days for 4-dione), there was a sharp peak in tissue androgen levels in the VP (P < 0.05 for all androgens); during the subsequent 6 weeks after castration, all of the tissue DHT, testosterone, DHEA and 4-dione levels gradually increased with time. CONCLUSIONS: These data show the changes which occur in androgen levels in rat VP after castration and support the concept that the adrenal glands compensate for the loss of testicular androgen.