The baicalein amorphous solid dispersion to enhance the dissolution and bioavailability and effects on growth performance, meat quality, antioxidant capacity and intestinal flora in Taihang chickens.

Baicalein (BAI) is a natural flavonoid with antioxidant, antitumor and antibacterial properties. However, the bioavailability of BAI was limited due to low solubility. This study aims to improve the solubility of BAI through the amorphous solid dispersion (ASD) and evaluate changes in its pharmacokinetics and pharmacodynamics in Taihang chickens. Polyethylene caprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus) was chosen as the carrier, and ASD was prepared by rotary evaporation and was characterized by powder X-ray diffractions (PXRD), differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FT-IR). In vitro dissolution assays were used to screen the optimal ratio of drug to carrier, in vivo pharmacokinetic assays were conducted to investigate the promoting effect on the absorption. In addition, the effects of ASD on the growth performance, meat quality, antioxidant capacity and intestinal flora were investigated. ASD (1:9 and 2:8) did not exhibit crystal diffraction peaks of BAI in PXRD or endothermic peaks in DSC, indicating the successful preparation of ASD. The results of in vitro dissolution assay showed that the cumulative dissolution rate of ASD (2:8) within 600 min was 52.67%, which was 7.84-fold higher than BAI. The pharmacokinetic results showed that the peak concentration (Cmax) and the area under the drug-time curve (AUC0∼24) of ASD (2:8) was (5.20 ± 0.82) µg/mL and (17.03 ± 0.67) µg·h/mL, which was 1.91 and 2.64-fold higher than BAI, respectively. Dietary supplementation of BAI and ASD could increase average daily gain (ADG), while decrease feed conversion ratio (FCR), but there was no significant difference (P > 0.05). The drip loss of BAIASD group was lower than BAI group (P < 0.05). In addition, the antioxidant capacity of Taihang chickens were enhanced, the diversity and the abundance of beneficial bacteria was improved. Results of BAI upon the dietary supplementation tested in Taihang chickens, after preparation of ASD, indicating a superior enhancement effect in growth performance, meat quality, antioxidant capacity and intestinal flora due to an improved solubility and optimized bioavailability.

Quantitative lipidomics reveals the changes of lipids and antioxidant capacity in egg yolk from laying hens with fatty liver hemorrhagic syndrome.

In laying hens, fatty liver hemorrhagic syndrome (FLHS) is a common metabolic disorder, which can affect egg production and nutritional value. However, the impact of FLHS on the lipid content in egg yolks was not clear. In this study, FLHS model was induced by using high-energy low-protein diet, and the egg quality was evaluated. Egg yolk lipids were quantitatively analyzed by using ultra-performance liquid chromatography-mass spectrometry combined with multivariate statistical analysis. Gene expressions of the lipoprotein were determined by qRT-PCR and antioxidant capacity of the egg yolk were determined by kits. The elevated blood lipids and extensive lipid droplets observed indicated successful establishment of the FLHS model in laying hens. Measurements of egg quality showed that egg yolk weight was increased in the FLHS group. Lipidomics revealed that 1,401 lipids, comprising 27 lipid subclasses in the egg yolk. According to score plots of principal component analysis and orthogonal partial least squares discriminant analysis, different lipid profile was observed between the control and FLHS groups. A total of 97 different lipid species were screen out. Sphingolipid and glycerophospholipid metabolism were identified as key pathways. Free polyunsaturated fatty acids (PUFA) exhibited an increase in the FLHS group (P < 0.05). Notably, the form of PUFAs was changed that the FLHS group showed an increase in triacylglycerol-docosahexenoic acid and triacylglycerol-arachidonic acid in the egg yolk, while triacylglycerol-α-linolenic acid was decreased (P < 0.05). Total superoxide dismutase was decreased in the egg yolks affected by FLHS. Gene expressions of vitellogenin 2 (VTG2), VTG3, very low-density apolipoprotein II and apolipoprotein B were increased in the liver of laying hens with FLHS (P < 0.05). In conclusion, FLHS promoted the lipid transport from the liver to the yolk by upregulating lipoprotein expression, which altered lipid profile, and reduced antioxidant capacity in the yolk. This study provided a foundation for understanding the changes in lipids, lipid transport and lipid antioxidation capacity in egg yolk from laying hens with FLHS.

Solid Dispersions of Genistein via Solvent Rotary Evaporation for Improving Solubility, Bioavailability, and Amelioration Effect in HFD-Induced Obesity Mice.

Genistein (GEN) is an active pharmaceutical ingredient that presents the challenges of poor water solubility and low oral bioavailability. To tackle these challenges, a GEN solid dispersion was prepared by solvent rotary evaporation using polyvinylpyrrolidone K30 (PVP K30) as a carrier. The optimal formulation was determined by drug loading efficiency and in vitro release. The physical state of the solid dispersion was characterized by DSC, XRD, SEM and FT-IR. And the results of the in vitro release study indicate that the drug release of SD (1:7) increased 482-fold that of pure GEN at 60 min. Following oral administration to rats, the Cmax and AUC0-24 of SD (1:7) was increased 6.86- and 2.06-fold to that of pure GEN. The adipose fat index and body weight of the SD (1:7) group were significantly lower than those of the GEN group (p < 0.05). Meanwhile, the levels of TC and TG in the serum were significantly decreased in the SD (1:7) group compared with the GEN group (p < 0.05). All experiments revealed that solid dispersion could be a promising formulation approach to improve the dissolution rate, oral bioavailability, and effect on the reduction of lipid accumulation in high-fat diet-induced obesity mice.

Trends of ischemic heart disease mortality attributable to smoking in the five countries with the highest number of smokers during 1990-2019: an age-period-cohort analysis.

Introduction: Smoking increases the risk of various cardiovascular diseases, including ischemic heart disease (IHD). This study aimed to assess the impact of age, period, and cohort on long-term trends in IHD mortality in China, India, Indonesia, the United States, and Russia, the five countries with the highest number of smokers, from 1990 to 2019. Material and methods: The data were obtained from the Global Burden of Disease (GBD) Study 2019, and the age-standardized mortality rate (ASMR) was calculated. Joinpoint regression analysis was used to assess the magnitude and direction of trends in smoking-attributable mortality from IHD. Age-period-cohort (APC) studies were used to estimate net drift (estimated annual percentage change (EAPC)s), local drift (age-specific EAPCs), and independent trends in age, period, and cohort effects. Results: The analysis revealed a significant downward trend in ASMRs attributable to IHD as a result of smoking in the United States, India, and Russia. Indonesia and China showed an upward trend. Age effects were increasing for both country and sex, with China showing the most significant increase in the older age group; period effects were decreasing in all countries except Indonesia, and cohort effects were increasing only in Indonesia and China. Conclusions: From 1990 to 2019, mortality from IHD caused by smoking showed a downward trend in these five countries. However, the pattern of increased mortality from IHD in women caused by smoking warrants further study.

Dysregulation of MTFR2, ATP5IF1 and BAK1 in Sertoli cells relates to idiopathic non-obstructive azoospermia via inhibiting mitochondrial fission and inducing mitochondrial dysfunction†.

Non-obstructive azoospermia affects more than 10% of infertile men with over 70% patients are idiopathic with uncharacterized molecular mechanisms, which is referred as idiopathic non-obstructive azoospermia. In this study, we checked the morphology of Sertoli cell mitochondria in testis biopsies from patients with idiopathic non-obstructive azoospermia and patients with obstructive azoospermia who have normal spermiogenesis. The expression of 104 genes controlling mitochondria fission and fusion were analyzed in three gene expression datasets including a total of 60 patients with non-obstructive azoospermia. The levels of 7 candidate genes were detected in testis biopsies from 38 patients with idiopathic non-obstructive azoospermia and 24 patients with obstructive azoospermia who have normal spermatogenesis by RT-qPCR. Cell viability, apoptosis, mitochondria membrane potential, adenosine triphosphate production, oxygen consumption, and mitochondria morphology were examined in primary human Sertoli cells. Mouse spermatogonial stem cells were used to detect the cell supporting capacity of Sertoli cells. We observed that patients with idiopathic non-obstructive azoospermia had elongated mitochondria. MTFR2 and ATP5IF1 were downregulated, whereas BAK1 was upregulated in idiopathic non-obstructive azoospermia testis and Sertoli cells. Sertoli cells from patients with idiopathic non-obstructive azoospermia had reduced viability, mitochondria membrane potential, adenosine triphosphate production, oxygen consumption rate, glycolysis and increased apoptosis. Knockdown MTFR2 in Sertoli cells increased the mitochondria size. Knockdown ATP5IF1 did not change mitochondrial morphology but increased adenosine triphosphate hydrolysis. Overexpression of BAK1 reduced membrane potential and upregulated cell apoptosis. The dysregulation of all these three genes contributed to the dysfunction of Sertoli cells, which provides a clue for idiopathic non-obstructive azoospermia treatment.

Single atom nanozymes for bacterial infection therapy.

Bacterial infection-related diseases continue to pose a significant challenge to global human health. Antibiotic therapy, as a conventional therapeutic strategy, has been extensively employed in clinical settings to treat bacterial infections. However, the effectiveness of these conventional strategies is often impeded by the antimicrobial resistance of bacteria. Consequently, the development of alternative antibacterial agents has emerged as a promising approach to addressing this issue. In recent years, single-atom nanozymes (SAzymes), a novel class of nanocatalytic medicines, have garnered increasing attention due to their numerous advantages, including uniformly dispersed metal active sites, tunable coordination structures, and maximal metal atomic utilization efficiency. To date, a variety of SAzymes have been developed and widely applied in antibacterial therapy. In this minireview, we provide an overview of the latest advances in the synthesis and antibacterial application of different metal-based SAzymes. Furthermore, we discuss the future challenges and opportunities of utilizing SAzymes for bacterial infection treatment. It is our hope that this minireview will contribute to the development of the next generation of SAzyme-based antibacterial agents.

Novel compound heterozygous pathogenic variants in the SLC3A1 gene in a Chinese family with cystinuria.

BACKGROUND: Cystinuria is an autosomal recessive disorder characterized by a cystine transport deficiency in the renal tubules due to mutations in two genes: SLC3A1 and SLC7A9. Cystinuria can be classified into three forms based on the genotype: type A, due to mutations in the SLC3A1 gene; type B, due to mutations in the SLC7A9 gene; and type AB, due to mutations in both genes. METHODS: We report a 12-year-old boy from central China with cystine stones. He was from a non-consanguineous family that had no known history of genetic disease. A physical examination showed normal development and neurological behaviors. Whole-exome and Sanger sequencing were used to identify and verify the suspected pathogenic variants. RESULTS: The compound heterozygous variants c.898_905del (p.Arg301AlafsTer6) is located in exon5 and c.1898_1899insAT (p.Asp634LeufsTer46) is located in exon10 of SLC3A1 (NM_000341.4) were deemed responsible for type A cystinuria family. The variant c.898_905del was reported in a Japanese patient in 2000, and the variant c.1898_1899insAT is novel. CONCLUSION: A novel pathogenic heterozygous variant pair of the SLC3A1 gene was identified in a Chinese boy with type A cystinuria, enriching the mutational spectrum of the SLC3A1 gene. We attempted to find a pattern for the association between the genotype of SLC3A1 variants and the manifestations of cystinuria in patients with different onset ages. Our findings have important implications for genetic counseling and the early clinical diagnosis of cystinuria.

The mechanisms of minocycline in alleviating ischemic stroke damage and cerebral ischemia-reperfusion injury.

Stroke is a group of diseases resulting from cerebral vascular rupture or obstruction and subsequent brain blood circulation disorder, leading to rapid neurological deficits. Ischemic stroke accounts for the majority of all stroke cases. The current treatments for ischemic stroke mainly include t-PA thrombolytic therapy and surgical thrombectomy. However, these interventions aimed at recanalizing cerebral vessels can paradoxically lead to ischemia-reperfusion injury, which exacerbates the severity of brain damage. Minocycline, a semi-synthetic tetracycline antibiotic, has been shown to possess a wide range of neuroprotective effects independent of its antibacterial activity. Here we summarize the mechanisms underlying the protective effects of minocycline against cerebral ischemia-reperfusion injury based on the pathogenesis of cerebral ischemia-reperfusion injury, including its modulation of oxidative stress, inflammatory response, excitotoxicity, programmed cell death and blood-brain barrier injury, and also introduce the role of minocycline in alleviating stroke-related complications, in order to provide a theoretical basis for the clinical application of minocycline in cerebral ischemia-reperfusion injury.

Charge Transfer and Level Lifetime in Molecular Photon-Absorption upon the Quantum Impedance Lorentz Oscillator.

On the strength of the new quantum impedance Lorentz oscillator (QILO) model, a charge-transfer method in molecular photon-absorption is proposed and imaged via the numerical simulations of 1- and 2-photon-absorption (1PA and 2PA) behaviors of the organic compounds LB3 and M4 in this paper. According to the frequencies at the peaks and the full width at half-maximums (FWHMs) of the linear absorptive spectra of the two compounds, we first calculate the effective quantum numbers before and after the electronic transitions. Thus, we obtain the molecular average dipole moments, i.e., 1.8728 × 10-29 C·m (5.6145 D) for LB3 and 1.9626 × 10-29 C·m (5.8838 D) for M4 in the ground state in the tetrahydrofuran (THF) solvent. Then, the molecular 2PA cross sections corresponding to wavelength are theoretically inferred and figured out by QILO. As a result, the theoretical cross sections turn out to be in good agreement with the experimental ones. Our results reveal such a charge-transfer image in 1PA near wavelength 425 nm, where an atomic electron of LB3 jumps from the ground-state ellipse orbit with the semimajor axis ai = 1.2492 × 10-10m = 1.2492 Å and semiminor axis bi = 0.4363 Å to the excited-state circle (aj = bj = 2.5399 Å). In addition, during its 2PA process, the same transitional electron in the ground state is excited to the elliptic orbit with aj = 2.5399 Å and bj =1.3808 Å, in which the molecular dipole moment reaches as high as 3.4109 × 10-29 C·m (10.2256 D). In addition, we obtain a level-lifetime formula with the microparticle collision idea of thermal motion, which indicates that the level lifetime is proportional (not inverse) to the damping coefficient or FWHM of an absorptive spectrum. The lifetimes of the two compounds at some excited states are calculated and presented. This formula may be used as an experimental method to verify 1PA and 2PA transition selection rules. The QILO model exhibits the advantage of simplifying the calculation complexity and reducing the high cost associated with the first principle in dealing with quantum properties of optoelectronic materials.

Polymorphs of a 1:1 salt of sulfadiazine and piperazine-relative stability, dissolution studies, pharmacokinetics and anti-meningitis efficiency.

Two new salt forms of sulfadiazine (SDZ) and piperazine (PIP) were synthesized and characterized. Out of the two polymorphs (SDZ-PIP Ⅰ and SDZ-PIP II), SDZ-PIP Ⅱ is the more stable form at low temperature, room temperature and high temperature. The solution-mediated phase transformation result shows that SDZ-PIP II can transform into pure SDZ within 15 s in phosphate buffer at 37 °C, which leads to a loss in solubility advantage. The addition of 2 mg/mL PVP K30, a polymeric crystallization inhibitor, maintains the solubility advantage and permits supersaturation for a longer period of time. SDZ-PIP II showed 2.5 times the solubility of SDZ alone. The area under the curve (AUC) of SDZ-PIP II with 2 mg/mL PVP K30 was approximately 165% of that of SDZ alone. Moreover, SDZ-PIP II with PVP K30 was more effective than SDZ alone in treating meningitis. Therefore, the SDZ-PIP II salt improves the solubility, bioavailability, and anti-meningitis activity of SDZ.

Amorphous solid dispersion preparation via coprecipitation improves the dissolution, oral bioavailability, and intestinal health enhancement properties of magnolol.

Magnolol (MAG) is a multifunctional plant polyphenol with anti-inflammatory, antibacterial, antioxidant and antitumor properties. In poultry, it has been shown to improve growth performance, antioxidant, immune functions and intestinal health. However, its applications are limited by poor solubility and low oral bioavailability. This study aimed at improving the water solubility of MAG through solid dispersion and investigating its effects in Arbor Acre (AA) broilers. Hydroxypropyl methylcellulose succinic acid (HPMCAS) was used as a carrier to prepare magnolol solid dispersions (MAG-HPMCAS SD) via antisolvent coprecipitation, which were characterized thereafter. Optimal formulation proportions for SD were screened by in vitro dissolution assays, while its effects on improving absorption were investigated via in vivo pharmacokinetic assays. In addition, we evaluated the effects of MAG-HPMCAS SD on growth performance, antioxidant status, and gut microbiota in AA broilers. The powder samples prepared via antisolvent coprecipitation did not exhibit a crystal diffraction peak of MAG in powder X-ray diffractions or melting point peak in differential scanning calorimetry, proving the successful preparation of an amorphous solid dispersion system. The in vitro dissolution assay showed that the cumulative dissolution rate of MAG-HPMCAS(LF) SD (2:8, w/w) was 100%. Pharmacokinetic analyses revealed that the peak concentration (Cmax) of MAG-HPMCAS SD was 5.07 ± 0.73 µg/mL, which was 1.76 times greater than that of MAG. In addition, AUC0-48 and t1/2 of MAG-HPMCAS SD were 40.49 ± 6.29 g·h/mL and 9.15 ± 3.23 h, respectively, which were 2.17 and 2.56 times higher than those of MAG. Supplementation of MAG-HPMCAS SD in AA broilers significantly increased ADG (7-14 d and 15-21 d) and reduced feed conversion ratio (15-21 d) (P < 0.05). Bacterial diversity in the MAG-HPMCAS SD-supplemented group was greater than in the Control and MAG-supplemented group. Supplementation of MAG-HPMCAS SD stimulated the proliferation of beneficial bacteria, such as Lactobacillaceae and Bifidobacteriaceae. In conclusion, the MAG-HPMCAS SD prepared by coprecipitation improved the dissolution rate, the bioavailability of MAG, growth promotion, antioxidant effects and gut health in broilers.

Quantitative lipidomics reveals lipid perturbation in the liver of fatty liver hemorrhagic syndrome in laying hens.

Fatty liver hemorrhagic syndrome (FLHS) is a metabolic disease that causes decreased egg production and even death in laying hens, which brings huge economic losses to the poultry industry. However, the pathogenesis of FLHS is unclear. The purpose of the present study was to identify the changes in lipid profile and the lipid species related to FLHS. In the present study, the FLHS disease model in Chinese commercial Jing Fen laying hens was induced by a high-energy low-protein diet. A lipidomics approach based on ultra-performance liquid chromatography-mass spectrometry coupled with multivariate statistical analysis was performed for the qualitative and quantitative analyses of the liver lipids. The results showed that a total of 29 lipid subclasses, including 1,302 lipid species, were detected and identified. Among them, the proportions of phosphatidylserine (Control/FLHS, 33.1% vs. 29.1%), phosphatidylethanolamine (22.7% vs. 15.5%), phosphatidylcholine (15.7% vs. 11.7%) and phosphatidylinositol (7% vs. 6%) were reduced, while triacylglycerol (7.1% vs. 18.3%) and diglyceride (3.9% vs. 11.7%) were increased. Between the Control and FLHS groups, distinct changes in lipid profile were observed in the score plots of principal component analysis and orthogonal partial least squares discriminant analysis. Twelve differential lipid species mainly involved in glycerophospholipid metabolism and linoleic acid metabolism were identified and considered to be related to the pathogenesis of FLHS. Fatty acid chain length and unsaturation were reduced, while the mRNA levels of elongation of very long chain fatty acids-2 (ELOVL2) were increased in the liver of laying hens with FLHS. Collectively, this study characterized the liver lipid profile and explored the changes in lipid species related to FLHS, which provided insights into the pathogenesis of FLHS from the view of lipid metabolism.

Protective Effects of Abrus cantoniensis Hance on the Fatty Liver Hemorrhagic Syndrome in Laying Hens Based on Liver Metabolomics and Gut Microbiota.

As a metabolic disease, fatty liver hemorrhagic syndrome (FLHS) has become a serious concern in laying hens worldwide. Abrus cantoniensis Hance (AC) is a commonly used plant in traditional medicine for liver disease treatment. Nevertheless, the effect and mechanism of the decoction of AC (ACD) on FLHS remain unclear. In this study, ultra-high performance liquid chromatography analysis was used to identify the main phytochemicals in ACD. FLHS model of laying hens was induced by a high-energy low-protein (HELP) diet, and ACD (0.5, 1, 2 g ACD/hen per day) was given to the hens in drinking water at the same time for 48 days. Biochemical blood indicators and histopathological analysis of the liver were detected and observed to evaluate the therapeutic effect of ACD. Moreover, the effects of ACD on liver metabolomics and gut microbiota in laying hens with FLHS were investigated. The results showed that four phytochemicals, including abrine, hypaphorine, vicenin-2, and schaftoside, were identified in ACD. ACD treatment ameliorated biochemical blood indicators in laying hens with FLHS by decreasing aspartate aminotransferase, alanine aminotransferase, triglycerides, low-density lipoprotein cholesterol, and total cholesterol, and increasing high-density lipoprotein cholesterol. In addition, lipid accumulation in the liver and pathological damages were relieved in ACD treatment groups. Moreover, distinct changes in liver metabolic profile after ACD treatment were observed, 17 endogenous liver metabolites mainly associated with the metabolism of arachidonic acid, histidine, tyrosine, and tryptophan were reversed by ACD. Gut microbiota analysis revealed that ACD treatment significantly increased bacterial richness (Chao 1, P < 0.05; Ace, P < 0.01), and upregulated the relative abundance of Bacteroidetes and downregulated Proteobacteria, improving the negative effects caused by HELP diet in laying hens. Taken together, ACD had a protective effect on FLHS by regulating blood lipids, reducing liver lipid accumulation, and improving the dysbiosis of liver metabolomics and gut microbiota.

Simultaneous improvement of physical stability, dissolution, bioavailability, and antithrombus efficacy of Aspirin and Ligustrazine through cocrystallization.

A novel 1:1 cocrystal between two cardiovascular drugs, aspirin (ASA) and ligustrazine (tetramethylpyrazine, TMP) has been synthesized and characterized. The structure of this drug-drug cocrystal, ASA-TMP, was determined using single crystal X-ray crystallography. The ASA-TMP cocrystal exhibits a significantly reduced sublimation tendency than TMP. Importantly, cocrystallization simultaneously improves bioavailability of both parent drugs. This suggests the possibility of developing a more effective antithrombosis drug therapy given the synergistic pharmacological effects of the two parent drugs.

Ningmitai capsule promotes calculi expulsion after RIRS for 10-20-mm upper urinary stones: a multicenter, prospective, randomized controlled trial.

To evaluate the efficacy and safety of the use of Ningmitai capsule as an adjunctive stone expulsion therapy after RIRS. All patients were diagnosed with upper urinary tract calculi measuring 10-20 mm. The patients who successfully underwent RIRS were randomly assigned to the NMT capsule group (Ningmitai capsule, 1.52 g, three times daily) or the control group for 4 weeks based on the random number table method. The primary endpoints were the stone expulsion rate (SER) and stone-free rate (SFR). The average stone expulsion time (SET), average stone-free time (SFT) and complications were recorded. Between July 2, 2019, and December 17, 2020, 220 participants successfully underwent RIRS across 6 centers; 123 of them were randomized according to the exclusion criteria, and 102 (83%) were included in the primary analysis. The SERs on the 3rd, 7th, 14th and 28th days were significantly increased in the NMT capsule group compared with the control group (78.95% vs. 31.11%, 92.98% vs. 55.56%, 94.74% vs. 64.44%, 100% vs. 82.22%, respectively, p < 0.05). The SFRs on the 3rd and 7th days were not different (p > 0.05), while those on the 14th and 28th days were higher in the NMT capsule group (63.16% vs. 24.44% and 92.98% vs. 68.89%, p < 0.05). The average SET and average SFT of the NMT capsule group were remarkably shorter than those of the control group (p < 0.001). During the follow-up period, there were no significant differences in urine RBC counts between the two groups (p > 0.05). The urine WBC counts of the NMT capsule group were significantly lower than those of the control group on the 14th day (p = 0.011), but there was no difference on the 3rd, 7th or 28th day (p > 0.05). The analgesic aggregate of the NMT capsule group was also much lower (p = 0.037). There were no significant differences in adverse events (p > 0.05), and they improved significantly without sequelae. This study indicated that NMT capsules can significantly promote stone clearance and are more effective and safer for upper urinary calculi after RIRS.Trial registration Chinese Clinical Trial Registration No. ChiCTR1900024151.Date of registration June 28, 2019.

The complete chloroplast genome sequence of Clivia robusta.

In this study, we reported the complete chloroplast genome sequence of Clivia robusta for the first time. The complete chloroplast genome of C. robusta was 157,130 bp in length, containing a large single-copy region (LSC, 85,430 bp), a small single-copy region (SSC, 18,278 bp), and two inverted repeat regions (IRs, 26,711 bp). The overall GC content was 38.01%. The chloroplast genome contained 128 genes in total, including 86 protein-coding, 34 tRNA, and eight rRNA genes. The phylogenetic tree showed that C. robusta formed a monophyletic clade with other Clivia species.

Identification of evodiamine as a suppressor of prostate cancer progression by reducing AR transcriptional activity via targeting Src.

Evodiamine (EVO) is a bioactive alkaloid that exerts antitumor activity in various cancers, including prostate cancer (PCa). In this paper, we further investigated the molecular mechanisms underlying the anti-PCa effect of evodiamine. In the present study, cell proliferation, colony formation, migration, and invasion were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and transwell assays, respectively. Animal studies were used to evaluate the effect of evodiamine on the tumorigenicity of LNCaP cells in vivo. The expression levels of steroid receptor coactivator (Src), androgene receptor (AR), and prostate-specific antigen (PSA) were detected by western blot, quantitative real-time PCR (qRT-PCR) or ELISA assay. Association between Src and AR was examined by Co-Immunoprecipitation (CoIP). The impact of evodiamine on AR-mediated transcriptional activity was confirmed by dual-luciferase reporter assay. The results showed that evodiamine reduced LNCaP and 22Rv1 cell proliferation, colony formation, migration, and invasion induced by dihydrotestosterone (DHT) in vitro, as well as diminished tumor growth in vivo. Mechanistically, evodiamine directly targeted Src and reduced DHT-induced Src activation. Moreover, the restoration of Src activation abolished evodiamine-mediated suppression of proliferation, migration, and invasion of DHT-treated LNCaP and 22Rv1 cells. Furthermore, evodiamine inhibited DHT-induced AR transcriptional activity through targeting Src. As a conclusion, our findings demonstrate the antitumor property of evodiamine in PCa by blocking AR transcriptional activity through targeting Src and provide a rationale for developing evodiamine as a promising antitumor agent against PCa.

Construction of Gambogic Acid HPMA Copolymer Coupling Drug System and Study on Anti-tumor Activity.

AIM: An active-passive dual-targeting gambogic acid HPMA Copolymer Coupling drug system with high efficiency, low toxicity and high selectivity was constructed. METHODS: The gambogic acid HPMA copolymer coupling drug system was constructed and its structure was characterized. The cytotoxicity of gambogic acid HPMA copolymer was detected by MTT assay. The pharmacokinetics of gambogic acid HPMA copolymer was evaluated in mice. Targetability of gambogic acid HPMA copolymer was evaluated by tissue distribution experiment. The in vitro antitumor activity of gambogic acid HPMA copolymer was evaluated by pharmacodynamics experiment in mice. RESULTS: Two copolymers of gambogic acid HPMA were successfully prepared. The copolymers showed reduced cytotoxicity and a certain sustained release effect and targeting property. In vivo pharmacodynamic experiments also showed better anti-tumor effects than GA. DISCUSSION: In this study, gambogic acid was combined with HPMA polymer and the targeting molecule D-galactose/folic acid to form a polymer micelle with high efficiency, low toxicity and high selectivity for active-passive dual targeting. The construction of the drug system provides new ideas for future formulation research and development.

The feasibility and efficacy of a community-based multifactorial intervention to improve the cardiovascular risk factor control among patients with type 2 diabetes: A 2-year cluster randomized trial.

TRIAL DESIGN: Our study is to investigate the feasibility and effectiveness of multiple cardiovascular factors intervention (MFI) in type 2 diabetes patients in China's primary care setting. METHODS: We performed a cluster randomized trial to compare the proportion of patients achieved the targets between usual care group (control, 9 sites, n = 868) and MFI group (8 sites, n = 739) among patients with type 2 diabetes in primary care setting. Logistic regression model with random effects was used to estimate the association of the effect of intervention and the proportion achieved the targets. RESULTS: At baseline, the end of 1 year, and 2 years follow-up, the proportion of patients achieved all 3 target goals (HbA1c < 7.0%, blood pressure < 130/80 mm Hg and low-density lipoprotein cholesterol < 2.6 mmol/L) were 5.7%, 5.9%, 5.7% in the control group and 5.9%, 10.6%, 12.3% in the MFI group. After adjusting sex, age, diabetes duration, body mass index, HbA1c, blood pressure, and low-density lipoprotein cholesterol at baseline, there was no difference between the 2 groups (OR (95% CI): 1.27 (0.38-4.27) and 1.86 (0.79-4.38) for the first year and second year, respectively). When stratified by payment method, the patients with medical insurance or public expenses had a higher proportion achieved target goals (6.9% vs 16.4%, OR (95% CI): 2.30 (1.04-5.08)) in the second year. CONCLUSIONS: The controlling of cardiovascular risk factor targets remains suboptimal among patients with type 2 diabetes in primary care setting. MFI in type 2 diabetes improved cardiovascular disease risk profile, especially in the patients with medical insurance.

The complete chloroplast genome sequence of Clivia miniata var. citrina.

The complete chloroplast genome of Clivia miniata var. citrina was assembled and subjected to phylogenetic analysis in this study. The complete chloroplast genome of C. miniata var. citrina was 158,112 bp in length, containing a large single-copy region (LSC, 86,202 bp), a small single-copy region (SSC, 18,334 bp), and two inverted repeat regions (IRs, 26,788 bp). The GC content was 37.97%. A total of 130 genes were annotated, including 86 protein-coding genes, 36 tRNA and 8 rRNA genes. Phylogenetic analysis showed that C. miniata var. citrina was the most related with C. miniata and they formed a monophyletic group that was sister to the clade of Hippeastrum, Leucojum, Narcissus and Lysoris.