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.

Panax notoginseng Saponins Ameliorate Gamma Radiation-Mediated Damages in Human Peripheral Blood Monocytes and Swiss Albino Mice.

In this study, the protective effects of Panax notoginseng saponins (PNS) against gamma radiation-induced DNA damage and associated physiological alterations in Swiss albino mice were investigated. Exposure to gamma radiation led to a dose-dependent increase in cytokinesis-blocked micronuclei (CBMN) double-strand DNA breaks (DSBs), dicentric aberrations (DC), formation in peripheral blood mononuclear cells. However, pretreatment with PNS at concentrations of 1, 5, and 10 µg/mL significantly attenuated the frequencies of DC and CBMN in a concentration-dependent manner. PNS administration before radiation exposure also reduced radiation-induced DSBs in BL, indicating protection against reactive oxygen species generation and DNA damage. Notably, pretreatment with PNS at 10 µg/mL prevented the overexpression of γ-H2AX, proteins associated with DNA damage response, in irradiated mice. In addition, in vivo studies showed intraperitoneal administration of PNS (25 mg/kg body weight) for 1 h before radiation exposure mitigated lipid peroxidation levels and restored antioxidant status, countering oxidative damage induced by gamma radiation. Furthermore, PNS pretreatment reversed the decrease in hemoglobin (Hb) content, white blood cell count, and red blood cell count in irradiated mice, indicating preservation of hematological parameters. Overall, PNS demonstrated an anticlastogenic effect by modulating radiation-induced DSBs and preventing oxidative damage, thus highlighting its potential as a protective agent against radiation-induced DNA damage and associated physiological alterations. Clinically, PNS will be beneficial for cancer patients undergoing radiotherapy, but their pharmacological properties and toxicity profiles need to be studied.

An Indole-Chalcone Inhibits Multidrug-Resistant Cancer Cell Growth by Targeting Microtubules.

Multidrug resistance and toxic side effects are the major challenges in cancer treatment with microtubule-targeting agents (MTAs), and thus, there is an urgent clinical need for new therapies. Chalcone, a common simple scaffold found in many natural products, is widely used as a privileged structure in medicinal chemistry. We have previously validated tubulin as the anticancer target for chalcone derivatives. In this study, an α-methyl-substituted indole-chalcone (FC77) was synthesized and found to exhibit an excellent cytotoxicity against the NCI-60 cell lines (average concentration causing 50% growth inhibition = 6 nM). More importantly, several multidrug-resistant cancer cell lines showed no resistance to FC77, and the compound demonstrated good selective toxicity against cancer cells versus normal CD34+ blood progenitor cells. A further mechanistic study demonstrated that FC77 could arrest cells that relate to the binding to tubulin and inhibit the microtubule dynamics. The National Cancer Institute COMPARE analysis and molecular modeling indicated that FC77 had a mechanism of action similar to that of colchicine. Overall, our data demonstrate that this indole-chalcone represents a novel MTA template for further development of potential drug candidates for the treatment of multidrug-resistant cancers.

[Identification of Fertilized Chicken Eggs Based on Visible/Near-Infrared Spectrum During Early Stage of Incubation].

In the process of chicken egg hatching, some eggs can not be hatched successfully due to the absence of fertilization. These eggs not only cause a lot of waste, but also infect other normal eggs with bacteria. In the study, the fertilized eggs and clear eggs is identified by using the visible/near-infrared spectrum. It is of great necessity to get the best time of identifying the clear eggs in the early of hatching, so the variation of eggs' quality in the condition of hatching over time is studied. The results show that eggs are fresh after 24 hours' hatching and eggs can not be eaten after 72 hours' hatching while the best time of identification is within 36 hours. Static acquisition system is developed based on visible/near-infrared transmission spectrum for acquiring spectrum. Comparing the effect of the model of the different samples of same breed and samples of different breed, the different part of spectrum among fertilized eggs and clear eggs is deleted which caused by the color of eggshell and yolk, the effective spectral band are 355～590 and 670～1 025 nm. Adopting the pretreatment of PCA and comparing the accuracy of the various mathematical models with different time and the number of principal components decide the best number of principal components. Considering the production efficiency and comparing the different pretreatment methods of spectrum, for examples, SNV, MSC, Derivative correction and PCA, and various mathematical models are combined to establish the most efficient discriminant model. The result shows that the most efficient discriminant model is established with Fisher and based on the pretreatment of PCA after 24 hours' hatching. And the precision rate is 87.18%. The study provides a new way for nondestructive and online identification of the fertilized eggs and clear eggs.

Lentibacillus populi sp. nov., a moderately halophilic, endophytic bacterium isolated from a poplar tree, and emended description of the genus Lentibacillus.

A Gram-staining-positive, moderately halophilic, aerobic, endospore-forming, rod-shaped bacterial strain, designated WD4L-1T was isolated from surface-sterilized stem tissue of a poplar tree planted in the Wudalianchi National Geopark of Heilongjiang province, PR China. This novel isolate grew in the presence of 0-15 % (w/v) NaCl, at pH 6.0-9.0 and 15-50 °C; optimum growth was observed with 7-8 % (w/v) NaCl, at pH 7.0 and 30 °C. The 16S rRNA gene sequence analysis indicated that the strain WD4L-1T belonged to the genus Lentibacillus, and was most closely related to Lentibacillus garicola SL-MJ1T with a sequence similarity of 96.1 %. The DNA G+C content of strain WD4L-1T was determined to be 36.9 mol%. The respiratory quinone was identified as menaquinone-7 (MK-7) and the major lipids were diphosphatidylglycerol and phosphatidylglycerol and one unidentified phospholipid. The major fatty acids of strain WD4L-1T were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. The results of the physiological and biochemical tests and the minor differences in the fatty acid profiles allowed a clear phenotypic differentiation of strain WD4L-1T from the closely related Lentibacillus garicola JCM 30131T. Thus, strain WD4L-1T represents a novel species of the genus Lentibacillus, for which the name Lentibacillus populi sp. nov. is proposed. The type strain is WD4L-1T (=CGMCC 1.15454T=DSM 101738T). An emended description of the genus Lentibacillus is also provided.

4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization.

Anti-inflammatory and in-vitro antibacterial activities of Traditional Chinese Medicine Formula Qingdaisan.

BACKGROUND: Qingdaisan (Formulated Indigo powder, QDS) are widely used for treatment of aphtha, sore throat and bleeding gums in China. The aim of the study is to evaluate the anti-inflammatory, antibacterial and dental ulcer therapeutic effects of QDS. METHODS: Dimethylbenzene-induced ear edema test and cotton pellet-induced granuloma test were used to evaluate anti-inflammatory activities of QDS on acute and chronic inflammatory. The healing time and local pathologic changes were used to assess the therapeutic effects of QDS on dental ulcer. The antibacterial activities of each component and the whole formulation of QDS were determined by agar well diffusion assay. High-dose and low-dose QDS were tested in this experiment and Gui Lin Watermelon Frost Powder (GLWFP) was used as positive control. RESULTS: Oral treatment with QDS significantly accelerated the healing of ulcerative lesions induced by phenol injury. The dental ulcers of high-dose QDS group were all healed within 6 days. It was shorter than those of low-dose QDS group and GLWFP group. Less quantity of inflammatory cells and plenty fibroblasts were observed in pathological section of QDS groups. QDS also exhibited significant anti-inflammatory activity both in acute and chronic animal models. Although some of the components exhibited antibacterial activities, the whole formulation of QDS didn't show any significant antibacterial activity in vitro. CONCLUSION: The study showed that QDS has obviously anti-inflammatory activity for both acute and chronic inflammatory, also has a remarkable effect for healing dental ulcer caused by phenol. QDS didn't have antibacterial activity to selected strains in vitro.

Association between the cytotoxic T-lymphocyte antigen 4 +49A/G polymorphism and bladder cancer risk.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by downregulating T cell activation. The most studied CTLA-4 +49A/G polymorphism has been associated with various cancers risks. However, little is known about the association between CTLA-4 +49A/G polymorphism and bladder cancer risk. A hospital-based case-control study was conducted in 300 patients with bladder cancer and 300 healthy controls matched with age and sex. The CTLA-4 +49A/G polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism. Patients with bladder cancer had a significantly lower frequency of CTLA-4 +49GG genotype [odds ratio (OR) = 0.44, 95 % confidence interval (CI) = 0.23, 0.85; P = 0.01] and G allele (OR = 0.73, 95 % CI = 0.56, 0.96; P = 0.02) than healthy controls. When stratifying by the stage, grade, and histological type of bladder cancer, we found no statistical association. This is the first study to highlight the significant association between CTLA-4 +49A/G polymorphism and bladder cancer risk. Additional studies are needed to confirm this finding.

Perception matters: How air pollution influences life satisfaction in China.

Academic studies on environmental pollution have convincingly acknowledged the salient relevance of ambient pollutant emissions on individual life satisfaction. However, an understanding of how the different dimensions of air pollution influence public self-assessment of their living condition is required. This research investigates whether objective pollutant emissions and subjective evaluation influence individual life satisfaction. The findings were based on data from the China Environment Yearbook and China Social Survey in 2019. The multi-level linear regression model found that air pollutants emissions, including particulate matter (PM) and sulfur dioxide (SO2), failed to explain the variations in public life satisfaction because of the lag effect of public perception. A significant nexus between perceived air pollution and public life satisfaction was observed at a significance level of 0.01. Specially, as the perceived air pollution by the public increased by one-point, life satisfaction decreased by 0.22 on a scale of 1-10, on average. Heterogeneous analysis based on income further suggested the salient negative effect of PM emissions on life satisfaction only occurred in the high-income group. The findings were robust after various methodological analyses. This study has theoretical implications for understanding the effects of air pollution on public subjective perception and provides guidance for how the government can manage the relationship between environmental governance and life satisfaction.

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.

A new crystalline daidzein-piperazine salt with enhanced solubility, permeability, and bioavailability.

To overcome the poor solubility, permeability, and bioavailability of the plant isoflavone daidzein (DAI), a novel salt of DAI with anhydrous piperazine (PIP) was obtained based on cocrystallization strategy. The new salt DAI-PIP was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, and optical microscopy. The results showed that the maximum apparent solubility (Smax) of DAI-PIP increased by 7.27-fold and 1000-fold compared to DAI in pH 6.8 buffer and water, respectively. The peak apparent permeability coefficient (P app ) of DAI-PIP in the Caco-2 cell model was 30.57 ± 1.08 × 10-6 cm/s, which was 34.08% higher than that of DAI. Additionally, compared to DAI, the maximum plasma concentration (Cmax) value of DAI-PIP in beagle dogs was approximately 4.3 times higher, and the area under the concentration-time curve (AUC0-24) was approximately 2.4 times higher. This study provides a new strategy to enhance the dissolution performance and bioavailability of flavonoid drugs, laying a foundation for expanding their clinical applications.

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.

Effects of supplemental feeding of Chinese herbal mixtures to perinatal sows on antioxidant capacity and gut microbiota of sows and their offspring piglets.

The stress response of pig herds poses a significant challenge in the pig breeding industry, and investigating strategies to mitigate this stress is of paramount importance. The objective of this study was to investigate the impacts of supplemental feeding of Chinese herbal mixtures to perinatal sows on antioxidant capacity and gut microbiota of sows and their offspring piglets. A total of 60 healthy sows (Large white) at fourth parity were randomly assigned to five treatment groups. The control group received a basal diet, while the TRT1 group received a basal diet supplemented with 2kg/t Bazhen powder (BZP). The TRT2, TRT3, and TRT4 groups were fed a basal diet supplemented with 1kg/t, 2kg/t, and 3kg/t Qi-Zhu- Gui-Shao soothing liver and replenishing blood powder (QZGSP), respectively. The trial lasted for 5weeks, starting from day 100 of gestation until day 21 of delivery. The results demonstrated that the inclusion of 2kg/t and 3kg/t QZGSP significantly enhanced the antioxidant capacity of sows and their offspring piglets to different degrees, thereby effectively alleviating oxidative stress. Analysis of gut microbiota revealed that QZGSP influenced the composition of gut microbiota in both sows and their offspring piglets. Specifically, at the genus level, the abundance of Christensenellaceae_R-7_group in the gut microbiota of sows in the TRT4 group was significantly lower than that in the TRT1 group (p < 0.05), while the relative abundance of Lactobacillus in the gut microbiota of sows in the TRT4 group was significantly higher than that in the CON group (p < 0.05). Furthermore, at the genus level, compared to those in the TRT1 group, piglets from the TRT4 group exhibited a significant decrease in relative abundance of Escherichia-Shigella, Parabacteroides, and Methanobrevivacter (p < 0.05), but a significant increase in Phascolarctobacterium (p < 0.05). Spearman correlation analysis indicated a positive correlation between relative abundance of Christensenellaceae_R-7_group and serum contents of T-AOC and CAT (p < 0.05), as well as a negative correlation with serum concentration MDA (p < 0.05). Additionally, there was a positive correlation between relative abundance Lactobacillus and serum levels SOD (p < 0.01) and GSH-Px (p < 0.05). Therefore, supplementation of 3kg/t QZGSP in the periparturient sow diet significantly augmented antioxidant capacity in both sows and offspring piglets, while concurrently modulating the composition and structure of their intestinal microflora. The findings from this study demonstrate that QZGSP represents a beneficial feed additive for perinatal sows.

Application value of magnetic resonance spectroscopy imaging in the diagnosis of prostate cancer.

Magnetic resonance spectroscopy (MRSI) can distinguish between benign and malignant prostate diseases. This study investigated the potential of MRSI for diagnosing prostate cancer and guiding prostate biopsy. We retrospectively reviewed 234 patients with suspected prostate cancer who underwent MRSI with targeted prostate biopsy. Patients were divided into two groups according to their puncture pathology: prostate cancer (n = 103, 44.02%) and benign prostatic disease (n = 131, 55.98%). The t-test, Mann-Whitney U test, or chi-square test was used to compare the groups. The diagnostic abilities of MRSI, prostate-specific antigen level, digital rectal examination, and magnetic resonance imaging without contrast for prostate cancer were compared using the area under the receiver operating characteristic curve (AUC-ROC); the ARC-ROC values were 0.831, 0.768, 0.692, and 0.656, respectively. The AUC-ROC value for diagnosing prostate cancer using the CC/c ratio was 0.853. CC/c ratio > 0.97 was identified as the optimal threshold for diagnosing prostate cancer (sensitivity, 86.5%; specificity, 78.6%; Youden index, 0.651). Spearman correlation analysis revealed a correlation between the CC/c ratio and Gleason score (r = 0.737, p < 0.001). Using the CC/c ratio of MRSI as an adjunct to targeted prostate biopsy can improve the detection rate of positive biopsies and evaluate prostate cancer invasiveness.

Alterations of meat quality, lipid composition and flavor in breast meat of laying hens with fatty liver hemorrhagic syndrome.

Fatty liver hemorrhagic syndrome (FLHS) has a high incidence rate in laying hens, and lots of FLHS-affected meat products enter the market every year. At the same time, the meat of laying hens is an important component of the human diet. However, the impact of FLHS on meat of laying hens is unknown, which could have a negative impact on consumers. To explore the effects of FLHS on chicken breast meat, a total of 36 twenty-five-wk-old Jingfen laying hens were used in the experiment. The hens were randomly divided into Control group and Model group, with 6 replicates per group and 3 hens per replicate. All chickens were raised in double-story step cages with individual pens. After a 3-wk acclimation period, the formal experiment began at 28 wk of age and lasted for 8 wk. Blood, liver, and breast meat samples were collected for the study of FLHS effects on breast meat. The impact of FLHS on meat quality was assessed by measuring indicators such as water-holding capacity and tenderness of the breast meat. Absolute quantitative lipidomics was employed to reveal the impact of FLHS on the lipid composition of chicken breast meat, and then validated by using RT-qPCR. Moreover, the volatilomics was utilized to detect changes in volatile organic compounds (VOCs) in chicken breast meat and to elucidate the resulting flavor changes. This research results showed that the meat quality of chicken breast meat decreased under FLHS, mainly manifested as reduced water holding capacity and decreased tenderness. The lipid content in the breast meat of FLHS-affected hens was significantly increased (P < 0.05). Among the affected lipids, 38 triglycerides exhibited notable elevation, possibly linked to heightened gene expression, such as lysophosphatidylcholine acyltransferase 3. The breast meat of laying hens with FLHS demonstrated an increased presence of VOCs, with 20 differential VOCs identified. Notably, 14 VOCs, particularly in 2-Undecenal, trans-Geranylacetone and ethyl nonanoate, exhibited substantial increases. These 3 VOCs had been identified as playing an important role in the formation of flavor in the breast meat of FLHS-affected laying hens. Correlation analysis suggested that the increase in these 3 VOCs might be related to the increase in lipid molecules such as phosphatidylethanolamine (38;3e) and acyl carnitine (10:3). In summary, FLHS reduced the breast meat quality of laying hens, altered its lipid profiles, and enhanced its flavor. These findings underscore the profound impact of FLHS on lipid and VOC profiles in chicken breast meat, offering valuable insights for chicken meat quality affected by FLHS.

Predictive value of NCCT quantitative analysis for proximal and middle impacted ureteral stones.

The purpose of the study was to explore the predictive value of preoperative quantitative NCCT analysis for proximal and middle ureteral stone impaction. Data of 128 patients who diagnosed with proximal and middle ureteral stones were analyzed. Stone size, upper diameter of the ureter(D1), lower diameter of the ureter (D2), CT attenuation of the ureter above the stone (HA, 'HU above'), CT attenuation of the ureter below the stone (HB, 'HU below'), CT attenuation values of the stone's proximal segments (C1), CT attenuation values of the stone's distal segments (C2), and ureteral wall thickness(UWT)were recorded. Logistic regression was used to perform univariate and multivariate analyses of the data to determine the independent predictors of proximal and middle ureteral stone impaction. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performance. Among the 128 patients, 52 (40.6%) had impacted stones, while 76 (59.4%) did not. Multivariate logistic regression analysis showed that stone size > 9.45 mm (OR = 1.372, 95% CI = 1.071-1.756, P = 0.012), UWT > 3.22 mm (OR = 4.217, 95% CI = 2.165 ~ 8.213, P < 0.001)、DDR > 2.10 (OR = 4.901, 95% CI = 1.797 ~ 13.365, P = 0.002)and HBA > 1.58 (OR = 5.237,95% CI = 1.502 ~ 18.259, P = 0.009)were independent risk factors for predicting ureteral stone impaction. In conclusion, stone size, UWT, DDR, and HBA show crucial predictive value for impaction of stones.

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.

Poria cocos polysaccharide-loaded Alum Pickering emulsion as vaccine adjuvant to enhance immune responses.

Traditional Alum adjuvants mainly elicit a Th2 humoral immune response, but fail to generate a robust Th1 cellular immune response. However, the cellular immune response is essential for vaccination against cancer and a number of chronic infectious diseases, including human immunodeficiency virus infection and tuberculosis. In our previous study, we demonstrated that the polysaccharide from Poria cocos (PCP) has the potential to serve as an immunologic stimulant, enhancing both humoral and cellular immune responses. However, this effect was only observed at high concentrations. In this study, to enhance the immune-stimulation effect of PCP and modify the type of immune response elicited by Alum adjuvant, we successfully developed a Pickering emulsion delivery system (PCP-Al-Pickering) using PCP-loaded Alhydrogel particles as the stabilizer. After optimization, the Pickering emulsion exhibited excellent storage capacity and effectively adsorbed the PCP and antigen. As an adjuvant delivery system, the PCP-Al-Pickering emulsion facilitated the antigen uptake by macrophages, increased the recruitment of cells at injection sites, improved the activation of dendritic cells in draining lymph nodes, elicited a potent and durable antibody response, and promoted the activation of CD4+ and CD8+ T cells. Importantly, the PCP-Al-Pickering emulsion adjuvant elicited a balanced Th1 and Th2 immune response, in comparison to Alum adjuvant. The PCP-Al-Pickering emulsion may serve as a safe and promising adjuvant delivery system to enhance immune responses.

Research progress of propofol in alleviating cerebral ischemia/reperfusion injury.

Ischemic stroke is a leading cause of adult disability and death worldwide. The primary treatment for cerebral ischemia patients is to restore blood supply to the ischemic region as quickly as possible. However, in most cases, more severe tissue damage occurs, which is known as cerebral ischemia/reperfusion (I/R) injury. The pathological mechanisms of brain I/R injury include mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium overload, neuroinflammation, programmed cell death and others. Propofol (2,6-diisopropylphenol), a short-acting intravenous anesthetic, possesses not only sedative and hypnotic effects but also immunomodulatory and neuroprotective effects. Numerous studies have reported the protective properties of propofol during brain I/R injury. In this review, we summarize the potential protective mechanisms of propofol to provide insights for its better clinical application in alleviating cerebral I/R injury.

Structural characterization and adjuvant activity of a water soluble polysaccharide from Poria cocos.

Adjuvants, as the essential component of vaccines, are crucial in enhancing the magnitude, breadth and durability of immune responses. Unfortunately, commonly used Alum adjuvants predominantly provoke humoral immune response, but fail to evoke cellular immune response, which is crucial for the prevention of various chronic infectious diseases and cancers. Thus, it is necessary to develop effective adjuvants to simultaneously induce humoral and cellular immune response. In this work, we obtained a water soluble polysaccharide isolated and purified from Poria cocos, named as PCP, and explored the possibility of PCP as a vaccine adjuvant. The PCP, with Mw of 20.112 kDa, primarily consisted of →6)-α-D-Galp-(1→, with a small amount of →3)-ß-D-Glcp-(1 â†’ and →4)-ß-D-Glcp-(1→. Our results demonstrated that the PCP promoted the activation of dendritic cells (DCs) and macrophages in vitro. As the adjuvant to ovalbumin, the PCP facilitated the activation of DCs in lymph nodes, and evoked strong antibody response with a combination of Th1 and Th2 immune responses. Moreover, compared to Alum adjuvant, the PCP markedly induced a potent cellular response, especially the cytotoxic T lymphocytes response. Therefore, we confirmed that the PCP has great potential to be an available adjuvant for simultaneously inducing humoral and cellular immune responses.