[Analysis of differential metabolites of spikes of Prunella vulgaris at different stages based on UPLC-MS/MS].

Prunella vulgaris, aptly named for its withering at the summer solstice, displays significant variation in quality arising from differing harvest time. However, research on the chemical composition changes of its spikes at various stages is limited, and the specific metabolites remain unclear. In order to elucidate the metabolites and metabolic pathways of the spikes of P. vulgaris, the current study deployed ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) and targeted metabolomics to characterize the compound variability in the spikes of P. vulgaris across different periods. Multivariate statistical techniques such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to identify the differences in metabolites, and relevant metabolic pathways were analyzed. A total of 602 metabolites were identified by metabolomics, of which organic acids and their derivatives were the most abundant, followed by flavonoids. Multiple differential metabolites, including p-hydroxybenzoic acids and gallic acids were identified based on variable importance in projection(VIP)>1 and P<0.05. The results of enrichment analysis suggested that isoflavonoids biosynthesis, aminobenzoate degradation, benzoate degradation, anthocyanins biosynthesis, metabolic pathways, microbial metabolism in different environments, secondary plant metabolite biosynthesis, tryptophan metabolism, and phenylpropanoid synthesis were the main metabolic pathways. These results intend to elucidate the dynamic changes of differential metabolites of P. vulgaris and provide a theoretical basis for further study of the harvesting mechanism of spikes of P. vulgaris.

Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.

Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob.

ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. AIM OF THE STUDY: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. MATERIALS AND METHODS: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G-, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. RESULTS: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. CONCLUSIONS: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G- bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.

Transcriptome data reveal beneficial effects of Rickettsia (Rickettsiales: Rickettsiaceae) on Bemisia tabaci (Hemiptera: Aleyrodidae) through nutritional factors and defense mechanisms.

Whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a destructive insect pest of many crops. Rickettsia infection in different cryptic species of B. tabaci has been observed worldwide. Understanding the interactions between these 2 organisms is critical to developing Rickettsia-based strategies to control B. tabaci and thereby reduce the transmission of related vector-borne viruses. In this study, we investigated the effects of Rickettsia infection on the biological characteristics of the Middle East Asia Minor 1 (MEAM1) strain of B. tabaci through biological analysis of infected and uninfected individuals. The results of this study suggest that Rickettsia may confer fitness benefits. These benefits include increased fertility, improved survival rates, accelerated development, and resulted in female bias. We also investigated the transcriptomics impact of Rickettsia infection on B. tabaci by performing a comparative RNA-seq analysis of nymphs and adult females, both with and without the infection. Our analysis revealed 218 significant differentially expressed genes (DEGs) in infected nymphs compared to uninfected ones and 748 significant DEGs in infected female adults compared to their uninfected whiteflies. Pathway analysis further revealed that Rickettsia can affect many important metabolic pathways in whiteflies. The results suggest that Rickettsia plays an essential role in energy metabolism, and nutrient synthesis in the B. tabaci MEAM1, and depends on metabolites obtained from the host to ensure its survival. Overall, our findings suggest that Rickettsia has beneficial effects on B. tabaci and offered insights into the potential molecular mechanisms governing the interactions between Rickettsia and B. tabaci MEAM1.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.

Behavioral and biochemical responses of the marine polychaete Perinereis aibuhitensis to 2-ethylhexyl-4-methoxycinnamate (EHMC) exposure.

2-ethylhexyl-4-methoxycinnamate (EHMC) is a commonly used UV filter, and is receiving increasing concerns due to its ubiquitous occurrence in a variety of environmental media and potential adverse effects. This study was aimed to assess the ecotoxicological potentials of EHMC on the marine polychaete Perinereis aibuhitensis. To this end, ragworms were exposed to 2, 20, 200 µg/L EHMC for 14 days and multiple toxicological endpoints were investigated. The results showed that EHMC significantly reduced burrowing rate, but did not affect AChE activity. Exposure to EHMC significantly elevated the activities of SOD and CAT and decreased the levels of lipid peroxidation. Besides, the induction of AKP activity indicated a stimulated immune response in the ragworms when exposed to high concentration of EHMC. Furthermore, the upregulated expression of caspase-8 suggested that EHMC might induce apoptosis in ragworms via the death receptor-mediated extrinsic pathway. Our findings highlight the potential environmental risks of EHMC to marine ecosystems.

The use of combined hormonal contraceptive for in-vitro fertilization cycle priming is not associated with decreased pregnancy rate in frozen embryo transfer cycles: a cohort study.

BACKGROUND: The objectives of this study are to evaluate the cycle outcomes from IVF treatment preceded by oral contraceptive pills (OCP) priming compared to estradiol pretreatment and to determine if there is a role for OCP priming for those undergoing frozen embryo transfers. METHODS: The study took place at a university-affiliated fertility center in Canada. The study included in-vitro fertilization (IVF) antagonist cycles from Jan 2016 to Jun 2019. Those with protocol deviation or treatment cancellation were excluded. RESULTS: There were 2237 cycles by 1958 patients; 27% of cycles utilized OCP priming. The average age in the OCP group was 34 years old compared to 36.5 in the estradiol group (P<0.01). AMH was reported in 43% of patients and was 3.7ng/mL in the OCP group versus 2.2 ng/mL in the estradiol group (P<0.01). The number of oocytes (15.2 vs. 12.5) and number of blastocysts (4.6 vs. 3.3) were higher in the OCP group (P all <0.01). After adjusting for age and AMH with linear regression for the 978 cycles with recorded AMH (24% with OCP prime), a significantly higher number of oocytes (13.8 vs. 11.9, P=0.002) was still noted in the OCP group. There were 866 euploid embryo transfer cycles (28% with OCP prime). There were no significant differences in implantation (77% vs. 76%) or ongoing pregnancy rates (56% vs. 54%) between those who had a frozen embryo transfer after OCP primed compared to estradiol primed stimulation cycles (P all >0.6). CONCLUSIONS: There were no differences in pregnancy outcomes from euploid frozen blastocyst transfers after OCP primed antagonist cycles compared to estradiol pretreatment. In fact, the use of OCP pretreatment was associated with increased oocyte yield, keeping in mind demographic differences with the OCP pretreatment group being younger with higher anti-Müllerian hormone and a higher prevalence of PCOS. Thus, OCP priming should still be considered in specific populations, such as those with oligo-ovulation or adequate ovarian reserve.

Reduction in NGAL at 48 h predicts the progression to CKD in patients with septic associated AKI: a single-center clinical study.

BACKGROUND: In this study, our objective was to investigate the predictive value of serum and urine fluctuations of neutrophil gelatinase-associated lipid transporters (NGAL) in relation to the progression of chronic kidney disease (CKD) among patients with septic associated AKI (SA-AKI). METHODS: A total of 425 SA-AKI patients were enrolled in this study and divided into the recovery group (n = 320) and the AKI-to-CKD group (n = 105) based on 3-month follow-up data. The serum and urine NGAL levels on the day of AKI diagnosis (T0) and 48 h after anti-AKI treatment (T1) were recorded and calculated. RESULTS: The levels of NGAL in serum and urine were found to be higher in the AKI-to-CKD group compared to the recovery group at T1 point (P < 0.05). The reductions of NGAL at 48 h in serum and urine were lower in the AKI-to-CKD group than those observed in the recovery group (P < 0.05). In comparison to T0, a significant decrease was noted for both serum and urine NGAL levels on T1 among patients who recovered from AKI (P < 0.05), whereas no such trend was observed among those with AKI-to-CKD transition (P > 0.05). After adjusting age, sex, and BMI through partial correlation analysis, the reduction of serum NGAL was found to be most strongly associated with the transition from AKI to CKD. ROC analysis showed an AUC of 0.832 for serum NGAL reduction, with a cut-off value of - 111.24 ng/ml and sensitivity and rates of 76.2% and 81.2%, respectively. Logistic regression analysis indicated that a reduction of serum NGAL ≥ - 111.24 ng/ml was the early warning indicator for the progression of CKD in SA-AKI patients. CONCLUSION: The reduction of serum NGAL following 48 h of anti-AKI therapy represents a distinct hazard factor for the advancement of CKD in patients with SA-AKI, independent of other variables.

Comparing safety and efficacy: MemoLefort versus watchman for left atrial appendage closure.

BACKGROUND: The MemoLefort is a new plug occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation (AF). This study compares the safety and efficacy of MemoLefort and the well-established Watchman occluder for LAAC. METHODS: Between January 2021 and September 2022, a cohort of 189 consecutive patients who underwent LAAC with MemoLefort or Watchman at The Second Affiliated Hospital of Wenzhou Medical University were included. Patients with MemoLefort or Watchman devices were compared in terms of the primary safety endpoints encompassing major periprocedural complications and major bleeding events at follow-up, the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death, and the combined hazard endpoint, a composite of all the above-mentioned hazards. RESULTS: Of the MemoLefort group (n = 83) and Watchman group (n = 106), the mean age, CHA2DS2-VASc score, and HAS-BLED score were 67.6 ± 9.2 vs. 69.0 ± 10.6 years, 3.9 ± 1.9 vs. 3.8 ± 1.9, and 1.6 ± 1.0 vs. 1.7 ± 1.2, respectively. After a median follow-up duration of 198 (99-329) vs. 334 (171-497) days, the primary endpoints of efficacy [2/49, 4.1% (MemoLefort) vs. 2/97, 2.1% (Watchman); hazard ratio (HR), 1.50; 95% confidence interval (CI), 0.20-11.08; P = 0.68] and safety (1/49, 2.0% vs. 5/97, 5.2%; HR, 0.26; 95% CI, 0.05-1.31; P = 0.19), as well as the combined hazard endpoint (3/49, 61% vs. 6/97, 6.2%; HR, 0.70; 95% CI, 0.18-2.58; P = 0.59) were similar between groups. CONCLUSIONS: In the short term, LAAC with MemoLefort provided similar efficacy, safety, and net clinical benefit in comparison to Watchman devices.

Uptake and toxicity of micro-/nanoplastics derived from naturally weathered disposable face masks in developing zebrafish: Impact of COVID-19 pandemic on aquatic life.

The unprecedented proliferation of disposable face masks during the COVID-19 pandemic, coupled with their improper disposal, threatens to exacerbate the already concerning issue of plastic pollution. This study evaluates the role of environmentally weathered masks as potential sources of microplastics (MPs) and nanoplastics (NPs) and assesses their adverse impact on the early life stages of zebrafish. Experimental findings revealed that a single disposable mask could release approximately 1.79 × 109 particles, with nearly 70% measuring less than 1 µm, following 60 days of sunlight exposure and subsequent sand-induced physical abrasion. Remarkably, the MPs/NPs (MNPs) emanating from face masks have the potential to permeate the outer layer (chorion) of zebrafish embryos. Furthermore, due to their minute size, these particles can be consumed by the larvae's digestive system and subsequently circulated to other tissues, including the brain. Exposure to mask-derived MNPs at concentrations of 1 and 10 µg/L led to significant cases of developmental toxicity, incited oxidative stress, and prompted cell apoptosis. A subsequent metabolomics analysis indicated that the accumulation of these plastic particles perturbed metabolic functions in zebrafish larvae, primarily disrupting amino acid and lipid metabolism. The outcomes of this research underscore the accelerating possibility of environmental aging processes and physical abrasion in the release of MNPs from disposable face masks. Most importantly, these results shed light on the possible ecotoxicological risk posed by improperly disposed of face masks.

Single-center retrospective assessment of robotic-assisted simultaneous pancreas-kidney transplants: Exploring clinical utility.

The diabetic population is witnessing a rise in obesity rates, creating specific hurdles for individuals seeking pancreas transplantation because they are frequently disqualified due to their elevated body weight. Introducing a robotic-assisted approach to transplantation has been proven to yield improved outcomes, particularly in patients with obesity. A retrospective analysis was conducted between January 2015 and September 2023. The study included a total of 140 patients, with 16 receiving robotic-assisted simultaneous pancreas-kidney transplantation (RSPK) and 124 undergoing open approach simultaneous pancreas-kidney transplantation (OSPK) during the study period. The median age was 45 (36.8-52.7) and 44.5 years (36.8-51.8) (RSPK vs OSPK, P = .487). There were no significant differences in demographics except body mass index (RSPK vs OSPK, 34.9 vs 28.1, P < .001) and a higher percentage of patients with high cardiac risk in the RSPK group. The robotic approach has a lengthier overall operative time and warm ischemia time. Surgical and nonsurgical complications at 30-days and 1-year grafts and patient survival (93.8% vs 96.8%, RSPK vs OSPK, P = .521) were similar. Our findings suggest that employing robotic assistance in simultaneous pancreas-kidney transplantation is safe. Wider adoption and utilization of this technique could potentially improve transplant accessibility for individuals with obesity and diabetes.

Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism / 中国药房

OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene pharm_chenjing@163.com family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （P＜ 0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （P＜0.01）. CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.

Konjac Mannan Oligosaccharides enhanced intestinal barrier function to improve alcoholic nervous injury / 中国药理学通报

Aim Excessive cerebral inflammation caused by chronic alcohol intake is an important risk factor for central nervous system injury. The purpose of this study was to explore the protective effect of konjac mannan oligosaccharide (KMOS) on central nervous system inflammation in alcohol-fed mice and its mechanism. Methods The chronic alcohol fed model of C57BL/6J mice was established using Gao-binge method. And the different doses of KMOS were gavaged every day for 6 weeks. The neuronal damage and microglia activation were evaluated in cerebral cortex and hippocampus. The damage of colon tissue was assessed and serum LPS concentrations were measured. In vitro, Caco-2 cells were stimulated with LPS to establish intestinal mucosal injury model. Results Chronic alcohol intake can cause brain neuron damage in mice, and different doses of KMOS effectively reduced the activation state of microglia, decreased the expression of inflammatory factors caused by the activation of the NLRP3 inflammasome and alleviated neuronal damage in the brain tissue of alcohol-fed mice. The results of colon tissue analysis showed that the use of KMOS effectively reduced the concentration of endotoxin LPS in serum of alcohol-fed mice, alleviated the pathological injury and inflammatory response of colon tissue, and enhanced the expression of Occludin in intestinal tissue. In vitro experiments also showed that KMOS significantly inhibited the inflammatory reaction of Caco-2 cells exposed to alcohol and increased the expression of Occludin protein. Conclusions KMOS treatment effectively inhibited intestinal inflammation caused by alcohol intake, repaired intestinal barrier to prevent the entry of intestinal LPS into brain tissue, decreased the activation of microglia, and then improved brain neuron damage. KMOS had the potential to prevent alcoholic nerve injury.

Neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating SIRT1/NF-κB signaling pathway / 中国药房

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB） signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group， sodium aescinate low-dose group （1.8 mg/kg）， sodium aescinate high-dose group （3.6 mg/kg）， sodium aescinate+EX527 （sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg） group， with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally， once a day， for 21 consecutive days. Twenty-four hours after the end of the last administration， the motor and cognitive functions of rats were detected， and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine （DA） in the nigrostriatal and the expression levels of tyrosine hydroxylase （TH） and α-synuclein （α-Syn） in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 （IL-6）， IL-18]， anti-inflammatory factor （IL-10）， and the expression levels of SIRT1， phosphorylated NF-κB p65 （p-NF-κB p65） and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group， the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group； the number of rotations， escape latency， the expression levels of α-Syn in substantia nigra， the levels of serum pro-inflammatory factors， the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly （P＜0.05）； the target quadrant residence time， the content of DA in nigrostriatal， the expression level of TH in substantia nigra， the serum level of anti-inflammatory factor， and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened （P＜0.05）. Compared with model group， the damage degrees of neuron in sodium aescinate groups were alleviated， and the quantitative indicators were significantly improved， which were more significant in the high-dose group （P＜0.05）； EX527 could reverse the improvement effect of high-dose sodium aescinate （P＜0.05）. CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1， thereby reducing the neuroinflammation of rats with Parkinson’s disease， improving the motor and cognitive dysfunctions， and finally playing a neuroprotective role.

Facet-Specific Photocatalytic Degradation of Extracellular Antibiotic Resistance Genes by Hematite Nanoparticles in Aquatic Environments.

The persistence of extracellular antibiotic resistance genes (ARGs) in aquatic environments has attracted increasing attention due to their potential threat to public health and the environment. However, the fate of extracellular ARGs in receiving water remains largely unknown. This study investigated the influence of hematite nanoparticles, a widespread natural mineral, on the photodegradation of extracellular ARGs in river water. Results showed that under exposure to visible light, hematite nanoparticles, at environmental concentrations, resulted in a 3-5 orders of magnitude reduction in extracellular ARGs. This photodegradation of extracellular ARGs is shown to be facet-dependent; the (001) facet of hematite demonstrates a higher removal rate than that of the (100) facet, which is ascribed to its enhanced adsorption capability and higher hydroxyl radical (•OH) production. Density functional theory (DFT) calculations corroborate this finding, indicating elevated iron density, larger adsorption energy, and lower energy barrier of •OH formation on the (001) facet, providing more active sites and •OH generation for extracellular ARG interaction. Gel electrophoresis and atomic force microscopy analyses further confirm that the (001) facet causes more substantial damage to extracellular ARGs than the (100) facet. These findings pave the way for predicting the photodegradation efficiency of hematite nanoparticles with varied facets, thereby shedding light on the inherent self-purification capacity for extracellular ARGs in both natural and engineered aquatic environments.

Knowledge About Renal Transplantation Among African, Caribbean, and Black Canadian Patients With Advanced Kidney Failure.

Introduction: Variable transplant-related knowledge may contribute to inequitable access to living donor kidney transplant (LDKT). We compared transplant-related knowledge between African, Caribbean, and Black (ACB) versus White Canadian patients with kidney failure using the Knowledge Assessment of Renal Transplantation (KART) questionnaire. Methods: This was a cross-sectional cohort study. Data were collected from a cross-sectional convenience sample of adults with kidney failure in Toronto. Participants also answered an exploratory question about their distrust in the kidney allocation system. Clinical characteristics were abstracted from medical records. The potential contribution of distrust to differences in transplant knowledge was assessed in mediation analysis. Results: Among 577 participants (mean [SD] age 57 [14] years, 63% male), 25% were ACB, and 43% were White Canadians. 45% of ACB versus 26% of White participants scored in the lowest tertile of the KART score. The relative risk ratio to be in the lowest tertile for ACB compared to White participants was 2.22 (95% confidence interval [CI]: 1.11, 4.43) after multivariable adjustment. About half of the difference in the knowledge score between ACB versus White patients was mediated by distrust in the kidney allocation system. Conclusion: Participants with kidney failure from ACB communities have less transplant-related knowledge compared to White participants. Distrust is potentially contributing to this difference.

Life-cycle exposure to tris (2-chloroethyl) phosphate (TCEP) causes alterations in antioxidative status, ion regulation and histology of zebrafish gills.

Tris (2-chloroethyl) phosphate (TCEP) has been receiving great concerns owing to its ubiquitous occurrence in various environmental compartments and potential risks to wildlife and humans. Gill is structural basis for ion regulation and homeostasis in fish and susceptible to xenobiotics. However, current knowledge on the impacts of long-term exposure to TCEP on the structure and physiological function of fish gills are insufficient. In this work, zebrafish were exposed to environmental realistic concentrations (0.8, 4, 20 and 100 µg/L) of TCEP from 3 h post ferterlization (hpf) till 120 days post ferterlization (dpf). Our results demonstrated that life-cycle exposure to TCEP significantly decreased the activity of glutathione S-transferase (GST), but elevated the activities of antioxidative enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased malondialdehyde (MDA) content in zebrafish gills. Gene transcription analysis implied that the mRNA expressions of antioxidant-related genes (nrf2, cat and nqo1) were induced, while the transcription of gstα1, hmox1, keap1 were down-regulated, indicating that Nrf2-Keap1 pathway might be activated to defend the oxidative stress induced by TCEP. Additionally, the ion homeostasis was disrupted by TCEP exposure, evidenced by reduced activities of Na+/K+-ATPase (NKA), Ca2+-ATPase and Mg2+-ATPase and downregulated transcription levels of ncc, nkcc, cftr and clc-3. Besides, whole-life exposure to TCEP resulted in a series of structural damages to gills, including epithelial lifting, epithelial rupture, telangiectasis, vacuolation, edema and shortened gill lamellae. Overall, our results demonstrated that long-term TCEP exposure could induce oxidative stress, affect ion regulation and cause histological changes in zebrafish gills.

The effect of image resolution on convolutional neural networks in breast ultrasound.

Purpose: The objective of this research was to investigate the efficacy of various parameter combinations of Convolutional Neural Networks (CNNs) models, namely MobileNet and DenseNet121, and different input image resolutions (REZs) ranging from 64×64 to 512×512 pixels, for diagnosing breast cancer. Materials and methods: During the period of June 2015 to November 2020, two hospitals were involved in the collection of two-dimensional ultrasound breast images for this retrospective multicenter study. The diagnostic performance of the computer models MobileNet and DenseNet 121 was compared at different resolutions. Results: The results showed that MobileNet had the best breast cancer diagnosis performance at 320×320pixel REZ and DenseNet121 had the best breast cancer diagnosis performance at 448×448pixel REZ. Conclusion: Our study reveals a significant correlation between image resolution and breast cancer diagnosis accuracy. Through the comparison of MobileNet and DenseNet121, it is highlighted that lightweight neural networks (LW-CNNs) can achieve model performance similar to or even slightly better than large neural networks models (HW-CNNs) in ultrasound images, and LW-CNNs' prediction time per image is lower.

A Dataset on the Dynamic Monitoring of Health and Family Planning of China's Internal Migrants: A Multi-Wave Large-Scale, National Cross-Sectional Survey from 2009 to 2018.

This data article presents data from the China Migrants Dynamic Survey (CMDS), a multi-wave, large-scale national cross-sectional survey of China's internal migrants from 2009 to 2018. The CMDS is an annual questionnaire survey conducted by the former National Health and Family Planning Commission (NHFPC) of the People's Republic of China. The respondents included in this survey are internal migrants over 15 years old. The sample was drawn from the China Migrant Population Information System, using multi-stage stratified sampling method and the probability proportional-to-size (PPS) cluster sampling strategy. Between 2009 and 2018, there were 1,527,650 internal migrants from 23 provinces, 5 autonomous regions and 4 municipalities participated in the surveys. The survey tools were a series of self-designed questionnaires with high inheritance and consistency designed and implemented by the NHFPC. The questionnaires mainly contain basic information of the respondents and their family members, migration status, healthcare or health behaviors, public health service utilization, social insurance, social integration, and family planning. The dataset is currently the most widely used survey data on China's internal migrants, offering information on migration patterns, healthcare and health behaviors, use of public health services, access to social security, social integration, and family planning, which are valuable for health planning, health decision-making, and health equity research.

A novel chiral oxazoline copper(II)-based complex inhibits ovarian cancer growth in vitro and in vivo by regulating VEGF/VEGFR2 downstream signaling pathways and apoptosis factors.

A novel chiral oxazoline copper(II)-based complex {[Cu(C13H14NO3S)2]}2 (Cu-A) was synthesized by an in situ reaction using L-methioninol, 4-hydroxyisophthalaldehyde, sodium hydroxide and copper(II) nitrate trihydrate as reactants. Its crystal structure was characterized. In vitro, Cu-A was superior to cis-dichlorodiammineplatinum (DDP) in cytotoxicity and angiogenesis inhibition. Cu-A significantly induced apoptosis of ovarian cancer cells (SKOV3) and human umbilical vein endothelial cells (HUVECs), showing significant anti-ovarian cancer and anti-angiogenesis effects. Notably, Cu-A significantly inhibits the growth of ovarian cancer in nude mice xenografted with SKOV3 cells, and it is less renal toxic than DDP. The molecular mechanism of anti-ovarian cancer and anti-angiogenesis is possibly that it down-regulates the expression of the proteins ERK1/2, AKT, FAK, and VEGFR2 and their phosphorylated proteins p-ERK1/2, p-AKT, p-FAK, and p-VEGFR2 in the VEGF/VEGFR2 signal transduction pathway to inhibit SKOV3 cell and HUVEC proliferation, induce apoptosis, suppress migration and metastasis, and inhibit angiogenesis. What's more, Cu-A significantly inhibits ovarian tumor growth in vivo by inhibiting tumor cells from inducing vascular endothelial cells to form their own vasculature and by inhibiting the expression of the anti-apoptotic protein Bcl-2 and up-regulating the expression of the pro-apoptotic proteins Caspase-9 and Bax to induce apoptosis of tumor cells.