Molecular cloning and characterization of a salt overly sensitive3 (SOS3) gene from the halophyte Pongamia.

A high concentration of sodium (Na+) is the primary stressor for plants in high salinity environments. The Salt Overly Sensitive (SOS) pathway is one of the best-studied signal transduction pathways, which confers plants the ability to export too much Na+ out of the cells or translocate the cytoplasmic Na+ into the vacuole. In this study, the Salt Overly Sensitive3 (MpSOS3) gene from Pongamia (Millettia pinnata Syn. Pongamia pinnata), a semi-mangrove, was isolated and characterized. The MpSOS3 protein has canonical EF-hand motifs conserved in other calcium-binding proteins and an N-myristoylation signature sequence. The MpSOS3 gene was significantly induced by salt stress, especially in Pongamia roots. Expression of the wild-type MpSOS3 but not the mutated nonmyristoylated MpSOS3-G2A could rescue the salt-hypersensitive phenotype of the Arabidopsis sos3-1 mutant, which suggested the N-myristoylation signature sequence of MpSOS3 was required for MpSOS3 function in plant salt tolerance. Heterologous expression of MpSOS3 in Arabidopsis accumulated less H2O2, superoxide anion radical (O2-), and malondialdehyde (MDA) than wild-type plants, which enhanced the salt tolerance of transgenic Arabidopsis plants. Under salt stress, MpSOS3 transgenic plants accumulated a lower content of Na+ and a higher content of K+ than wild-type plants, which maintained a better K+/Na+ ratio in transgenic plants. Moreover, no development and growth discrepancies were observed in the MpSOS3 heterologous overexpression plants compared to wild-type plants. Our results demonstrated that the MpSOS3 pathway confers a conservative salt-tolerant role and provided a foundation for further study of the SOS pathway in Pongamia.

Small-molecule agonist AdipoRon alleviates diabetic retinopathy through the AdipoR1/AMPK/EGR4 pathway.

BACKGROUND: Diabetes mellitus (DM) is a progressive disease that involves multiple organs due to increased blood glucose, and diabetic retinopathy (DR) is the main complication of DM in the eyes and causes irreversible vision loss. In the pathogenesis of diabetic vascular disease, oxidative stress caused by hyperglycemia plays an important role in Müller cell impairment. In recent years, AdipoRon, an adiponectin analog that demonstrated important physiological functions in obesity, diabetes, inflammation, and cardiovascular diseases, demonstrated cellular protection from apoptosis and reduced inflammatory damage through a receptor-dependent mechanism. Here, we investigated how AdipoRon reduced oxidative stress and apoptosis in Müller glia in a high glucose environment. RESULTS: By binding to adiponectin receptor 1 on Müller glia, AdipoRon activated 5' adenosine monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase phosphorylation downstream, thereby alleviating oxidative stress and eventual apoptosis of cells and tissues. Transcriptome sequencing revealed that AdipoRon promoted the synthesis and expression of early growth response factor 4 (EGR4) and inhibited the cellular protective effects of AdipoRon in a high-glucose environment by reducing the expression of EGR4. This indicated that AdipoRon played a protective role through the EGR4 and classical AMPK pathways. CONCLUSIONS: This provides a new target for the early treatment of DR.

Integration of Vitreous Lipidomics and Metabolomics for Comprehensive Understanding of the Pathogenesis of Proliferative Diabetic Retinopathy.

As a vision-threatening complication of diabetes mellitus (DM), proliferative diabetic retinopathy (PDR) is associated with sustained metabolic disorders. Herein, we collected the vitreous cavity fluid of 49 patients with PDR and 23 control subjects without DM for metabolomics and lipidomics analyses. Multivariate statistical methods were performed to explore relationships between samples. For each group of metabolites, gene set variation analysis scores were generated, and we constructed a lipid network by using weighted gene co-expression network analysis. The association between lipid co-expression modules and metabolite set scores was investigated using the two-way orthogonal partial least squares (O2PLS) model. A total of 390 lipids and 314 metabolites were identified. Multivariate statistical analysis revealed significant vitreous metabolic and lipid differences between PDR and controls. Pathway analysis showed that 8 metabolic processes might be associated with the development of PDR, and 14 lipid species were found to be altered in PDR patients. Combining metabolomics and lipidomics, we identified fatty acid desaturase 2 (FADS2) as an important potential contributor to the pathogenesis of PDR. Collectively, this study integrates vitreous metabolomics and lipidomics to comprehensively unravel metabolic dysregulation and identifies genetic variants associated with altered lipid species in the mechanistic pathways for PDR.

Improvement of vaginal probiotics Lactobacillus crispatus on intrauterine adhesion in mice model and in clinical practice.

BACKGROUND: Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration of L. crispatus could prevent endometrial fibrosis and ameliorate IUA. RESULTS: First, we created a mechanically injured mouse model of IUA and restored the mice's vaginal microbiota by the addition of L. crispatus convolvulus. The observations suggested that intrauterine injections of L. crispatus significantly decreased the degree of uterine fibrosis, the levels of IL-1ß and TNF-α in blood, and downregulated the TGF-ß1/SMADs signaling pathway in IUA mice. A therapy with L. crispatus considerably raised the abundance of the helpful bacteria Lactobacillus and Oscillospira and restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect of L. crispatus with estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen. CONCLUSIONS: This study confirmed that L. crispatus could restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/ , identifier (ChiCTR1900022522), registration time: 15/04/2019.

Changes in vaginal microbiome after focused ultrasound treatment of high-risk human papillomavirus infection-related low-grade cervical lesions.

BACKGROUND: In this study, the changes of vaginal microbiome after focused ultrasound (FU) treatment were evaluated to explore the possible mechanism of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection. METHODS: This study was nested in the FU arm of a prospective cohort study. A total of 37 patients diagnosed with HR-HPV infection-related cervical low-grade squamous intraepithelial lesion (LSIL) who met the inclusion criteria were enrolled in this study from October 2020 to November 2021, and these patients were treated with FU. We used 16S ribosomal RNA (16S rRNA) gene amplicon sequencing to profile the vaginal microbiota composition of patients before and 3 months after FU treatment. RESULTS: After FU treatment, HR-HPV was cleared in 24 patients, with a clearance rate of 75.0% (24/32). Lactobacillus iners was the predominant species among all samples. No significant difference was found in alpha-diversity index before and 3 months after FU treatment (P > 0.05), but the rarefaction curves showed that the vaginal microbial diversity before FU treatment was higher than that after FU treatment. Linear discriminant analysis (LDA) effect size (LEfSe) showed that Bifidobacterium contributed the most to the difference between the two groups at the genus level, and the abundance after FU treatment was significantly higher than that before treatment (P = 0.000). CONCLUSIONS: The decrease of vaginal microbial diversity may be related to the clearance of HR-HPV infection, and FU treatment contributed to the decrease of vaginal microbial diversity. Increased Bifidobacterium abundance in the vaginal microbiome may be associated with clearance of HR-HPV infection, and FU treatment may contribute to the increase in Bifidobacterium abundance. TRIAL REGISTRATION NUMBER:  This study was registered in the Chinese Clinical Trial Registry on 23/11/2020 (ChiCTR2000040162).

Efficacy and pregnancy outcomes of focused ultrasound for cervical high-grade squamous intraepithelial lesions.

OBJECTIVE: To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients. METHODS: This retrospective study recruited 57 patients aged 20-40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023. RESULTS: During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46-6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed. CONCLUSION: FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes.

Serum Ang-1/Ang-2 ratio may be a promising biomarker for evaluating severity of diabetic retinopathy.

PURPOSE: To investigate the predictive role of serum angiopoietin-1 and angiopoietin-2 (Ang-1/Ang-2) in evaluating the severity of diabetic retinopathy (DR). METHODS: A total of 101 outpatients with type 2 diabetes mellitus (T2DM) were recruited and were further divided into the following five groups: T2DM without DR (non-DR), mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR) in accordance with the International Clinical Diabetic Retinopathy Guidelines. Furthermore, 101 serum samples were included in the further analysis using enzyme-linked immunosorbent assays. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of each index. RESULTS: The expression of Ang-1 in the PDR group was significantly lower than that in the non-DR group, while Ang-2 showed an opposite upward trend (p < 0.05). The Ang-1/Ang-2 ratio of the non-DR group was significantly lower than that of the moderate NPDR, severe NPDR and PDR (p < 0.05, p < 0.01 and p < 0.01, respectively). Differences in the Ang-1/Ang-2 ratio were observed earlier than those in the individual Ang-1 and Ang-2 measurements. The maximal Youden index was 0.512 with a calculated area under the curve (AUC) value of 0.734 (p < 0.01). CONCLUSIONS: The Ang-1/Ang-2 ratio was helpful in assessing the severity of DR and may provide potential clinical benefits as a biomarker and early warning signs for DR diagnosis.

Focused ultrasound for high-risk human papillomavirus infection-related low-grade cervical lesions: a prospective cohort study.

OBJECTIVES: To assess the efficacy and safety of focused ultrasound (FU) for high-risk human papillomavirus (HR-HPV) infection-related cervical low-grade squamous intraepithelial lesions (LSIL). METHODS: Of 185 patients who met the inclusion criteria for this prospective study from October 2020 to November 2021, 95 received FU and 90 were followed up only. At the six-month follow-up, the HR-HPV clearance and LSIL regression rates of the groups were compared and factors affecting HR-HPV clearance were analyzed. The safety and side effects of FU were evaluated. RESULTS: No significant difference was found in the baseline clinical data between the two groups (p > 0.05). At the six-month follow-up, the HR-HPV clearance rates were 75.6% in the FU group and 25.6% in the observation group (p = 0.000). The LSIL regression rates were 89.5% in the FU group and 56.4% in the observation group (p = 0.000). Multivariate logistic regression analysis showed that the HR-HPV clearance rate in the FU group was 9.03 times higher than that in the observation group (95% confidence interval [CI], 3.75-21.73, p = 0.000), and the clearance rate of single-type HR-HPV infections was 5.28 times higher than that of multi-type infections (95% CI, 1.83-15.23, p = 0.002). The mean intraoperative bleeding was 1.8 ± 0.6 (1-3) mL; the mean intraoperative pain score was 2.6 ± 1.0 (1-6). CONCLUSIONS: For patients with HR-HPV infection-related histological LSIL, FU can eliminate HR-HPV infection and cause lesions to regress in a short time, with few adverse effects and good tolerance.

[Preparation of microemulsion gel loading enriched ingredients of Epimedii Folium and its pharmacodynamics evaluation].

On the basis of previous studies, this study prepared and evaluated microemulsion gel loading enriched ingredients of Epimedii Folium and investigated its protective effect against peripheral nervous system damage caused by chemotherapeutics. The preparation method and the type and dosage of the matrix were investigated from rheology, preparation difficulty, and drug loading. Then the optimal prescription was determined and the microemulsion gel loading enriched ingredients of Epimedii Folium was prepared. The in vitro release and transdermal behaviors of the gel were investigated in the Franz diffusion cell with epimedin A1,A,B,C, and icariin as evaluation indicators. The oxaliplatin-induced peripheral neuropathy(OIPN) model was established in Wistar rats. The protective effect of the microemulsion gel loading enriched ingredients of Epimedii Folium against peripheral nervous system damage caused by chemotherapeutics was evaluated by behavioral measurement after drug administration and histopathological examination of dorsal root ganglia and sciatic nerve. The preparation process of the microemulsion gel loading enriched ingredients of Epimedii Folium was stable, and the release of the five components was consistent with the Hixson-Crowell cube root law. Behavioral indicators intuitively showed that the drug could effectively relieve mechanical allodynia caused by oxaliplatin. The histopathological examination showed that the drug can improve neuron damage in the dorsal root ganglia, axon degeneration, and demyelination caused by oxaliplatin. Therefore, the preparation process of the microemulsion gel loading enriched ingredients of Epimedii Folium is feasible, which can achieve stable drug release. It has a certain therapeutic effect on chemotherapy-induced peripheral neuropathy(CIPN).

Multiple lenses athermalization and achromatization by the quantitative replacement method of combined glasses on athermal visible glass map.

This report proposes an athermalization and achromatization method based on combined glasses and comprehensive distance weight to select and replace optical and housing tube materials quantitatively without multiple iterations. In addition, it presents a new achromatic and athermal condition of the replacement search method using combined glasses. It establishes an athermal glass map model combining the cluster center, tube materials, two combined lenses, and a rest equivalent lens to analyze the characteristics of the glass distribution. A cluster analysis method was introduced to analyze the distribution characteristics of the athermal glass map in the visible catalog. The athermal ability of the housing tube and the replacement of combined glass material are evaluated by distance weight in athermal glass map. A complex aerial multiple lenses system was designed using this method and maintained high imaging quality from -40 °C to 70 °C. This method can reduce the number of iterations for the selection of combined glass and significantly improves the optimization efficiency of athermalization.

Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma.

BACKGROUND: Icaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway. METHODS: Real-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting. RESULTS: Our results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis. CONCLUSION: Our findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

Single cell RNA sequencing (scRNA-Seq) deciphering pathological alterations in streptozotocin-induced diabetic retinas.

Diabetic retinopathy (DR) is an irreversible and progressive diabetic complication leading to visual impairment, even blindness. Due to the delicate and complicated structure of the retina, the pathology of DR has not been completely elucidated yet. We constructed a transcriptome atlas of >14,000 single cells from healthy and streptozotocin (STZ)-induced diabetic murine retinas to decipher pathological alterations of DR. We found four stress-inducible genes Cirbp, Rmb3, Mt1 and Mt2 commonly induced in most types of retinal cells. Bipolar cells were little affected on both number and gene expression. Diabetes increased expression of inflammatory factor genes in retinal microglia, and stimulated expression of immediate early genes (IEGs) in retinal astrocytes. A large number of genes were deregulated in diabetic vascular endothelial cells (ECs), and the differentially expressed genes were paired to the pathways functioning in metabolism, shear stress and vascular permeability. These pathways were mapped by more deregulated genes in a subpopulation of ECs specifically presented in diabetic retinas (diabetic retinal ECs, DRECs). Moreover, several inflammation pathways were activated in DRECs, and the most significant one is the IL-17 signaling pathway. According to the EC markers, DRECs were mainly capillary ECs, confirmed by immunofluorescent staining of S100a9, a target gene of the IL-17 signaling pathway. This study deciphered pathological alterations of DR, and provided clues for potential targets for DR therapy.

Successive biochar amendment affected crop yield by regulating soil nitrogen functional microbes in wheat-maize rotation farmland.

Biochar has attracted increased attention because of its potential benefits for carbon sequestration, soil fertility, and contaminant immobilization. However, mechanism of long-term successive biochar amendment affected crop yield by regulating soil properties and nitrogen (N) functional microbes is still unclear by now. A field fixed experiment was carried out from 2011 to 2018 that aimed to study the effects of successive biochar on soil properties, soil nitrogen functional microbial genes, and grain yield in wheat and maize rotation farmland in Northern China. Four straw biochar treatments were tested in this study: 0 (BC0, CK), 2.25 (BC2.25), 6.75 (BC6.75), and 11.25 (BC11.25) Mg ha-1. The results showed that, after seven wheat-maize rotations, the total organic carbon (TOC), total N (TN), NO3-, available potassium (AK), and the C/N ratio in 0-20 cm topsoil were increased significantly following biochar application; however, there were no obvious differences in available phosphorus (AP) and NH4+ among biochar treatments. Biochar also resulted in a significant increase in crop yield and NO3- accumulation in 0-200 cm soil layer, with the highest yield in BC6.75. Furthermore, a marked increase was found in the amoA gene abundance in topsoil; however, it decreased significantly with excessive biochar application (BC11.25). At wheat maturity, the nirS gene abundance consistently decreased following biochar application, whereas the nosZ gene abundance initially increased and then decreased (peaking in BC6.75); however, no obvious changes in the nirK gene were observed. At maize maturity, biochar significantly increased the nirS and nosZ gene abundance in topsoil, especially in BC6.75. In addition, redundancy analysis indicated that the soil moisture content, AP, AK, TN, TOC, NO3-, NH4+, pH, and C/N ratio had markedly effects on the abundance of the amoA, nirK, nirS, and nosZ genes. In general, biochar-induced alterations of soil properties resulted in changes of gene abundance of soil nitrifying and denitrifying bacteria, and eventually affecting crop yields.

Effectiveness of focused ultrasound for high risk human papillomavirus infection-related cervical lesions.

OBJECTIVE: The purpose of this study was to compare the efficacy of focused ultrasound (FU) and interferon drug therapy for cervical intraepithelial neoplasia 1 (CIN1) and chronic cervicitis associated with high risk human papillomavirus (HR-HPV) infection, as well as analyze the influencing factors. METHODS: A retrospective cohort study was performed from January 2017 to December 2019. A total of 592 patients were enrolled, of which 300 patients were treated with FU and 292 patients were treated with interferon drugs. Kaplan-Meier curves and a COX regression model were used to compare the curative effects of the two therapeutic methods using HR-HPV clearance as the main outcome. The relationship between age, HR-HPV infection type, pathological type, preoperative HR-HPV status and HR-HPV clearance were also analyzed. RESULTS: The median time for HR-HPV clearance was 6.00 months (95% CI: 5.24-6.76) in the FU group and 26.00 months (95% CI: 22.32-29.68) in the medication group. A significant difference was observed between the two groups (χ2 =198.902, p = 0.000). The HR-HPV clearance rate was 4.927 (95% CI 3.840-6.321; p = 0.000) times higher in the patients treated with FU than those treated with interferon drugs. In the FU group, no significant difference was observed in HR-HPV clearance rate between CIN1 and chronic cervicitis (χ2=0.660, p = 0.416), which was also insignificant between HR-HPV persistent and non-persistent infections (χ2=0.751, p = 0.386). CONCLUSION: FU therapy can eliminate HR-HPV infections in a short period of time. Moreover, the treatment efficacy of FU was significantly superior to that of interferon drugs.

Method for exposure dose monitoring and control in scanning beam interference lithography.

To improve grating manufacturing process controllability in scanning beam interference lithography (SBIL), a novel method for exposure dose monitoring and control is proposed. Several zones in a narrow monitoring region are fabricated on a grating substrate by piecewise uniform scanning. Two monitoring modes are given based on the different widths of the monitoring region. The monitoring curve of the latent image diffraction efficiency to scanning velocity is calculated by rigorous coupled wave analysis. The calculation results show that the exposure dose in SBIL can be monitored by the shape change of the monitoring curve, and an optimized scanning velocity can be selected in the monitoring curve to control the exposure dose.

Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells.

Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.

Isolation and Functional Characterization of a Salt-Responsive Calmodulin-Like Gene MpCML40 from Semi-Mangrove Millettia pinnata.

Salt stress is a major increasing threat to global agriculture. Pongamia (Millettia pinnata), a semi-mangrove, is a good model to study the molecular mechanism of plant adaptation to the saline environment. Calcium signaling pathways play critical roles in the model plants such as Arabidopsis in responding to salt stress, but little is known about their function in Pongamia. Here, we have isolated and characterized a salt-responsive MpCML40, a calmodulin-like (CML) gene from Pongamia. MpCML40 protein has 140 amino acids and is homologous with Arabidopsis AtCML40. MpCML40 contains four EF-hand motifs and a bipartite NLS (Nuclear Localization Signal) and localizes both at the plasma membrane and in the nucleus. MpCML40 was highly induced after salt treatment, especially in Pongamia roots. Heterologous expression of MpCML40 in yeast cells improved their salt tolerance. The 35S::MpCML40 transgenic Arabidopsis highly enhanced seed germination rate and root length under salt and osmotic stresses. The transgenic plants had a higher level of proline and a lower level of MDA (malondialdehyde) under normal and stress conditions, which suggested that heterologous expression of MpCML40 contributed to proline accumulation to improve salt tolerance and protect plants from the ROS (reactive oxygen species) destructive effects. Furthermore, we did not observe any measurable discrepancies in the development and growth between the transgenic plants and wild-type plants under normal growth conditions. Our results suggest that MpCML40 is an important positive regulator in response to salt stress and of potential application in producing salt-tolerant crops.

[Enhancing effect and mechanism of muscone on transdermal penetration of traditional Chinese medicine ingredients with different log P value].

This study aimed to investigate the enhancing effect of muscone on the transdermal penetration of traditional Chinese medicine ingredients and explore its possible mechanism of action. The Franz diffusion cells were employed to investigate the effect of muscone on the transdermal permeation of a series of model drugs with a wide range of log P values. The solubilities at saturation and the stratum corneum(SC)/vehicle partition coefficients of model drugs were measured to evaluate the effect of muscone on drug thermodynamic activities and partition of drugs into SC. Attenuated total reflectance-Fourier transform infrared spectroscopy(ATR-FTIR) was employed to explore the effect of muscone on the molecular structure of SC. The results showed that muscone significantly promoted the transdermal penetration of hydrophilic and lipophilic drugs, and the enhancement ratio(ER) increased with the decrease in the log P. Muscone could interact with the SC lipids to increase the disorder and fluidity of lipid bilayer packing, which improved skin permeability and promoted transdermal absorption of drugs. This study provides a scientific basis for the application of muscone in traditional Chinese medicine topical preparations.

Time trends analysis of statin prescription prevalence, therapy initiation, dose intensity, and utilization from the hospital information system of Jinshan Hospital, Shanghai (2012-2018).

BACKGROUND: Statin remains a mainstay in the prevention and treatment of cardiovascular diseases. Statin utilization has evolved over time in many countries, but data on this topic from China are quite limited. This study aimed to investigate the changing trends of statins prescription, as well as detail the statin utilization through a successive longitudinal study. METHODS: The prescription database was established based on electronic health records retrieved from the hospital information system of Jinshan Hospital, Fudan University from January 2012 to December 2018 in Shanghai, China. The prescription rates and proportions of different statin types and doses among all patients were examined. Sub-analyses were performed when stratifying the patients by age, gender, dose intensity, and preventative intervention. RESULTS: During the study period, a total of 51,083 patients, who were prescribed for statins, were included in this study (mean [SD] age, 59.78 [±13.16] years; 53.60% male, n = 27, 378). The overall statins prescription rate in which patients increased from 2012 (1.24, 95% CI: 1.21-1.27%) to 2018 (3.16, 95% CI: 3.11-3.20%), P < 0.001. Over 90% of patients were given a moderate dose of statins. Patients with a history of coronary and cerebrovascular events (over 32%) were more likely to be prescribed with statins for preventative intervention. Furthermore, our study has witnessed a significant rise in statin therapy in primary and secondary prevention. CONCLUSIONS: In conclusion, statins were frequently prescribed and steadily increased over time in our study period. There were also changes in statin drug choices and dosages. A coordinated effort among the patient, clinical pharmacist, stakeholders and health system is still needed to improve statin utilization in clinical practice in the future.

Long Non-Coding RNA MACC1-AS1 Is Involved in Distant Recurrence of Hepatocellular Carcinoma After Surgical Resection.

BACKGROUND We explored the role of MACC1-AS1 in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Measurement of preoperative plasma levels of MACC1-AS1 was performed by qPCR, and the comparison between the HCC and Control group was performed by unpaired t test. The overexpression of TGF-ß1 in SNU-182 and SNU-398 cells was confirmed by qPCR. RESULTS MACC1-AS1 was overexpressed in HCC patients. In comparison to pretreatment level, distant recurrence (DR) was accompanied by increased levels of MACC1-AS1 in plasma, but this phenomenon was not observed in cases of local recurrence (LR) or non-recurrence (NR). In HCC cells, MACC1-AS1 positively regulated the expression of TGF-ß1. MACC1-AS1 overexpression resulted in increased invasion and migration rates of HCC cells, while siRNA silencing resulted in reduced rates. Moreover, TGF-ß1 overexpression reduced the effects of MACC1-AS1 siRNA silencing. CONCLUSIONS MACC1-AS1 is involved in the distant recurrence of HCC, and its actions are possibly mediated by TGF-ß1.