Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species

The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Effectiveness of groundwater extraction in Beijing since the ingauration of the first phase of the South-to-North Water Diversion Project, China

This study assess the effectiveness of groundwater pressure extraction in Beijing since the opening of the first phase of the South-to-North Water Diversion Project,using survey and evaluation methods.Firstly,an analysis of water consumption structure and the usage of diverted river water in Beijing in recent years was conducted.Secondly,the volume of groundwater pressure extraction in Beijing after the 33 project's inauguration was examined,revealing a decrease from 1.96 billion m^(3) in 2014 to 1.35 billion m^(3) in 2020.The proportion of water supply reduced from 52.3%in 2014 to 33.3%in 2020,leading to an optimized water supply structure.By the end of 2020,groundwater pressure extraction in Beijing is estimated at 446 million m3,with a substantial reduction in over-exploitation of groundwater.Groundwater resources have been effectively replenished,and the strategic reserve capacity has been enhanced.Furthermore,this study evaluates the change in groundwater levels as an indicator of the effectiveness of pressure extraction.The declining trend of groundwater levels in Beijing has been effectively mitigated,and there has been a consistent rebound in groundwater levels over the past five years.

Estimated prevalence and sociodemographic correlates of mental disorders in medical students of Hebei Province,China:A crosssectional study

BACKGROUND In China,the identification rate and treatment rate of mental disorders are low,and there are few surveys on the prevalence of mental disorders among college students using diagnostic tools such as Mini-International Neuropsychiatric Interview(MINI),so the prevalence and treatment of mental disorders among college students are unclear.AIM To estimate prevalence of mental disorders among medical students in Hebei Province,and provide guidance for improving their mental health.METHODS This was a cross-sectional study based on an Internet-based survey.Three levels of medical students in Hebei Province were randomly selected(by cluster sampling)for screening.Using the information network assessment system,the subjects scanned the 2D code with their mobile phones,clicked to sign the informed consent,and answered a scale.A self-designed general status questionnaire was used to collect information about age,gender,ethnicity,grade,and origin of students.The MINI 5.0.was used to investigate mental disorders.Data analysis was performed with SPSS software.Statistically significant findings were determined using a two-tailed P value of 0.05.RESULTS A total of 7117 subjects completed the survey between October 11 and November 7,2021.The estimated prevalence of any mental disorders within 12 mo was 7.4%.Mood disorders were the most common category(4.3%),followed by anxiety disorders(3.9%);15.0%had been to psychological counseling,while only 5.7%had been to a psychiatric consultation,and only 10%had received drug therapy in the past 12 mo.CONCLUSION Although the estimated prevalence of mental disorders in medical students is lower than in the general population,the rate of adequate treatment is low.We determined that improving the mental health of medical students is an urgent matter.

The role of pineal microRNA-325 in regulating circadian rhythms after neonatal hypoxic-ischemic brain damage

Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine,Soochow University,China(approval No.XD-2016-1)on January 15,2016.

Effects of Lycium barbarum polysaccharide on the photoinduced autophagy of retinal pigment epithelium cells

AIM:To investigate the relationship between autophagy and apoptosis in photoinduced injuries in retinal pigment epithelium(RPE)cells and how Lycium barbarum polysaccharide(LBP)contributes to the increased of RPE cells to photoinduced autophagy.METHODS:In vitro cultures of human RPE strains(ARPE-19)were prepared and randomly divided into the blank control,model,low-dose LBP,middle-dose LBP,high-dose LBP,and 3-methyladenine(3MA)groups.The viability of the RPE cells and apoptosis levels in each group were tested through cell counting kit-8(CCK8)method with a flow cytometer(Annexin V/PI double staining technique).The expression levels of LC3II,LC3I,and P62 proteins were detected with the immunofluorescence method.The expression levels of beclin1,LC3,P62,PI3K,P-mTOR,mTOR,P-Akt,and Akt proteins were tested through Western blot.RESULTS:LBP considerably strengthens cell viability and inhibits the apoptosis of RPE cells after photoinduction.The PI3K/Akt/mTOR signal pathway is activated because of the upregulation of the phosphorylation levels of Akt and mTOR proteins,and thus autophagy is inhibited.CONCLUSION:LBP can inhibit the excessive autophagy in RPE cells by activating the PI3K/Akt/mTOR signaling pathways and thereby protect RPE cells from photoinduced injuries.

Post-synthetic modifications of MOFs by different bolt ligands for controllable release of cargoes

Post-synthetic modifications(PSM)have drawn great attention as a vigoroso tool to tune or enhance the performance of metal-organic frameworks(MOFs).However,the current PSM method usually have to sacrifice the porosity of MOFs to enrich their functionality,such as pore space partition(PSP)and postsynthetic elimination and insertion(PSE&I),causing a trade-off in this aspect.To address this issue,we herein propose a new PSM strategy of using the size-matching ligands as the bolts to lock MOFs'pores,which could be anchored onto open metal sites(OMSs)after guest loading through a stepwise manipulation.As a result,the loaded cargoes undergo a controlled releasing process with respect to different bolt ligands.Our proposed strategy provides a promising way to balance the functionality and porosity of MOFs.

In vitro antioxidant activity of phenolic-enriched extracts from Zhangping Narcissus tea cake and their inhibition on growth and metastatic capacity of 4T1 murine breast cancer cells

Phenolics,as the main bioactive compounds in tea,have been suggested to have potential in the prevention of various human diseases.However,little is known about phenolics and their bioactivity in Zhangping Narcissue tea cake which is considered the most special kind of oolong tea.To unveil its bioactivity,three phenolic-enriched extracts were obtained from Zhangping Narcissue tea cake using ethyl acetate,n-butanol,and water.Their main chemical compositions and in vitro bioactivity were analyzed by high-performance liquid chromatography(HPLC)and ultraperformance liquid chromatography-mass spectrometry(UPLC-MS).The ethyl acetate fraction(ZEF)consisted of higher content of phenolics,flavonoids,procyanidins,and catechin monomers(including epigallocatechin gallate(EGCG),epicatechin gallate(ECG),and gallocatechin gallate(GCG))than n-butanol fraction(ZBF)and water fraction(ZWF).ZEF exhibited the strongest antioxidant capacity in vitro due to its abundant bioactive compounds.This was validated by Pearson correlation and hierarchical clustering analyses.ZEF also showed a remarkable inhibition on the growth,migration,and invasion of 4T1 murine breast cancer cells.

A thermosensitive chitosan-based hydrogel for controlled release of insulin

Present study aims at synthesizing a thermosensitive hydrogel for controlled release of insulin. According to a modified method, hydroxybutyl chitosan （HBC） hydrogel possessed thermal sensitivity is prepared which can form hydrogel at over 25℃. The HBC hydrogel is non-cytotoxic to mice fibroblasts cells （L929）. Insulin is 100% entrapped in the hydrogel, 38% of which is released in vitro from the concentration of 5% hydrogel after 48 h, whereas by enzymolysis with lysozyme, 80% of the total insulin is released after 48h. This study suggests that HBC hydrogel could be utilized for controlled release of insulin in a non-invasive manner.

Velocity Calculation by Automatic Camera Calibration Based on Homogenous Fog Weather Condition

A novel algorithm for vehicle average velocity detection through automatic and dynamic camera calibration based on dark channel in homogenous fog weather condition is presented in this paper. Camera fixed in the middle of the road should be calibrated in homogenous fog weather condition, and can be used in any weather condition. Unlike other researches in velocity calculation area, our traffic model only includes road plane and vehicles in motion. Painted lines in scene image are neglected because sometimes there are no traffic lanes, especially in un-structured traffic scene. Once calibrated, scene distance will be got and can be used to calculate vehicles average velocity. Three major steps are included in our algorithm. Firstly, current video frame is recognized to discriminate current weather condition based on area search method （ASM）. If it is homogenous fog, average pixel value from top to bottom in the selected area will change in the form of edge spread function （ESF）. Secondly, traffic road surface plane will be found by generating activity map created by calculating the expected value of the absolute intensity difference between two adjacent frames. Finally, scene transmission image is got by dark channel prior theory, camera s intrinsic and extrinsic parameters are calculated based on the parameter calibration formula deduced from monocular model and scene transmission image. In this step, several key points with particular transmission value for generating necessary calculation equations on road surface are selected to calibrate the camera. Vehicles pixel coordinates are transformed to camera coordinates. Distance between vehicles and the camera will be calculated, and then average velocity for each vehicle is got. At the end of this paper, calibration results and vehicles velocity data for nine vehicles in different weather conditions are given. Comparison with other algorithms verifies the effectiveness of our algorithm.

A corn straw-based diet increases release of inflammatory cytokines in peripheral blood mononuclear cells of dairy cows

Recent studies have shown that diet can affect the body＇s immunity. Roughage of dairy cows consists of a variety of plant materials which make different contributions to health. This study investigated the effect of different roughages on the immunity of dairy cows. Serum, peripheral blood mononuclear cells （PBMCs）, and milk samples were collected from 20 multiparous mid-lactation cows fed mixed forage （MF）- or corn straw （CS）-based diets. Ex- pression profile analysis was used to detect the differentially expressed genes （DEGs） from PBMCs. The results showed that milk protein in the MF group increased to 3.22 g/100 ml, while that of the CS group milk was 2.96 g/100 ml; by RNA sequencing, it was found that 1615 genes were differentially expressed between the CS group and the MF group among the 24027 analyzed probes. Gene ontology （GO） and pathway analysis of DEGs suggested that these genes （especially genes coding cytokines, chemokine and its receptors） are involved in the immune response. Results were confirmed at the protein level via detecting the levels of interleukin-2 （IL-2）, IL-6, IL-10, IL-12, leptin （LEP）, interferon-γ （IFN-γ）, transforming growth factor-βl （TGF-β1）, and tumor necrosis factor-α （TNF-α） in peripheral blood by enzyme-linked immunosorbent assay （ELISA） and radioimmunoassay analysis. Our data supported the conclusions that the protein content in milk of the MF group was higher than that of the CS group, the CS-based diets induced more release of cytokines than the MF-based diets in dairy cows＇ PBMCs, and milk protein content may be affected by cytokines.

Combination of ionic liquid dispersive liquid-phase microextraction and high performance liquid chromatography for the determination of triazine herbicides in water samples

A temperature-controlled ionic liquid dispersive liquid-phase microextraction in combination with high performance liquid chromatography was developed for the enrichment and determination of triazine herbicides such as cyanazine,simazine,and atrazine in water samples.1-Octyl-3-methylimidazolium hexafluorophosphate（[C8MIM][PF6]） was selected as the extraction solvent.Several experimental parameters were optimized.Under the optimal conditions,the linear range for cyanazine was in the concentration range of 0.5–80 mg/L and the linear range for simazine and atrazine was in the range of1.0–100 mg/L.The limit of detection（LOD,S/N = 3） was in the ranges of 0.05–0.06 mg/L,and the intra day and inter day precision（RSDs,n = 6） was in the ranges of 3.2%–6.6% and 4.8%–8.9%,respectively.Four real water samples were analyzed with the developed method,and the experimental results showed that the spiked recoveries were satisfactory.All these exhibited that the developed method was a valuable tool for monitoring such pollutants.

Response of prostate cancer to addition of dutasteride after progression on abiraterone

Dear Editor,Abiraterone has achieved great success in clinic by targeting cytochrome P45017A1(CYP17A)for prostate cancer therapy.1,2 However,drug resistance is inevitable and novel strategy is urgently required.Our previous work unveils a steroidal metabolic pathway for abiraterone in patients.3,4 Steroidogenic enzyme 3β-hydroxysteroid dehydrogenase 1(3βHSD1)catalyzes abiraterone toΔ4-abiraterone(D4A),which is further catalyzed to 5α-abiraterone(5α-Abi)by steroid-5α-reductase(SRD5A).The metabolite 5α-Abi binds to androgen receptor(AR)directly and activates AR signaling.