Expression and function of long non-coding RNA DLX6-AS1 in endometrial cancer

Background:LncRNA DLX6-AS1 has been uncovered to exert effects on various cancers.Nevertheless,the impacts of DLX6-AS1 on endometrial cancer(EC)development remained obscure.The study explored the influence of DLX6-AS1 on EC progression via the microRNA(miR)-374a-3p/zinc-finger protein(ZFX)axis.Methods:EC cell lines were collected and DLX6-AS1,miR-374a-3p,and ZFX levels in EC cell lines were detected.The EC cells were transfected with DLX6-AS1,miR-374a-3p,and ZFX constructs to examine the biological functions of EC cells.The xenograft model was established for detecting tumor growth.Rescue experiments were conducted to verify the interaction of DLX6-AS1,miR-374a-3p,and ZFX in EC cells.Results:DLX6-AS1 and ZFX levels were elevated,while miR-374a-3p exhibited a reduced level in EC cells.Silencing DLX6-AS1 and elevated miR-374a-3p expressions repressed the biological activities of EC cells.Reduced DLX6-AS1 repressed tumor development.MiR-374a-3p silencing reversed the impacts of DLX6-AS1 silencing,while ZFX overexpression abrogated the impacts of miR-374a-3p elevation on EC cell growth.Mechanically,DLX6-AS1 was found to bind to miR-374a-3p,and miR-374a-3p targeted ZFX.Conclusion:DLX6-AS1 depletion restricts the malignant phenotype of EC cells.The study might provide novel therapeutic biomarkers for EC treatment.

The Impacts of Maternal Gestational Diabetes Mellitus (GDM) on Fetal Hearts

Objective To evaluate the fetal cardiac function in gestational diabetes mellitus （GDM） pregnancies under different maternal glycemic controls. Methods Forty four GDM mothers received 78 fetal echocardiographic evaluations at three gestational periods （〈28, 28-34 and ≥34 weeks） and were divided into poorly-（DM1） and well-（DM2） controlled groups according to their glycemic control at examination. Seventy uncomplicated mothers were selected as controls. Parameters of fetal cardiac anatomy and function were measured and analyzed. Results GDM fetuses＇ cardiac ventricular walls were thicker than controls＇, and the differences between DM1 and DM2 were not significant except for end-diastolic left ventricular walls. In both GDM groups, the aortic flow velocities increased earlier than pulmonary artery and DM1 fetuses changed earlier than DM2 ones. GDM fetuses＇ left atrial shortening fraction was smaller than the controls＇ in the period of ≥34 weeks and negatively correlated with thicknesses of left ventricular walls and interventricular septum in DM1 fetuses （r=-0.438 and -0.506）. The right ventricular diastolic function in DM1 and DM2 fetuses decreased after the period of 28-34 weeks and in the period of ≥34 weeks respectively. Tel index of both left and right ventricles increased in DM1 group after the period of 〈28 weeks and in DM2 group only in the period of ≥ 34 weeks, with no significant differences between DM1 and DM2 groups in this period. Conclusion Fetuses of GDM mothers showed cardiac function impairments. Good maternal glycemic control may delay the impairments, but cannot reduce the degree. Some cardiac changes in GDM fetuses were similar to those in pregestational diabetic pregnancies except for several parameters and their changing time.

Evaluating the Nutritional Status of Oncology Patients and Its Association with Quality of Life

Objective The primary aim of the study was to compare two nutritional status evaluation tools： the Patient-Generated Subjective Global Assessment（PG-SGA） and Nutritional Risk Screening（NRS-2002）. Using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30（EORTC QLQ-C30）, the second aim was to provide constructive advice regarding the quality of life of patients with malignancy. Methods This study enrolled 312 oncology patients and assessed their nutritional status and quality of life using the PG-SGA, NRS-2002, and EORTC QLQ-C30. Results The data indicate that 6% of the cancer patients were well nourished. The SGA-A had a higher sensitivity（93.73%） but a poorer specificity（2.30%） than the NRS-2002（69.30% and 25.00%, respectively） after comparison with albumin. There was a low negative correlation and a high similarity between the PG-SGA and NRS-2002 for evaluating nutritional status, and there was a significant difference in the median PG-SGA scores for each of the SGA classifications（P 〈 0.001）. The SGA-C group showed the highest PG-SGA scores and lowest body mass index. The majority of the target population received 2 points for each item in our 11-item questionnaire from the EORTC QLQ-C30. Conclusion The data indicate that the PG-SGA is more useful and suitable for evaluating nutritional status than the NRS-2002. Additionally, early nutrition monitoring can prevent malnutrition and improve the quality of life of cancer patients.

Endometrial Mucin-1 and Pinopode in Peri-implantation Phase in Ovarian High Responders during Controlled Ovarian Hyperstimulation Cycles

Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response was defined as serum E2 〉 15 000 pmol/L on the day of hCG administration in COH cycle using GnRH agonist and recombinant FSH （n=8）. Healthy and fertile women were used as the natural control （n=10）. Endometrial biopsies were performed on the day of LH＋ 7/hCG＋ 7. Pinopode formation was observed by scanning electron microscope. Expression of MUC1 was detected with quantitative Real-time PCR and immunohistochemistry. Results In high response group, the lumen surface was covered with variant pinopodes and microvillous. The expression of MUC1 mRNA in high response group was lower than that in the natural control （P〈0.05）. Immunostaining for MUC1 protein in glandular and luminal epithelium in high response group was lower than that in the natural control （P〈0. 05）. Conclusion Asynchronized pinopode appearance and lower expression of MUC1 during peri-implantation period were the characteristics of endometrium in high response group, Which may provide a clue of decreased endometrial receptivity in the supraphysiological hormone milieu.

PERINATAL FETAL WELL-BEING MONITORING: A COMPARISON BETWEEN RANDOMIZED URINARY ESTRIOL/CREATININE AND SERUM FREE ESTRIOL DETERMINATION

Randomized urinary and blood samples were obtained from three hundred and ninety-two cases of late pregnancies simultaneously for comparison of the validity in perinatal fetal monitoring. The results of randomized urinary estriol/creatinine （RUE3/C） and serum free estriol （SFE3） tests revealed that Ⅰ. The coefficient of correlation between RUE3/C and SFE3 level were close in either normal or high-risk pregnancies （y=0.1477X+14.2368, r=0.4586, n=170; y=0.1724X+8.6698, r=0.5868, n=222, respectively, P【0.001）; 2.92%cases of the false positive rate of RUE3/C were corrected by SFE3 test. In cases of pregnancy-induced hypertension （PIH） the false positive rate of RUE3/C were highest in comparison with those in cuses of other high-risk pregnancies （53.6%）; 3. The correct rate of SFE3 test in prenatal predication of fetal well-being was significantly higher （95.6%） than that of RUE3/C （87.3%） （X2=17.77, P【0.001）. This paper suggests that RUE3/C can be used as a first line test for perinatal monitoring. When RUE3/C value is lower than normal, SFE3 test should be added to ensure the reliability of perinatal diagnosis, especially in PIH cases. Obviously, to use these two tests for perinatal fetal monitoring simultaneously is better than to use any one test alone.

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

Ovarian cancer(OV)is highly heterogeneous tumor with a very poor prognosis.Studies increasingly show that T cell exhaustion is prognostically relevant in OV.The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis.The single RNA-sequencing(scRNA-seq)data of five OV patients were analyzed,and six major cell clusters were identified after threshold screening.Further clustering of T cell-associated clusters revealed four subtypes.Pathways related to oxidative phosphorylation,G2M checkpoint,JAK-STAT and MAPK signaling were significantly activated,while the p53 pathway was inhibited in the CD8+exhausted T cells.The standard marker genes of CD8+T cell exhaustion were screened to develop a T-cell related gene score(TRS)based on random forest plots in TCGA cohort.The patients with low TRS have better prognosis compared to the patients with high TRS in both TCGA and GEO.In addition,most genes included in the TRS showed significant differences in expression levels between the high-and low-risk groups.Immune cell infiltration was analyzed using the MCPcounter and xCell algorithms,which revealed significant differences between the two risk groups,indicating that the different prognoses may stem from the respective immune landscapes.In addition,CD38 knockdown in OV cell lines increased apoptosis and inhibited invasion in vitro.Finally,we performed a drug sensitivity analysis and identified six potential drug candidates for OV.To summarize,we identified the heterogeneity and clinical significance of T cell exhaustion in OV and built a superior prognostic model based on T cell exhaustion genes,which can contribute to the development of more precise and effective therapies.

Hepatoprotective effects of baicalein against CCl 4-induced acute liver injury in mice

AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic baicalein was given twice a day for 4 d.The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement.Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation.Serum interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6,TNF-α,transforming growth factor-α(TGF-α),hepatocyte growth factor(HGF) and epidermal growth factor(EGF) genes expression were determined by quantitative real-time polymerase chain reaction.RESULTS:CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice.The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl 4 treatment in baicalein administration groups,but at 24,48 and 72 h,the expression of IL-6 and TNF-α was kept at lower levels compared with the control.The expression of TGF-α,HGF and EGF was enhanced dramatically in baicalein administration group at 12,24,48 and 72 h.Furthermore,we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase,which indicated that baicalein could facilitate the initiating events in liver regeneration.CONCLUSION:Baicalein may be a therapeutic candidate for acute liver injury.Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.

Comparison of the Reference Intervals Used for the Evaluation of Maternal Thyroid Function During Pregnancy Using Sequential and Nonsequential Methods

Background： Maternal thyroid dysfunction is common during pregnancy, and physiological changes during pregnancy can lead to the overdiagnosis of hyperthyroidism and misdiagnosis of hypothyroidism with nongestation-specific reference intervals. Our aim was to compare sequential with nonsequential methods for the evaluation of thyroid function in pregnant women. Methods： We tested pregnant women who underwent their trimester prenatal screening at our hospital from February 2011 to September 2012 for serum thyroid stimulating hormone （TSH） and free thyroxine （FT4） using the Abbott and Roche kits. There were 447 and 200 patients enrolled in the nonsequential and sequential groups, respectively. The central 95% range between the 2.5th and the 97.5th percentiles was used as the reference interval for the thyroid function parameter. Results： The nonsequential group exhibited a significantly larger degree of dispersion in the TSH reference interval during the 2nd and 3rd trimesters as measured using both the Abbott and Roche kits （all P 〈 0.05）. The TSH reference intervals were significantly larger in the nonsequential group than in the sequential group during the 3rd trimester as measured with both the Abbott （4.95 vs. 3.77 mU/L, P 〈 0.001） and Roche kits （6.62 vs. 5.01 mU/L, P〈 0.004）. The nonsequential group had a significantly larger FT4 reference interval as measured with the Abbott kit during all trimesters （ 12.64 vs. 5.82 pmol/L; 7,96 vs. 4.77 pmol/L; 8.10 vs. 4.77 pmol/L, respectively, all P 〈 0.05）, whereas a significantly larger FT4 reference interval was only observed during the 2nd trimester with the Roche kit （7.76 vs. 5.52 pmol/L, P = 0.002）. Conclusions： It was more reasonable to establish reference intervals for the evaluation of maternal thyroid function using the sequential method during each trimester of pregnancy. Moreover, the exclusion of pregnancy-related complications should be considered in the inclusion criteria for thyroid function tests.

Microglia in neurodegenerative diseases

A major feature of neurodegeneration is disruption of central nervous system homeostasis,during which microglia play diverse roles.In the central nervous system,microglia serve as the first line of immune defense and function in synapse pruning,injury repair,homeostasis maintenance,and regulation of brain development through scavenging and phagocytosis.Under pathological conditions or various stimulations,microglia proliferate,aggregate,and undergo a variety of changes in cell morphology,immunophenotype,and function.This review presents the features of microglia,especially their diversity and ability to change dynamically,and reinterprets their role as sensors for multiple stimulations and as effectors for brain aging and neurodegeneration.This review also summarizes some therapeutic approaches for neurodegenerative diseases that target microglia.

An appropriate level of autophagy reduces emulsified isoflurane-induced apoptosis in fetal neural stem cells

Autophagy plays essential roles in cell survival.However,the functions and regulation of the autophagy-related proteins Atg5,LC3B,and Beclin 1 during anesthetic-induced developmental neurotoxicity remain unclear.This study aimed to understand the autophagy pathways and mechanisms that affect neurotoxicity,induced by the anesthetic emulsified isoflurane,in rat fetal neural stem cells.Fetal neural stem cells were cultured,in vitro,and neurotoxicity was induced by emulsified isoflurane treatment.The effects of pretreatment with the autophagy inhibitors 3-methyladenine and bafilomycin and the effects of transfection with small interfering RNA against ATG5(siRNA-Atg5)were observed.Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,and apoptosis was assessed using flow cytometry.Ultrastructural changes were analyzed through transmission electron microscopy.The levels of the autophagy-related proteins LC3B,Beclin 1,Atg5,and P62 and the pro-apoptosis-related protein caspase-3 were analyzed using western blot assay.The inhibition of cell proliferation and that of apoptosis rate increased after treatment with emulsified isoflurane.Autophagolysosomes,monolayer membrane formation due to lysosomal degradation,were observed.The autophagy-related proteins LC3B,Beclin 1,Atg5,and P62 and caspase-3 were upregulated.These results confirm that emulsified isoflurane can induce toxicity and autophagy in fetal neural stem cells.Pre-treatment with 3-methyladenine and bafilomycin increased the apoptosis rate in emulsified isoflurane-treated fetal neural stem cells,which indicated that the complete inhibition of autophagy does not alleviate emulsified isoflurane-induced fetal neural stem cell toxicity.Atg5 expression was decreased significantly by siRNA-Atg5 transfection,and cell proliferation was inhibited.These results verify that the Atg5 autophagy pathway can be regulated to maintain appropriate levels of autophagy,which can inhibit the neurotoxicity induced by emulsified isoflurane anesthetic in fetal neural stem cells.

Clinical Analysis of 45 Cases of Caesarean Scar Pregnancy

Objective To summarize the clinical characteristics of caesarean scar pregnancy and to investigate its treatment.Methods Clinical case records of 45 cases of caesarean scar pregnancy from June 2003 to September 2007 were reviewed. The characteristics and management of cases were analyzed.Results The women＇s average age was 32.8 ± 5.1 years. All cases had amenorrhoea, and 27 cases had vaginal bleeding from spotting to morderate. Seven cases were misdiagnosed as normal early intrauterine pregnancy or inevitable miscarriage before dilation and curettage（D ＆ C）. In case of massive bleeding, caesarean scar pregnancy was diagnosed after D ＆ C. Bleeding was controlled and uterus was conserved in 6 cases, and 1 case underwent hysterectomy because of uncontrollable bleeding. The remaining 38 cases had ultrasound scan, which indicated scar pregnancy before primary treatment, Eight cases were primarily treated with dilation and curettage, in which only 2 cases had slight bleeding in the operation and no further treatment, Nineteen cases were primarily treated with dilation and curettage after uterine artery embolization, in which 17 cases needed no further treatment and had no complications. The success rate was 89.4% （17/19）. Eleven cases were primarily treated with trichosanthin 1.2 mg intramuscular. No one encountered massive bleeding, but 7 cases of these 11 cases needed extra treatment.Conclusion Caesarean scar pregnancy must be cautious of especially in cases of inevitable miscarriage. Dilation and curettage followed uterine artery embolization can be used as the primary treatment for caesarean scar pregnancy.

Laparoscopic repair of uterine rupture following successful second vaginal birth after caesarean delivery: A case report

BACKGROUND With the increasing trend of vaginal birth after caesarean delivery(VBAC),evaluation of the feasibility and safety of a second VBAC with grand multiparity is worth considering.Intrapartum uterine rupture is diagnosed in approximately one-fifth of all VBAC cases following successful vaginal delivery.To our knowledge,no report is available on the application of laparoscopy to repair postpartum uterine rupture after a successful second VBAC in China.CASE SUMMARY A 31-year-old woman(gravida 5,para 2)at 39 wk and 5 d of gestation was admitted to the hospital in labour.After a successful VBAC and observation for approximately 13 h,the patient complained of progressive abdominal pain.Given the symptoms,signs,and auxiliary examination results,intraperitoneal bleeding was considered.Because the patient was stable and ultrasound imaging was the only method available to assess the possibility of rupture,we recommended laparoscopy to clarify the diagnosis and for prompt laparoscopic uterine repair or exploratory laparotomy if necessary.Operative findings included transverse uterine scar rupture at the lower uterine segment of approximately 5.0 cm in length and 800 mL of intraoperative pelvic haemoperitoneum.Finally,she successfully underwent laparoscopic repair of uterine rupture and recovered very well according to three-dimensional magnetic resonance imaging at 42 d postpartum.CONCLUSION Routine postpartum intrauterine exploration is not beneficial to the mother and may even increase the risk of rupture.This case highlights a laparoscopic approach for repairing uterine rupture in the immediate postpartum period.

Clinical characteristics of perineal endometriosis:A case series

BACKGROUND The prevalence of perineal endometriosis(PEM)is low among women with endometriosis(EM)treated by surgery.It manifests as hard or cystic nodules with pain in the perineal wounds and surrounding areas.Implantation theory is regarded as the main pathogenesis of PEM.There are few clinical studies on the incidence and clinical characteristics of PEM.This study aims to summarize the clinical data of 14 PEM cases and analyze the factors that may be related to the incubation period and pain.AIM To analyze the medical history,clinical manifestations,diagnosis,treatment and treatment effect of PEM.METHODS The present study is a case series.We collected the clinical data and follow-up data of 14 patients with PEM who visited The International Peace Maternal and Child Health Hospital Affiliated to Shanghai Jiaotong University from January 2009 to December 2019.Paired t test and Pearson correlation analysis were used for statistical analysis.P<0.05 was considered statistically significant.RESULTS The 14 patients included had a history of vaginal delivery.All patients underwent PEM lesion resection.Three patients were treated by levator ani muscle repair at the same time and 1 patient underwent extensive PEM lesion resection and anal sphincter repair.Body mass index(BMI)at delivery and BMI within 1 mo after delivery were negatively correlated with the latent period,respectively(R2=0.53/0.86,P<0.05).The average visual analog scale score in lesions at the third month after surgery was 0.57±1.28 for all patients,which was significantly lower than that prior to surgery(P<0.05).One patient relapsed during the sixth month after surgery,and to date,no recurrence occurred after the second surgery.CONCLUSION The higher the BMI during delivery and within 1 mo after delivery,the shorter the incubation period of PEM.It is very important to evaluate the location of lesions before surgery.Surgical resection of the lesion is the best treatment for PEM and results in significant alleviation of symptoms.Therefore,following the diagnosis of PEM,immediate surgery is recommended.

Analysis of Factors Influencing Pregnancy Rate in Frozenthawed Embryo Transfer

Objective To analyse factors influencing the outcome of frozen-thawed embryo transfer （FET）. Method A retrospective analysis was performed in our center on 129 thawing cycles from March 2001 to April 2003. The related parameters were compared between conceived and non-conceived cycles. Results There were totally 129 clinical pregnancies in these transfers （pregnancy rate： 27.1%）. Frozen-thawed embryos were transferred to natural cycles and CC cycling and hormone replacement treatment had equal success. Groups of IVF and ICSI did not differ significantly in pregnancy rates （P〉0.05）. The pregnancy rates for one, two, three and four pre-embryos transfer were 0, 20.0%,44.1% and 75.0%, respectively （P〈0.05）. There were statistical differences between pregnancy group or non- pregnancy group in the endometrial thickness, CES, CES/No. of embryo. A higher pregnancy rate was observed in embryo transfers which had at least one 4-cell grade I embryo （d 2）（P〈0.01）. Conclusions The most important factors influencing the implantation rate and pregnancy rate of frozen-thawed embryo transfer are age, endometrium thickness, and the number, morphology and growth rate of transferred frozen embryos of women participants.

A NEW TEST IN ANTENATAL MONITORING-THE EVALUATION OF SALIVARY UNCONJUGATED ESTRIOL MEASUREMENT

A new unconjugated saliva estriol （SE3） determination by radioimmunoassay（3H-E3） was used to monitor 497 fetuses of late pregnancies, including 280 high-risk and217 normal pregnant women. The normal pregnant SE3 values had been established by themeasurement of 1378 cases from 20 to 41 weeks of gestation. The results of SE3 assaysrevealed that 1. In prenatal prediction of fetal well-being, the total false negative andfalse positive rates were 2.0% and 0.6%, respectively, the correct rate which was similarto that of serum free E3 （SFE3） values was 97.4%, and was significantly higher thanthat of overnight 12-hour urine E3/C analyses as formerly reported. 2. There were 8 fetaldeathe in 11 cases with low SE3 levels. No perinatal death occurred in the 486 cases withnormal SE3 values, except one fetus who died of nuchal cord strangulation. It is highlyimportant that the saliva specimen be correctly collected and the technique ofmeasurement of SE3 be carefully carried out. Our observations suggest that the clinicaluse of SE3 assays are scientific, reliable, and it is more practicable than that of SFE3 as-says. The determination of SFE3 can be replaced by SE3 test for assessing fetal-placentalwell-being.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer:a retrospective population-based study in China

To the Editor:In China,very young breast cancer patients(≤35-year-old)make up approximately 10%of all breast cancer cases,compared to 2%in Western countries.This suggests that different morbidity may be caused by different geographic regions and ethnicities,even leading to different clinicopathological characteristics and prognoses.Tang et al[1]reported that very young breast cancer patients had poor disease-free survival(DFS),and the risk of disease progression was 1.557-fold higher than that for the elderly patients,but no difference was observed in overall survival(OS).However,few studies have focused on very young patients with breast cancer in China.Therefore,we conducted a retrospective population-based study to investigate the oncological outcomes of very young breast cancer patients.The studies involving human participants were reviewed and approved by the Ethics Committee of the International Peace Maternity and Child Health Hospital([No.GKLW]2021-37).

An engineered xCas12i with high activity,high specificity,and broad PAM range

Dear Editor,The clustered regularly interspaced short palindromic repeats-Cas(CRISPR-Cas)systems,including type II Cas9 and type V Cas12 systems,which serve in the adaptive immunity of prokaryotes against viruses,have been developed into genome-editing tools(Anzalone et al.,2020;Doudna,2020).Compared with type II systems,the type V systems including V-A to V-K showed more functional diversity(Yan et al.,2019).Amongst them,Cas12i has a relatively smaller size(1,033-1,093 aa),compared to SpCas9 and Cas12a,and has a 5'-TTN protospacer adjacent motif(PAM)preference(Yan et al.,2019).

RNA‑Sequencing Reveals Gene Expression and Pathway Signatures in Umbilical Cord Blood Affected by Birth Delivery Mode

Cesarean section(CS)confers increased risk of type I diabetes,asthma,inflammatory bowel disease,celiac disease,over-weight and obesity,etc.,in the offspring.However,the underlying mechanism remains unknown.To investigate the influence of CS on gene expression in cord blood,we have performed RNA-sequencing followed by single-gene analysis,gene set enrichment analysis,gene co-expression network analysis,and interacting genes/proteins analysis in eight full-term infants born by elective CS and eight matched vaginally delivered(VD)infants.Crucial genes identified above were further vali-dated in another 20 CS and 20 VD infants.We found for the first time that mRNA expression of genes involved in immune response(IL12A,INFG,IL1B,TNF,MIF,IL4,CA1,IFI27,HLA-DOB and EPHB1)and metabolism(DLK1,CYP2A6 and GATM)were significantly influenced by CS.Notably,serum TNF-αand IFN-γwere remarkably up-regulated in the CS infants(p=5.0×10^(–4)and 3.0×10^(–3),respectively)compared to the VD infants.It is biologically plausible that CS may exert adverse impacts on offspring health through influencing expression of genes in the above processes.These findings will help understand the potential underlying mechanisms of the adverse health impacts of CS and identify biomarkers for future health of offspring born with different delivery modes.

Advanced nano drug delivery systems for neuroprotection against ischemic stroke

Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.

Functional characterization of Bmcap in uric acid metabolism in the silkworm

After a millennium of domestication,numerous silkworm mutants have emerged that exhibit transparent epidermis,which is caused by abnormally low levels of uric acid.We identified the Bombyx mori gene Bmcap(BMSK0003832)as the homolog of cappuccino,a subunit of the biogenesis of lysosome-related organelles complex-1(BLOC-1)that has been extensively characterized in human,mouse,and insect species,by analyzing the amino acid sequences of putative purine metabolism genes.Using the clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9 system,we disrupted Bmcap,resulting in decreased uric acid levels in the silkworm epidermis and a translucent skin phenotype.In the Bmcap mutant,the purine metabolism,nitrogen metabolism,pyrimidine metabolism,and membrane system were altered compared to the wild type.Biogenesis of lysosome-related organelle complex genes play a role in the pigmentation and biogenesis of lysosome-related organelles(LROs)in platelets,melanocytes,and megakaryocytes.LROs exhibit unique morphologies and functions in various tissues and cells.Investigation of the Bmcap mutant will enhance our understanding of the uric acid metabolic pathway in silkworms,and this mutant offers a valuable silkworm model for LRO studies.