Developmental programming and lineage branching of early human telencephalon.

The dorsal and ventral human telencephalons contain different neuronal subtypes, including glutamatergic, GABAergic, and cholinergic neurons, and how these neurons are generated during early development is not well understood. Using scRNA-seq and stringent validations, we reveal here a developmental roadmap for human telencephalic neurons. Both dorsal and ventral telencephalic radial glial cells (RGs) differentiate into neurons via dividing intermediate progenitor cells (IPCs_div) and early postmitotic neuroblasts (eNBs). The transcription factor ASCL1 plays a key role in promoting fate transition from RGs to IPCs_div in both regions. RGs from the regionalized neuroectoderm show heterogeneity, with restricted glutamatergic, GABAergic, and cholinergic differentiation potencies. During neurogenesis, IPCs_div gradually exit the cell cycle and branch into sister eNBs to generate distinct neuronal subtypes. Our findings highlight a general RGs-IPCs_div-eNBs developmental scheme for human telencephalic progenitors and support that the major neuronal fates of human telencephalon are predetermined during dorsoventral regionalization with neuronal diversity being further shaped during neurogenesis and neural circuit integration.

Multislip-enabled morphing of all-inorganic perovskites.

All-inorganic lead halide perovskites (CsPbX3, X = Cl, Br or I) are becoming increasingly important for energy conversion and optoelectronics because of their outstanding performance and enhanced environmental stability. Morphing perovskites into specific shapes and geometries without damaging their intrinsic functional properties is attractive for designing devices and manufacturing. However, inorganic semiconductors are often intrinsically brittle at room temperature, except for some recently reported layered or van der Waals semiconductors. Here, by in situ compression, we demonstrate that single-crystal CsPbX3 micropillars can be substantially morphed into distinct shapes (cubic, L and Z shapes, rectangular arches and so on) without localized cleavage or cracks. Such exceptional plasticity is enabled by successive slips of partial dislocations on multiple [Formula: see text] systems, as evidenced by atomic-resolution transmission electron microscopy and first-principles and atomistic simulations. The optoelectronic performance and bandgap of the devices were unchanged. Thus, our results suggest that CsPbX3 perovskites, as potential deformable inorganic semiconductors, may have profound implications for the manufacture of advanced optoelectronics and energy systems.

Intrauterine adhesions treated with hysteroscopic adhesiolysis and subsequent obstetric outcome: A retrospective matched cohort study.

OBJECTIVE: To examine whether a history of hysteroscopic adhesiolysis (HA)-treated intrauterine adhesions (IUAs) was associated with an increased risk of adverse obstetrical outcomes in subsequent pregnancies. DESIGN: Retrospective cohort study. SETTING: A tertiary-care hospital in Shanghai, China. POPULATION: A cohort of 114 142 pregnant women who were issued an antenatal card and received routine antenatal care in Shanghai First Maternity and Infant Hospital, between January 2016 and October 2021. METHODS: From the cohort of 114 142 pregnant women, each woman with a history of HA-treated IUA prior to the current pregnancy (n = 780) was matched with four women without a history of IUAs (n = 3010) using propensity score matching. The matching variables were maternal age and parity, mode of conception, pre-pregnancy body mass index and prior history of abortion. MAIN OUTCOME MEASURES: Pregnancy complications, placental abnormalities, postpartum haemorrhage and adverse birth outcomes. RESULTS: Compared with women with no history of IUAs, women with a history of HA-treated IUAs were at higher risk of pre-eclampsia (RR 1.69, 95% CI 1.23-2.33), placenta accreta spectrum (RR 4.72, 95% CI 3.9-5.73), placenta praevia (RR 4.23, 95% CI 2.85-6.30), postpartum haemorrhage (RR 2.86, 95% CI 1.94-4.23), preterm premature rupture of membranes (RR 3.02, 95% CI 1.97-4.64) and iatrogenic preterm birth (RR 2.86, 95% CI 2.14-3.81). Those women were also more likely to receive cervical cerclage (RR 5.63, 95% CI 3.95-8.02) during pregnancy and haemostatic therapies after delivery (RR 2.17, 95% CI 1.75-2.69). Moreover, we observed that the RRs of those adverse obstetrical outcomes increased with the increasing number of hysteroscopic surgeries. CONCLUSIONS: This study found that a history of HA-treated IUAs, especially a history of repeated HAs, was associated with an increased risk of adverse obstetrical outcomes.

Effect of ropivacaine, mepivacaine or the combination of ropivacaine and mepivacaine for epidural anaesthesia on the postoperative recovery in patients undergoing caesarean section: a randomized, prospective, double-blind study.

BACKGROUND: Anaesthetic methods and drugs with rapid onset, rapid recovery and better postoperative analgesia are more suitable for rapid recovery in obstetric anaesthesia. We formulated the following hypothesis: a combination of mepivacaine and ropivacaine could provide a longer analgesic effect and have more advantages in terms of rapid-recovery indicators. METHODS: A total of 180 pregnant women scheduled to undergo elective caesarean sections were randomly assigned to three surgical groups, which received 2% mepivacaine (Group M), 2% mepivacaine + 0.75% ropivacaine (Group MR) (Volume 1:1) or 0.75% ropivacaine (Group R) through an epidural catheter. The situation of postoperative analgesia and other indicators of rapid recovery were recorded. RESULTS: One hundred and fifty patients were included in the final analysis. Their demographic data were similar. The visual analogue scale (VAS) scores of Group MR and Group R were lower than Group M at 1 and 2 h after surgery both at rest and with movement (P < 0.05), and the time to first ambulation in Group MR (17.38 ± 2.06 h) and Group M (17.20 ± 2.09 h) was shorter than that in Group R (22.18 ± 1.74 h) (P < 0.05). CONCLUSION: Application of 2% mepivacaine combined with 0.75% ropivacaine for epidural anaesthesia can provide longer postoperative analgesia and earlier ambulation, these effect may be more suitable than that of 2% mepivacaine or 0.75% ropivacaine alone for caesarean section. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (Registration number: ChiCTR 2300078288; date of registration: 04/12/2023).

Pseudogene TDGF1P3 regulates the proliferation and metastasis of colorectal cancer cells via the miR-338-3p-PKM2 axis.

Research in the past decade has revealed significant roles of pseudogenes in colorectal cancer (CRC). Here, the role of teratocarcinoma-derived growth factor 1 pseudogene 3 (TDGF1P3) in regulating the proliferation and invasion of CRC cells was investigated; in addition, its downstream targets were analyzed, and the underlying mechanisms were elucidated. TDGF1P3 was determined to be upregulated in CRC cells and tissues. Silencing TDGF1P3 substantially repressed cell proliferation, migration, and invasion in vitro. Similarly, in vivo assays showed that TDGF1P3 knockdown attenuated tumor growth in nude mice. Mechanistic investigations revealed that TDGF1P3 directly bound to miR-338-3p, thereby preventing miR-338-3p from binding to its target mRNA pyruvate kinase M2 (PKM2). Functional rescue tests indicated that TDGF1P3 regulates CRC cell proliferation and invasion by restraining the miR-338-3p-PKM2 axis. Thus, these data illustrated that TDGF1P3 exerts its oncogenic activity by upregulating PKM2 via competitively binding miR-338-3p, which may be a therapeutic target for CRC.

Nonlinear Relationship Between Serum Total Cholesterol Levels and the Severity of Hypertriglyceridemic Acute Pancreatitis: A Cohort Study in China.

BACKGROUND: The relationship between total cholesterol (TC) levels and the severity of hypertriglyceridemic acute pancreatitis (HTGAP) remains unclear. AIMS: The aim of this study was to investigate the relationship between the levels of TC at admission with the severity of HTGAP, in order to apply it as a reliable predictor at early stage in clinical practice. METHODS: We performed a cohort study including 249 patients with AHTGP between November 2012 and April 2022 in XuanWu Hospital. Fasting TC was assayed within 24 h of admission, age, gender, body mass index, hypertension, diabetes mellitus, drinking, smoking, neutrophil-lymphocyte ratio, C-reactive protein and glucose were recorded as confounding factors. To evaluate the relationship of TC and the severity of HTGAP, we used smooth curve fitting and a segmented regression model with adjustment of confounding factors to analyze the threshold effect between TC and SAP occurrence risk. RESULTS: 249 Patients were enrolled. The incidence of SAP was 25.3% (63/249). A nonlinear relationship between TC level and the severity of HTGAP. 6.09 mmol/L was the optimal TC value associated with the lowest risk of SAP occurrence. Moreover, TC level was negatively correlated with risk of severe HTGAP occurrence for TC < 6.09 mmol/L (OR 0.45, 95% CI 0.23-0.85, P = 0.014) and positively correlated for TC > 6.09 mmol/L in HTGAP patients (OR 1.14, 95% CI 1.04-1.26, P = 0.006). CONCLUSIONS: We found that serum TC level is nonlinearly associated with the severity of HTGAP, and it can be a reliable predictor for early intervention and intensive care.

BRM-SWI/SNF chromatin remodeling complex enables functional telomeres by promoting co-expression of TRF2 and TRF1.

TRF2 and TRF1 are a key component in shelterin complex that associates with telomeric DNA and protects chromosome ends. BRM is a core ATPase subunit of SWI/SNF chromatin remodeling complex. Whether and how BRM-SWI/SNF complex is engaged in chromatin end protection by telomeres is unknown. Here, we report that depletion of BRM does not affect heterochromatin state of telomeres, but results in telomere dysfunctional phenomena including telomere uncapping and replication defect. Mechanistically, expression of TRF2 and TRF1 is jointly regulated by BRM-SWI/SNF complex, which is localized to promoter region of both genes and facilitates their transcription. BRM-deficient cells bear increased TRF2-free or TRF1-free telomeres due to insufficient expression. Importantly, BRM depletion-induced telomere uncapping or replication defect can be rescued by compensatory expression of exogenous TRF2 or TRF1, respectively. Together, these results identify a new function of BRM-SWI/SNF complex in enabling functional telomeres for maintaining genome stability.

The LncRNA AK018453 regulates TRAP1/Smad signaling in IL-17-activated astrocytes: A potential role in EAE pathogenesis.

The pro-inflammatory cytokine interleukin 17 (IL-17), that is mainly produced by Th17 cells, has been recognized as a key regulator in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Reactive astrocytes stimulated by proinflammatory cytokines including IL-17 are involved in blood brain barrier destruction, inflammatory cells infiltration and spinal cord injury. However, the role of long non-coding RNAs (lncRNAs) induced by IL-17 in the pathogenesis of MS and EAE remains unknown. Herein, we found that an IL-17-induced lncRNA AK018453 promoted TGF-ß receptor-associated protein 1 (TRAP1) expression and Smad-dependent signaling in mouse primary astrocytes. Knockdown of AK018453 significantly suppressed astrocytosis, attenuated the phosphorylation of Smad2/3, reduced NF-κB p65 and CBP/P300 binding to the TRAP1 promoter, and diminished pro-inflammatory cytokine production in the IL-17-treated astrocytes. AK018453 knockdown in astrocytes by a lentiviral vector in vivo dramatically inhibited inflammation and prevented the mice from demyelination in the spinal cord during the progression of EAE. Together, these results suggest that AK018453 regulates IL-17-dependent inflammatory response in reactive astrocytes and potentially promotes the pathogenesis of EAE via the TRAP1/Smad pathway. Targeting this pathway may have a therapeutic potential for intervening inflammatory demyelinating diseases.

Bulleyaconitine A is a sensitive substrate and competitive inhibitor of CYP3A4: One of the possible explanations for clinical adverse reactions.

Bulleyaconitine A (BLA), a toxic Aconitum alkaloid, is a potent analgesic that is clinically applied to treat rheumatoid arthritis, osteoarthritis and lumbosacral pain. BLA-related adverse reactions occur frequently, but whether the underlying mechanism is related to its metabolic interplay with drug-metabolizing enzymes remains unclear. This study aimed to elucidate the metabolic characteristics of BLA and its affinity action and mechanism to drug-metabolizing enzymes to reveal whether BLA-related adverse reactions are modulated by enzymes. After incubation with human liver microsomes and recombinant human cytochrome P450 enzymes, we found that BLA was predominantly metabolized by CYP3A, in which CYP3A4 had an almost absolute advantage. In vitro, the CYP3A4 inhibitor ketoconazole noticeably suppressed the metabolism of BLA. In vivo, the AUC0-∞ values, cardiotoxicity and neurotoxicity of BLA in Cyp3a-inhibited mice were all obviously enhanced (P < 0.05) compared to those in normal mice. In the enzyme kinetics study, BLA was found to be a sensitive substrate of CYP3A4, and its characteristics were consistent with substrate inhibition (Km = 39.36 ± 10.47 µmol/L, Ks = 83.42 ± 19.65 µmol/L). BLA was further identified to be a competitive inhibitor of CYP3A4 with Ki = 53.64 µmol/L, since the intrinsic clearance (CLint) of midazolam, a selective CYP3A4 substrate, decreased significantly (P < 0.05) when incubated with BLA together in mouse liver microsomes. Overall, BLA is a sensitive substrate and competitive inhibitor of CYP3A4, and clinical adverse reactions of BLA may mechanistically related to the CYP3A4-mediated drug-drug interactions.

The role of SK3 in progesterone-induced inhibition of human fallopian tubal contraction.

BACKGROUND: Normal motor activity of the fallopian tube is critical for human reproduction, and abnormal tubal activity may lead to ectopic pregnancy (EP) or infertility. Progesterone has an inhibitory effect on tubal contraction; however, the underlying mechanisms remain unclear. Small-conductance calcium-activated K+ channel 3 (SK3) is abundantly expressed in platelet-derived growth factor receptor α positive (PDGFRα+) cells and was reported to be important for the relaxation of smooth muscle. The present study aims to explore the expression of SK3 in the human fallopian tube and its role in progesterone-induced inhibition of tubal contraction. METHODS: We collected specimens of fallopian tubes from patients treated by salpingectomy for EP (EP group) and other benign gynecological diseases (Non-EP group). The expression of SK3 was detected by quantitative real-time polymerase chain reaction, western blot, immunocytochemistry, and immunohistochemistry analyses. Isometric tension experiments were performed to investigate the role of SK3 in progesterone-induced inhibition of tubal contraction. RESULTS: The baseline amplitude and frequency of human fallopian tube contraction were both statistically lower in the EP group compared with the non-EP group. The expression levels of SK3 in different portions of fallopian tubes from the non-EP group were significantly higher than in those from the EP group. Progesterone had an inhibitory effect on tubal contraction, mainly on the amplitude, in both groups, and SK3 as well as other calcium-activated K+ channels may be involved. SK3-expressing PDGFRα (+) cells were detected in the human fallopian tube. CONCLUSIONS: The expression of SK3 is lower in the EP group, and SK3 is involved in the progesterone-induced inhibition of human fallopian tube contraction.

Strand break-induced replication fork collapse leads to C-circles, C-overhangs and telomeric recombination.

Telomerase-independent ALT (alternative lengthening of telomeres) cells are characterized by high frequency of telomeric homologous recombination (HR), C-rich extrachromosomal circles (C-circles) and C-rich terminal 5' overhangs (C-overhangs). However, underlying mechanism is poorly understood. Here, we show that both C-circle and C-overhang form when replication fork collapse is induced by strand break at telomeres. We find that endogenous DNA break predominantly occur on C-rich strand of telomeres in ALT cells, resulting in high frequency of replication fork collapse. While collapsed forks could be rescued by replication fork regression leading to telomeric homologous recombination, those unresolved are converted to C-circles and C-overhang at lagging and leading synthesized strand, respectively. Meanwhile, multiple hallmarks of ALT are provoked, suggesting that strand break-induced replication stress underlies ALT. These findings provide a molecular basis underlying telomeric HR and biogenesis of C-circle and C-overhang, thus implicating the specific mechanism to resolve strand break-induced replication defect at telomeres in ALT cells.

Genome-wide identification, phylogenetic and expression of MAPKKK gene family in Arabidopsis pumila.

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are important components of the MAPK cascade and play crucial roles in development and stress responses. Arabidopsis pumila is an ephemeral Brassicaceae plant growing in Xinjiang desert regions, which possesses salt tolerance. To explore the evolution and function of the MAPKKK gene family in A. pumila, 143 ApMAPKKK genes were identified from A. pumila genome by genome-wide analysis, which were categorized into three subfamilies: ZIK (20), MEKK (36) and RAF (87). There existed 74 and 72 colinear genes between A. thaliana, A. lyrata and A. pumila, respectively, indicating that this gene family expanded obviously in A. pumila genome. Evolutionary analysis revealed that there were 64 duplicated gene pairs with Ka/Ks less than 1, and purifying selection was dominant. RNA-seq data were used to analyze the expression characteristics of ApMAPKKK genes in response to salt stress and in different tissues. The results showed that most ApMAPKKK genes were up-regulated under 250 mmol/L NaCl stress. For example, ApMAPKKK18-1/2 and ApMAPKKK17-1/2 were substantially up-regulated. Tissue expression profiles showed that ApMAPKKK mainly presented six expression patterns. Some duplicated genes were differentially expressed in response to salt stress and in different tissues. These results lay a foundation for further understanding the complex mechanism of MAPKKK gene family transduction pathway in response to abiotic stresses in A. pumila.

IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis.

BACKGROUND: Interleukin 9 (IL-9), produced mainly by T helper 9 (Th9) cells, has been recognized as an important regulator in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Astrocytes respond to IL-9 and reactive astrocytes always associate with blood-brain barrier damage, immune cell infiltration, and spinal injury in MS and EAE. Several long non-coding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of MS. Here, we examined the effects of lncRNA Gm13568 (a co-upregulated lncRNA both in EAE mice and in mouse primary astrocytes activated by IL-9) on the activation of astrocytes and the process of EAE. METHODS: In vitro, shRNA-recombinant lentivirus with glial fibrillary acidic protein (GFAP) promoter were performed to determine the relative gene expression and proinflammatory cytokines production in IL-9 treated-astrocytes using Western blot, real-time PCR, and Cytometric Bead Array, respectively. RIP and ChIP assays were analyzed for the mechanism of lncRNA Gm13568 regulating gene expression. Immunofluorescence assays was performed to measure the protein expression in astrocytes. In vivo, H&E staining and LFB staining were applied to detect the inflammatory cells infiltrations and the medullary sheath damage in spinal cords of EAE mice infected by the recombinant lentivirus. Results were analyzed by one-way ANOVA or Student's t test, as appropriate. RESULTS: Knockdown of the endogenous lncRNA Gm13568 remarkably inhibits the Notch1 expression, astrocytosis, and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) as well as the production of inflammatory cytokines and chemokines (IL-6, TNF-α, IP-10) in IL-9-activated astrocytes, in which Gm13568 associates with the transcriptional co-activators CBP/P300 which are enriched in the promoter of Notch1 genes. More importantly, inhibiting Gm13568 with lentiviral vector in astrocytes ameliorates significantly inflammation and demyelination in EAE mice, therefore delaying the EAE process. CONCLUSIONS: These findings uncover that Gm13568 regulates the production of inflammatory cytokines in active astrocytes and affects the pathogenesis of EAE through the Notch1/STAT3 pathway. LncRNA Gm13568 may be a promising target for treating MS and demyelinating diseases.

Proteomic analysis of decidua in patients with recurrent pregnancy loss (RPL) reveals mitochondrial oxidative stress dysfunction.

BACKGROUND: Pregnancy is a complicated physiological process. The multifaceted regulation of maternal-fetal interface is of great importance for maintaining normal pregnancy and avoiding fetal rejection and secondary abortion. Previous studies have focused on the clinical features or pathological biomarkers of fetal rejection and abortion. However, no significant breakthrough has been made. Therefore, it is important to understand the molecular mechanisms of recurrent pregnancy loss (RPL) to identify potential therapeutic strategies. The aim of this study was to investigate the pathogenesis of RPL. METHODS: In this study, Relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify differentially expressed proteins in decidual from RPL patients and matched normal controls. Further, Molecules NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 (ndufb3) and cyclooxygenase-2 (COX-2) were validated by immunohistochemistry (IHC), Western blotting, CCK8 and mitochondrial red fluorescent probe (Mito-Tracker Red CMXRos). RESULTS: A total of 456 proteins reached the threshold of a 1.5-fold change were identified for further bioinformatics analysis. Upon mapping the differentially expressed proteins using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways database, iTRAQ results were confirmed by assessing NDUFB3 and COX-2 protein levels in specimens of decidual tissue by Western blotting. Our study indicates that the level of COX-2 and NDUFB3 were significantly increased in decidual cell from RPL patients. Overexpression of NDUFB3 inhibited cell vitality and oxidative stress of decimal cell. Further, our found that overexpression NDUFBD3 in decidual cell decreased the mitochondrial membrane potential expression levels. These results suggest that NDUFB3 might play an important role in promote the pathological process of RPL. CONCLUSIONS: This comprehensive analysis of RPL proteomics reveals novel candidate: NDUFB3, which could be further investigated for explanation of the pathological mechanism of RPL.

Factors predicting the severity of acute pancreatitis in elderly patients.

BACKGROUND: Moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) are associated with organ failure (OF), which can be lethal. AIMS: This study determined the factors that predict the severity of AP at admission in elderly patients. METHODS: In this retrospective study, the data from elderly patients (> 60 years of age) admitted within 72 h of onset of symptoms without OF were collected. These data at admission were analyzed and correlated with the severity of AP. To identify the factors associated with more serious AP (i.e. MSAP and SAP), patients were divided into mild acute pancreatitis (MAP) and MSAP + SAP groups. RESULTS: A total of 198 patients [MAP group (n = 135) and MSAP + SAP group (n = 63)] were included. Biliary disease was the most common etiology. Respiratory failure was the most common OF. Logistic regression analyses indicated that idiopathic etiology (odds ratio [OR]: 3.029, 95% confidence interval [CI]: 1.017-9.022, p = 0.047), pre-existing pulmonary disease (OR: 7.104, CI 1.750-28.84, p = 0.006), increased hematocrit level (OR: 3.717, 95%CI 1.372-10.070, p = 0.010), serum calcium (OR: 0.023, 95%CI 0.001-0.371, p = 0.008), serum glucose (OR: 1.157, 95%CI 1.031-1.299, p = 0.013), arterial partial pressure of oxygen (PaO2) (OR: 0.914, 95%CI 0.874-0.956, p < 0.001), and pleural effusion (OR: 4.979, 95%CI 1.863-13.303, p = 0.001) were independent predictors of more serious AP. CONCLUSION: This study found that idiopathic etiology, pre-existing pulmonary diseases, increased hematocrit level or pleural effusion, higher serum glucose, and lower serum calcium or PaO2 at the time of admission independently correlated with more serious AP in the elderly patients.

Mdr1a, Bcrp and Mrp2 regulate the efficacy and toxicity of mesaconitine and hypaconitine by altering their tissue accumulation and in vivo residence.

Mesaconitine (MA) and hypaconitine (HA) are the main bioactive/toxic alkaloids of Aconitum carmichaelii Debx, and MDR1, BCRP and MRP2 are involved in their efflux in vitro. This study aimed to explore the effects of Mdr1a, Bcrp and Mrp2 on the efficacy/toxicity of MA and HA by using efflux transporter gene knockout mouse models. The analgesic and anti-inflammatory effects, neurotoxicity/cardiotoxicity, and pharmacokinetic profiles of MA and HA were studied. Compared to wild-type mice, the analgesic effects of MA or HA were significantly enhanced in Mdr1a--/-, Bcrp1-/- and Mrp2-/- mice, and the anti-inflammatory effects notably increased in Bcrp1-/- and Mrp2-/- mice. Compared to wild-type mice, Mdr1a-/-, Bcrp1-/- and Mrp2-/- mice suffered from severe karyopyknosis and edema in the brain after MA or HA treatment. Meanwhile, significant arrhythmia appeared, and the heart rate and RR-interval were greatly altered in Mdr1a-/-, Bcrp1-/- and Mrp2-/- mice. Additionally, obvious disorder of cardiomyocytes were observed, and the CK and cTnT (indicators of heart injury) levels were greatly enhanced in efflux transporter gene knockout mice. The brain levels of MA and HA were markedly increased in Mdr1a-/-, Bcrp1-/- and Mrp2-/- mice, and the heart levels of MA and HA enhanced greatly in Mdr1a-/- mice. The MRT0-t values of MA and HA were remarkably enhanced in most efflux transporter gene knockout mice. In conclusion, Mdr1a, Bcrp and Mrp2 were all involved in regulating the efficacy/toxicity of MA and HA by altering their tissue accumulation and in vivo residence. Among the three efflux transporters, Mdr1a had a superior regulatory effect.

Systematic retrospective analysis of 13 cases of uterine arteriovenous fistula: Pathogeny, diagnosis, treatment and follow-up.

AIM: To analyze the causes, clinical manifestations, diagnosis and treatment of uterine arteriovenous fistula (UAVF). METHODS: We retrospectively analyzed 13 patients with UAVF admitted to our hospital from October 2016 to April 2019. RESULTS: All patients had a history of intrauterine surgery (curettage for abortion, artificial removal of placenta, hysteroscopy, diagnostic curettage and intrauterine device removal). The main clinical manifestation of UAVF is paroxysmal massive vaginal bleeding; this involved a massive gush of vaginal blood that stopped suddenly. Sonographic images with typical features of UAVF were observed for 12 patients. Pelvic contrast-enhanced magnetic resonance imaging was performed as a noninvasive adjuvant examination method for diagnosis. Twelve patients underwent uterine arteriography and a diagnosis of UAVF was confirmed. Then, bilateral uterine artery embolization (UAE) was performed. One patient underwent laparoscopic hysterectomy directly instead of uterine arteriography because of unstable vital signs and one patient underwent laparoscopic hysterectomy 25 weeks after the second UAE. The median time until menstrual recovery was 33 days (range, 20-70 days) after UAE. The median time until normal ultrasound examination results was 10 weeks (range, 2-35 weeks). CONCLUSION: Acquired UAVF was associated with a history of previous intrauterine surgery. The ultrasound examination and pelvic contrast-enhanced MRI were noninvasive adjuvant examination method to effectively assist in diagnosis. Uterine arteriography is considered the gold standard for the diagnosis of UAVF, and UAE is considered an effective intervention for treating UAVF and maintaining reproductive function with less damage. Hysterectomy is an appropriate option when conservative measures have failed to prevent a life-threatening hemorrhage.

Highly Active Core-Shell Carbon/NiCo2 O4 Double Microtubes for Efficient Oxygen Evolution Reaction: Ultralow Overpotential and Superior Cycling Stability.

Developing highly efficient electrocatalysts with earth abundant elements for oxygen evolution reaction (OER) is a promising way to store light or electrical energy in the form of chemical energy. Here, a new type of electrocatalyst with core-shell carbon/NiCo2 O4 double microtubes architecture is successfully synthesized through a hydrothermal method combined with the calcination process with wet tissues as the template and carbon resource. The outer NiCo2 O4 nanosheet arrays contain abundant defects, which come from reduction of the carbon in wet tissues. This indicates that carbon is a very excellent defect inducer. The inner carbon microtubes can act as the robust structure skeleton and these core-shell double microtubes provide abundant diffusion channels for oxygen and electrolyte, both of which contribute to improving the stability by avoiding damage to the electrode from produced O2 bubbles and the collapse of the outer NiCo2 O4 microtubes. Electrochemical results show that the electrode, core-shell carbon/NiCo2 O4 double microtubes loaded on carbon cloth, exhibits prominent electrocatalytic activity with an overpotential of only 168 mV at 10 mA cm-2 and a Tafel slope as low as 57.6 mV dec-1 in 1.0 mol L-1 KOH. This new type of electrocatalyst possesses great potential in water electrolyzers and rechargeable metal-air batteries.

A cross-sectional survey based on blood VOCs, hematological parameters and urine indicators in a population in Jilin, Northeast China.

The objective of this study was to examine whether long-term exposure to low-dose volatile organic compounds (VOCs) will have an effect on the health of non-occupational population. A total of 499 non-occupational participants aged more than 18 that live around Jilin Petrochemical Industrial Zone were chosen by stratified cluster random sampling. Their blood VOCs' levels, hematological parameters and urine indicators together with detailed questionnaire data were used to find possible relationships using binary logistic regression analysis. The detection rate of benzene in the blood was high in the non-occupational population around the industrial area, and it even reached 82.3% in males but no significant difference was recorded between male and female population. In addition, trichloroethane (male: 33.2% V female: 21.7%; p = 0.002), carbon tetrachloride (males: 20.3% V females: 7.5%; p < 0.001) and trichlorethylene (male: 34.9% V female: 24.7%; p = 0.004) all showed significant differences in gender, and without exception, the prevalence of males was higher in these three VOCs than of females. The changes in red blood cell (RBC), hematocrit (HCT) and basophils are correlated with carbon tetrachloride, trichloroethylene and chloroform, respectively. And RBC, HCT and basophils are statistically significant in male compared with female of the study population. The increase in trichlorethylene was associated with an increase of 1.723% (95% CI 1.058-2.806) in HCT. The increase in carbon tetrachloride showed a more significant correlation with an increase of 2.638% in RBC count (95% CI 1.169-5.953). And trichloromethane led to a 1.922% (95% CI 1.051-3.513) increase in basophils. The changes in urinary WBC, urine ketone (KET) and urinary bilirubin (BIL) showed significant correlation with benzene, carbon tetrachloride and dibromochloromethane, respectively. The correlation in females is more significant than in males. The increase of benzene in the female population increased urinary leukocyte count by 2.902% (95% CI 1.275-6.601). The effect of carbon tetrachloride on KET was particularly pronounced, resulting in an increase of 7.000% (95% CI 1.608-30.465). Simultaneously, an increase in dibromochloromethane caused an increase of 4.256% (95% CI 1.373-13.192) in BIL. The changes in RBC, HCT and basophils can only serve as an auxiliary indicator for disease diagnosis, so they have no significant clinical significance. However, the alteration of urinary WBC, KET and BIL has great clinical significances, and it is suggested that the monitoring of the above indicators from low-dose long-term exposure be strengthen in this area.

[Roles and mechanisms of traditional Chinese medicine and its active ingredients in treating epilepsy].

At present,Western medicine is widely used in the treatment of epilepsy.However,about 30%-40% of epileptic patients are resistant to them and are affected by the side effects of these drugs.Traditional Chinese medicine is effective in treating epileptic seizures and relieving complications caused by Western medicine.However,the active ingredients and mechanisms of traditional Chinese medicine remain unclear.This article reviews and summarizes the advances and mechanisms in treating epilepsy,such as Chinese medicine monomer,the extracts of single Chinese medicine and Chinese medicine compound.Chinese medicine monomers,including gastrodin,asarone,rhynchophylline,ligustrazine,tanshinone ⅡA,curcumin,etc.,have antiepileptic effects via regulating excitatory neurotransmitters and receptors,the expression of inflammatory factors,sodium/potassium ion channels and the expression of apoptotic protein,therefore protecting neurons.The extracts of single Chinese herbal including the extracts of Gastrodiae Rhizoma,Acori Tatarinowii Rhizoma,Ginseng Radix et Rhizoma,Ganoderma,Scutellariae Radix and Ginkgo Folium,etc.,have antiepileptic effects related to the inhibition of γ-aminobutyric acid receptor,upregulation of phosphatidylinositol 3-kinase signaling pathway and reduction of glutamate-induced excitotoxicity and oxidative stress response.Furthermore,these extracts can regulate ion channels and reduce oxidative damage of neurons.Chinese medicine compounds including Dianxian Qing Granules,Danxing Ningxian Granules,Huoxue Dingxian formulae,etc.,can improve the therapeutic effect on epilepsy through simultaneously regulating excitatory transmitters,apoptosis factors and cytokines.