Observation of unconventional chiral fermions with long Fermi arcs in CoSi.

Chirality-the geometric property of objects that do not coincide with their mirror image-is found in nature, for example, in molecules, crystals, galaxies and life forms. In quantum field theory, the chirality of a massless particle is defined by whether the directions of its spin and motion are parallel or antiparallel. Although massless chiral fermions-Weyl fermions-were predicted 90 years ago, their existence as fundamental particles has not been experimentally confirmed. However, their analogues have been observed as quasiparticles in condensed matter systems. In addition to Weyl fermions1-4, theorists have proposed a number of unconventional (that is, beyond the standard model) chiral fermions in condensed matter systems5-8, but direct experimental evidence of their existence is still lacking. Here, by using angle-resolved photoemission spectroscopy, we reveal two types of unconventional chiral fermion-spin-1 and charge-2 fermions-at the band-crossing points near the Fermi level in CoSi. The projections of these chiral fermions on the (001) surface are connected by giant Fermi arcs traversing the entire surface Brillouin zone. These chiral fermions are enforced at the centre or corner of the bulk Brillouin zone by the crystal symmetries, making CoSi a system with only one pair of chiral nodes with large separation in momentum space and extremely long surface Fermi arcs, in sharp contrast to Weyl semimetals, which have multiple pairs of Weyl nodes with small separation. Our results confirm the existence of unconventional chiral fermions and provide a platform for exploring the physical properties associated with chiral fermions.

Acute kidney injury in patients with idiopathic membranous nephropathy: influencing factors and prognosis.

AIM: Idiopathic membranous nephropathy (IMN) is a common type of nephrotic syndrome, and is associated with acute kidney injury (AKI). We investigated the association of multiple variables with AKI in patients with IMN. METHODS: The data of 187 patients with biopsy-proven IMN were examined. Renal outcome was defined as progression to end-stage renal disease (ESRD). Binary logistic regression and Kaplan-Meier's analysis were used for statistical analysis. RESULTS: During follow-up, 46 (24.6%) patients developed AKI. The incidence of AKI was greater in males than females (p < .01). The AKI group had higher uric acid, lower serum PLA2R antibody positive, and worse baseline kidney function (all p < .01). Most patients in the AKI group had stage I (71.74%) or stage II (21.74%). The AKI group had higher renal tubular injury score and chronicity index (both p < .05). Binary logistic regression indicated that uric acid and baseline estimated glomerular filtration rate (eGFR) were independent risk factors for AKI in patients with IMN (p < .05). The optimal cutoff value of serum uric acid for predicting AKI was 402.50 µmol/L and the baseline eGFR was 96.83 mL/min/1.73 m2. Kaplan-Meier's analysis showed that the cumulative renal survival rate was lower in the AKI group (p = .047). CONCLUSIONS: AKI increases the risk of poor prognosis in IMN patients and the high uric acid and low baseline eGFR were considered independent predictors for developing AKI in patients with IMN.

Clinical value of serum miR-92 and miR-122 expression level combined with pulmonary ultrasound score in the prognosis of neonatal acute respiratory distress syndrome.

PURPOSE: To explore the value of the expression of serum miR-92 and miR-122 combined with lung ultrasound score (LUS) in the prognosis of neonatal acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: This study involved 148 neonatal ARDS cases from January 2018 to October 2021, of which 77 children were discharged from hospital and 31 died. The children with ARDS were classified according to disease severity based on X-ray examination as mild (n = 69 cases) and severe (n = 39 cases). The expression of serum miR-92 and miR-122 was detected by real-time fluorescence quantitative PCR and the LUS score was recorded. The data were subjected to ROC curve analysis and Pearson correlation analysis. RESULTS: The expression of serum miR-92, miR-122, and LUS score in the patients that died were significantly higher than in those who survived (p < 0.05). These indicators were also significantly higher in the severe disease group compared to the mild disease group (p < 0.05). ROC curve showed that serum miR-92 and miR-122 combined with the LUS score had the largest area under the curve (0.920, 95% CI: 0.860-0.977) for predicting death, with a sensitivity and specificity of 92.0% and 87.0%, respectively. Pearson correlation analysis showed that the expression levels of serum miR-92 and miR-122 were positively correlated with the LUS score (all p < 0.01). CONCLUSIONS: The increased expression of serum miR-92 and miR-122 is related to the severity and prognosis of children with ARDS, combined with the LUS score are of value to predict the prognosis of children with ARDS.

[Value of autotaxin in predicting refractory Mycoplasma pneumoniae pneumonia in children and its correlation with inflammatory cytokines]. / Autotaxinå¯¹å„¿ç«¥éš¾æ²»æ€§è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žçš„é¢„æµ‹ä»·å€¼åŠå ¶ä¸Žç‚Žæ€§ç»†èƒžå› å­çš„ç›¸å ³æ€§.

OBJECTIVES: To study the value of autotaxin (an autocrine motility factor) level in serum and bronchoalveolar lavage fluid (BALF) in predicting refractory Mycoplasma pneumoniae pneumonia (RMPP) in children and its correlation with interleukin-6 (IL-6), interleukin-8 (IL-8), and C-reactive protein (CRP). METHODS: A retrospective analysis was performed on 238 children with Mycoplasma pneumoniae pneumonia who were admitted from January 2019 to December 2021. According to disease severity, they were divided into two groups: RMPP (n=82) and general Mycoplasma pneumoniae pneumonia (GMPP; n=156). The two groups were compared in terms of the levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF to study the value of autotaxin level in serum and BALF in predicting RMPP in children, as well as the correlation of autotaxin level with IL-6, IL-8, and CRP in children with RMPP. RESULTS: Compared with the GMPP group, the RMPP group had significantly higher levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF (P<0.05). For the children with RMPP, the levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF in the acute stage were significantly higher than those in the convalescent stage (P<0.05). The receiver operating characteristic (ROC) curve showed that the level of autotaxin in serum and BALF had a good value in predicting RMPP in children, with an area under the curve of 0.874 (95%CI: 0.816-0.935) and 0.862 (95%CI: 0.802-0.924), respectively. The correlation analysis showed that the level of autotaxin in serum and BALF was positively correlated with IL-6, IL-8, and CRP levels (P<0.001). CONCLUSIONS: The level of autotaxin in serum and BALF increases and is correlated with the degree of disease recovery and inflammatory cytokines in children with RMPP. Autotaxin can be used as a predictive indicator for RMPP in children.

Pachymic acid protects oocyte by improving the ovarian microenvironment in polycystic ovary syndrome mice†.

Women with polycystic ovary syndrome (PCOS) are characterized by endocrine disorders accompanied by a decline in oocyte quality. In this study, we generated a PCOS mice model by hypodermic injection of dehydroepiandrosterone, and metformin was used as a positive control drug to study the effect of pachymic acid (PA) on endocrine and oocyte quality in PCOS mice. Compared with the model group, the mice treated with PA showed the following changes (slower weight gain, improved abnormal metabolism; increased development potential of GV oocytes, reduced number of abnormal MII oocytes, and damaged embryos; lower expression of ovarian-related genes in ovarian tissue and pro-inflammatory cytokines in adipose tissue). All these aspects show similar effects on metformin. Most notably, PA is superior to metformin in improving inflammation of adipose tissue and mitochondrial abnormalities. It is suggested that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice. These findings suggest that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice.

A Multifaceted Directing Group Switching Ynones as Michael Donors in Chemo-, Enantio-, and γ-Selective 1,4-Conjugate Additions with Nitroolefins.

α,ß-Unsaturated ynones have historically been used as Michael acceptors in conjugate addition reactions. Herein, we have demonstrated for the first time that ynones can be harnessed as Michael donors for use in catalytic asymmetric conjugate addition reactions by strategically introducing a CO2t-Bu group as a multitasking directing group. Furthermore, this concept has enabled designer ynones as versatile synthetic equivalents of both α' anions of ynones and γ monoanions of 1,3-diketones, which are synthetically valued but difficult to generate. The first catalytic enantioselective conjugate addition of ynones as Michael donors has been realized in good yields with high enantioselectivities. A unified approach to regiospecifically and chemo- and enantioselectively access hitherto elusive γ-Michael adducts of 1,3-diketones has been achieved in a divergent manner. The strategy described here by exploring new reactivity and creating new reagents holds great potential applications in other still unsolved transformations.

Efficacy of calcitriol in treating glucocorticoidinduced osteoporosis in patients with nephrotic syndrome: an open-label, randomized controlled study.

OBJECTIVE: To evaluate the efficacy and safety of calcitriol in the prevention and treatment of glucocorticoid-induced osteoporosis. METHODS: 66 patients treated with glucocorticoids (GC) for primary nephrotic syndrome (NS) were randomly assigned to 3 groups. Groups were designated as follows: calcitriol alone (n = 22), calcitriol plus calcium carbonate (n = 23), or calcium carbonate alone (n = 21). Serum markers of bone metabolism and bone mineral density (BMD) were tested at 3 different time points: the initiation of GC treatment (baseline), 12 weeks, and 24 weeks after the initiation of treatment. RESULTS: Levels of serum 25-hydroxy vitamin D, serum osteocalcin, and total serum collagen type N-terminal extension of the peptide were significantly decreased following GC therapy (p < 0.05). ß-collagen serum-specific sequences were significantly increased following GC therapy. The above-mentioned changes were less dramatic in patients treated with calcitriol, although the differences were significant (p < 0.05). Changes in serum levels of calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) were not significant. 24 weeks after the initiation of treatment, BMD of the lumbar spine and femoral bone significantly decreased in all of 3 groups. However, patients who received calcitriol had significantly higher BMD of the lumbar spine than patients who received calcium carbonate alone (calcitriol plus calcium carbonate vs. calcium carbonate alone: 0.82 ± 0.19 g/cm2 vs. 0.62 ± 0.23 g/cm2 p < 0.05; calcitriol vs. calcium carbonate alone 0.805 ± 0.203 g/cm2 vs. 0.615 ± 0.225 g/cm2 p < 0.05), respectively. No serious adverse events were observed. CONCLUSION: Calcitriol may be more effective than calcium carbonate in preventing and treating GC-induced osteoporosis in patients with NS.

Metabolomics reveals early pregnancy biomarkers in sows: a non-invasive diagnostic approach.

In an effort to enhance reproductive management and reduce non-productive periods in swine breeding, this study presents a novel, non-invasive metabolomics approach for the identification of early pregnancy biomarkers in sows. Utilizing an untargeted metabolomics approach with mass spectrometry analysis, we examined saliva samples from pregnant (n = 6) and non-pregnant control sows (n = 6, artificially inseminated with non-viable sperm). Our analysis revealed 286 differentially expressed metabolites, with 152 being up-regulated and 134 down-regulated in the pregnant group. Among these, three metabolites, namely Hyodeoxycholic acid, 2'-deoxyguanosine, and Thymidine, emerged as potential early pregnancy biomarkers. These biomarkers were further evaluated using targeted LC-MS/MS quantification and qualification, accompanied by ROC curve analysis. The study confirmed Hyodeoxycholic acid and 2'-deoxyguanosine as promising biomarkers for early pregnancy detection, offering potential for future implementation in swine production environments. This research establishes a robust theoretical foundation for the development of innovative molecular diagnostic techniques and explores new avenues for molecular genetic breeding and non-invasive diagnostics, ultimately enhancing fertility and productivity in sow herds.

Association of time-averaged serum uric acid level with clinicopathological information and long-term outcomes in patients with IgA nephropathy.

Objective: Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long- term SUA control levels must be monitored. We aimed to investigate the relevant factors affecting time-averaged SUA (TA-SUA) and to assess the prognostic value of TA-SUA in IgAN. Methods: This retrospective study included 152 patients with IgAN. The relationships between TA-SUA and clinicopathological features and renal outcomes (defined as the doubling of the baseline serum creatinine level or end-stage renal disease) were analyzed in groups divided by quartiles of TA-SUA levels, the presence of hyperuricemia, and sex. Results: Patients with high TA-SUA levels had higher levels of baseline SUA, blood urea nitrogen (BUN), triglycerides, serum C3 and serum C4 and were more likely to be male and have hypertension, proteinuria, poor renal function, and pathological injuries including high grades of tubular atrophy/interstitial fibrosis (T1-T2). These patients had a poorer prognosis compared with patients with low TA-SUA levels. The TA-SUA level was positively correlated with baseline age and BUN, triglycerides, serum C3, and serum C4 levels, and negatively correlated with baseline eGFR. Survival curve analysis indicated that persistent hyperuricemia was associated with significantly poorer renal outcomes than normo-uricemia in both men and women. The TA-SUA level also was an independent predictor of renal outcome in patients with IgAN, with optimal cutoû values of 451.38 µmol/L (area under the curve (AUC) = 0.934) for men and 492.83 µmol/L (AUC = 0.768) for women. Conclusions: The TA-SUA level is associated with triglyceride level, complement component levels, renal function, and pathological severity of IgAN, and it may be a prognostic indicator in male and female patients with IgAN.

Co-hydrothermal carbonization of polyvinyl chloride and lignocellulose biomasses for chlorine and inorganics removal.

Co-hydrothermal carbonization (co-HTC) of lignocellulose biomass (LB) and chlorinated waste can simultaneously remove organic chlorine and inorganics, however, the interaction mechanisms are unclear owing to the variety of operating conditions and complexity of biomass compositions. Pine, bamboo, corncob, corn stalk, and wheat straw were co-hydrothermally carbonized with polyvinyl chloride (PVC) at the mass ratio of 9:1 for 30 min under 260 °C to explore the fundamental interactions. The synergistic index (SI) of dechlorination efficiency ranged from -20.3 % to 19.9 %, indicating the interaction depended on the content and composition of cellulose, hemicellulose, and lignin in the LB feedstocks. Hydroxyl functional groups in cellulose and soluble lignin dehydration intermediates promoted PVC substitution. The LB fragments prevented PVC aggregation while promoted PVC fragmentation, thereby facilitating dechlorination. The polyaromatic hydrochar derived from insoluble lignin and polymeric hydrochar derived from hemicellulose, cellulose, and soluble lignin can coat the surface of molten PVC and act as significant dechlorination inhibitors. All SI of removal efficiency of inorganics (RE) were positive, ranging from 0.74 % to 154 %, with large variations for different inorganics, indicating that inorganics contents in LB influenced RE significantly. A large amount of water-insoluble/acid-soluble inorganics was removed via a metathesis reaction. Soluble inorganics were dissolved in the process water by HCl leaching.

Association Between Social Support and Perceived Stress: A Cross-Sectional Study on Staffs of the Epidemic Prevention During the Covid-19 Epidemic in China.

Background: The Coronavirus Disease 2019 (COVID-19) lockdown considerably affects people's life in China, both physically and mentally. Staffs of the epidemic prevention and control in the community have played an irreplaceable role during community lockdown period in Wuhan. However, few studies have focused on their health status during epidemic prevention. This study aimed to appraise the available evidence of health conditions of them and explore the influencing factors. Method: Used a multistage sampling method, we conducted a survey in staffs of the epidemic prevention and control in the community (N = 503). Descriptive analysis was used to characterize the respondents. T-test and analysis of variance were for group differences analysis. Confirmatory factor analysis (CFA) was used to verify the scale validity, correlation analysis and pathway analysis and Structural equation model (SEM) was used to study the relationship between stress perception, social support, mental resilience and sleep quality. Statistical analysis was performed with SPSS 26.0, R version 4.1.3 and Mplus 8.3. Results: The mean Perceived Stress Scale (PSS) score of the respondents was 13.28 ± 7.31 and 51.1% had higher PSS score than the normal. In the absence of social support, people's sleeping quality and psychological resilience may decrease, their perceived stress may elevate and compromise mental health correspondingly. Social support could affect perceived stress directly, while Sleep quality and psychology resilience played significant partial mediating roles in social support affecting perceived stress. The mediating effects accounted for 50.8% of the total. Conclusion: Staffs of the epidemic prevention and control in the community suffered from poor sleep quality and high level of stress perception. Establishment of good social support may effectively reduce their stress and this effect is mediated by sleep quality and psychological resilience. Physical health status would affect the staffs' mental health and they more attention should be paid to those with poor physical health.

Time-Averaged Hematuria as a Prognostic Indicator of Renal Outcome in Patients with IgA Nephropathy.

We aim to investigate the association of time-averaged hematuria (TA-hematuria) with the progression of IgA nephropathy (IgAN). Based on TA-hematuria during follow-up, 152 patients with IgAN were divided into a hematuria remission group (≤28 red blood cells [RBCs]/µL) and a persistent hematuria group (>28 RBCs/µL). The persistent hematuria group had a higher percentage of patients with macroscopic hematuria, lower levels of hemoglobin and TA-serum albumin, and more severe renal pathologic lesions. The composite endpoint is defined as a doubling of the baseline SCr level (D-SCr), or the presence of ESRD. During the mean follow-up of 58.08 ± 23.51 months, 15 patients (9.9%) reached the primary outcome of ESRD and 19 patients (12.5%) reached the combined renal endpoint. Kaplan-Meier analysis showed that the persistent hematuria group had a lower renal survival rate. The persistent hematuria patients who were incorporated with proteinuria (≥1.0 g/day) and low TA-serum albumin (<40 g/L) had the worst renal outcomes. Multivariate Cox regression indicated that TA-hematuria (hazard ratio [HR] = 0.004, 95% CI: 0.001, 0.008; p = 0.010) was independently associated with the progression of IgAN. Receiver operating characteristic analysis indicated the optimal TA-hematuria cutoff value for predicting the progression of IgAN was 201.21 RBCs/µL in females and 37.25 RBCs/µL in males.

Discovery of [Formula: see text] rotation anomaly in topological crystalline insulator SrPb.

Topological crystalline insulators (TCIs) are insulating electronic states with nontrivial topology protected by crystalline symmetries. Recently, theory has proposed new classes of TCIs protected by rotation symmetries [Formula: see text], which have surface rotation anomaly evading the fermion doubling theorem, i.e., n instead of 2n Dirac cones on the surface preserving the rotation symmetry. Here, we report the first realization of the [Formula: see text] rotation anomaly in a binary compound SrPb. Our first-principles calculations reveal two massless Dirac fermions protected by the combination of time-reversal symmetry [Formula: see text] and [Formula: see text] on the (010) surface. Using angle-resolved photoemission spectroscopy, we identify two Dirac surface states inside the bulk band gap of SrPb, confirming the [Formula: see text] rotation anomaly in the new classes of TCIs. The findings enrich the classification of topological phases, which pave the way for exploring exotic behavior of the new classes of TCIs.

Facile in situ synthesis of cellulose microcrystalline-manganese dioxide nanocomposite for effective removal of Pb(II) and Cd(II) from water.

A novel cellulose microcrystalline-manganese dioxide nanocomposite (CMC-NMO) was synthesized by the redox reaction between potassium permanganate and ethanol based on cellulose microcrystalline. The cellulose microcrystalline (CMC) as support providing growth sites for the manganese dioxide nanowhiskers produced by the redox reaction and its application for Pb(II) and Cd(II) removal from aqueous was investigated. The characterization of as-synthesized material was revealed by various spectroscopic and microscopic techniques. Infrared-transform infrared (FITR) indicates that the incorporation of manganese oxide to CMC does not change the initial structure of it. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) data show that the manganese dioxide nanowhiskers with a few nanometers are uniformly dispersed on the surface of cellulose. Kinetics experiments reveal that Pb(II) and Cd(II) adsorption on CMC-NMO is a fast process and pseudo-second-order model fits the adsorption better. The maximum adsorption capacities of Pb(II) and Cd(II) obtained from the Langmuir model are 290.8 mg/g and 67.4 mg/g, respectively. The mechanism is mainly attributed to surface complexation and electrostatic attraction by energy dispersive analysis of X-rays (EDAX), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analysis. In addition, depth removal experiments show that the residual concentrations of Pb(II) and Cd(II) in natural water after adsorption are lower than 0.01 mg/L. The regeneration and cyclic utilizing studies indicate that CMC-NMO has good adsorption stability. Therefore, the results indicate that this material can be employed as a potential adsorbent for current serious Pb(II) and Cd(II) pollution caused by industrial emissions. Graphical abstract.

The removal of Pb (II) and Cd (II) with hydrous manganese dioxide: mechanism on zeta potential and adsorption behavior.

In this study, the removal of Pb (II) and Cd (II) in aqueous solution by employing hydrous manganese dioxide (HMO) is investigated. The HMO synthesized was characterized by SEM, XRD, BET, FT-IR, and XPS. Simultaneously, the effect of Zeta potential (ZP), solution pH and contact time were discussed. The results reveal that at pH 5.0, 1-HMO (-51.7 mV) with the highest |ZP| value can reach equilibrium and reach 95.7% removal rate within 30 mins. The isotherm and kinetic data fitted Langmuir and pseudo-second-order models well. The maximum adsorption capacities calculated by Langmuir equation are 475.4 mg/g for Pb (II) and 140.3 mg/g for Cd (II) at 303.15 K, respectively. The binary experiment indicates the HMO showed a better affinity for Pb (II) than Cd (II). Thermodynamic studies (ΔG < 0, ΔH > 0, ΔS > 0) implies the both adsorptions are endothermic and spontaneous process. The intraparticle model analysis indicates that the film discussion controls the metal ions adsorption at the earlier stage and the intraparticle diffusion at the middle stage, while a chemical bonding process at the equilibrium stage. The FTIR and XPS analysis further proves Pb (II) and Cd (II) being adsorbed onto the surface of HMO as Pb-O and Cd-O, resulting from ion exchange and complexation. The reacted HMO could be recycled and reused for several times in a high efficiency above 90% by adding HCl or new HMO adsorbent. Simple preparation, low cost and remarkable removal efficiency make HMO a promising material in the treatment of heavy metal-contaminated water.

Effects of fine particulate matter (PM2.5) on ovarian function and embryo quality in mice.

Fine particulate matter (PM2.5) has an adverse effect on reproductive function, in particular causing reduced male reproductive function, but relatively few studies have directly targeted its effects on female reproduction. To investigate the effects of PM2.5 exposure on female reproduction, we exposed female mice to PM2.5 by intratracheal instillation for 28 days, and evaluated apoptosis of ovarian granulosa cells and oocytes and the quality embryos after insemination. Our results showed increased numbers of apoptotic granulosa cells and oocytes after exposure to elevated concentrations of PM2.5, which had adverse effects on female fertility via compromising embryo development and quality. We conclude that PM2.5 induced apoptosis of ovarian granulosa cells and oocytes leading to disrupted embryo development and female fertility in mice.

Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes.

Mancozeb, a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Mancozeb could lead to mitochondria dysfunction, cellular anti-oxidation enzymes depletion and apoptotic pathways activation. Previous studies indicated the exposure of mancozeb through mother would lead to irregular estrous cycles, decreased progesterone levels, reduced litter sizes, and more frequent delivery of dead fetuses. In this study, we investigated mancozeb inducing reproductive toxicity, especially focusing on its apoptotic effect and epigenetic modifications. We also showed that resveratrol, a kind of phytoalexin found in peanuts and grapes, can alleviate mancozeb's adverse effects, such as declined fertility, decreased ovary weight and primary follicles. Besides, mancozeb treated oocytes displayed suboptimal developmental competence and this can also be improved by treatment of resveratrol. More detailed investigation of these processes revealed that mancozeb increased reactive oxygen species, causing cell apoptosis and abnormal epigenetic modifications, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can alleviate mancozeb induced infertility and this was mainly through the correction of apoptotic tendency and the abnormity of cellular epigenetic modification.

SKAP2 regulates Arp2/3 complex for actin-mediated asymmetric cytokinesis by interacting with WAVE2 in mouse oocytes.

SKAP2 (Src kinase-associated phosphoprotein 2), a substrate of Src family kinases, has been suggested to be involved in actin-mediated cellular processes. However, little is known about its role in mouse oocyte maturation. In this study, we thus investigated the expression, localization, and functions of SKAP2 during mouse oocyte asymmetric division. SKAP2 protein expression was detected at all developmental stages in mouse oocytes. Immunofluorescent staining showed that SKAP2 was mainly distributed at the cortex of the oocytes during maturation. Treatment with cytochalasin B in oocytes confirmed that SKAP2 was co-localized with actin. Depletion of SKAP2 by injection with specific short interfering RNA caused failure of spindle migration, polar body extrusion, and cytokinesis defects. Meanwhile, the staining of actin filaments at the oocyte membrane and in the cytoplasm was significantly reduced after these treatments. SKAP2 depletion also disrupted actin cap and cortical granule-free domain formation, and arrested a large proportion of oocytes at the telophase stage. Moreover, Arp2/3 complex and WAVE2 expression was decreased after the depletion of SKAP2 activity. Our results indicate that SKAP2 regulates the Arp2/3 complex and is essential for actin-mediated asymmetric cytokinesis by interacting with WAVE2 in mouse oocytes.

Autophagy and apoptosis in tubular cells following unilateral ureteral obstruction are associated with mitochondrial oxidative stress.

Tubular epithelial loss has been shown to be responsible for the formation of atubular glomeruli leading to nephron decomposition and interstitial fibrosis in obstructive uropathy. Cells undergoing apoptosis and autophagic cell death play an important role in this process, yet the mechanisms are not fully understood. In this study, we aimed to investigate whether autophagy cooperating with apoptosis is associated with mitochondrial damage and whether oxidative stress plays an important role in the loss of tubular epithelium following unilateral ureteral obstruction. In this model, we demonstrated that there is coexistence of autophagy and apoptosis with tubular atrophy in obstructed proximal tubules. After unilateral ureteral obstruction (UUO), autophagy in proximal tubular cells was enhanced steadily up to 7 days in the obstructed kidney and declined thereafter, while apoptosis was induced in a time-dependent manner from 3 to 14 days. Mitochondrial structure and number also changed during UUO. Lipid peroxidation products, NOX4, and NADPH oxidase activity were also increased in the obstructed renal cortex, and peaked at 7 days. In vitro, we showed that H2O2 induced mitochondrial injury leading to autophagy and apoptosis through the Beclin 1 pathway and interference with Bcl-2 expression. Thus, our data demonstrate that oxidative stress leading to mitochondrial damage and driven autophagy-dependent cell death and apoptosis are important mechanisms of tubular decomposition in obstructive nephropathy.

[Clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure induced by chronic glomerulonephritis].

OBJECTIVE: To evaluate the clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure caused by chronic glomerulonephritis. METHODS: Sixty-three patients with chronic renal failure due to chronic glomerulonephritis, after receiving a 2-week-long conventional treatment, were randomly divided into alprostadil group (n=20, with alprostadil injection at 10 µg/d for 2 weeks), sequential treatment group (n=21, with alprostadil injection at 10 µg/d for 2 weeks and oral beraprost sodium at 20 µg three times a day for 12 weeks), and strengthened sequential treatment group (n=22, with alprostadil injection at 20 µg/d for 2 weeks and a double dose of oral beraprost sodium for 12 weeks). Urinary albumin excretion rate (UAER), cystatin C (Cys C), blood urea nitrogen, creatinine, fibrinogen, D-dimer, prothrombin time (PT), and platelets were tested before and after the treatment, and the changes in urinary albumin discharge rate, serum creatinine, and glomerular filtration rate were determined. RESULTS: The patients in strengthened sequential treatment group showed a significantly decreased change rate of urinary albumin discharge rate (P<0.01) than those in the other two groups. In the two sequential treatment groups, especially the strengthened treatment group, the change rate of glomerular filtration rate increased significantly compared with that in alprostadil group (P<0.01). Strengthened sequential treatment resulted also in significantly decreased increment of serum creatinine compared that in the other 2 groups (P<0.01). After 14 weeks of treatment, fibrinogen and D-dimer were decreased in all the 3 groups (P<0.05) to a comparable level between the 3 groups (P>0.05), and prothrombin time (PT) or platelet showed no significant changes (P>0.05). CONCLUSION: Sequential treatment with alprostadil and beraprost sodium can improve the glomerular filtration rate and decrease urine albumin excretion rate, serum creatinine increase rate, and lower blood fibrinogen and D-dimer levels, thus delaying the progression of chronic renal failure caused by chronic glomerulonephritis. This therapy shows a dose-related effect with good clinical safety.