Observation of fractionally quantized anomalous Hall effect.

The integer quantum anomalous Hall (QAH) effect is a lattice analogue of the quantum Hall effect at zero magnetic field1-3. This phenomenon occurs in systems with topologically non-trivial bands and spontaneous time-reversal symmetry breaking. Discovery of its fractional counterpart in the presence of strong electron correlations, that is, the fractional QAH effect4-7, would open a new chapter in condensed matter physics. Here we report the direct observation of both integer and fractional QAH effects in electrical measurements on twisted bilayer MoTe2. At zero magnetic field, near filling factor ν = -1 (one hole per moiré unit cell), we see an integer QAH plateau in the Hall resistance Rxy quantized to h/e2 ± 0.1%, whereas the longitudinal resistance Rxx vanishes. Remarkably, at ν = -2/3 and -3/5, we see plateau features in Rxy at [Formula: see text] and [Formula: see text], respectively, whereas Rxx remains small. All features shift linearly versus applied magnetic field with slopes matching the corresponding Chern numbers -1, -2/3 and -3/5, precisely as expected for integer and fractional QAH states. Additionally, at zero magnetic field, Rxy is approximately 2h/e2 near half-filling (ν = -1/2) and varies linearly as ν is tuned. This behaviour resembles that of the composite Fermi liquid in the half-filled lowest Landau level of a two-dimensional electron gas at high magnetic field8-14. Direct observation of the fractional QAH and associated effects enables research in charge fractionalization and anyonic statistics at zero magnetic field.

A LC-MS/MS method for determination of clenbuterol enantiomers in animal tissues and its application to the enantioselective distribution in Bama mini-pigs.

OBJECTIVES: To establish and validate a simple and reliable analytical method for separation and determination of clenbuterol enantiomers (R-(-)-clenbuterol & S-(+)-clenbuterol) in animal tissues, and apply it to the enantioselective distribution of clenbuterol in Bama mini-pigs. METHODS: A LC-MS/MS analytical method was developed and validated in positive multiple reaction monitoring mode with electrospray ionization. After perchloric acid deproteinization, samples were pretreated only by one step liquid-liquid extraction using tert-butyl methyl ether under strong alkaline condition. Teicoplanin was used as chiral selector and 10 mM ammonium formate methanol solution was used as mobile phase. The optimized chromatographic separation conditions were completed in 8 min. Two chiral isomers in 11 edible tissues from Bama mini-pigs were investigated. RESULTS: R-(-)-clenbuterol and S-(+)-clenbuterol can be baseline separated and accurately analyzed with a linear range of 5-500 ng/g. Accuracies ranged from -11.9-13.0% for R-(-)-clenbuterol and -10.2-13.2% for S-(+)-clenbuterol, intra-day and inter-day precisions were between 0.7 and 6.1% for R-(-)-clenbuterol and 1.6-5.9% for S-(+)-clenbuterol. R/S ratios in edible tissues of pigs were all significantly lower than 1. CONCLUSIONS: The analytical method has good specificity and robustness in determination of R-(-)-clenbuterol and S-(+)-clenbuterol in animal tissues, and can be used as a routine analysis method for food safety and doping control. There is a significant difference in R/S ratio between pig feeding tissues and pharmaceutical preparations (racemate with R/S ratio of 1), which makes it possible to identify the source of clenbuterol in doping control and investigation.

Signatures of fractional quantum anomalous Hall states in twisted MoTe2.

The interplay between spontaneous symmetry breaking and topology can result in exotic quantum states of matter. A celebrated example is the quantum anomalous Hall (QAH) state, which exhibits an integer quantum Hall effect at zero magnetic field owing to intrinsic ferromagnetism1-3. In the presence of strong electron-electron interactions, fractional QAH (FQAH) states at zero magnetic field can emerge4-8. These states could host fractional excitations, including non-Abelian anyons-crucial building blocks for topological quantum computation9. Here we report experimental signatures of FQAH states in a twisted molybdenum ditelluride (MoTe2) bilayer. Magnetic circular dichroism measurements reveal robust ferromagnetic states at fractionally hole-filled moiré minibands. Using trion photoluminescence as a sensor10, we obtain a Landau fan diagram showing linear shifts in carrier densities corresponding to filling factor v = -2/3 and v = -3/5 ferromagnetic states with applied magnetic field. These shifts match the Streda formula dispersion of FQAH states with fractionally quantized Hall conductance of [Formula: see text] and [Formula: see text], respectively. Moreover, the v = -1 state exhibits a dispersion corresponding to Chern number -1, consistent with the predicted QAH state11-14. In comparison, several non-ferromagnetic states on the electron-doping side do not disperse, that is, they are trivial correlated insulators. The observed topological states can be electrically driven into topologically trivial states. Our findings provide evidence of the long-sought FQAH states, demonstrating MoTe2 moiré superlattices as a platform for exploring fractional excitations.

Every-other-layer dipolar excitons in a spin-valley locked superlattice.

Monolayer semiconducting transition metal dichalcogenides possess broken inversion symmetry and strong spin-orbit coupling, leading to a unique spin-valley locking effect. In 2H stacked pristine multilayers, spin-valley locking yields an electronic superlattice structure, where alternating layers correspond to barriers and quantum wells depending on the spin-valley indices. Here we show that the spin-valley locked superlattice hosts a kind of dipolar exciton with the electron and hole constituents separated in an every-other-layer configuration: that is, either in two even or two odd layers. Such excitons become optically bright via hybridization with intralayer excitons. This effect is also manifested by the presence of multiple anti-crossing patterns in the reflectance spectra, as the dipolar exciton is tuned through the intralayer resonance by an electric field. The reflectance spectra further reveal an excited state orbital of the every-other-layer exciton, pointing to a sizable binding energy in the same order of magnitude as the intralayer exciton. As layer thickness increases, the dipolar exciton can form a one-dimensional Bose-Hubbard chain displaying layer number-dependent fine spectroscopy structures.

Safety profile of 0.0015% tafluprost eye drops in China: a post-marketing observational study.

AIM: To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension (OH) in clinical practice in China. METHODS: This post-marketing observational study included patients who received tafluprost to lower intraocular pressure (IOP) within 30d between September 2017 and March 2020 in 20 hospitals in China. Adverse drug reactions (ADRs) during tafluprost treatment and within 30d after the treatment were collected. RESULTS: A total of 2544 patients were included in this study, of them 58.5% (1488/2544) had primary open angle glaucoma (POAG), 21.9% (556/2544) had OH and 19.7% (500/2544) used tafluprost for other reasons. Of 359 ADRs occurred in 10.1% (258/2544) patients, and no serious adverse event occurred. The most common ADR was conjunctival hyperemia (128 ADRs in 124 patients, 4.9%). Totally 1670 participants (65.6%) combined tafluprost with carbonic anhydrase inhibitors (CAIs; 37.1%, 620/1670), sympathomimetics (33.5%, 559/1670), ß-blockers (33.2%, 555/1670), other prostaglandin analogs (PGAs; 15.6%, 260/1670) and other eye drops (15.1%, 253/1670). The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs (23 ADRs in 23 patients, 8.8%, 23/260) and the lowest was in combination with CAIs (16 ADRs in 16 patients, 2.6%, 16/620). Tafluprost was applied in primary angle-closure glaucoma (41.6%, 208/500), after glaucoma surgery (17.8%, 89/500) and after non-glaucoma surgery (15.8%, 79/500). CONCLUSION: Tafluprost is safe for POAG and OH, and tolerable when combined with other eye drops and under various clinical circumstances.

Maternal sevoflurane exposure affects neural stem cell differentiation in offspring rats through NRF2 signaling.

Studies have shown that sevoflurane, a halogenated inhalational anesthetic, interferes with neurogenesis in the developing rodent brain. However, the mechanisms by which sevoflurane affects neural stem cells (NSCs) differentiation require further elucidation. Pregnant rats (gestational day 14) were anesthetized with 3.5% sevoflurane for 2 h, with or without ML385 pretreatment. ML385 is a specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor. NRF2 expression and the downstream Sonic Hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) signaling cascade were determined by western blotting in the fetal brain at 24 h and 72 h after maternal sevoflurane exposure. Immunofluorescence and western blotting were performed to evaluate NSC neuronal and astrocytic differentiation in fetal brain tissues at 24 h and 72 h post-anesthesia as well as in the hippocampus on postnatal day (P) 28. Nissl staining was performed to measure the neuronal density on P28. Morris Water Maze tests were used to evaluate learning and memory function on P28-33. Neuronal and astrocytic differentiation of NSCs was markedly promoted in the fetal brain at 24 h and 72 h after maternal sevoflurane exposure, accompanied by upregulated NRF2. However, neuronal reduction and astrocyte proliferation were observed in the rat hippocampus at P28. Pretreatment with ML385 reversed sevoflurane-induced premature differentiation of NSCs, accompanied by suppression of SHH/GLI1 signaling. Furthermore, ML385 rescued sevoflurane-induced decreased neuronal density and impaired learning and memory function in the offspring. Prenatal sevoflurane exposure promotes neuronal and astrocytic differentiation of NSCs in the fetal rat brain, leading to long-term neuron reduction but astrocyte proliferation in the postnatal rat hippocampus. Prenatal sevoflurane exposure modulates NSC differentiation through NRF2/SHH/GLI1.

A novel process for anammox pretreatment of municipal wastewater: semi-partial nitrification, biological phosphorus removal and recovery.

Achieving simultaneous semi-partial nitrification and deep phosphorus removal is a preferred process technology for Anammox pretreatment. In this study, semi-partial nitrification combined with in-situ phosphorus recovery (PNPR) was used to treat municipal wastewater. The SRT conflict between the nitrification and phosphorus removal was resolved by in-situ phosphorus recovery every 20 cycles of Anaerobic/Oxid, and a supernatant with more than 10 times the influent phosphorus concentration was obtained, thus achieving bio-enhanced phosphorus removal and recovery with satisfactory semi-partial-nitrification effluent. Interestingly, the results showed that phosphorus removal and recovery process could improve the activity of AOB. The PNPR system's nitrite accumulation rate (NAR) and phosphorus removal rate (PRR) were more than 90% each, whereas the relative abundance of AOB and PAOs increased from 0.04% to 0.74% and from 0.25% to 0.70%, respectively (P < 0.01). Furthermore, on average, the NO2--Neff/NH4+-Neff value was 1.96, which laid the foundation for the subsequent anammox treatment.

Multiple conformations of trimeric spikes visualized on a non-enveloped virus.

Many viruses utilize trimeric spikes to gain entry into host cells. However, without in situ structures of these trimeric spikes, a full understanding of this dynamic and essential process of viral infections is not possible. Here we present four in situ and one isolated cryoEM structures of the trimeric spike of the cytoplasmic polyhedrosis virus, a member of the non-enveloped Reoviridae family and a virus historically used as a model in the discoveries of RNA transcription and capping. These structures adopt two drastically different conformations, closed spike and opened spike, which respectively represent the penetration-inactive and penetration-active states. Each spike monomer has four domains: N-terminal, body, claw, and C-terminal. From closed to opened state, the RGD motif-containing C-terminal domain is freed to bind integrins, and the claw domain rotates to expose and project its membrane insertion loops into the cellular membrane. Comparison between turret vertices before and after detachment of the trimeric spike shows that the trimeric spike anchors its N-terminal domain in the iris of the pentameric RNA-capping turret. Sensing of cytosolic S-adenosylmethionine (SAM) and adenosine triphosphate (ATP) by the turret triggers a cascade of events: opening of the iris, detachment of the spike, and initiation of endogenous transcription.

The clinical and genetic findings in a Chinese family with Axenfeld-Rieger syndrome.

Objecive: To describe the clinical and genetic findings of an Axenfeld-Rieger syndrome (ARS) family with a new PITX2 splicing mutation. Methods: A Chinese ARS family with five affected individuals was recruited. Exome sequencing was performed on the proband and the variant (C.253-9C > A) in PITX2 gene was detected as a pathogenic mutation. Sanger sequencing was performed for verification and cosegregation analysis. Real-time polymerase chain reaction (RT- PCR) and Western blotting were performed to verify the expression of the pathogenic gene. Results: All the patients showed abnormalities in the anterior segment of both eyes including posterior embryotoxon, corectopia, iris dysplasia, and iridocorneal tissue adhesions. In addition, they all presented systemic features, including maxillary hypoplasia, underbite, hypodontia, conical teeth. Only III-7 showed obvious umbilical skin. In the PITX2 family, we identified a novel heterozygous splicing mutation (C.253-9C > A) which was confirmed by Sanger sequencing to be completely cosegregated with the ARS phenotype. Real-time quantitative PCR and Western results showed that PITX2 mRNA and protein expression were significantly lower in patients compared with unrelated normal controls. Conclusion: In the ARS pedigree, we summarized the variable phenotype, described a novel PITX2 splicing mutation which expand the genetic spectrum of ARS. We further confirmed the possibility of development of ARS induced by this PITX2 gene deficiency.

The Evolution of Organosilicon Precursors for Low-k Interlayer Dielectric Fabrication Driven by Integration Challenges.

Since the application of silicon materials in electronic devices in the 1950s, microprocessors are continuously getting smaller, faster, smarter, and larger in data storage capacity. One important factor that makes progress possible is decreasing the dielectric constant of the insulating layer within the integrated circuit (IC). Nevertheless, the evolution of interlayer dielectrics (ILDs) is not driven by a single factor. At first, the objective was to reduce the dielectric constant (k). Reduction of the dielectric constant of a material can be accomplished by selecting chemical bonds with low polarizability and introducing porosity. Moving from silicon dioxide, silsesquioxane-based materials, and silica-based materials to porous silica materials, the industry has been able to reduce the ILDs' dielectric constant from 4.5 to as low as 1.5. However, porous ILDs are mechanically weak, thermally unstable, and poorly compatible with other materials, which gives them the tendency to absorb chemicals, moisture, etc. All these features create many challenges for the integration of IC during the dual-damascene process, with plasma-induced damage (PID) being the most devastating one. Since the discovery of porous materials, the industry has shifted its focus from decreasing ILDs' dielectric constant to overcoming these integration challenges. More supplementary precursors (such as Si-C-Si structured compounds), deposition processes (such as NH3 plasma treatment), and post porosity plasma protection treatment (P4) were invented to solve integration-related challenges. Herein, we present the evolution of interlayer dielectric materials driven by the following three aspects, classification of dielectric materials, deposition methods, and key issues encountered and solved during the integration phase. We aim to provide a brief overview of the development of low-k dielectric materials over the past few decades.

Mutant Huntingtin Impairs Pancreatic ß-cells by Recruiting IRS-2 and Disturbing the PI3K/AKT/FoxO1 Signaling Pathway in Huntington's Disease.

Patients with Huntington's disease (HD) have an increased incidence of diabetes. However, the molecular mechanisms of pancreatic ß-cell dysfunction have not been entirely clarified. Revealing the pathogenesis of diabetes can provide a novel understanding of the onset and progression of HD, as well as potential clues for the development of new therapeutics. Here, we demonstrated that the mouse pancreatic insulinoma cell line NIT-1 expressing N-terminal mutant huntingtin (mHTT) containing 160 polyglutamine (160Q cells) displayed lower cell proliferative ability than the cells expressing N-terminal wild-type HTT containing 20 polyglutamine (20Q cells). In addition, 160Q cells were more prone to apoptosis and exhibited deficient glucose-stimulated insulin expression and secretion. Furthermore, insulin signaling molecule insulin receptor substrate 2 (IRS-2) expression decreased and was recruited into mHTT aggregates. Consequently, glucose stimulation failed to activate the downstream molecule phosphatidylinositol-3 kinase (PI3K) in 160Q cells, leading to reduced phosphorylation levels of serine-threonine protein kinase AKT and forkhead box protein O1 (FoxO1). These data indicate that activation of the glucose-stimulated PI3K/AKT/FoxO1 signaling pathway is significantly blocked in pancreatic ß-cells in HD. Importantly, insulin treatment inhibited the aggregation of mHTT and significantly improved the activation of PI3K/AKT/FoxO1 signaling in 160Q cells. These results suggest that the inhibition of the PI3K/AKT/FoxO1 pathway might be due to the recruitment of IRS-2 into mHTT aggregates in HD ß-cells, ultimately contributing to the impairment of pancreatic ß-cells. In conclusion, our work provides new insight into the underlying mechanisms of the high incidence of diabetes and abnormal glucose homeostasis in HD.

Heat Shock Protein 75 (TRAP1) facilitate the proliferation of the Bombyx mori nucleopolyhedrovirus.

The viruses utilize multiple cellular proteins to facilitate their proliferation. The Heat Shock Protein (HSP), the highly conserved protein in eukaryotes and prokaryotes, plays a critical role in facilitating viral proliferation. However, less is known about the role of the HSPs in the life cycles of the Baculoviruses. We constructed recombinant Bombyx mori nucleopolyhedrovirus and discovered the Heat Shock Protein 75 (TRAP1) in the B. mori ovary (BmN) cells by the co-immunoprecipitation experiment using the GP64 (glycoprotein 64) as the bait protein. Tissue expression profile analysis of B. mori indicated that the TRAP1 gene has higher expression levels in the ovary, midgut, and hemolymph. Down-regulation of TRAP1 via RNA interference (RNAi) and geldanamycin (GA, a TRAP1 inhibitor) treatment can reduce the expression level of the major capsid protein VP39 (viral protein 39) of BmNPV. In contrast, the up-regulation of TRAP1 via overexpression can increase the expression level of the VP39. These results indicated that the TRAP1 of B. mori could facilitate the proliferation of the BmNPV. This study provided new insights into the function of TRAP1, and the basic mechanisms of the baculoviruses life cycle for disease prevention.

Alkaline phosphatase can promote the replication of Bombyx mori cypovirus 1 by interaction with its turret protein.

Bombyx mori cypovirus 1 (BmCPV1) is a member of the Reoviridae family which is characterized by its single-layered capsid. Similar with other turreted viruses in the Reoviridae, transcription of BmCPV1 occurs inside the capsid, and the nascent mRNA is released to the turret which consists of five turret proteins (TPs) and located at the 5-fold axis of the outer capsid, then the capping enzyme TP will guanylate and methylate the nascent viral mRNA to produce a matured mRNA. However, during these processes, how the BmCPV1 draws other cellular proteins to facilitate its replication is still lesser-known. Here we used an ELISA to investigate the interaction between ALP and BmCPV1. A co-immunoprecipitation technique was employed to detect the interaction of ALP with the Methylase domain of TP. We further studied whether ALP affects the replication of BmCPV1 inside the cell, results show that reducing the expression of ALP through RNAi reduced the transcription level of the BmCPV1 VP1 gene, which was increased by overexpression of ALP. In summary, our data demonstrate an interaction between ALP and BmCPV1 and that ALP promoted the replication of BmCPV1, and support our hypothesis of the ALP is an RTPase to facilitate the capping process of BmCPV1.

Application of online two-dimensional high-performance liquid chromatography as purification procedure to determine the origin of 19-norandrosterone in urine by gas chromatography-combustion-isotope ratio mass spectrometry.

19-Norandrosterone (19-NA) is the main metabolite of nandrolone and/or its precursors, which can be found naturally in human urine in trace amount. Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) confirmation procedure can be used to identify a potential exogenous origin of 19-NA in urine sample. Sample purification for GC-C-IRMS analysis is crucial to the whole confirmation procedure because the concentration of 19-NA in the urine to be tested is very low. Online two-dimensional high-performance liquid chromatography (2D-HPLC) clean-up procedure with high separation capacity is used to isolate and enrich 19-NA as a sample pretreatment process. Linearity, lowest detectable concentration, uncertainty, and selectivity of the method are validated according to the World Anti-doping Agency's (WADA) requirement. Isotope fractionation effect was not observed during the 2D-HPLC purification process. The validated method provides a high efficient and convenient confirmation procedure to determine the origin of 19-NA.

Maternal sevoflurane exposure affects differentiation of hippocampal neural stem cells by regulating miR-410-3p and ATN1.

BACKGROUND: Currently, numerous animal studies have shown that exposure to commonly used general anesthetics during pregnancy may cause neurocognitive impairment in the offspring. Reportedly, exposure to sevoflurane during mid-trimester of pregnancy can inhibit proliferation of neural stem cells (NSCs) and lead to early apoptosis. Whether exposure to sevoflurane during pregnancy affects the differentiation of NSCs remains unclear. METHODS: In the present study, pregnant rats were exposed to 3% sevoflurane once for 2 h on gestational day 14 (G14) or 3 times for 2 h on G13, G14, and G15. Next, the differentiation of NSCs was measured using neuron marker ß-tubulin III and astrocyte marker glial fibrillary acidic protein (GFAP) in fetal brain tissues 24 h and 72 h after anesthesia and in hippocampus on postnatal day 28. Primary cultured rat NSCs were exposed to 4.1% sevoflurane to explore the mechanism. RESULTS: The results showed that during mid-trimester, multiple exposures to sevoflurane can cause premature differentiation of NSCs in developing brains of offspring and lead to long-term neuron reduction and astrocyte proliferation in hippocampus. The data from the present study indicated that repeated exposure to sevoflurane downregulated atrophin-1 (ATN1) expression and caused early differentiation of NSCs. Overexpression of ATN1 via lentivirus transfection attenuated the influence of sevoflurane. Using dual luciferase assay, ATN1 was found to be a target gene of microRNA-410-3p (miR-410-3p). MiR-410-3p suppression via lentivirus transfection recovered the ATN1 expression and differentiation of NSCs. CONCLUSIONS: The results from the present study demonstrated that repeated exposure to sevoflurane leads to early differentiation of NSCs and long-term effects via the miR-410-3p/ATN1 pathway.

Outcomes of effective goniosynechialysis under an endoscopic view combined with phacoemulsification in residual angle-closure glaucoma with lens opacity: 6-month results.

PURPOSE: We aimed to evaluate the efficacy and safety of effective goniosynechialysis (GSL) under an endoscopic view combined with phacoemulsification in residual angle-closure glaucoma with lens opacity. METHODS: This was a retrospective study. Patients with residual angle-closure glaucoma, lens opacity, and uncontrolled intraocular pressure (IOP) who were receiving anti-glaucoma medications were selected to undergo effective GSL under an endoscopic view combined with phacoemulsification. Follow-up examinations were conducted until 6 months postoperatively. RESULTS: Twenty-five eyes of 24 patients diagnosed with residual angle-closure glaucoma and lens opacity and peripheral anterior synechiae (PAS) at least ≥ 270° were included. Their mean age was 61.32 ± 6.11 years. Preoperatively, the mean (standard error) IOP was 29.69 (11.22) mmHg, and the median number of IOP-lowering medications used was 3.0. The decreases in the rates of IOP of the patients were 44.29%, 52.17%, 46.95%, 48.37%, and 47.29% at 1 day, 1 week, 1 month, 2.5 months, and 6 months after the surgery, respectively. At 6 months, the median number of IOP-lowering medications used decreased from 3 to 0 and the range of PAS compared to the baseline decreased from 312° to 107° (P < 0.001). We also found that 21/25 eyes achieved improved or stable visual acuity after surgery. Postoperative complications included transiently elevated IOP (12.0%), exudation (8.0%), and hyphema (4.0%). CONCLUSIONS: Phacoemulsification combined with effective GSL under an endoscopic view may reopen residual angle-closure glaucoma and reduce the number of IOP-lowering medications for up to 6 months. It is an effective and safe method for patients with residual angle-closure glaucoma and lens opacity.

Maternal Treadmill Exercise Reduces the Neurotoxicity of Prenatal Sevoflurane Exposure in Rats via Activation of p300 Histone Acetyltransferase.

Repeated or prolonged use of general anesthetics in pregnant women may disturb the neurodevelopment of infants. Compelling evidence indicates that maternal exercise during pregnancy has positive effects on the cognitive function of offspring. We previously confirmed the preventive potential of maternal treadmill training for cognitive deficits induced by in utero exposure to sevoflurane in rat pups. However, the underlying mechanism(s) needed further clarification. Thus, the aim of the present study was to investigate the effects of maternal exercise on the epigenetic regulation of genes linked to brain plasticity and function. Pregnant rats on gestational day 13 (GD 13) received 2 h of 3% sevoflurane or 30% oxygen daily on three consecutive days (GD 13-15). Pregnant rats in the exercise groups were forced to run on a treadmill for 60 min/day, 5 days/week, for a duration of 3 weeks. On postnatal day 0 (PND 0), the brains of rat pups were harvested for biochemical and histochemical studies. On PNDs 28-33, the learning and memory ability of rat pups was assessed using Morris water maze task. Maternal exercise ameliorated sevoflurane-induced decreases in p300 histone acetyltransferase (HAT) expression and inhibition of BDNF signaling. Maternal exercise improved performance in the Morris water maze task. However, these effects were reversed by p300 inhibitor. Our results indicated that maternal treadmill exercise during pregnancy can ameliorate cognitive dysfunction induced by prenatal sevoflurane exposure; p300 HAT-mediated BDNF signaling activation might contribute to the neuroprotective effects of maternal exercise.

Sirtuin 2 Inhibition Attenuates Sevoflurane-Induced Learning and Memory Deficits in Developing Rats via Modulating Microglial Activation.

Sevoflurane is a widely used inhalational anesthetic in pediatric medicine that has been reported to have deleterious effects on the developing brain. Strategies to mitigate these detrimental effects are lacking. Sirtuin 2 (SIRT2) is a member of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases involved in a wide range of pathophysiological processes. SIRT2 inhibition has emerged as a promising treatment for an array of neurological disorders. However, the direct effects of SIRT2 on anesthesia-induced damage to the immature brain are unclear. Neonatal rats were exposed to 3% sevoflurane or 30% oxygen for 2 h daily with or without SIRT2 inhibitor AK7 pretreatment from postnatal day 7 (P7) to P9. One cohort of rats were euthanized 6, 12, and/or 24 h after the last gas exposure, and brain tissues were harvested for biochemical analysis and/or immunohistochemical examination. Cognitive functions were evaluated using the open field and Morris water maze tests on P25 and P28-32, respectively. SIRT2 was significantly up-regulated in neonatal rat hippocampus at 6 and 12 h post-anesthesia. Pretreatment with SIRT2 inhibitor AK7 reversed sevoflurane-induced hippocampus-dependent cognitive impairments. Furthermore, AK7 administration mitigated sevoflurane-induced neuroinflammation and microglial activation. Concomitantly, AK7 inhibited pro-inflammatory/M1-related markers and increased anti-inflammatory/M2-related markers in microglia. AK7 might prevent sevoflurane-induced neuroinflammation by switching microglia from the M1 to M2 phenotype. Downregulation of SIRT2 may be a novel therapeutic target for alleviating anesthesia-induced developmental neurotoxicity.

Conservative transcription in three steps visualized in a double-stranded RNA virus.

Endogenous RNA transcription characterizes double-stranded RNA (dsRNA) viruses in the Reoviridae, a family that is exemplified by its simple, single-shelled member cytoplasmic polyhedrosis virus (CPV). Because of the lack of in situ structures of the intermediate stages of RNA-dependent RNA polymerase (RdRp) during transcription, it is poorly understood how RdRp detects environmental cues and internal transcriptional states to initiate and coordinate repeated cycles of transcript production inside the capsid. Here, we captured five high-resolution (2.8-3.5 Å) RdRp-RNA in situ structures-representing quiescent, initiation, early elongation, elongation and abortive states-under seven experimental conditions of CPV. We observed the 'Y'-form initial RNA fork in the initiation state and the complete transcription bubble in the elongation state. These structures reveal that de novo RNA transcription involves three major conformational changes during state transitions. Our results support an ouroboros model for endogenous conservative transcription in dsRNA viruses.

Raman Signatures of Broken Inversion Symmetry and In-Plane Anisotropy in Type-II Weyl Semimetal Candidate TaIrTe4.

The layered ternary compound TaIrTe4 is an important candidate to host the recently predicted type-II Weyl fermions. However, a direct and definitive proof of the absence of inversion symmetry in this material, a prerequisite for the existence of Weyl Fermions, has so far remained evasive. Herein, an unambiguous identification of the broken inversion symmetry in TaIrTe4 is established using angle-resolved polarized Raman spectroscopy. Combining with high-resolution transmission electron microscopy, an efficient and nondestructive recipe to determine the exact crystallographic orientation of TaIrTe4 crystals is demonstrated. Such technique could be extended to the fast identification and characterization of other type-II Weyl fermions candidates. A surprisingly strong in-plane electrical anisotropy in TaIrTe4 thin flakes is also revealed, up to 200% at 10 K, which is the strongest known electrical anisotropy for materials with comparable carrier density, notably in such good metals as copper and silver.