BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.

Octopus-like Microstructure of Graphene Oxide Generated through Laser-Microdroplet Interaction for Adhesive Coating.

The octopus, as one of the most famous celebrities in bionics, has provided various inspirations for camouflage materials, soft-bodied robots, and flexible grabbers. The miniaturization of such structures will help the development of microrobots, microdelivery of drugs, and surface coating. With the lack of relevant effective preparation approaches, however, the generation of such octopus-like structures with a size of ∼1 µm or below is challenging. Here, we develop an approach based on laser-microdroplet interaction for generating an octopus-like structure with a size of ∼1 µm. The developed approach uses laser-microdroplet interaction to provide a large driving force of ∼107 Pa at a confined space (<1 µm), locally crumpling the precursor in the microdroplet. The locally crumpled particles possess both crumpled and uncrumpled structures that resemble an octopus's head and soft body. In the adhesion test, the octopus-like particles exhibit high adhesive properties in air, in water, and on a flexible substrate. In the electrochemical test, the octopus-like particles on flexible electrodes show good electrochemical and adhesive properties under hundreds of bending cycles. Benefiting from the combination of crumpled and uncrumpled morphologies, the created particles with octopus-like microstructure are demonstrated to possess comprehensive performance, exhibiting wide application potentials in the fields of microswimmers, surface coatings, and electrochemistry. Additionally, the method developed in this work has the advantages of concentrated energy in a confined space, displaying prospective potentials in micro- and nanoprocessing.

Secondhand smoke increases the risk of developing chronic obstructive pulmonary disease.

Smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD), however evidence from large-scale studies on whether secondhand smoke (SHS) increases the risk of COPD is still lacking. We conducted this large longitudinal study to investigate the association between SHS and the development of COPD. This is a longitudinal study. Data on 6519 subjects who were never-smokers, had no history of COPD, and had complete lung function records were extracted from the Taiwan Biobank. They were divided into two groups according to SHS exposure: no exposure and exposure groups. Data were collected when participants enrolled in the study and during regular follow-up. Cox proportional hazards regression models were used to estimate the relative risk (RR) and 95% confidence interval (CI) for the association between SHS and the risk of developing COPD. At 48 months of follow-up, 260 (4%) participants in the no exposure group and 34 (7%) participants in the exposure group developed COPD. The RR of incident COPD development was significantly higher in the exposure group than that in the no exposure group after adjusting for confounders (RR = 1.49; 95% CI 1.04 to 2.14; P value = 0.031). There is a dose-response relationship between the duration of exposure to SHS and the risk of incident COPD, which demonstrates that an additional hour of exposure to SHS per week was associated with a 1.03-fold increased likelihood of developing COPD after adjusting for confounders (RR = 1.03; 95% CI 1.00 to 1.05; P value = 0.027). SHS exposure contributes to the development of COPD. This finding can help raise awareness of the harms of SHS and provide a reference for formulating anti-smoking policies.

From ZnF2 to ZnF2(H2O)4: Partial Substitution Achieves Structural Transformation and Nonlinear Optical Activity while Keeping Short Ultraviolet Cutoff Edge.

Exploring nonlinear optical (NLO) materials with short ultraviolet cutoff edges are significant for developing an all-solid-state laser. Here, a noncentrosymmetric zinc fluoride hydrate, ZnF2(H2O)4, was synthesized by a hydrothermal method. It crystallizes in the polar space group of Pca21. The compound consists of the central Zn2+ combined with F- and coordination water to form the [ZnF2(H2O)4] octahedra, and each octahedron is isolated from each other to form a 0-dimensional structure. As an acentric compound, ZnF2(H2O)4 shows a phase-matchable second-harmonic-generation (SHG) activity with an intensity about 0.5 times that of KH2PO4. More attractively, it also shows a short ultraviolet cutoff edge below 200 nm, which is rare in reported halide hydrate systems. Interestingly, from ZnF2 to ZnF2(H2O)4, the partial substitution of the coordinated F atoms by H2O molecules leads to the structural transformation from centric to acentric with SHG activity off to on. Structural analyses, NLO activity, and theoretical calculations are presented in this work.

Burden of stroke in China and the different SDI regions over the world.

Background: Stroke is a significant global health issue, ranking as the second leading cause of death and the third leading cause of death and disability combined. This study aimed to examine the changes and differences in stroke burden from 1990 to 2019 in China and various global socio-demographic index (SDI) regions. Methods: Data were obtained from the Global Burden of Diseases Study 2019, which included the incidence, prevalence, mortality, disability-adjusted life years (DALY), years of life with disability (YLD), and years of life lost (YLL) of stroke. The change trend of stroke burden was assessed based on age-standardised rates per 100 000 person-years and estimated annual percentage changes. The average annual rate of change in stroke burden was analysed using the average annual percentage change from 1990 to 2019. Pearson correlation analysis was used to explore the strength and direction of the correlation between stroke burden and SDI. Results: Regions with high SDI showed the largest decline in age-standardised incidence, death, DALY, YLD, and YLL rates of stroke from 1990 to 2019. China experienced the largest increase in age-standardised prevalence and YLD rates of stroke from 1990 to 2019. There were significant differences in the average annual percent change in stroke burden among the majority of SDI regions. The burden for stroke at the national level was inversely correlated with SDI, despite some exceptions (Incidence: R = -0.417, P < 0.001; prevalence: R = -0.297, P < 0.001; mortality: R = -0.510, P < 0.001; DALY: R = -0.550, P < 0.001; YLD: R = -0.125, P = 0.075; YLL: R = -0.569, P < 0.001). Conclusions: There were significant differences in the stroke burden across different regions with varying SDI levels from 1990 to 2019. The age-standardised prevalence rate and attributable disability burden of stroke remain substantial in different SDI regions, making it a major contributor to the overall disease burden. The severe burden of stroke highlights the importance of primary and secondary stroke-prevention strategies. Therefore, future strategies to prevent and reduce the burden of stroke should be formulated and implemented according to the SDI of each country.

Melatonin alleviates early brain injury by inhibiting the NRF2-mediated ferroptosis pathway after subarachnoid hemorrhage.

Ferroptosis is a novel form of cell death that plays a critical role in the pathological and physiological processes of early brain injury following subarachnoid hemorrhage. Melatonin, as the most potent endogenous antioxidant, has shown strong protective effects against pathological changes following subarachnoid hemorrhage, but its impact on ferroptosis induced by subarachnoid hemorrhage remains unexplored. In our study, we established a subarachnoid hemorrhage model in male SD rats. We found that subarachnoid hemorrhage induced changes in ferroptosis-related indicators such as lipid peroxidation and iron metabolism, while intraperitoneal injection of melatonin (40 mg/kg) effectively ameliorated these changes to a certain degree. Moreover, in a subset of rats with subarachnoid hemorrhage who received pre-treatment via intravenous injection of the melatonin receptor antagonist Luzindole (1 mg/kg) and 4P-PDOT (1 mg/kg), we found that the protective effect of melatonin against subarachnoid hemorrhage includes inhibition of lipid peroxidation and reduction of iron accumulation depended on melatonin receptor 1B (MT2). Furthermore, our study demonstrated that melatonin inhibited neuronal ferroptosis by activating the NRF2 signaling pathway, as evidenced by in vivo inhibition of NRF2. In summary, melatonin acts through MT2 and activates NRF2 and downstream genes such as HO-1/NQO1 to inhibit ferroptosis in subarachnoid hemorrhage-induced neuronal injury, thereby improving neurological function in rats. These results suggest that melatonin is a promising therapeutic target for subarachnoid hemorrhage.

Na4[B6O9 (OH)3](H2O) Cl: A Deep-Ultraviolet Transparent Nonlinear Optical Borate Chloride with {[B6O9 (OH)3]3-}∞ Chains.

The development of nonlinear-optical (NLO) crystals with short ultraviolet cutoff edges is significant and challenging. Here, a new sodium borate chloride, Na4[B6O9 (OH)3](H2O) Cl, was successfully obtained by the mild hydrothermal method, which crystallizes in a polar space group Pca21. The structure of the compound is characterized by {[B6O9 (OH)3]3-}∞ chains. Measurements of optical properties indicate the compound exhibits a deep-ultraviolet (DUV) cutoff edge (≤200 nm) and moderate second harmonic generation response (0.4 × KH2PO4). It presents the first DUV hydrous sodium borate chloride NLO crystal and the first sodium borate chloride possessing a one-dimensional B-O anion framework. Probing into the connection of structure and optical properties has been performed based on theoretical calculations. These results are instructive for designing and obtaining new DUV NLO materials.

Pb5(GeO4)(Ge2O7) and Pb3.32Ca1.68(GeO4)(Ge2O7): Two Nonlinear Optical Germanates Induced by Diverse PbOx Polyhedra.

Oxide nonlinear optical (NLO) crystals have drawn wide interest for their comprehensive physical performances including wide infrared (IR) transparency ranges, large band gaps, and good stability in open air. Here, two isostructural germanate oxides, Pb5(GeO4)(Ge2O7) (1) and Pb3.32Ca1.68(GeO4)(Ge2O7) (2), adopting the noncentrosymmetric (NCS) space group P6̅, were composed via a conventional solid-state reaction. The latter was designed by the partial cation substitution strategy based on parent 1. The whole structures of 1 and 2 are composed of isolated distorted GeO4 tetrahedra, Ge2O7 dimers, and diverse M (M = Pb, Ca, or Pb/Ca)-centered polyhedra. They exhibit second-harmonic generation (SHG) responses around 3.3 and 1.4 times that of KH2PO4 (KDP) under 1.064 µm laser radiation, respectively. Theoretical calculation results reveal that the Pb2+ cations with stereo-active long pair (SCALP) electrons of 1 favor the large SHG response, while Pb-based polyhedra showing inert SCALP electrons make predominant contributions to the moderate SHG effect of 2.

The complete plastid genome of Amphicarpaea ferruginea Bentham (Leguminosae), a grass species with development and utilization prospect.

We are reporting the complete plastid genome of Amphicarpaea ferruginea, a grass species with development and utilization prospect. The A. ferruginea plastome is 152,531 bp long, with two inverted repeat(IR) regions (25,616 bp each) that separate a large single copy (LSC) region (83,364 bp) and a small single copy (SSC) region (17,935 bp). A total of 130 genes were annotated, including 85 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The phylogenetic tree shows that Amphicarpaea edgeworthii is closely related to Amphicarpaea ferruginea with strong bootstrap support.

From CsKTaF7 to CsNaTaF7 : Alkali Metal Cations Regulation to Generate SHG Activity.

Inorganic metal halides play important roles in wide range of areas including fluorescence, X-ray detection, and nonlinear-optics. Herein, two new mixed alkali metal tantalum fluorides, CsKTaF7 and CsNaTaF7 , have been obtained based on the strategy of cations regulation in A2 MF7 (A represents monovalent cations and M is d0 transition-metal cation) system by a conventional hydrothermal route. CsKTaF7 crystallizes in the centric Pnma space group, while CsNaTaF7 crystallizes in the polar Cmc21 space group and exhibits moderate and phase-matchable NLO activity. Both halides possess large optical band gaps above 5.0 eV. The crystal structure evolution, optical properties, and detailed theory calculations of these two halides were elucidated in this work.

The complete plastid genome of Terminalia myriocarpa Vaniot Huerck et Muell.-Arg (Combretaceae), a tropical rainforest indicator species in Southern China.

Terminalia myriocarpa Vaniot Huerck et Muell.-Arg is a tropical rainforest indicator species in Southern China. The chloroplast genome of T. myriocarpa was analyzed by high-throughput sequence technology, and its genetic relationship to related species was discussed. The chloroplast genome is 159,854 bp in length, with a total GC content of 37%. It has a typical chloroplast tetrad structure, including 88,015 bp of large single copy (LSC), 18,814 bp of small single copy (SSC), and 26,319 bp of inverted repeats (IR). A total of 130 genes were annotated, including 85 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. Phylogenetic analysis indicated T. myriocarpa was closely related to Terminalia phillyreifolia.

[Prenatal diagnosis and genetic analysis of 17 fetuses with skeletal dysplasia].

OBJECTIVE: To explore strategies of prenatal genetic testing for fetuses featuring abnormal skeletal development. METHODS: Clinical data of 17 fetuses with skeletal dysplasia was collected. The results of genetic testing and outcome of pregnancy were analyzed. RESULTS: For 12 fetuses, the femur-to-foot length ratio was less than 0.9. Thirteen fetuses had a positive finding by genetic testing. One fetus was diagnosed with chromosomal aneuploidy, three were diagnosed with microdeletion/microduplications, and nine were diagnosed with hereditary bone diseases due to pathological variants of FGFR3, COL1A2, GPX4 or ALPL genes. CONCLUSION: For fetuses with skeletal dysplasia characterized by short femur, in addition to chromosomal karyotyping and microarray analysis, sequencing of FGFR3 and other bone disease-related genes can improve the diagnostic rate.

Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method.

Mitochondrial 12S rRNA A1555G and C1494T mutations are the major contributors to hearing loss. As patients with these mutations are sensitive to aminoglycosides, mutational screening for 12S rRNA is therefore recommended before the use of aminoglycosides. Most recently, we developed a novel multiplex allele-specific PCR (MAS-PCR) that can be used for detecting A1555G and C1494T mutations. In the present study, we employed this MAS-PCR to screen the 12S rRNA mutations in 500 deaf patients and 300 controls from 5 community hospitals. After PCR and electrophoresis, two patients with A1555G and one patient with C1494T were identified, this was consistent with Sanger sequence results. We further traced the origin of three Chinese pedigrees. Clinical evaluation revealed variable phenotypes of hearing loss including severity, age at onset and audiometric configuration in these patients. Sequence analysis of the mitochondrial genomes from matrilineal relatives suggested the presence of three evolutionarily conserved mutations: tRNACys T5802C, tRNALys A8343G and tRNAThr G15930A, which may result the failure in tRNAs metabolism and lead to mitochondrial dysfunction that was responsible for deafness. However, the lack of any functional variants in GJB2, GJB3, GJB6 and TRMU suggested that nuclear genes may not play active roles in deafness expression. Hence, aminoglycosides and mitochondrial genetic background may contribute to the clinical expression of A1555G/C1494T-induced deafness. Our data indicated that the MAS-PCR was a fast, convenience method for screening the 12S rRNA mutations, which was useful for early detection and prevention of mitochondrial deafness.

A review of traditional Chinese medicine for treatment of glioblastoma.

Glioblastoma (GBM) is the most common primary malignant intracranial tumor. Due to its high morbidity, high mortality, high recurrence rate, and low cure rate, it has brought great difficulty for treatment. Although the current treatment is multimodal, including surgical resection, radiotherapy, and chemotherapy, it does not significantly improve survival time. The dismal prognosis and inevitable recurrence as well as resistance to chemoradiotherapy may be related to its highly cellular heterogeneity and multiple subclonal populations. Traditional Chinese medicine has its own unique advantages in the prevention and treatment of it. A comprehensive literature search of anti-glioblastoma active ingredients and derivatives from traditional Chinese medicine was carried out in literature published in PubMed, Scopus, Web of Science Cochrane library, CNKI, Wanfang, and VIP database. Hence, this article systematically reviews experimental research progress of some traditional Chinese medicine in treatment of glioblastoma from two aspects: strengthening vital qi and eliminating pathogenic qi. Among, strengthening vital qi medicine includes panax ginseng, licorice, lycium barbarum, angelica sinensis; eliminating pathogenic medicine includes salvia miltiorrhiza bunge, scutellaria baicalensis, coptis rhizoma, thunder god vine, and sophora flavescens. We found that the same active ingredient can act on different signaling pathways, such as ginsenoside Rg3 inhibited proliferation and induced apoptosis via the AKT, MEK signal pathway. Hence, this multi-target, multi-level pathway may bring on a new dawn for the treatment of glioblastoma.

P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5.

Gliomas are the most common central nervous system tumors. They show malignant characteristics indicating rapid proliferation and a high invasive capacity and are associated with a poor prognosis. In our previous study, p68 was overexpressed in glioma cells and correlated with both the degree of glioma differentiation and poor overall survival. Downregulating p68 significantly suppressed proliferation in glioma cells. Moreover, we found that the p68 gene promoted glioma cell growth by activating the nuclear factor-κB signaling pathway by a downstream molecular mechanism that remains incompletely understood. In this study, we found that dual specificity phosphatase 5 (DUSP5) is a downstream target of p68, using microarray analysis, and that p68 negatively regulates DUSP5. Upregulating DUSP5 in stably expressing cell lines (U87 and LN-229) suppressed proliferation, invasion, and migration in glioma cells in vitro, consistent with the downregulation of p68. Furthermore, upregulating DUSP5 inhibited ERK phosphorylation, whereas downregulating DUSP5 rescued the level of ERK phosphorylation, indicating that DUSP5 might negatively regulate ERK signaling. Additionally, we show that DUSP5 levels were lower in high-grade glioma than in low-grade glioma. These results suggest that the p68-induced negative regulation of DUSP5 promoted invasion by glioma cells and mediated the activation of the ERK signaling pathway.

MicroRNA-27a Promotes Inefficient Lysosomal Clearance in the Hippocampi of Rats Following Chronic Brain Hypoperfusion.

Chronic brain hypoperfusion (CBH) induces the accumulation of abnormal cellular proteins, accompanied by cognitive decline, and the autophagic-lysosomal system is abnormal in dementia. Whether CBH accounts for autophagic-lysosomal neuropathology remains unknown. Here, we show that CBH significantly increased the number of autophagic vacuoles (AVs) with high LC3-II levels, but decreased SQSTM1 and cathepsin D levels in the hippocampi of rats following bilateral common carotid artery occlusion (2VO) for 2 weeks. Further studies showed that microRNA-27a (Mir27a) was upregulated at 2 weeks compared with the sham group. Additionally, LAMP-2 proteins were downregulated by Mir27a overexpression, upregulated by Mir27a inhibition, and unchanged by binding-site mutations or miR-masks, indicating that lamp-2 is the target of Mir27a. Knockdown of endogenous Mir27a prevented the reduction of LAMP-2 protein expression as well as the accumulation of AVs in the hippocampi of 2VO rats. Overexpression of Mir27a induced, while the knockdown of Mir27a reduced, the accumulation of AVs and the LC3-II level in cultured neonatal rat neurons. The results revealed that CBH in rats at 2 weeks could induce inefficient lysosomal clearance, which is regulated by the Mir27a-mediated downregulation of LAMP-2 protein expression. These findings provide an insight into a novel molecular mechanism of autophagy at the miRNA level.

Replacing Alpha-Fetoprotein With Alpha-Fetoprotein-L3 Increases the Sensitivity of Prenatal Screening for Trisomy 21.

This study aimed to investigate the serum concentration of alpha-fetoprotein (AFP)-L3 in midterm pregnancies and its potential application in prenatal trisomy screening. The serum samples from 27 women with trisomy 21 fetuses and 800 women with normal fetuses were examined to measure the concentrations of AFP, AFP-L3, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The screening results of various tests consisting of these markers were analyzed. In normal pregnancies within 15-20 weeks of gestation, the medians of serum AFP-L3 were 4.63, 5.70, 5.78, 6.58, 7.03, and 7.25 pg/mL. The median of AFP-L3 MoM in the trisomy 21 group was 0.46, which was significantly lower than the value of 1 in the normal group (P < 0.05). When using a cutoff value of 1/270, the sensitivity of the triple marker test (AFP, hCG, uE3) was improved from 74% to 81% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 5.4% to 6.8%. Similarly, the sensitivity of the quad marker test (AFP, hCG, uE3, inhibin-A) was improved from 81% to 89% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 4.6% to 5.6%. Serum AFP-L3 concentration increases along with more weeks of gestation in the midterm pregnancies. Trisomy 21 screening tests with AFP replaced by AFP-L3 have higher sensitivities at the expense of slightly increased false-positive rates. This improvement in screening may help to better prepare the parents and caregivers for the special needs of newborns with trisomy 21.

Pathological-Condition-Driven Construction of Supramolecular Nanoassemblies for Bacterial Infection Detection.

A pyropheophorbide-α-based building block (Ppa-PLGVRG-Van) can be used to construct self-aggregated superstructures in vivo for highly specific and sensitive diagnosis of bacterial infection by noninvasive photoacoustic tomography. This in vivo supramolecular chemistry approach opens a new avenue for efficient, rapid, and early-stage disease diagnosis with high sensitivity and specificity.

MicroRNA-9 induces defective trafficking of Nav1.1 and Nav1.2 by targeting Navß2 protein coding region in rat with chronic brain hypoperfusion.

BACKGROUND: Previous studies have demonstrated that the trafficking defects of Nav1.1/Nav1.2 are involved in the dementia pathophysiology. However, the detailed mechanisms are not fully understood. Moreover, whether the impaired miRNAs regulation linked to dementia is a key player in sodium channel trafficking disturbance remains unclear. The cognitive impairment induced by chronic cerebral ischemia through chronic brain hypoperfusion (CBH) is likely reason to precede dementia. Therefore, our goal in the present study was to examine the role of microRNA-9 (miR-9) in regulating Nav1.1/Nav1.2 trafficking under CBH generated by bilateral common carotid artery occlusion (2VO). RESULTS: The impairment of Nav1.1/Nav1.2 trafficking and decreased expression of Navß2 were found in the hippocampi and cortices of rats following CBH generated by bilateral 2VO. MiR-9 was increased in both the hippocampi and cortices of rats following CBH by qRT-PCR. Intriguingly, miR-9 suppressed, while AMO-miR-9 enhanced, the trafficking of Nav1.1/Nav1.2 from cytoplasm to cell membrane. Further study showed that overexpression of miR-9 inhibited the Navß2 expression by targeting on its coding sequence (CDS) domain by dual luciferase assay. However, binding-site mutation or miR-masks failed to influence Navß2 expression as well as Nav1.1/Nav1.2 trafficking process, indicating that Navß2 is a potential target for miR-9. Lentivirus-mediated miR-9 overexpression also inhibited Navß2 expression and elicited translocation deficits to cell membrane of Nav1.1/Nav1.2 in rats, whereas injection of lentivirus-mediated miR-9 knockdown could reverse the impaired trafficking of Nav1.1/Nav1.2 triggered by 2VO. CONCLUSIONS: We conclude that miR-9 may play a key role in regulating the process of Nav1.1/Nav1.2 trafficking via targeting on Navß2 protein in 2VO rats at post-transcriptional level, and inhibition of miR-9 may be a potentially valuable approach to prevent Nav1.1/Nav1.2 trafficking disturbance induced by CBH.