An early transition to magnetic supercriticality in star formation.

Magnetic fields have an important role in the evolution of interstellar medium and star formation1,2. As the only direct probe of interstellar field strength, credible Zeeman measurements remain sparse owing to the lack of suitable Zeeman probes, particularly for cold, molecular gas3. Here we report the detection of a magnetic field of +3.8 ± 0.3 microgauss through the H I narrow self-absorption (HINSA)4,5 towards L15446,7-a well-studied prototypical prestellar core in an early transition between starless and protostellar phases8-10 characterized by a high central number density11 and a low central temperature12. A combined analysis of the Zeeman measurements of quasar H I absorption, H I emission, OH emission and HINSA reveals a coherent magnetic field from the atomic cold neutral medium (CNM) to the molecular envelope. The molecular envelope traced by the HINSA is found to be magnetically supercritical, with a field strength comparable to that of the surrounding diffuse, magnetically subcritical CNM despite a large increase in density. The reduction of the magnetic flux relative to the mass, which is necessary for star formation, thus seems to have already happened during the transition from the diffuse CNM to the molecular gas traced by the HINSA. This is earlier than envisioned in the classical picture where magnetically supercritical cores capable of collapsing into stars form out of magnetically subcritical envelopes13,14.

Upgrade of vacuum ultraviolet spectroscopy system on J-TEXT tokamak.

The vacuum ultraviolet (VUV) spectroscopy system on the Joint Texas Experimental Tokamak has been upgraded to achieve fast acquisition for the study of impurity transport in transient modulated experiments. In this upgrade, the previous high-energy charge-coupled device detector was replaced by a microchannel plate with a CsI-coated photocathode and P43 phosphor to transform the VUV light to visible light, which is then acquired by a high-speed electron-multiplying charge-coupled device. Two-stage focusing was achieved using a reference slit plate illuminated successively by a green light source and the Lyman series hydrogen spectral lines from the vacuum-conditioning plasma. The spatial resolution was evaluated as ∼4 mm based on the level of image blurring from the alignment plate. A response time of ∼2 ms was obtained with the ten-vertical-track setup.

Impact of the combined timing of PD-1/PD-L1 inhibitors and chemotherapy on the outcomes in patients with refractory lung cancer.

BACKGROUND: PD-1/PD-L1 inhibitors in combination with chemotherapy are widely used in clinical practice. However, the ideal combined timing of them has not been fully explored. METHODS: In this study, simulation experiments to explore the impacts of the combination of anti-PD-1 antibody (anti-PD-1 Ab) on the cytotoxic effects of chemotherapeutic drugs in peripheral blood mononuclear cells were performed. In addition, the effects of the combined timing of PD-1/PD-L1 inhibitors and chemotherapy on efficacy and safety were retrospectively analysed in patients with refractory lung cancer. RESULTS: Experiments in vitro showed that administering the anti-PD-1 Ab 3 days after chemotherapy (represented by dicycloplatin) resulted in significantly weaker cytotoxic effects on lymphocytes, compared with administering the anti-PD-1 Ab before or concurrent with chemotherapy. Moreover, data from 64 lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy as a second- or higher-line therapy were retrospectively analysed. The results showed that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy was associated with longer overall survival [17.3 months versus 12.7 months; hazard ratio (HR) = 0.58, 95% confidence interval (CI) 0.28-1.19, P = 0.137 in univariate analysis; HR = 0.36, 95% CI 0.16-0.80, P = 0.012 in multivariate analysis] and a trend of improved progression-free survival (5.1 months versus 4.2 months; HR = 0.81, 95% CI 0.42-1.54, P = 0.512) compared with administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy. CONCLUSION: Our findings suggest that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy is superior to administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy in patients with refractory lung cancer, but this result needs to be further explored by prospective studies.

Impacts of Glycemic Control on Intracranial Plaque in Patients with Type 2 Diabetes Mellitus: A Vessel Wall MRI Study.

BACKGROUND AND PURPOSE: The relationship between glycemic control in patients with type 2 diabetes mellitus and intracranial atherosclerotic plaque features has remained understudied. This study aimed to investigate the association of type 2 diabetes mellitus and glycemic control with the characteristics of intracranial plaques using vessel wall MR imaging. MATERIALS AND METHODS: In total, 311 patients (217 [69.8%] men; mean age, 63.24 ± 11.44 years) with intracranial atherosclerotic plaques detected on vessel wall MR imaging were enrolled and divided into 3 groups according to type 2 diabetes mellitus and glycemic control statuses: the non-type 2 diabetes mellitus group, the type 2 diabetes mellitus with good glycemic control group, and the type 2 diabetes mellitus with poor glycemic control group. The imaging features of intracranial plaque were analyzed and compared among the groups. The clinical risk factors for atherosclerosis were also analyzed using logistic regression analysis. RESULTS: The plaque length and thickness were significantly higher in the type 2 diabetes mellitus with poor glycemic control group than in the non-type 2 diabetes mellitus group. The prevalence of strongly enhanced plaques was significantly higher in the type 2 diabetes mellitus with poor glycemic control group than in the non-type 2 diabetes mellitus and type 2 diabetes mellitus with good glycemic control groups (92.9%, 63.4%, and 72.7%, respectively; P < .001). Multivariate logistic regression analysis showed a significant association of poor glycemic control with the plaque length (OR = 1.966; 95% CI, 1.170-3.303; P = .011), plaque thickness (OR = 1.981; 95% CI, 1.174-3.340; P = .010), and strongly enhanced plaque (OR = 5.448; 95% CI, 2.385-12.444; P < .001). CONCLUSIONS: Poor glycemic control, compared with the history of diabetes, might have a greater impact on the burden and vulnerability of intracranial atherosclerotic plaques.

[Phase â ¢ randomized controlled, multicenter, prospective study of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer: the HOPES Study].

Objective: To evaluate the clinical efficacy and safety of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer. Methods: Patients were randomized 2∶1 to test group and control group. Patients in test group received Cipterbin (4 mg/kg loading dose and 2 mg/kg maintenance dose each week, IV) combined with vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV). Patients in control group received vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV).The primary end point was progression free survival (PFS). Results: A total of 315 patients were enrolled from Jan 2009 to Jan 2013 (212 in test group and 103 in control group). The median PFS of test group was significantly longer than that of control group, 39.1 weeks vs 14.0 weeks (HR=0.24; 95%CI, 0.16-0.36; P<0.000 1). The objective response rate (ORR) and disease control rate (DCR) in test group were significantly higher than those in control group, ORR was 46.7% vs 18.45% (P<0.000 1) and DCR was 79.72% vs 45.63% (P<0.000 1). The incidence of neutropenia, leucopenia and erythrocytopenia were higher in both groups, but there was no significant difference between two groups.The most common adverse events associated with Cipterbin were infusion reactions. Left ventricular ejection fraction reduced to less than 50% in 5 patients, which were recovered. No serious cardiotoxicity. Conclusion: The recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine has significant efficacy and good safety. It is the optimized therapy regime for patients with taxane-pretreated HER2 positive metastatic breast cancer, which provides more targeted therapy opportunities for HER2 positive breast cancer patients in China.

Structural Characterization and Immune Activity Screening of Polysaccharides With Different Molecular Weights From Astragali Radix.

Saccharides are the most abundant substance with the strongest immunological activity in Astragali Radix (AR). However, systematic structure study and immunoactivity screening of polysaccharides with different molecular weights (Mw) in AR have yet to be conducted. In this study, Astragalus polysaccharides (APSs) were divided into three fragments of different Mw values, >2,000 kDa (APS-Ⅰ), about 10 kDa (APS-Ⅱ), and about 300 Da (APS-Ⅲ), by using ultrafiltration for the first time. The structural differences of the three products were determined on the basis of monosaccharide composition, FT-IR spectrum, linkage analysis, and nuclear magnetic resonance analysis. Cellular immune activity experiments in vitro and cyclophosphamide immunosuppression animal model experiments in vivo for nonspecific and specific immunoactivity screening were applied to identify the most immunogenic fragment in APSs. Linkage analysis results showed that APS-Ⅰ, APS-Ⅱ, and APS-Ⅲ have different attachment sites of monosaccharide residues. Immune screening experiments indicated that the Mw of the APSs influenced their activity, and APS-Ⅱ had the strongest immunoenhancing activity among the products. This research may serve as a reference for further study on APSs with different structures and immune activities, and as a guidance for the quality control of APSs and the development of new APS products.

[Clinical features of cerebral amyloid angiopathy characterized by cortical superficial siderosis].

Objective: To study the clinical and imaging characteristics of cerebral amyloid angiopathy characterized by cortical superficial siderosis and improve clinicians' understanding of the disease. Methods: Retrospective analysis was performed on 16 patients with cerebral amyloid angiopathy characterized by cortical superficial siderosis from June 2013 to August 2016 in Beijing Hospital, and the information including epidemiological data, clinical features, cranial MRI and electroencephalogram (EEG) results were analyzed. Results: The ratio of male to female in 16 patients was 1.67∶1, and the average age of onset was 73 (69-79) years. The most common clinical symptoms were transient focal neurological episodes (TFNEs)(12/16). Cranial MRI showed localized (9/16) and diffuse type cortical superficial siderosis (7/16); few of them were associated with different degrees of cerebral microbleeds. Most of the EEG findings were normal (6/9) and a few showed focal slow waves (3/9). During a mean follow-up of 17 (17±11) months, 5 patients developed repeated TFNE, of which 1 had cerebral hemorrhage. Conclusions: Cerebral amyloid angiopathy characterized by cortical superficial siderosis occurs predominantly in the elderly. TFNE is the most common clinical manifestation. Cranial MRI is the most important diagnostic method, and antithrombotic therapy should be avoided as much as possible.

LncRNA PRNCR1 promoted the progression of eclampsia by regulating the MAPK signal pathway.

OBJECTIVE: We aimed to explore the expression level and biological function of lncRNA PRNCR1 in preeclampsia (PE). PATIENTS AND METHODS: 57 PE patients and 57 normal pregnant women were enrolled in this study. The expression level of PRNCR1 in the maternal placenta of PE patients and normal pregnancy was detected by qRT-PCR. The CCK-8 assay was carried out to determine the cell viability after interference and overexpression of PRNCR1 on trophoblasts. We utilized Western blot to examine the protein level of PRNCR1. RESULTS: Higher systolic blood pressure, diastolic blood pressure and urinary protein levels in PE patients were observed in comparison with those in normal pregnant women, while the neonatal weight in PE group was markedly lower than that in normal pregnant women. LncRNA PRNCR1 was overexpressed in PE patients, which was positively correlated with systolic blood pressure, diastolic blood pressure and urine protein, whereas negatively correlated with fetal birth weight of PE patients. In addition, the expression of PRNCR1 in BeWo trophoblast cells was significantly decreased after the interference with PRNCR1, while the cell viability increased. However, overexpression of PRNCR1 in HTR-8 cells significantly reduced the viability of cells. Expression levels of p-p38 and p-JNK in PE patients were higher than those in normal pregnancy women, and the expression level of p-ERK was decreased, which suggested that PRNCR1 promoted the progression of PE by modulating the MAPK signaling pathway. CONCLUSIONS: PRNCR1 is highly expressed in PE and promotes the progression of PE by modulating the MAPK signaling pathway.

A novel HLA-A*31 allele, A*31:126N, was identified by sequence-based typing.

A novel allele A*31:126N was identified in a Chinese individual by sequence-based typing method.

The novel allele, HLA-A*11:264, was identified in a Chinese individual by sequence-based typing.

The novel allele, A*11:264, was identified in a Chinese individual by sequence-based typing.

EZH2 contributes to the response to PARP inhibitors through its PARP-mediated poly-ADP ribosylation in breast cancer.

Inhibitors against poly (ADP-ribose) polymerase (PARP) are promising targeted agents currently used to treat BRCA-mutant ovarian cancer and are in clinical trials for other cancer types, including BRCA-mutant breast cancer. To enhance the clinical response to PARP inhibitors (PARPis), understanding the mechanisms underlying PARPi sensitivity is urgently needed. Here, we show enhancer of zeste homolog 2 (EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells. Mechanistically, upon oxidative stress or alkylating DNA damage, PARP1 interacts with and attaches poly-ADP-ribose (PAR) chains to EZH2. PARylation of EZH2 by PARP1 then induces PRC2 complex dissociation and EZH2 downregulation, which in turn reduces EZH2-mediated H3 trimethylation. In contrast, inhibition of PARP by PARPi attenuates alkylating DNA damage-induced EZH2 downregulation, thereby promoting EZH2-mediated gene silencing and cancer stem cell property compared with PARPi-untreated cells. Moreover, the addition of an EZH2 inhibitor sensitizes the BRCA-mutant breast cells to PARPi. Thus, these results may provide a rationale for combining PARP and EZH2 inhibition as a therapeutic strategy for BRCA-mutated breast and ovarian cancers.

AIB1 regulates the ovarian cancer cell cycle through TUG1.

OBJECTIVE: To explore the mechanism of amplified in breast cancer 1 (AIB1) to promote ovarian cancer progress. MATERIALS AND METHODS: Cor correlation analysis was performed to obtain the top 100 lncRNAs that were positively correlated with AIB1. The relationship of taurine upregulated gene 1 (TUG1) and clinicopathological characteristics. Moreover, Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were performed to predict the biological process where TUG1 may be involved in. At last, Cell Counting Kit-8 (CCK-8), colon formation and flow cytometry were conducted to explore the biological process that TUG1 may influence. Meanwhile, Western blot was performed to explore the mechanism of TUG1. RESULTS: In this study, it was found that P73 antisense RNA 1T (TP73-AS1), LINC00654 and TUG1 had the tumor-promoting effect in the top 100 lncRNAs that were positively correlated with AIB1. The expression level of TUG1 was significantly decreased after intervention of AIB1. Then, the clinical data were analyzed and the results showed that TUG1 was related to the tumor residue, tumor staging, tumor grade and lymph node metastasis. Moreover, the bioinformatics analysis revealed that TUG1 was mainly involved in the regulation of cell cycle. After intervention in TUG1, it was found that the cell proliferation capacity was significantly decreased, and the cell cycle was arrested in G1 phase. Finally, Western blot revealed that the expressions of G1 phase-related proteins were significantly changed. This study indicated that AIB1 regulates the cycle of ovarian cancer cells through TUG1. CONCLUSIONS: This study proved that AIB1 can regulate the cell cycle through regulating TUG1.

[Domestic external fixator application in the treatment of limb deformities: 7 289 cases application report].

Objective: To discuss the clinical application and effects of domestic external fixator in the treatment of patients with malformations of limbs. Methods: A total of 7 289 patients with malformation of limbs who had been operated in Qin Sihe orthopedic surgery team from January 1989 to June 2016 were retrospective analyzed. The patients were treated with domestic external fixator, including 4 033 males and 3 256 females, aging from 2 to 82 years with a mean age of 23.4 years. There were 2 732 patients using Ilizarov external fixator, 4 713 patients using hybrid external fixator, 57 patients using monobrachial external fixator, 232 patients using Ilizarov external fixator and hybrid external fixator. The Ilizarov, hybrid and monobrachial external fixator were used in 67, 65 and 0 patients on the upper limbs and in 2 665, 4 616 and 57 patients on the lower limbs. There were 3 028 patients operated on the left limbs, 3 260 patients operated on the right limbs and 1 001 patients operated on the bilateral limbs. The top three types of diseases were sequelae of poliomyelitis, cerebral palsy and post-traumatic stress disorder peromely. Deformity types inclued talipes equinovarus, knee flexion deformity, cavus foot and so on. Results: All the patients were followed up for a period of 2.5 months to 22.4 years, with an average follow-up time of 5.4 years. All of the external fixators were used for single once, and there was no substitute for external fixator quality problem. All the patients were completed surgery goal until removing external fixation except 1 patient gave up treatment and 1 removed the fixator because of metal allergy. The common complications included wire or pin infection and joint movement limitation and so on. Conclusions: The domestic external fixator developed and produced based on the characteristics of Chinese limb deformity disability. The domestic external fixator can be used to treat kinds of limb deformities with the advantages of practical, economical, adjustable, universal and portable. The domestic external fixator could meet the clinical demand for fixation of the osteotomy end of the limbs, the correction of the deformity, the repair of the defects and the limb lengthening.

The relationship between different measures of feed efficiency and feeding behavior traits in Duroc pigs.

Utilization of feed in livestock species consists of a wide range of biological processes, and therefore, its efficiency can be expressed in various ways, including direct measurement, such as daily feed intake, as well as indicator measures, such as feeding behavior. Measuring feed efficiency is important to the swine industry, and its accuracy can be enhanced by using automated feeding systems, which record feed intake and associated feeding behavior of individual animals. Each automated feeder space is often shared among several pigs and therefore raises concerns about social interactions among pen mates with regard to feeding behavior. The study herein used a data set of 14,901 Duroc boars with individual records on feed intake, feeding behavior, and other off-test traits. These traits were modeled with and without the random spatial effect of Pen_Room, a concatenation of room and pen, or random social interaction among pen mates. The nonheritable spatial effect of common Pen-Room was observed for traits directly measuring feed intake and accounted for up to 13% of the total phenotypic variance in the average daily feeding rate. The social interaction effect explained larger proportions of phenotypic variation in all the traits studied, with the highest being 59% for ADFI in the group of feeding behaviors, 73% for residual feed intake (RFI; RFI4 and RFI6) in the feed efficiency traits, and 69% for intramuscular fat percentage in the off-test traits. After accounting for the social interaction effect, residual BW gain and RFI and BW gain (RIG) were found to have the heritability of 0.38 and 0.18, respectively, and had strong genetic correlations with growth and off-test traits. Feeding behavior traits were found to be moderately heritable, ranging from 0.14 (ADFI) to 0.52 (average daily occupation time), and some of them were strongly correlated with feed efficiency measures; for example, there was a genetic correlation of 0.88 between ADFI and RFI6. Our work suggested that accounting for the social common pen effect was important for estimating genetic parameters of traits recorded by the automated feeding system. Residual BW gain and RIG appeared to be two robust measures of feed efficiency. Feeding behavior measures are worth further investigation as indicators of feed efficiency.

DNA-binding mechanism of the Hippo pathway transcription factor TEAD4.

TEA domain (TEAD) family transcription factors are key regulators in development, tissue homeostasis and cancer progression. TEAD4 acts as a critical downstream effector of the evolutionarily conserved Hippo signaling pathway. The well-studied oncogenic protein YAP forms a complex with TEAD4 to regulate gene transcription; so does the tumor suppressor VGLL4. Although it is known that TEAD proteins can bind promoter regions of target genes through the TEA domain, the specific and detailed mechanism of DNA recognition by the TEA domain remains partially understood. Here, we report the crystal structure of TEAD4 TEA domain in complex with a muscle-CAT DNA element. The structure revealed extensive interactions between the TEA domain and the DNA duplex involving both the major and minor grooves of DNA helix. The DNA recognition helix, α3 helix, determines the specificity of the TEA domain binding to DNA sequence. Structure-guided biochemical analysis identified two major binding sites on the interface of the TEA domain-DNA complex. Mutation of TEAD4 at either site substantially decreases its occupancy on the promoter region of target genes, and largely impaired YAP-induced TEAD4 transactivation and target gene transcription, leading to inhibition of growth and colony formation of gastric cancer cell HGC-27. Collectively, our work provides a structural basis for understanding the regulatory mechanism of TEAD-mediated gene transcription.

Tumor-associated immune factors are associated with recurrence and metastasis in non-small cell lung cancer.

Dynamic interaction between tumor cells and the microenvironment is critical for tumorigenesis, and cancer immunosurveillance plays an important role in the tumor evolution. In some tumors (such as esophageal cancer, pancreatic cancer and colorectal cancer), studies have shown that the number of tumor-infiltrating lymphocytes (TILs) has a significant relationship with the prognosis, but there is little research on the prognosis of TILs and non-small cell lung cancer (NSCLC) has been performed. Therefore, it is necessary to discover the relationship between the TILs and cytokines with NSCLC prognosis and metastasis in patients. Tumor samples were carefully examined for tissue preservation and complete follow-up. A total of 107 tumor samples from NSCLC patients with radical surgical resection were enrolled for the analysis. All samples were subjected to immunohistochemistry for detection of CD3, CD4, CD8, CD28, forkhead box protein P3 (Foxp3), cytotoxic T lymphocyte-associated protein-4, cyclooxygenase2 (COX-2), transforming growth factor ß 1, interleukin-2 (IL-2), interleukin-6, interleukin-10, interleukin-12 receptor and hypoxia inducible factor 1a (HIF-1a). The number, function and location of the targets were analyzed to determine their correlation with disease-free survival (DFS) and overall survival (OS). Immunhistochemical results from 107 samples indicated that the FoxP3+ regulatory TIL (HR=1.336, P=0.031), IL-2 (HR=0.595, P=0.007) and HIF-1a (HR=1.510, P=0.002) levels in tumor cells closely correlated with DFS in a COX analysis model. FoxP3+ regulatory TILs (HR=1.566, P=0.002) significantly correlated with OS and tumor node metastasis staging. The patients were divided into two groups due to the coexpression pattern of the IL-2, FoxP3+ and HIF-1a. The high-risk group had an overall worse survival than those at low risk. We confirmed that Foxp3 expression in lymphocyte and IL-2 expression in tumor cells were associated with recurrence or transfer. Furthermore, we also observed that HIF-1a expression significantly correlated with DFS and OS.

Defective expression of polarity protein Par3 promotes cervical tumorigenesis and metastasis.

OBJECTIVES: The aim of this study was to investigate whether the partition-defective 3 protein (Par3) regulates cervical carcinoma growth and metastasis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to analyze the expression of Par3 protein in samples from 89 cervical squamous cell carcinoma (CSCC) patients among Uyghur women. The specific short hairpin (shRNA) vector as well as eu- karyotic expression vector of PARD3 was transfected into SiHa cell lines. The variation of migration and invasion after transfection was determined using Transwell assays, cell cycle, and apoptosis were assayed by flow cytometry, respectively. RESULTS: The incidence of CSCC was associated with reduced expression of Par3. Downregulation of Par3 was significantly associated with more advanced tumors (i.e., higher histological grade, lymph node involvement, and higher tumor stages) (p < 0.05 for all). Lost expression of Par3 promotes prolif- eration, inhibits apoptosis, and enhances migration and invasion. Loss of Par3 induces MMP9 expression and epithelial to mesenchymal transition (EMT) related genes (N-cadherin, E-cadherin, and ß-catenin) expression changed in SiHa cells. CONCLUSIONS: The reduced Par3 expression in cervical cancer indicates tumor-suppressive properties of Par3 that may be a marker of poor prognosis in cervical cancer patients, and the molecular determinants of epithelial polarity which have tumorigenesis enhancing impact, might through EMT.

A novel HLA-A*24 allele, A*24:02:61, confirmed in a Chinese individual.

A novel HLA-A*24 allele, A*24:02:61, confirmed in a Chinese individual.

Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease.

Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aß) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aß-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy.

A novel HLA-A*24 allele, A*24:337, was identified by sequencing-based typing.

A novel allele A*24:337 was identified in a Chinese individual by sequence-based typing.