High beam quality continuous-wave 320 nm UV laser from a walk-off compensated intracavity frequency-doubled Pr:YLF laser.

We report a high beam quality continuous-wave (CW) 320 nm ultra-violet (UV) laser. An end-pumped praseodymium-doped yttrium lithium fluoride (Pr:YLF) laser is constructed in a typical V-shaped cavity structure, while the UV output is obtained through intracavity frequency doubling using L i B 3 O 5 (LBO). We investigate the dependence of the UV output power, as well as the spot profile on the LBO length, and find that the "walk-off" within LBO severely affects both the frequency-doubling efficiency and the beam quality of the UV output. Rotated twin LBO crystals are then applied to substitute for single long LBO crystal to compensate the walk-off effect, resulting in high-power 320 nm output up to 410 mW under the absorbed pump power of 4.0 W at 444 nm, with a high beam quality of M x2=1.02 and M y2=1.04.

Epidemiological feature analysis of SVEIR model with control strategy and variant evolution.

The complex interactions were performed among non-pharmaceutical interventions, vaccinations, and hosts for all epidemics in mainland China during the spread of COVID-19. Specially, the small-scale epidemic in the city described by SVEIR model was less found in the current studies. The SVEIR model with control was established to analyze the dynamical and epidemiological features of two epidemics in Jinzhou City led by Omicron variants before and after Twenty Measures. In this study, the total population (N) of Jinzhou City was divided into five compartments: the susceptible (S), the vaccinated (V), the exposed (E), the infected (I), and the recovered (R). By surveillance data and the SVEIR model, three methods (maximum likelihood method, exponential growth rate method, next generation matrix method) were governed to estimate basic reproduction number, and the results showed that an increasing tendency of basic reproduction number from Omicron BA.5.2 to Omicron BA.2.12.1. Meanwhile, the effective reproduction number for two epidemics were investigated by surveillance data, and the results showed that Jinzhou wave 1 reached the peak on November 1 and was controlled 7 days later, and that Jinzhou wave 2 reached the peak on November 28 and was controlled 5 days later. Moreover, the impacts of non-pharmaceutical interventions (awareness delay, peak delay, control intensity) were discussed extensively, the variations of infection scales for Omicron variant and EG.5 variant were also discussed. Furthermore, the investigations on peaks and infection scales for two epidemics in dynamic zero-COVID policy were operated by the SVEIR model with control. The investigations on public medical requirements of Jinzhou City and Liaoning Province were analyzed by using SVEIR model without control, which provided a possible perspective on variant evolution in the future.

PatWRKY71 transcription factor regulates patchoulol biosynthesis and plant defense response.

Patchoulol, a valuable compound belonging to the sesquiterpenoid family, is the primary component of patchouli oil produced by Pogostemon cablin (P. cablin). It has a variety of pharmacological and biological activities and is widely used in the medical and cosmetic industries. However, despite its significance, there is a lack of research on the transcriptional modulation of patchoulol biosynthesis.Salicylic acid (SA), is a vital plant hormone that serves as a critical signal molecule and plays an essential role in plant growth and defense. However, to date, no studies have explored the modulation of patchoulol biosynthesis by SA. In our study, we discovered that the application of SA can enhance the production of patchoulol. Utilizing transcriptome analysis of SA-treated P. cablin, we identified a crucial downstream transcription factor, PatWRKY71. The transcription level of PatWRKY71 was significantly increased with the use of SA. Furthermore, our research has revealed that PatWRKY71 was capable of binding to the promoter of PatPTS, ultimately leading to an increase in its expression. When PatWRKY71 was silenced by a virus, the expression of both PatWRKY71 and PatPTS was reduced, resulting in the down-regulation of patchoulol production. Through our studies, we discovered that heterologous expression of PatWRKY71 leads to an increase in the sensitivity of Arabidopsis to salt and Cd, as well as an outbreak of reactive oxygen species (ROS). Additionally, we uncovered the regulatory role of PatWRKY71 in both patchoulol biosynthesis and plant defense response. This discovery provided a theoretical basis for the improvement of the content of patchoulol and the resistance of P. cablin through genetic engineering.

A new metal ion chelator attenuates human tau accumulation-induced neurodegeneration and memory deficits in mice.

Neuronal neurofibrillary tangles containing Tau hyperphosphorylation proteins are a typical pathological marker of Alzheimer's disease (AD). The level of tangles in neurons correlates positively with severe dementia. However, how Tau induces cognitive dysfunction is still unknown, which leads to a lack of effective treatments for AD. Metal ions deposition occurs with tangles in AD brain autopsy. Reduced metal ion can improve the pathology of AD. To explore whether abnormally phosphorylated Tau causes metal ion deposition, we overexpressed human full-length Tau (hTau) in the hippocampal CA3 area of mice and primary cultured hippocampal neurons (CPHN) and found that Tau accumulation induced iron deposition and activated calcineurin (CaN), which dephosphorylates glycogen synthase kinase 3 beta (GSK3ß), mediating Tau hyperphosphorylation. Simultaneous activation of CaN dephosphorylates cyclic-AMP response binding protein (CREB), leading to synaptic deficits and memory impairment, as shown in our previous study; this seems to be a vicious cycle exacerbating tauopathy. In the current study, we developed a new metal ion chelator that displayed a significant inhibitory effect on Tau phosphorylation and memory impairment by chelating iron ions in vivo and in vitro. These findings provide new insight into the mechanism of memory impairment induced by Tau accumulation and develop a novel potential treatment for tauopathy in AD.

High-Dose Influenza Vaccine Is Associated With Reduced Mortality Among Older Adults With Breakthrough Influenza Even When There Is Poor Vaccine-Strain Match.

BACKGROUND: High-dose (HD) influenza vaccine offers improved protection from influenza virus infection among older adults compared with standard-dose (SD) vaccine. Here, we explored whether HD vaccine attenuates disease severity among older adults with breakthrough influenza. METHODS: This was a retrospective cohort study of US claims data for influenza seasons 2016-2017, 2017-2018, and 2018-2019, defined as 1 October through 30 April, among adults aged ≥65 years. After adjusting the different cohorts for the probability of vaccination conditional on patients' characteristics, we compared 30-day mortality rate post-influenza among older adults who experienced breakthrough infection after receipt of HD or SD influenza vaccines and among those not vaccinated (NV). RESULTS: We evaluated 44 456 influenza cases: 23 109 (52%) were unvaccinated, 15 037 (33.8%) received HD vaccine, and 6310 (14.2%) received SD vaccine. Significant reductions in mortality rates among breakthrough cases were observed across all 3 seasons for HD vs NV, ranging from 17% to 29% reductions. A significant mortality reduction of 25% was associated with SD vaccination vs NV in the 2016-2017 season when there was a good match between circulating influenza viruses and selected vaccine strains. When comparing HD vs SD cohorts, mortality reductions were higher among those who received HD in the last 2 seasons when mismatch between vaccine strains and circulating H3N2 viruses was documented, albeit not significant. CONCLUSIONS: HD vaccination was associated with lower post-influenza mortality among older adults with breakthrough influenza, even during seasons when antigenically drifted H3N2 circulated. Improved understanding of the impact of different vaccines on attenuating disease severity is warranted when assessing vaccine policy recommendations.

A Co-Designed Neuromorphic Chip With Compact (17.9K F2) and Weak Neuron Number-Dependent Neuron/Synapse Modules.

Many efforts have been made to improve the neuron integration efficiency on neuromorphic chips, such as using emerging memory devices and shrinking CMOS technology nodes. However, in the fully connected (FC) neuromorphic core, increasing the number of neurons will lead to a square increase in synapse & dendrite costs and a high-slope linear increase in soma costs, resulting in an explosive growth of core hardware costs. We propose a co-designed neuromorphic core (SRCcore) based on the quantized spiking neural network (SNN) technology and compact chip design methodology. The cost of the neuron/synapse module in SRCcore weakly depends on the neuron number, which effectively relieves the growth pressure of the core area caused by increasing the neuron number. In the proposed BICS chip based on SRCcore, although the neuron/synapse module implements 1∼16 times of neurons and 1∼66 times of synapses, it only costs an area of 1.79 × 107 F2, which is 7.9%∼38.6% of that in previous works. Based on the weight quantization strategy matched with SRCcore, quantized SNNs achieve 0.05%∼2.19% higher accuracy than previous works, thus supporting the design and application of SRCcore. Finally, a cross-modeling application is demonstrated based on the chip. We hope this work will accelerate the development of cortical-scale neuromorphic systems.

Hydrogen Sulfide Attenuates Neuroinflammation by Inhibiting the NLRP3/Caspase-1/GSDMD Pathway in Retina or Brain Neuron following Rat Ischemia/Reperfusion.

Gasdermin D-executing pyroptosis mediated by NLRP3 inflammasomes has been recognized as a key pathogenesis during stroke. Hydrogen sulfide (H2S) could protect CNS against ischemia/reperfusion (I/R)-induced neuroinflammation, while the underlying mechanism remains unclear. The study applied the middle cerebral artery occlusion/reperfusion (MCAO/R) model to investigate how the brain and the retinal injuries were alleviated in sodium hydrogen sulfide (NaHS)-treated rats. The rats were assigned to four groups and received an intraperitoneal injection of 50 µmol/kg NaHS or NaCl 15 min after surgery. Neurological deficits were evaluated using the modified neurologic severity score. The quantification of pro-inflammatory cytokines, NLRP3, caspase-1, and GSDMD were determined by ELISA and Western blot. Cortical and retinal neurodegeneration and cell pyroptosis were determined by histopathologic examination. Results showed that NaHS rescued post-stroke neurological deficits and infarct progression, improved retina injury, and attenuated neuroinflammation in the brain cortexes and the retinae. NaHS administration inhibits inflammation by blocking the NLRP3/caspase-1/GSDMD pathway and further suppressing neuronal pyroptosis. This is supported by the fact that it reversed the high-level of NLRP3, caspase-1, and GSDMD following I/R. Our findings suggest that compounds with the ability to donate H2S could constitute a novel therapeutic strategy for ischemic stroke.

Pretreatment with metformin prevents microcystin-LR-induced tau hyperphosphorylation via mTOR-dependent PP2A and GSK-3ß activation.

Microcystin-leucine-arginine (MC-LR) is a toxin secreted by freshwater cyanobacteria that is considered a potential environmental risk factor for Alzheimer's disease (AD). A previous study indicated that tau protein hyperphosphorylation via protein phosphatase 2A (PP2A) and GSK-3ß inhibition was the mechanism by which MC-LR induces neurotoxicity; however, how MC-LR-induced neurotoxicity can be effectively prevented remains unclear. In this study, the reversal effect of metformin on MC-LR-induced neurotoxicity was investigated. The results showed that metformin effectively prevented tau hyperphosphorylation at Ser202 caused by MC-LR through PP2A and GSK-3b activity. The effect of metformin on PP2A activity was dependent on the inhibition of mTOR in MC-LR-treated SH-SY5Y cells. Metformin prevented spatial memory deficits in rats caused by intrahippocampal MC-LR administration. In sum, the results suggested that metformin can ameliorate the MC-LR-induced AD-like phenotype by preventing tau phosphorylation at Ser202, which was mainly mediated by mTOR-dependent PP2A and GSK-3ß activation.

aFGF Targeted Mediated by Novel Nanoparticles-Microbubble Complex Combined With Ultrasound-Targeted Microbubble Destruction attenuates Doxorubicin-Induced Heart Failure via Anti-Apoptosis and Promoting Cardiac Angiogenesis.

The purpose of this study was to evaluate the protective effect of acidic fibroblast growth factor targeted mediated by novel nanoparticles-cationic lipid microbubbles complex (aFGF-NP + CPMBs) combined with ultrasound targeted microbubble destruction (UTMD)on doxorubicin-induced heart failure (HF)and its mechanism. Heart failure rats induced by intraperitoneal injection with doxorubicin (DOX) to achieve cummulative dose of 15mg/kg for continuous 6 weeks showed left ventricular dysfunction, seriously oxidative stress, cardiomyocyte apoptosis, and decrease of myocardial vascular density. In contrast, aFGF-NP + CPMBs combined with UTMD therapy (3ug/kg, caudal vein injection, twice a week, 6weeks)prominently ameliorated left ventricular dysfunction by increased ejection fraction (EF) and fractional shortening (FS), decreased brain natriuretic peptide (BNP); strengthened the ability of antioxidant stress confirmed by increasing the activity of SOD and reducing the production of MDA; exerted the effect of anti-cardiomyocyte apoptosis and promotion angiogenesis by inhibited Bax expression and increased Bcl-2 expression and platelet endothelial cell adhesion molecule (CD31) expression. Taken together, the research suggested that aFGF targeted mediated by novel nanoparticles-cationic lipid microbubbles complex combined with UTMD should be a promising targeted treatment for heart failure.

Tau-induced upregulation of C/EBPß-TRPC1-SOCE signaling aggravates tauopathies: A vicious cycle in Alzheimer neurodegeneration.

Intracellular accumulating of the hyperphosphorylated tau plays a pivotal role in neurodegeneration of Alzheimer disease (AD), but the mechanisms underlying the gradually aggravated tau hyperphosphorylation remain elusive. Here, we show that increasing intracellular tau could upregulate mRNA and protein levels of TRPC1 (transient receptor potential channel 1) with an activated store-operated calcium entry (SOCE), an increased intraneuronal steady-state [Ca2+ ]i , an enhanced endoplasmic reticulum (ER) stress, an imbalanced protein kinases and phosphatase, and an aggravated tauopathy. Furthermore, overexpressing TRPC1 induced ER stress, kinases-phosphatase imbalance, tau hyperphosphorylation and cognitive deficits in cultured neurons and mice, while pharmacological inhibiting or knockout TRPC1 attenuated the hTau-induced deregulations in SOCE, ER homeostasis, kinases-phosphatase balance, and tau phosphorylation level with improved synaptic and cognitive functions. Finally, an increased CCAAT-enhancer-binding protein (C/EBPß) activity was observed in hTau-overexpressing cells and the hippocampus of the AD patients, while downregulating C/EBPß by siRNA abolished the hTau-induced TRPC1 upregulation. These data reveal that increasing intracellular tau can upregulate C/EBPß-TRPC1-SOCE signaling and thus disrupt phosphorylating system, which together aggravates tau pathologies leading to a chronic neurodegeneration.

High energy mid-infrared laser pulse output from a BaGa4Se7 crystal-based optical parametric oscillator.

We report a high energy, narrow spectral linewidth mid-infrared laser pulse output from a Nd:Y3Al5O12 laser-pumped BaGa4Se7 (BGSe) crystal-based optical parametric oscillator (OPO). Output pulse energy of 21.5 mJ was obtained at 3816 nm, with spectral width of 12 nm and pulse width of 11.4 ns, corresponding to peak power as high as 1.89 MW. A BGSe crystal with aperture size of 10mm×10mm and length of 16 mm was applied as the nonlinear crystal in a pump fed back OPO for achieving such high pulse energy output from the simple oscillator scheme.

Reduced methylation of PP2Ac promotes ethanol-induced lipid accumulation through FOXO1 phosphorylation in vitro and in vivo.

Although disturbance of the methionine cycle and sequent decrease in hepatic methylation capacity are known to be important factors in the development of alcoholic liver injury, the underlying mechanisms are not fully understood. Here, we investigated the importance of the methylation of protein phosphatase 2A (PP2A) in alcoholic liver disease (ALD). We found that the severity of ethanol-induced liver injury and the extent of demethylation of PP2A catalytic C subunit (PP2Ac) were reduced after treatment with betaine, a methyl donor involved in the methionine-homocysteine cycle. These results suggest that PP2Ac methylation is decreased due to a broad decrease in hepatic methylation capacity after exposure to ethanol. Moreover, we found that the reduction in PP2Ac methylation led to increased degradation of the regulatory Bα subunit, thus promoting the phosphorylation and nuclear exclusion of Forkhead box O1 (FOXO1) and reducing FOXO1 transcriptional activity. Ultimately, the reduced activity of FOXO1 led to increased expression of TXNIP, which caused hepatic lipid accumulation. Our findings suggest that the reduction of PP2A methylation, a result of decrease hepatic methylation capacity, played an important role in ethanol-induced lipid accumulation via down-regulation of PP2A/Bα and FOXO1 phosphorylation.

Tau inhibits PKA by nuclear proteasome-dependent PKAR2α elevation with suppressed CREB/GluA1 phosphorylation.

Intraneuronal accumulation of wild-type tau plays a key role in Alzheimer's disease, while the mechanisms underlying tauopathy and memory impairment remain unclear. Here, we report that overexpressing full-length wild-type human tau (hTau) in mouse hippocampus induces learning and memory deficits with remarkably reduced levels of multiple synapse- and memory-associated proteins. Overexpressing hTau inhibits the activity of protein kinase A (PKA) and decreases the phosphorylation level of cAMP-response element binding protein (CREB), GluA1, and TrkB with reduced BDNF mRNA and protein levels both in vitro and in vivo. Simultaneously, overexpressing hTau increased PKAR2α (an inhibitory subunit of PKA) in nuclear fraction and inactivated proteasome activity. With an increased association of PKAR2α with PA28γ (a nuclear proteasome activator), the formation of PA28γ-20S proteasome complex remarkably decreased in the nuclear fraction, followed by a reduced interaction of PKAR2α with 20S proteasome. Both downregulating PKAR2α by shRNA and upregulating proteasome by expressing PA28γ rescued hTau-induced PKA inhibition and CREB dephosphorylation, and upregulating PKA improved hTau-induced cognitive deficits in mice. Together, these data reveal that intracellular tau accumulation induces synapse and memory impairments by inhibiting PKA/CREB/BDNF/TrkB and PKA/GluA1 signaling, and deficit of PA28γ-20S proteasome complex formation contributes to PKAR2α elevation and PKA inhibition.

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR-135a-5p to prevent the progression of epilepsy.

Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR-135a-5p, as well as those between miR-135a-5p and 3' untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual-luciferase reporter gene assay. The expression of miR-135a-5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR-135a-5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv-shGAS5 and Lv-miR-135a-5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR-135a-5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR-135a-5p. After the treatment of Lv-shGAS5 and Lv-miR-135a-5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR-135a-5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.

Muscle Magnetic Resonance Imaging in Patients with Various Clinical Subtypes of LMNA-Related Muscular Dystrophy.

BACKGROUND: LMNA-related muscular dystrophy can manifest in a wide variety of disorders, including Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), and LMNA-associated congenital muscular dystrophy (L-CMD). Muscle magnetic resonance imaging (MRI) has become a useful tool in the diagnostic workup of patients with muscle dystrophies. This study aimed to investigate whether there is a consistent pattern of MRI changes in patients with LMNA mutations in various muscle subtypes. METHODS: Twenty-two patients with LMNA-related muscular dystrophies were enrolled in this study. MRI of the thigh and/or calf muscles was performed in them. The muscle MRI features of the three subtypes were compared by the Mann-Whitney U-test. The relationship between the clinical and MRI findings was also investigated by Spearman's rank analyses. RESULTS: The present study included five EDMD, nine LGMD, and eight L-CMD patients. The thigh muscle MRI revealed that the fatty infiltration of the adductor magnus, semimembranosus, long and short heads of the biceps femoris, and vasti muscles, with relative sparing of the rectus femoris, was the predominant change observed in the EDMD, LGMD, and advanced-stage L-CMD phenotypes, although the involvement of the vasti muscles was not prominent in the early stage of L-CMD. At the level of the calf, six patients (one EDMD, four LGMD, and one L-CMD) also showed a similar pattern, in which the soleus and the medial and lateral gastrocnemius muscles were most frequently observed to have fatty infiltration. The fatty infiltration severity demonstrated higher scores associated with disease progression, with a corresponding rate of 1.483 + 0.075 × disease duration (X) (r = 0.444, P = 0.026). It was noteworthy that in six L-CMD patients with massive inflammatory cell infiltration in muscle pathology, no remarkable edema-like signals were observed in muscle MRI. CONCLUSIONS: EDMD, LGMD and advanced-staged L-CMD subtypes showed similar pattern of muscle MRI changes, while early-staged L-CMD showed somewhat different changes. Muscle MRI of L-CMD with a muscular dystrophy pattern in MRI provided important clues for differentiating it from childhood inflammatory myopathy. The fatty infiltration score could be used as a reliable biomarker for outcome measure of disease progression.

Clinical and Genetic Features of Chinese X-linked Charcot-Marie-Tooth Type 1 Disease.

BACKGROUND: X-linked Charcot-Marie-Tooth type 1 (CMT1X) disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein (GJB1) gene (also known as connexin 32). This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations. METHODS: A total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJB1 mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing (NGS). Nucleotide alternations were confirmed with Sanger sequencing. RESULTS: The CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years (ranging from 1 year to 42 years). The sudden onset of cerebral symptoms appeared in four patients (18.2%); two were initial symptoms. One case had constant central nervous system (CNS) signs. There were 19 different heterozygous mutations, including 15 known mutations and four novel mutations (c.115G>T, c.380T>A, c.263C>A, and c.818_819insGGGCT). Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 (TM1), 4.5% in TM2, 22.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 (EC1), 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-terminal domain. CMT1X with CNS impairment appeared in five (22.7%) of these patients. CONCLUSIONS: This study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJB1 gene were hotspot in Chinese CMT1X patients.

Establishment of a reference interval for high-sensitivity cardiac troponin I in healthy adults from the Sichuan area.

High-sensitivity cardiac troponin I (hs-cTnI) has been used in the diagnosis and risk stratification of acute myocardial infarction. However, there is no common consensus on an hs-cTnI reference interval for the Chinese population. The aim of this study was to describe the distribution of hs-TnI and establish the 99th percentile reference interval for hs-cTnI in healthy adults from the Sichuan area.Serum specimens were collected from 1485 healthy adults (731 men and 754 women ranging in age from 18 to 85 years) in Sichuan Provincial People's Hospital. All specimens were divided into 4 groups according to age distribution: 18 to 35 years, 36 to 50 years, 51 to 65 years, and ≥66 years. Specimens were further divided into younger/middle and older-aged groups based on a cut-off age of 50 years. The serum hs-cTnI concentration was determined using the Abbott ARCHITECT STAT hs-cTnI assay.The serum hs-cTnI concentration increased with age (P < 0.05). The 99th percentiles of hsTnI were 28.0 pg/mL among the whole population, 31.1 pg/mL among men, and 22.7 pg/mL among women. The age-dependent 99th percentiles of hs-cTnI in men and women were as follows: 28.8 versus 12.5 pg/mL for 18 to 35 years, 20.4 versus 9.2 pg/mL for 36 to 50 years, 24.2 versus 13.6 pg/mL for 51 to 65 years, and 27.9 versus 32.2 pg/mL for ≥66 years.The 99th percentile reference interval for hs-cTnI in healthy adults from the Sichuan area was similar to the manufacturer's recommendation. Men had a higher 99th percentile hs-cTnI value than women in the age range of 18 to 65 years.

ACVR1-Fc suppresses BMP signaling and chondro-osseous differentiation in an in vitro model of Fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease of heterotopic endochondral ossification (HEO), and currently no effective therapies are available for this disease. A recurrent causative heterozygous mutation (c.617 G>A; R206H) for FOP was identified in activin receptor type IA (ACVR1), a bone morphogenetic protein (BMP) type I receptor. This mutation aberrantly activates the BMP-Smad1/5/8 signaling pathway and leads to HEO in FOP patients. Here we report development of a soluble recombinant ACVR1-Fc fusion protein by combining the extracellular domain of human wild type ACVR1 and the Fc portion of human immunoglobulin gamma 1 (IgG1). The ACVR1-Fc fusion protein significantly down-regulated the dysregulated BMP signaling caused by the FOP ACVR1 mutation and effectively suppressed chondro-osseous differentiation in a previously described cellular FOP model, human umbilical vein endothelial cells (HUVECs) that were infected with adenovirus-ACVR1R206H (HUVECR206H). This ACVR1-Fc fusion protein holds great promise for prevention and treatment of HEO in FOP and related diseases.

Clinical and Brain Magnetic Resonance Imaging Features in a Cohort of Chinese Patients with Kearns-Sayre Syndrome.

BACKGROUND: Kearns-Sayre syndrome (KSS) is a mitochondrial DNA (mtDNA) deletion disorder characterized by a triad of onset before 20 years of age, ophthalmoplegia, and pigmentary retinopathy. The heart and central nervous system are commonly involved. We summarized clinical and brain magnetic resonance imaging (MRI) features of a cohort of Chinese KSS patients. METHODS: Nineteen patients confirmed by muscle biopsy and mtDNA analysis were enrolled. We examined clinical profiles, mainly focusing on changes in electrocardiogram (ECG) and brain MRI. The correlation between genotype and phenotype was statistically analyzed. RESULTS: The mean age of onset was 9.6 ± 4.3 years, with all developing the classic triad at the time of diagnosis. Heart conduction block was detected in 63.2%, with four initially presenting as bundle branch block and developing into complete atrioventricular block over 3-72 months. Brain MRI showed symmetric high-T2 signals in 100% of cerebral and cerebellar white matter, as well as brainstem, 46.7% of basal ganglia, and 53.3% of thalamus. There were two patterns of cerebral white matter involvements, one with selective subcortical U-fibers and the other with periventricular white matter. The size of mtDNA deletion did not significantly correlate with age of onset or percentage of ragged blue fibers on muscle pathology. CONCLUSIONS: The clinical features of KSS evolve dynamically, affecting the cardiac conduction system predominantly, highlighting the significance of ECG monitoring. Brain MRI showed changes involving both the white matter and deep gray nuclei. Clinical presentation or severity of muscle pathological changes is not related to the size of mtDNA deletions.

[Study on Chemical Components of Tripterospermum chinense ( â ¡)].

Objective: To investigate the chemical components of Tripterospermum chinense. Methods: Various column chromatography were used in the isolation and purification,and physiochemical constant determination and spectral analysis were adopted to determine the chemical structures. Results: A novel monoterpenoid and seven known compounds were isolated and identified as tripterospermum acid ester A( 1),strychnovoline( 2),p-hydroxybenzaldehyde( 3),isovitexin( 4),7-O-rhamnopyransoyl-isoorientin( 5),trifoliside( 6),2″-O-rhamnopyransoyl-trifoliside( 7) and sweroside( 8). Conclusion: Compound 1 is a new monoterpenoid,compounds 2,3 are isolated from this plant for the first time.