Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

Estimation and projection of the burden of hearing loss in China: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: The comprehensive description of hearing loss in China and the shifting pattern remain unclear. We conducted the study to estimate the burden of hearing loss in China and project the trends from 2020 to 2034. STUDY DESIGN AND METHOD: Data on the disease burden of hearing loss were extracted from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of hearing loss burden were made until 2034 using Bayesian age-period-cohort analysis. RESULTS: In China, prevalent cases of hearing loss increased from 224.4 million in 1990 to 426.5 million in 2019, representing an increase of 90.1 %. The age-standardized prevalence rate of hearing loss ranged from 22,592.8/100,000 in 1990-22,612.4/100,000 in 2019, with an EAPC of 0.003 %, representing a stable trend. Of the category of hearing loss, mild hearing loss accounted for the highest proportion, with 331.4 million people. More than 95 million people had moderate-to-complete hearing loss. Moreover, hearing loss was mostly attributable to age-related and other factors for adults and otitis media for children younger than 10 years. Based on the projection results, there will be 561 million people (40.1 % of the total population) have hearing loss by 2034. CONCLUSIONS: The prevalent cases of hearing loss in China substantially increased over the last 30 years. Over two in five Chinese people will have hearing loss by 2034, thus suggesting more solutions should be established to reduce the burden of hearing loss.

New insights on the association of weight loss with the reduction in carotid intima-media thickness among patients with obesity: an updated systematic review and meta-analysis.

OBJECTIVES: Carotid intima-media thickness (CIMT) is a noninvasive marker of atherosclerosis, a typical pathologic process underlying cardiovascular diseases (CVDs). It is essential to explore the relationships between weight loss and the reduction of CIMT. STUDY DESIGN: This was an updated systematic review and meta-analysis. METHODS: A systematic literature search was conducted to collect relevant clinical trials. The pooled results of meta-analyses were assessed by weighted mean difference (WMD) and the corresponding 95 % confidence interval (95% CI). RESULTS: Thirty-three articles involving 2273 participants were collected in this meta-analysis. Among all participants with obesity, the pooled mean of weight loss was -23.26 kg (95% CI: -27.71 to -18.81), and the pooled mean change of CIMT was -0.06 mm (95% CI: -0.08 to -0.04). Compared with Non-surgical interventions, Surgical ones could lead to much higher weight loss (Pbetween groups < 0.001). A more significant CIMT reduction was identified among Surgical intervention patients than among Non-surgical intervention participants (Pbetween groups < 0.001). CONCLUSIONS: Effective interventions, especially Surgical interventions, could reduce the weight of patients with obesity, followed by the decline of CIMT, which might further disturb atherosclerosis progression and lower CVD risk.

[The mechanism of S100A7 inducing the migration and invasion in cervical cancer cells].

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.

[Epidemiological survey of hepatitis B and analysis of hepatitis B vaccine coverage rate among children aged 1-14 years in Lhasa in 2006, 2014 and 2020].

In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).

Cymbopogom Citratus Essential Oils: A Promising Source of Antifungals Against Panax Notoginseng-Associated Pathogenic Fungi.

Due to the great threat of chemical pesticides to the ecosystem environment, it is a long-term goal to find environmentally friendly green pesticides. Essential oils (EOs) are considered weapons in plant chemical defense and are important sources of green pesticides. Therefore, the antifungal effects and action mechanisms of Cymbopogom citratus (C. citratus) EOs against seven kinds of Panax notoginseng (P. notoginseng) pathogenic fungi were investigated. Oxford Cup results showed that C. citratus EOs had an excellent detraction effects against seven fungi of P. notoginseng. Gas chromatography-mass spectrometry (GC-MS) was used to construct the chemical profiles of C. citratus EOs, disclosed that the main categories are terpenes and oxygenated terpenes. In addition, compared with the hymexazol, the minimum inhibitory concentration (MIC) showed that EOs and their main components had strong antifungal activities. Besides, EOs had a synergistic effect with hymexazol (a chemical pesticide). The antifungal mechanism of C. citratus EOs was studied by using Fusarium oxysporum (F. oxysporum) as the dominant pathogen. C. citratus EOs may affect the metabolism of fungi and induce mycotoxins to destroy the cell wall to achieve antifungal effects. Finally, EOs were found to significantly retard P. notoginseng infection by F. oxysporum. According to our research, C. citratus EOs are potential green antifungal agent that can be used in the cultivation of P. notoginseng.

Genome and Phylogenetic Analysis of Cucumber Green Mottle Mosaic Virus Global Isolates and Validation of a Highly Sensitive RT-qPCR Assay.

The last two decades have seen exponential growth in the international movement of seeds for annual food crops, from a gross U.S. import value of $349 million in 1999 to $1.05 billion in 2019. This has led to the proportionate growth of seedborne pathogens dispersed with seed stocks. One such viral pathogen is cucumber green mottle mosaic virus (CGMMV), a tobamovirus that infects cucurbit crops such as melon, watermelon, cucumber, pumpkin, and squash. The first CGMMV introduction to California occurred in 2013, with subsequent annual outbreaks or detections since then. Here, we describe the use of next-generation sequencing to characterize the full genomes of 25 CGMMV isolates collected between 2013 and 2020 in California, either from CGMMV field detections or seed lots identified as CGMMV positive. We sequenced an additional 31 CGMMV isolates collected in Europe, Israel, and southeast Asia that were provided by industry collaborators. We also performed an in silico nucleotide database search in GenBank for full genome CGMMV sequences to include in all in silico analyses. Based on conserved regions within the coat protein gene, we then developed a quantitative reverse-transcription PCR assay for the sensitive and specific detection of CGMMV in seed and plant samples. Finally, based on our sequence and phylogenetic analysis, our data support that CGMMV has been introduced multiple times into California.

The Quest to Identify a New Virus Disease of Sunflower from Nebraska.

Between 2010 and 2018, sunflower plants exhibiting virus-like symptoms, including stunting, mottling, and chlorotic ringspots on leaves, were observed from commercial fields and research plots from four sites within three distinct counties of western Nebraska (Box Butte, Kimball, and Scotts Bluff). Near identical symptoms from field samples were reproduced on seedlings mechanically in the greenhouse on multiple occasions, confirming the presence of a sap-transmissible virus from each site. Symptomatic greenhouse-inoculated plants from the 2010 and 2011 Box Butte samples tested negative for sunflower mosaic virus (SuMV), sunflower chlorotic mottle virus (SuCMoV), and all potyviruses in general by ELISA and RT-PCR. Similar viral-like symptoms were later observed on plants in a commercial sunflower field in Kimball County in 2014, and again from volunteers in research plots in Scotts Bluff County in 2018. Samples from both of these years were again successfully reproduced on seedlings in the greenhouse as before following mechanical transmissions. Symptom expression for all years began 12 to 14 days after inoculation as mild yellow spots followed by the formation of chlorotic ringspots from the mottled pattern. The culture from 2014 tested negatively for three groups of nepoviruses via RT-PCR, ruling this group out. However, transmission electron microscopy assays of greenhouse-infected plants from both 2014 and 2018 revealed the presence of distinct, polyhedral virus particles. With the use of high throughput sequencing and RT-PCR, it was confirmed that the infections from both years were caused by a new virus in the tombusvirus genus and was proposed to be called Sunflower ring spot mottle virus (SuRSMV). Although the major objective of this project was to identify the causal agent of the disease, it became evident that the diagnostic journey itself, with all the barriers encountered on the 10-year trek, was actually more important and impactful than identification.

[Magnetic resonance imaging analysis on the effect of marathon on the dynamic changes of morphological characteristics of patellar tendon in amateur marathon runners after half marathon].

Objective: To explore the dynamic changes of morphological characteristics of patellar tendon (PT) in amateur athletes after a half-marathon using magnetic resonance imaging. Methods: A total of 19 male amateur marathon runners with 38 knee joints,aged from 26 to 53(41.5±7.9) years, running for 3 to 18 years, with a weekly running volume of 30-90 km and a monthly running volume of 100-300 km were enrolled and underwent 1.5T MRI scan before the half-marathon, within 3 hours after running and 3 days after running. Ten healthy male volunteers with 20 knee joints, who had never participated in marathon and exercised (including but not limited to running) per week for less than 150 minutes were recruited as the control group, aged from 26 to 54 (39.4±9.1) years. Firstly, the PT signal was qualitatively assessed on fat-suppressed proton density-weighted imaging (fs-PDWI) sequence to observe the presence of patellar tendinitis. Then, the length, proximal, middle and distal cross-sectional area (CSA), and volume of PT were measured using the post-processing tool ITK-SNAP, and the data were standardized. The independent sample t-test was used for comparing. One-way repeated measures analysis of variance was used to analyze the morphological changes of PT before and after half-marathon running. Results: The incidence of asymptomatic patellar tendinitis in amateur marathon runners was 26.3% (5/19). No significant MR signal changes of PT were observed in all runners after running. The proximal CSA in runners group was larger than that in controls [(4.20±0.62) mm2/kg3/4 vs (3.63±0.57) mm2/kg3/4, P<0.05], and there was no significant difference in length, medium and distal CSA and volume(all P>0.05). The length, proximal and distal CSA and volume of PT in runners group increased at 3 h after running [(47.35±3.22) mm vs (46.83±3.35) mm; (102.52±13.03) mm2 vs (98.98±13.14) mm2; (108.67±15.72) mm2 vs (100.27±14.37) mm2; (4 020.36±514.38) mm3 vs (3 826.57±499.23) mm3, all P<0.05]. There was no significant difference between before running and 3 days after running(all P>0.05). The middle CSA were not significantly different among different periods(all P>0.05). Conclusion: Marathon has effect on the normal PT morphology in male amateur marathon runners, showing an increase in proximal CSA. A half-marathon will cause reversible changes in PT length, regional CSA and volume.

[Tracing investigation and analysis of a Clostridium botulinum food poisoning incident in Bayingolin Mongolian Autonomous Prefecture, Xinjiang].

To analyze a suspected case of Clostridium botulinum food poisoning in Bayingolin Mongolian Autonomous Prefecture, Xinjiang and to help validating the diagnosis and providing technical support for clinical treatment. The basic information and clinical manifestations of food poisoning cases were investigated by using the epidemiological method of food safety accidents. The botulinum toxin genes in the samples were detected by real-time PCR and inoculation of KM mouse. The enriched bacteria were further purified and validated. PFGE and cluster analysis were performed on five isolates. Clostridium botulinum type A was detected in two homemade fermented bean samples and stool lavage fluid samples of three patients from enriched samples by toxin test and real-time PCR, and were further validated after isolation of Clostridium botulinum. PFGE showed 100% homology among five isolates. Five isolates of bacteria isolated from the stool lavage fluid of three patients and two homemade fermented bean curd were identified as the same source through PFGE. The cause of this food poisoning cases is food pollution of Clostridium botulinum type A.

[Effects of celastrol on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease].

Objective: To investigate the effect of celastrol (CEL) on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease (NAFLD). Methods: Eighteen male C57BL/6J mice were randomly divided into normal control (NC, n=6), high-fat diet (HFD, n=6) and celastrol group (HFD+CEL, n=6). The normal control group was fed with regular diet, and the high-fat diet and celastrol group were fed with high-fat diet for 12 weeks. After successful modeling, celastrol group were injected with 100 µg⋅kg-1⋅d-1 celastrol intraperitoneally for 4 weeks, and NC and HFD group were injected intraperitoneally with the same doses of normal saline. Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured in mouse after 4-weeks of intervention. HE and Oil Red O staining were used to observe the pathomorphological changes and lipid droplet deposition in mouse liver, and the findings were scored according to NAFLD activity score (NAS). Western blot was used to detect the expression levels of liver microtubule associated protein 1 light chain 3 (LC3), P62, glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), activated transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), cleaved Caspase-3(cleaved caspase-3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 related X protein (Bax).TUNEL staining was used to observe the apoptosis of hepatocytes. One-way analysis of variance was used for the intergroup comparison. Results: Serum levels of ALT (68.71±8.57) U/L, AST (209.63±28.64) U/L, TG (0.97±0.14) mmol/L, TC (4.12±0.64) mmol/L, and LDL -C (0.40±0.06) mmol/L were lower in celastrol group mouse than HFD group [(110.19±10.79) U/L, (399.72±73.47) U/L, (1.44±0.13) mmol/L, (5.65±0.54) mmol /L, (0.61±0.07) mmol/L] (P<0.05); while the serum HDL-C level (1.29±0.17) mmol/L was higher in celastrol than HFD group (0.72±0.13) mmol/L (P<0.05). HE and Oil Red O staining showed that lipid deposition and intralobular inflammation were apparent in the liver tissue of HFD group mouse, and the NAS score was significantly increased, while the hepatocyte steatosis and intralobular inflammation were alleviated after celastrol intervention, and the NAS score was decreased significantly (P<0.05). Compared with HFD group, the ratio of LC3II/I was significantly increased in the liver of celastrol group mouse, and the P62 was significantly decreased (P<0.05). Meanwhile, the expression level of GRP78, p-PERK/PERK , ATF4, and CHOP was significantly lower in celastrol than HFD group (P<0.05). In addition, the expressions of cleaved caspase-3 and Bax were significantly lower in celastrol than HFD group, and the expression of Bcl-2 was significantly increased (P<0.05). At the same time, the apoptosis rate of hepatocytes was also significantly lower in celastrol than HFD group (P<0.05). Conclusion: Celastrol can effectively alleviate the lipid deposition, protect hepatocytes and delay the progression of non-alcoholic fatty liver disease in mouse liver with non-alcoholic fatty liver disease. In addition, its mechanism of action may be related to the induction of autophagy, inhibition of endoplasmic reticulum stress PERK/ATF4/CHOP pathway and its mediated apoptosis.

[Dynamic changes of locus coeruleus damage in Parkinson's disease-like mice induced by paraquat].

Objective: To observe the dynamic changes of brainstem locus coeruleus (LC) damage in Parkinson' s disease (PD) -like mice by paraquat (PQ) . Methods: In October 2019, 36 male C57BL/6 mice were randomly divided into the exposure group and the control group, with 18 mice in each group. The mice in the exposure group were given intraperitoneal injection of 15 mg/kg PQ, and the mice in the control group were given intraperitoneal injection of 0.9% saline, twice a week for 8 weeks. Neurobehavioral changes (pole climbing test, swimming test, open field test, tail hanging test, high plus maze test and water maze test) were observed at 4 weeks, 6 weeks and 8 weeks, respectively, and the changes of motor ability, emotion and cognitive function were evaluated. The brain tissue of mice were taken and stained with Hematoxylin-Eosin (HE) to observe the pathological changes of LC. Nissl staining was used to detect the changes of neuronal Nissl bodies in LC. Immunohistochemistry (IHC) staining was used to detect the expression of neuron nuclear antigen (NeuN) , dopamine (DA) neurons and norepinephrine (NE) neuron markers tyrosine hydroxylase (TH) , α-synuclein (α-syn) in substantia nigra (SN) and LC. The expression levels of NeuN, TH and α-syn in the midbrain and brainstem were detected by Western blotting. TUNEL staining was used to detect neuronal apoptosis in LC. Results: Compared with the 4th week of PQ exposure group, the time of pole climbing and swimming immobility were gradually increased, the ratio of open arm residence time of high plus maze test and the number of times of the platform and the residence time of platform quadrant in water maze test were gradually decreased (P<0.05) in the exposure group with the progress of exposure time. The results of HE and Nissl staining showed that the neurons in LC gradually arranged loosely, the nucleus were deeply stained, the cytoplasm was pyknosis, and the number of Nissl bodies gradually decreased (P<0.05) in the exposure group with the progress of exposure time. IHC results showed that the number of NeuN and TH positive cells in SN and LC of mice were gradually decreased, and the positive expression of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. Western blotting results showed that the expression levels of NeuN and TH in the midbrain and brainstem were gradually decreased, and the expression level of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. TUNEL staining showed that the apoptosis rates of neurons in LC were gradually increased (P<0.05) in the exposure group with the progress of exposure time. Conclusion: PQ induces progressive damage in the LC area of PD-like mice, which may be caused by the abnormal accumulation of pathological α-syn in the LC area.

Relationship between Wound Age and Serum Marker Metabolites of Rats Skin Incised Wound.

ABSTRACT: Objective To observe the metabolomics changes of serum after skin incision of rats and to determine the wound age of skin incision. Methods A rat skin incision model was established, 21 SD rats were divided into 1 h, 2 h, 4 h, 8 h, 16 h, 24 h after skin incision groups and the control group, then blood was taken from rats in the experimental groups at the corresponding time points after injury, and taken from the control group directly. Gas chromatography-mass spectrometry （GC-MS） technology was used to detect serum metabolites and screen marker metabolites, then orthogonal partial least square-discriminant analysis （OPLS-DA） model was used to establish a regression model for the relationship between marker metabolite content and wound age to determine wound age of skin. Results GC-MS was used to detect the serum collected, and 21 marker metabolites were obtained through initial screening, and 4 marker metabolites were further analyzed and screened using multivariate statistical analysis methods. There was no correspondence between the change rule of the serum content and wound age, therefore it cannot be used directly to determine wound age. OPLS model could be used to obtain regression models of the content and wound age of 21 marker metabolites and 4 marker metabolites, both of which can determine wound age, but the prediction accuracy of the regression model of 21 marker metabolites was significantly higher. Conclusion Using metabolomics to establish a regression model of the metabolite content and wound age has the potential to be applied to skin incision wound age determination.

[The mechanism of HDAC6 in paraquat-induced autophagy dysfunction of dopaminergic neurons by mediating aggresome-autophagy-lysosomal pathway].

Objective: To explore the mechanism of HDAC6 mediated aggresome-autophagy-lysosome pathway in paraquat-induced autophagy in dopaminergic neurons. Methods: Human neuroblastoma cell (SH-SY5Y cell) was used as model of dopaminergic neurons in vitro. The cells were treated with terminal concentrations of 0, 25, 50, 100, 200 and 400µmol/L PQ for 24 hours, and the cells were induced by 100 µmol/L PQ for different time (0, 12, 24, 36, 48, 60 and 72 h) . Cell viability was detected by CCK-8 assay. The expression levels of HDAC6, α-syn, Dynein IC1/2, LC3, Beclin1, p62 and Lamp-1 were detected by Western blot. Immunofluorescence double-labeling method was used to observe the expression and localization of HDAC6, α-syn, Dynein IC1/2, LC3, Lamp-1 and γ-tubulin in cells. Results: CCK-8 assay showed PQ induced cell survival rate decrease in a time and dose dependent manner (R=-0.950、-0.960, P<0.05) .Western blot showed that compared with control group, the protein levels of HDAC6, α-syn, p62 in PQ-exposed group were significantly increased (P<0.05) , but there was a significant decrease in expression level of the ratio of autophagy-related protein LC3 Ⅱ/LC3 Ⅰ, Beclin1, Dynein IC1/2, Lamp-1in PQ-exposed group (P<0.05) . The results of immunofluorescence double-labeling showed that compared with the control group, the fluorescence signals of HDAC6 and α-syn in the PQ-exposed group increased, and the protein expression level increased, while the fluorescence signals of Dynein IC1/2, LC3, and Lamp-1 decreased. The protein expression level is reduced. HDAC6 gradually accumulates from the diffuse shape to the nucleus; Under normal circumstances, α-syn, Dynein IC1/2, γ-tubulin, LC3, and Lamp-1 are mainly distributed in the cytoplasm. After PQ is infected, they gather in the nucleus and co-localize with HDAC6 in the area around the nucleus. Conclusion: PQ may induce abnormal aggregation of α-syn by inducing HDAC6-mediated aggresome-autophagy-lysosomal pathway disorder.

Observation of Dynamical Quantum Phase Transitions with Correspondence in an Excited State Phase Diagram.

Dynamical quantum phase transitions are closely related to equilibrium quantum phase transitions for ground states. Here, we report an experimental observation of a dynamical quantum phase transition in a spinor condensate with correspondence in an excited state phase diagram, instead of the ground state one. We observe that the quench dynamics exhibits a nonanalytical change with respect to a parameter in the final Hamiltonian in the absence of a corresponding phase transition for the ground state there. We make a connection between this singular point and a phase transition point for the highest energy level in a subspace with zero spin magnetization of a Hamiltonian. We further show the existence of dynamical phase transitions for finite magnetization corresponding to the phase transition of the highest energy level in the subspace with the same magnetization. Our results open a door for using dynamical phase transitions as a tool to probe physics at higher energy eigenlevels of many-body Hamiltonians.

Endophytic Bacillus velezensis strain B-36 is a potential biocontrol agent against lotus rot caused by Fusarium oxysporum.

AIM: The aim of this study was to screen potential lotus plant endophytic bacterial isolate for effective inhibition against lotus rot causing fungal pathogen Fusarium oxysporum. METHODS AND RESULTS: In this study, endophytic bacteria were isolated from lotus tissues and tested for antagonistic activities against the pathogenic fungus F. oxysporum. Among the putative endophytic Bacillus strains identified, suspensions of the strain B-36 showed the highest inhibition rate against F. oxysporum growth. Pot assays indicated that B-36 was effective in controlling F. oxysporum-inducing lotus rot. However, the control efficiency varied with the inoculation method and concentration, where injection of 800 µl B-36 suspension per plant (2 × 108  CFU per ml) into stems showed the highest control efficiencies of 77·1 and 60·0% for pre-inoculation and post-inoculation. In addition, the colonizing population levels (CPLs) of B-36 on lotus also varied with the inoculation method and concentration, with the highest CPLs, that is, 3·05 and 2·83 log(CFU per gram), being observed on lotus leaves and stems respectively for stem injection of 200 µl per plant. Moreover B-36 showed no noticeable effects on lotus seed germination rate or seedling growth. Finally, B-36 was characterized as Bacillus velezensis based on its morphology, Gram-positive characteristics, as well as its 16S rDNA and gyrB sequences. CONCLUSION: The isolate B-36 can be applied as a biocontrol agent against F. oxysporum-inducing lotus rot. SIGNIFICANCE OF IMPACT OF THE STUDY: The soil-borne fungus F. oxysporum causes lotus rot and severe yield loss, and currently available control methods are very limited. Here we identify a new promising biocontrol agent against lotus rot caused by F. oxysporum.

[The clinical significance of plasma PTX3 in patients with secondary hemophagocytic lymphohistiocytosis].

Objective: To investigate the significance of plasma pentraxin 3 (PTX3) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). Methods: Plasma PTX3 levels were tested by ELISA in 48 newly diagnosed sHLH patients, 18 healthy volunteers and 9 lymphoma controls in the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2019. Clinical parameters were collected, and the correlations with PTX3 levels were analyzed. Results: PTX3 level in newly diagnosed group was significantly higher than that of healthy control group [16.29(1.17-66.00) vs. 0.76(0.01-7.86) µg/L, P<0.01]. Patients with lymphoma-associated HLH(LHLH) had higher plasma level of PTX3 than Fhose with infection-associated HLH (IHLH) [24.29(3.36-66.00) vs. 9.56(1.17-36.50)µg/L, P<0.05]. Plasma PTX3 levels in 48 sHLH patients were positively correlated with serum ferritin (P<0.05). Receiver operating characteristic (ROC) curve for plasma PTX3 levels of sHLH and healthy controls produced a cutoff value at 3.9 µg/L, with its 86.7% sensitivity and 94.4% specificity. And ROC analysis showed that PTX3 17.5 µg/L was the critical value for diagnosis of LHLH from non-LHLH group, that the sensitivity and specificity were 63.0% and 76.2% respectively. The 1-year overall survival (OS) rate in patients with PTX3≥17.5 µg/L was significantly lower in those with PTX3<17.5 µg/L (18.5% vs. 75.8%, P<0.01). Conclusion: These results indicate the potential of PTX3 as a biomarker for diagnosis and prognosis in patients with sHLH.

[Sequential Changes of Serum Biomarkers after Skeletal Muscle Contusion in Rats].

ABSTRACT: Objective To screen serum biomarkers after skeletal muscle contusion in rats based on gas chromatography-mass spectrometry （GC-MS） metabolomics technology, and support vector machine （SVM） regression model was established to estimate skeletal muscle contusion time. Methods The 60 healthy SD rats were randomly divided into experimental group （n=50）, control group （n=5） and validation group （n=5）. The rats in the experimental group and the validation group were used to establish the model of skeletal muscle contusion through free fall method, the rats in experimental group were executed at 0 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h and 240 h, respectively, and the rats in validation group were executed at 192 h, while the rats in the control group were executed after three days' regular feeding. The skeletal muscles were stained with hematoxylin-eosin （HE）. The serum metabolite spectrum was detected by GC-MS, and orthogonal partial least square-discriminant analysis （OPLS-DA） pattern recognition method was used to discriminate the data and select biomarkers. The SVM regression model was established to estimate the contusion time. Results The 31 biomarkers were initially screened by metabolomics method and 6 biomarkers were further selected. There was no regularity in the changes of the relative content of the 6 biomarkers with the contusion time and the SVM regression model can be successfully established according to the data of 6 biomarkers and the 31 biomarkers. Compared with the injury time ［（55.344±7.485） hï¼½ estimated from the SVM regression model based on the data of 6 biomarkers, the injury time ［（195.781±1.629） hï¼½ estimated from the SVM regression model based on the data of 31 biomarkers was closer to the actual value. Conclusion The SVM regression model based on metabolites data can be used for the contusion time estimation of skeletal muscles.

[Protective effects of taurine on neurons and microglia in Parkinson's disease-like mouse model induced by paraquat].

Objective: To investigate the protective effect of taurine (Tau) on hippocampus, substantia nigra neurons and microglia in paraquat (PQ) -induced Pakinson's disease-like mice. Methods: In April 2019, the specific pathogen free (SPF) C57BL/6 mice (n=36) were randomly divided into control group (NaCl) , Tau control group (150 mg/kg) , PQ exposure group (10 mg/kg PQ group, 15 mg/kg PQ group) , Tau intervention group (Tau+10 mg/kg PQ group, Tau+15 mg/kg PQ group) , respectively. Tau was used in 1 h before PQ administration for consecutive 6 weeks (twice per week) . General and neurobehavioral tests (Traction test, Open field test, Forced Swimming test, Tail suspension test, High plus maze and Object recognition test) were performed to test motor and cognitive function. After neuroethology detection, mice were euthanized and brains were collected. Nissl staining was used to detect the changes of the number and morphology of Nissl bodies in hippocampus and substantia nigra neurons of mice. Immunohistochemistry (IHC) was used to test the levels of neuron marker neuronal nuclei antigen (NeuN) , substantia nigra dopaminergic neuron marker tyrosine hydroxylase (TH) , α-synuclein (α-syn) , microglia markers ionized calcium bindingadaptor molecule-1 (Iba-1) , inducible nitric oxide synthase (iNOS) and interleukin-1ß (IL-1ß) in mice substantia nigra. The coexpression of Iba-1 and TH double-labeling, α-syn and TH double-labeling in mice substantia nigra were measured by immunofluorescence double staining. Results: General behavioral changes such as slow reaction and reduced action occurred in mice of PQ group. Compared with the control group, the scores of Traction test, and the time ratio of new object recognition in the PQ group decreased (P<0.05) , the fixed time of Swimming test and Tail suspension test increased (P<0.05) , the horizontal crawl number and vertical times of Open field test and the ratio of open arm residence time of High plus maze in the 15 mg/kg PQ group decreased (P<0.05) . Compared with the PQ group, the same dose of Tau+PQ group showed increased scores in Traction test (P<0.05) and decreased fixed time of Swimming test and Tail suspension test (P<0.05) . Compared with the 15 mg/kg PQ group, the horizontal crawl number of Open field test and the time ratio of new object recognition increased in the Tau+15 mg/kg PQ group (P<0.05) . Compared with the control group, the PQ group showed a decrease in the number of Nissl body in the hippocampus and substantia nigra (P<0.05) , a decrease in the number of NeuN and TH positive cells in the substantia nigra (P<0.05) , with a large number of α-syn deposition, Iba-1 activation of microglia cells, and an increase in the expression of inflammatory factors (IL-1ß, iNOS) in the hippocampus and substantia nigra (P<0.05) . Compared with the PQ group, the same dose of Tau+PQ group showed the number of Nissl in the hippocampus and substantia nigra was significantly increased (P<0.05) , the number of NeuN and TH positive cells in the substantia nigra was significantly increased (P<0.05) , the expression levels of α-syn, Iba-1 and inflammatory factors (IL-1ß, iNOS) in the substantia nigra were significantly decreased (P<0.05) . Conclusion: Tau could protect PQ-induced degeneration of substantia nigra dopaminergic neurons and hippocampal neuron loss by inhibiting the activation of microglia cells and release of inflammatory factors, and effectively improve the neurobehavioral and brain histopathological changes of PQ-induced PD-like mice.