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Abstract Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3′UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases.

The genus Illiesonemoura Baumann, 1975 (Plecoptera, Nemouridae) is a small-sized stonefly with slender and curved embranous cerci. Currently, 18 species of the genus are known worldwide, mainly distributed in the Palaearctic and Oriental Regions, with a total of two species known to China.Three new species of Illiesonemoura Baumann, 1975, I. bituberculata Wang & Du, sp. nov., I. motuoensis Du & Ji, sp. nov. and I. weii Du & Ji, sp. nov. are described and illustrated, based on male adults from China. Illiesonemoura bituberculata is characterised by two pairs of tubercles arising posteromedially from tergum 10 and by two rows of spinules outlining the lateral edge of the ventral sclerite of the epiproct. Illiesonemoura motuoensis is characterised by the heart-shaped epiproct with a thin and slightly sclerotised protrusion between the sclerotised bands. Illiesonemoura weii is characterised by a pair of small knobs on tergum 10, outer lobes of paraprocts basally broad, then slender towards apices with a pointed tip and the epiproct with lateral spinules.

Cell adhesion molecules (CAM) are crucial in several pathological inflammation processes in Alzheimer’s disease (AD). However, their potential for clinical diagnostics remains unknown. The present investigation evaluated the clinical significance of ALCAM, VCAM-1, NCAM, and ICAM-1 levels in the plasma of participants with cognitive impairment (44 patients with mild cognitive impairment, 71 patients with Alzheimer’s dementia, and 18 patients with other dementia) and 28 controls with normal cognitive ability. We also detected plasma levels of multiple inflammatory factors (IFN-gamma, IL-18, IL-1beta, IL-13, IL-8, IL-7, CCL11, MCP-1, TSLP, IL-10, BDNF, IL-17, IL-5, TREM-1) using Multiplex liquid chip and plasma levels of Abeta1-42 and Abeta1-40 using liquid-phase flow cytometry (FCM). Our findings demonstrated a correlation of ALCAM and VCAM-1 with age, the severity of cognitive decline, and MTA, but no significant difference between groups for NCAM and ICAM-1. ALCAM and VCAM-1 both demonstrated a positive correlation with the degree of atrophy in the medial temporal lobe structure. Further analysis revealed no significant correlation in plasma between VCAM-1, ALCAM and Abeta1-40, Abeta1-42. Nevertheless, there was a significant correlation between VCAM-1, ALCAM and many inflammatory factors. Furthermore, the predictive value of ALCAM and VCAM-1 for AD was assessed using a multi-parameter regression model. ALCAM and VCAM-1 in combination with ApoE4, education, age, and MMSE could predict AD with high precision (AUC=0.891; AIC=146.9) without imaging diagnosis. ALCAM and VCAM-1 combination improved the predictive accuracy significantly. In a nutshell, these findings revealed ALCAM and VCAM-1 as reliable indicators of Alzheimer’s disease.

Background: Cystic adenomyosis (CA) is a rare form of adenomyosis. Case: We present for the first time secondary CA in a young woman with increased menstrual volume as the main clinical manifestation. A 23-year-old woman with a history of two uterine surgeries was hospitalized with increased menstrual flow volume and no dysmenorrhea or other discomfort. Ultrasound resulted in misdiagnosis as myoma of the uterus. She underwent laparoscopic surgery for adenomyoma excision with levonorgestrel-releasing intrauterine system (LNG-IUS) placement. During surgery, the lesions were completely removed under ultrasound guidance, and a specimen bag was used to reduce residual lesions in the abdominal cavity. She was postoperative treated with gonadotropin-releasing hormone analog (GnRH-a). Surgical findings and postoperative pathology confirmed CA. She has been followed up for 2 years without recurrence. Conclusions: A CA diagnosis should be considered for clinical manifestations of increased menstrual volume and dysmenorrhea in young patients with previous uterine surgery histories. Magnetic resonance imaging (MRI) is very important for CA diagnosis. Conservative surgery along with GnRH-a and LNG-IUS therapy can effectively prevent recurrence.

Abstract. Background:. Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles. Methods:. A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC. Results:. The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc. Conclusions:. Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.

Abstract Background It is essential to accurately predict Postoperative liver failure (PHLF) which is a life-threatening complication. Liver hardness measurement (LSM) is widely used in non-invasive assessment of liver fibrosis. The aims of this study were to explore the application of preoperative liver stiffness measurements (LSM) by transient elastography in predicting postoperative liver failure (PHLF) in patients with hepatitis B related hepatocellular carcinoma. Methods The study included 247 consecutive patients with hepatitis B related hepatocellular carcinoma who underwent hepatectomy between May 2015 and September 2015. Detailed preoperative examinations including LSM were performed before hepatectomy. The endpoint was the development of PHLF. Results All of the patients had chronic hepatitis B defined as the presence of hepatitis B surface antigen (HBsAg) for more than 6 months and 76 (30.8%) had cirrhosis. PHLF occurred in 37 (14.98%) patients. Preoperative LSM (odds ratio, OR, 1.21; 95% confidence interval, 95% CI: 1.13–1.29; P

Abstract Background The phospholipase A2 receptor (PLA2R) associated with membranous nephropathy (MN) is an organ-specific autoimmune disease associated with PLA2R and human leukocyte antigen (HLA) genes. Familial PLA2R-related MN is rarely reported. The combination of anti-GBM disease and MN has been well documented, though the mechanism behind it remains unclear. Case presentation We describe two siblings diagnosed with pathology-confirmed PLA2R-related MN 1 year apart. And one of the two siblings developed an anti-GBM disease. The high-resolution HLA typing showed identical alleles in both siblings, specifically heterozygotes of DRB1*15:01/*03:01. Conclusion We describe a familial case of PLA2R-related MN supporting the role of genetic factors that HLA-DRB1*15:01 and DRB1*03:01 predispose patients in the development of PLA2R-related MN in the Han Chinese population. The combination of MN and anti-GBM disease may also partially be associated with the same susceptible HLA allele DRB1*15:01.

ABSTRACT Cognitive dysfunction is a common symptom experienced by elderly individuals after surgery, resulting in memory problems, difficulties with logical thinking, hallucinations, delusions, and an increased risk of dementia. Despite its prevalence, the underlying cause of postoperative cognitive dysfunction remains unclear. Recent research has uncovered a link between neurodegenerative diseases and the gut microbiota, indicating the need for further investigation into the role of the intestinal flora in postoperative cognitive dysfunction. To address this research gap, we conducted behavioral tests, gene and protein analyses, metagenomics, and non-targeted metabolomics to compare the gut microbiota and metabolomics of mice exposed to anesthesia/surgery that exhibited cognitive impairment with those of age-matched control mice. Our goal was to identify possible correlations between these factors. We found that mice experiencing postoperative cognitive dysfunction had a distinct microbial composition, neuroinflammation, and synaptic damage compared to the control group. Specifically, we observed significant increases in the relative abundances of Bacteroidetes unclassified, Bacteroides acidifaciens, Rikenellaceae bacterium, Muribaculaceae bacterium Isolate-104 HZI, Muribaculaceae bacterium Isolate-110 HZI, and Mucispirillum schaedleri in aged mice exposed to anesthesia and surgery, while the relative abundances of Lachnospiraceae bacterium A2, Lachnospiraceae bacterium A4, Lachnospiraceae bacterium, Blautia, Lachnoclostridium bacterium MD355, Eubacterium rectale, Ruminococcus sp. 1xD21-23, and Butyrivibrio were significantly decreased. Additionally, metabolites, such as thiamine, spermidine, and long-chain unsaturated fatty acids, were down-regulated compared to the control group. These findings suggest that the intestinal metabolic abnormalities observed in elderly mice exposed to anesthesia/surgery may be regulated by the intestinal microbiota, specifically the Lachnospiraceae, Lachnoclostridium, Butyrivibrio, and Eubacterium. Therefore, our study highlights the potential of manipulating the gut microbiota to modulate the host metabolism in order to prevent and manage postoperative cognitive dysfunction. IMPORTANCE As the population ages and medical technology advances, anesthesia procedures for elderly patients are becoming more common, leading to an increased prevalence of postoperative cognitive dysfunction. However, the etiology and correlation between the gut microbiota and cognitive dysfunction are poorly understood, and research in this area is limited. In this study, mice with postoperative cognitive dysfunction were found to have reduced levels of fatty acid production and anti-inflammatory flora in the gut, and Bacteroides was associated with increased depression, leading to cognitive dysfunction and depression. Furthermore, more specific microbial species were identified in the disease model, suggesting that modulation of host metabolism through gut microbes may be a potential avenue for preventing postoperative cognitive dysfunction.

To project possible future climate change, it is important to understand Earth system response to CO2 removal, a potential key method to limit global warming. Previous studies examined some aspects of Earth system response to different scenarios of CO2 removal, but lacked a systematic analysis of the carbon cycle and climate system response in a consistent modeling framework. We expanded previous studies by using an Earth system model to examine the response of land and ocean carbon cycle, as well as a set of climate variables to idealized scenarios of atmospheric CO2 removal with different removal rates. In the scenarios considered, atmospheric CO2 increases at a rate of 1% per year to four times of its preindustrial level, and then decreases at a rate of 0.5%, 1%, and 2% per year to the preindustrial level. Simulation results show that a reduction of atmospheric CO2 induces CO2 release from both the ocean and terrestrial biosphere, and to keep atmospheric CO2 at a lower level requires the removal of anthropogenic CO2 not only from the atmosphere, but from the ocean and land carbon reservoirs as well. The response of many variables of the Earth system, including temperature, ocean heat content, sea level, deep ocean acidity, and permafrost area and carbon, lags the decrease in atmospheric CO2 ranging from a few years to many centuries. A few centuries after atmospheric CO2 returns to the preindustrial level, sea level is still substantially higher than the preindustrial level, and permafrost continues losing CO2 to the atmosphere. Our study demonstrates that to offset previous positive CO2 emissions by atmospheric CO2 removal does not mean to offset climate consequence of positive CO2 emissions. Rapid and deep reduction in CO2 emissions is key to prevent and limit increasing risks from further warming. Our study provides new insights into the carbon cycle and climate system response to CO2 removal, which would help to assess future climate change and the associated impacts.

Carbon dioxide removal and solar radiation modification (SRM) are two classes of proposed climate intervention methods. A thorough understanding of climate system response to these methods calls for a good understanding of the carbon cycle response. In this study, we used an Earth system model to examine the response of global climate and carbon cycle to artificial ocean alkalinization (AOA), a method of CO2 removal, and reduction in solar irradiance that represents the overall effect of solar radiation modification. In our simulations, AOA is applied uniformly over the global ice-free ocean under the RCP8.5 scenario to bring down atmospheric CO2 to the level of RCP4.5, and SRM is applied uniformly over the globe under the RCP8.5 scenario to bring down global mean surface temperature to the level of RCP4.5. Our simulations show that with the same goal of temperature stabilization, AOA and SRM cause fundamentally different perturbations of the ocean and land carbon cycle. By the end of the 21st century, relative to the simulation of RCP8.5, AOA-induced changes in ocean carbonate chemistry enhances global oceanic CO2 uptake by 983 PgC and increases global mean surface ocean pH by 0.42. Meanwhile, AOA reduces land CO2 uptake by 79 PgC and reduces atmospheric CO2 concentration by 426 × 10−6. By contrast, relative to the simulation of RCP8.5, SRM has a minor effect on the oceanic CO2 uptake and ocean acidification. SRM-induced cooling enhances land CO2 uptake by 140 PgC and reduces atmospheric CO2 concentration by 63 × 10−6. A sudden termination of SRM causes a rate of temperature change that is much larger than that of RCP8.5. A sudden termination of AOA causes a rate of temperature change that is comparable to that of RCP8.5 and a rate of ocean acidification that is much larger than that of RCP8.5.

Background Anti-glomerular basement membrane (anti-GBM) disease is a rare but severe autoantibody-mediated immune disorder. The typical clinical presentation includes rapidly progressive glomerulonephritis and often concurrent pulmonary hemorrhage. The present study is aimed to investigate the therapeutic effects of rituximab either used alone or with other immunosuppressants.Methods Eight patients diagnosed with anti-GBM disease and treated with rituximab from 2014 to 2020 were retrospectively reviewed.Results Eight patients included 5 males and 3 females with a median age of 58.5 years. They all presented severe kidney injuries and 1 patient had lung hemorrhage. At diagnosis, the median of serum creatinine was 246 µmol/L (ranging from 91 to 850 µmol/L), with 3 patients requiring dialysis. All of them received corticosteroids and plasmapheresis. Rituximab was given as either standard four weekly doses or one pulse ranging from 100 to 600 mg. After a median follow-up of 34.5 months, kidney function was partially recovered or stabilized in 5/8 (62.5%) patients, free of dialysis. Anti-GBM antibodies remained undetected in all patients during follow-up. No severe adverse effect associated with rituximab was observed.Conclusion Rituximab may be an alternative therapy in the treatment of patient with severe or refractory anti-GBM disease.

IntroductionMacroalgae contain various polysaccharides that serve as nutrient sources Introduction: Macroalgae contain various polysaccharides that serve as nutrient sources for marine bacteria. Carbohydrate-active enzymes (CAZymes) are the primary feature of marine bacteria that utilize these polysaccharides. In this study, we describe Tamlana sp. S12, a novel strain of marine flavobacteria that can degrade alginate and Laminaria japonica biomass, isolated from the intestines of the sea cucumber Apostichopus japonicas collected at Weihai coast.MethodsWe sequenced the entire genome of strain S12 and constructed a phylogenetic tree using the core genome sequences of related strains. We determined the enzymatic activity of strain S12 using the DNS method and measured its growth curve under different carbon sources using spectrophotometry.ResultsStrain S12 degraded dehydrated L. japonica fragments as the sole nutrient source within 48h. Strain S12 harbors a diverse array of CAZymes at multiple polysaccharide utilization loci (PUL). One PUL encoding lyases from PL6, 7, and 17 families may be used for the degradation of alginate. Additionally, strain S12 harbors PULs encoding carrageenan- and agar-targeting CAZymes. Comparative analysis with related flavobacteria from Algibacter, Maribacter, and Zobellia showed shared CAZymes among these strains, potentially derived from a common ancestor and stably maintained within strains. Genomic signatures, algal degradation ability, and CAZyme patterns suggest that strain S12 has the potential to degrade complex algal polysaccharides.ConclusionThese results expand our knowledge of CAZymes and enrich our understanding of how marine Flavobacteriaceae adapt to marine algal polysaccharide environments. The availability of the genome of Tamlana sp. S12 will be beneficial for further analyses of marine Flavobacteriaceae.

PurposeOpioid-based anesthesia is a traditional form of anesthesia that has a significant analgesic effect; however, it can cause nausea, vomiting, delirium, and other side effects. Opioid-free anesthesia with dexmedetomidine and lidocaine has attracted widespread attention. This study aimed to compare the effects of opioid-free and opioid-based anesthesia (OFA and OBA, respectively) on postoperative recovery in patients who had undergone video-assisted thoracic surgery.MethodsEighty patients undergoing video-assisted thoracic surgery were assigned to receive either opioid-free anesthesia (OFA group) or opioid-based anesthesia (OBA group) according to random grouping. The primary outcome of the study was the quality of recovery-40 scores (QoR-40) 24 h postoperatively. The secondary outcome measure was numerical rating scale (NRS) scores at different times 48 h postoperatively. In addition to these measurements, other related parameters were recorded.ResultsPatients who received opioid-free anesthesia had higher QoR-40 scores (169.1 ± 5.1 vs. 166.8 ± 4.4, p = 0.034), and the differences were mainly reflected in their comfort and emotional state; however, the difference between the two groups was less than the minimal clinically important difference of 6.3. We also found that the NRS scores were lower in the OFA group than in the OBA group at 0.5 h (both p

Background and aimsNonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease with a high incidence, and the situation is not optimistic. Intestinal flora imbalance is strongly correlated with NAFLD pathogenesis. Zhishi Daozhi Decoction (ZDD) is a water decoction of the herbs used in the classical Chinese medicine prescription Zhishi Daozhi Pills. Zhishi Daozhi Pills has shown promising hepatoprotective and hypolipidemic properties, but its specific mechanism remains unclear.MethodsMice were fed on a high fat-rich diet (HFD) for ten weeks, and then the animals were administrated ZDD through oral gavage for four weeks. The serum liver function and blood lipid indexes of the mice were then tested using an automatic biochemical analyzer. H&E and Oil Red O staining were used to observe the pathological conditions of mice liver tissue, and 16S rRNA sequencing technology was used to analyze the changes in intestinal flora of mice. The concentration of short-chain fatty acids (SCFAs) in the gut of mice was analyzed by gas chromatography-mass spectrometry (GC-MS). The expression of tight junction (TJ) proteins between ileal mucosal epithelial cells was analyzed using the immunofluorescence technique.ResultsZDD was found to reduce the bodyweight of NAFLD mice, reduce serum TG, CHO, ALT, and AST levels, reduce fat accumulation in liver tissue, make the structure of intestinal flora comparable to the control group, and increase the concentration of intestinal SCFAs. It was also found to increase the expression of TJ proteins such as occludin and ZO-1, making them comparable to the control group.ConclusionsZDD has a therapeutic effect on NAFLD mice induced by HFD, which may act by optimizing the intestinal flora structure.

Abstract Background Anti-glomerular basement membrane disease (GBM) is an autoimmune disease caused by the deposition of circulating anti-GBM antibodies. Non-collagen region of α3 chain of type IV collagen (α3(IV)NC1) is one of the main target antigens, in which EA and EB are the most classical antigen epitopes. It has been reported that anti-GBM antibodies can be detected in HIV patients; however, its immunological characteristics are still unclear. Objectives In this study, the positive rate of the anti-GBM antibodies in HIV and the immunological characteristics of the target antigens were clarified. Methods A total of 93 HIV patients diagnosed in Beijing Youan Hospital from November 2017 to January 2018 were included. Enzyme-linked immunosorbent assay was used to measure the serum IgG autoantibodies specifically against GBM in these patients, as well as their subtypes and antigen spectra. Results It was found that five out of the 93 patients with HIV had low to moderate levels of anti-GBM antibodies. However, these patients presented with no clinical manifestation of any kidney injury or pulmonary hemorrhages. Compared with HIV patients with negative antibodies, there were no significant differences in gender, age, CD4+T cell count and HIV viral load. All sera of five patients recognized non-collagenous domain1 (NC1) of alpha 3 chain of type IV collagen [(α3(IV)NC1] as classic anti-GBM patients, followed by α5(IV)NC1. The antibodies against α3(IV)NC1 were IgG3 predominant, while these antibodies did not react with either of the classic epitopes on α3 (EA and EB). Conclusion These data suggest a distinct immunological profile of anti-GBM antibodies in patients with HIV, and might explain the non-pathogenic features of HIV associated anti-GBM antibodies.

The ladybird Coccinella septempunctata L., a predatory insect, serves as an excellent biological control agent against common agricultural pests. It undergoes a diapause phenomenon, during which a large amount of fat accumulates in the abdomen. A comprehensive analysis of this lipid accumulation can reveal the molecular mechanisms underlying diapause regulation, which can be exploited to improve the shipping and transport of the insect for agricultural applications. In this study, we compared the transcriptome of C. septempunctata during non-diapause, diapause, and post-diapause and screened four key genes related to lipid metabolism. The cDNA of these four relevant enzymes, acetyl-CoA carboxylase (ACC), long-chain fatty acid-CoA ligase (ACSL), elongase of very-long-chain fatty acids (ELO), and very-long-chain 3-oxoacyl-CoA reductase (KAR), were cloned using reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. Their expression profiles were analyzed during the preparation and maintenance phases of diapause and the post-diapause phase. The functions of these four key enzymes in diapause were further verified using RNA interference. All four genes were most closely related to the homeotic gene from Tribolium castaneum. The expression profiles of these four genes were significantly affected under diapause-inducing conditions; their expression level was the highest in the diapause preparation phase, and it gradually decreased with the diapause induction time. RNA interference showed that the target genes play important roles in fat storage during early diapause, and the decrease in their expression leads to a decrease in lipid content in C. septempunctata. These results indicate an important role of ACC, ACSL, ELO, and KAR in lipid accumulation. Our findings could help elucidate the production and accumulation of lipids by insects during the preparation for diapause and improve biological control.

Liver fibrosis: cleaning up injured mitochondria helps reverse tissue scarring Clearing away defective mitochondria helps destroy cells in the liver that contribute to tissue scarring; the signaling pathway involved offers a new therapeutic target. Hui-Qing Jiang and colleagues from the Hebei Institute of Gastroenterology in Shijiazhuang, China, induced liver fibrosis in mice and showed that as the animals recovered and the damage to their liver tissue was reversed, injured mitochondria were cleared from fibrosis-causing cells in tandem with the cells’ controlled destruction. Experimentally inhibiting the process of mitochondrial clearance also inhibited cell death and aggravated fibrotic scarring in the mice. The researchers identified a signaling pathway that regulates mitochondrial cleanup and, in turn, also controlled cell death. Targeting this pathway offer a potential new therapeutic strategy for reversing liver fibrosis in patients.

Acute lung injury (ALI), which is induced by renal ischemia-reperfusion (IR), is one of the leading causes of acute renal IR-related death. Obesity raises the frequency and severity of acute kidney injury (AKI) and ALI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) was employed to lessen the lung apoptosis led by renal IR and to evaluate whether TIIA combined with CsA could alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Hematoxylin-eosin (HE) staining was used to assess the histology of the lung injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used to assess apoptosis of the lung. Electron microscopy was used to assess mitochondrial morphology in lung cells. Arterial blood gas and pulmonary function were used to assess the external respiratory function. Mitochondrial function was used to assess the internal respiratory function and mitochondrial dynamics and biogenesis. Western blot (WB) was used to examine the PI3K/Akt/Bad pathway-related proteins. TIIA combined with CsA can alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

Three new Chinese species of the genus Mesonemoura (Plecoptera: Nemouridae), Mesonemoura dilatata Du & Ji, sp. nov., M. sichuanensis Du & Ji, sp. nov. and M. sinistracurva Du & Wang, sp. nov., are described and illustrated. Mesonemoura dilatata is characterized by the flagellum of the epiproct being long and curved, forming a swollen membranous apex. Mesonemoura sichuanensis is characterized by tergum 9 forming a pair of obtuse angles mid-posteriorly, and by the ventral sclerite of the epiproct being basally broad, 2 x the width of the dorsal sclerite. Mesonemoura sinistracurva is characterized by the presence of a long stylus that curves abruptly to the left as it leaves the tip of the epiproct. A key to the Chinese species of this genus is presented. [ABSTRACT FROM AUTHOR]

Four new species of the genus Amphinemura (Plecoptera: Nemouridae) were described from Sichuan, China with morphological descriptions and illustrations, i.e., A. gyracantha Ji & Du sp. nov., A. digitata Ji & Du sp. nov., A. spinellosa Du & Ji sp. nov., and A. qingchengshana Ji & Du sp. nov. A. gyracantha is similar to Amphinemura dispositspina Du & Wang, 2007 in the epiproct, but the morphology of the lateral arm of the epiproct and the median paraproct lobe of the new species is diagnostic. A. digitata is related to A. sclerotica Du and Zhou, 2007 in having a similar paraproct in the ventral view, but the epiproct of two new species is distinct. A. spinellosa is similar to A. lii Zhu and Yang, 2003 in the paraproct, but A. denticulat can be easily separated by inner lobe slightly sclerotized and outer lobe separated from median lobe. A. qingchengshana is related to A. claassenia Wu, 1935 in having a similar epiproct, but they differ mostly in the details of paraproct. [ABSTRACT FROM AUTHOR]

Two new species of the genus Amphinemura Ris from China are described and illustrated, i.e. A. annulata Du & Ji, sp. n. from Zhejiang, Shanxi, Shaanxi and Guizhou Province, and A. lingulata Du & Wang, sp. n. from Shaanxi and Sichuan Province. A. annulata is similar to A. tricintusidens Wang & Zhu in having an apical cavity of the epiproct, but the epiproct ventral sclerite and the median paraproct lobe of the two species are different. A. lingulata is related to A. didyma Zhu & Yang in having the similar epiproct, but they differ mostly in paraproct median and outer lobes. [ABSTRACT FROM AUTHOR]

This study determined the mitochondrial genome sequence of the stonefly, Kamimuria wangi. In order to investigate the relatedness of stonefly to other members of Neoptera, a phylogenetic analysis was undertaken based on 13 protein-coding genes of mitochondrial genomes in 13 representative insects. The mitochondrial genome of the stonefly is a circular molecule consisting of 16,179 nucleotides and contains the 37 genes typically found in other insects. A 10-bp poly-T stretch was observed in the A+T-rich region of the K. wangi mitochondrial genome. Downstream of the poly-T stretch, two regions were located with potential ability to form stem-loop structures; these were designated stem-loop 1 (positions 15848–15651) and stem-loop 2 (15965–15998). The arrangement of genes and nucleotide composition of the K. wangi mitogenome are similar to those in Pteronarcys princeps, suggesting a conserved genome evolution within the Plecoptera. Phylogenetic analysis using maximum likelihood and Bayesian inference of 13 protein-coding genes supported a novel relationship between the Plecoptera and Ephemeroptera. The results contradict the existence of a monophyletic Plectoptera and Plecoptera as sister taxa to Embiidina, and thus requires further analyses with additional mitogenome sampling at the base of the Neoptera. [ABSTRACT FROM AUTHOR]

Background: Atypical cases of anti-glomerular basement membrane (GBM) disease had absent circulating antibodies but linear IgG deposits along GBM in the kidneys. Herein, we reported the clinical-pathological features and outcome of these rare cases.Methods: Linear IgG deposit along GBM were examined by immunofluorescence on renal specimens, with exclusion of diabetic kidney disease. Circulating anti-GBM antibodies were tested by commercial ELISA assay. Clinical, pathological and follow-up data were retrospectively analyzed.Results: From 2013 to 2018, a total of 60 patients were diagnosed as atypical anti-GBM disease. They had a male predominance, with an average age of 51.7 ± 15.6 years. Three (5.0%) patients had alveolar hemorrhage. Forty five percent of them presented with acute kidney disease. All patients had linear IgG deposit along GBM, some in addition on tubular basement membrane and/or Bowmans' capsules. C3 deposition was found in 65.0% of the patients. 41.7% (25/60) of the patients showed crescent formation and the percentage of crescent was (34.7 ± 23.5)% in those patients. They had higher prevalence of hematuria and C3 deposit, higher levels of serum creatinine, worse renal and patient survival than those without crescent (P < 0.05). During the follow-up of 35.7 ± 21.4 months, 14 (23.3%) patients progressed to ESRD. The serum creatinine on diagnosis [per 200 μmol/L increase, HR (95% CI): 2.663 (1.372, 5.172), P = 0.004], serum C3 [per 0.1 g/L increase, HR (95% CI): 0.689(0.483, 0.984), P = 0.040] and the intensity of kidney C3 staining [per 1+ increase, HR (95% CI): 2.770 (1.115, 6.877), P = 0.028] were independent predictive factors for kidney outcome. Nine (15.0%) patients died of all causes.Conclusions: Atypical anti-GBM disease manifested milder kidney injury and scarce pulmonary hemorrhage compared to the classical cases. Though heterogeneous, a substantial number of the patients had complement activation and crescent formation. Patients having crescents presented with more severe clinical course and worse outcomes. The poor kidney and patient prognosis emphasize prompt interventions from physicians. The immunosuppressive intervention was not associated with kidney or patient outcome. Further studies are needed to address the optimal therapeutic regimen.

Background: Cerebral cavernous malformation (CCM), especially the familial form, is a relatively rare congenital and occult vascular disease of the central nervous system. The familial form of CCM has been linked to three different genes: KRIT1 / CCM1, MGC4607 / CCM2 , and PDCD10 / CCM3 ; however, the genetic basis of CCM is not well understood. The PDCD10 / CCM3 is the most recent gene to be identified that results in worse clinical symptoms. Early diagnosis and treatment is important for patient prognosis. Case report: The proband is a 38-year-old male who has been suffering from weakness in the limbs for 7 months. Investigation of his family history revealed that his mother also suffered from limbs paralysis and had been bedridden for a long time. His older brother suffered from headache for years, whereas his younger brother was asymptomatic. Brain computed tomography analysis of all family members showed multiple high-density shadows. Subsequently, magnetic resonance imaging analysis identified more prominent and similar multiple intracranial lesions in all family members. The lesions were hypo-intense, or showed mixed signs on T1-weighted imaging, and were significantly more intense on T2-weighted imaging. To understand the genetic basis of the disease in the family, DNA sequencing analysis was performed. A novel deletion mutation in the PDCD10 / CCM3 gene was identified in the proband and his relatives. The deletion resulted in a frameshift mutation and premature termination of translation of the protein, and potentially caused the disease in this family. Conclusions: Our study identified a novel PDCD10 / CCM3 heterozygous deletion (c.165delT) associated with CCM. This finding expands the CCM gene mutation profile, which will be beneficial for genetic counseling and clinical therapy.

Salvia miltiorrhiza has exhibited various bioactive functions due to the existence of polysaccharides, hydrophilic phenolic acids, diterpenoid quinones, and essential oils. However, little research has reported the glycoprotein preparation and corresponding bioactivities. In this study, the water-soluble glycoprotein from S. miltiorrhiza roots was firstly isolated with the extraction process optimized by response surface methodology, and then, the preliminary structural properties, and the antioxidant and immunoregulatory activities were investigated. Results showed that the extraction conditions for higher extraction yields were identified as follows: ultrasonic power of 220 W, ultrasonic time of 2.0 h, extraction temperature of 60 °C, liquid/solid ratio of 20 mL/g, and the glycoprotein yields of 1.63 ± 0.04%. Structural analysis showed that the glycoprotein comprised protein and polysaccharide (contents of 76.96% and 20.62%, respectively), with an average molecular weight of 1.55 × 105 Da. Besides, bioactivities analysis showed that the glycoprotein presented strong scavenging effects on multiple free radicals, and effectively enhanced the antioxidant enzyme activities and immunological indicators in cyclophosphamide-induced immunocompromised mice dose-dependently. These data demonstrated that S. miltiorrhiza glycoprotein presented the potential to be a novel edible functional compound, and could be practically applied in the food industry.

54 human genes were selected as test targets for parallel cloning, expression, purification and crystallization. Proteins from these genes were selected to have a molecular weight of between 14 and 50 kDa, not to have a high percentage of hydrophobic residues (i.e. more likely to be soluble) and to have no known crystal structures and were not known to be subunits of heterocomplexes. Four proteins containing transmembrane regions were selected for comparative tests. To date, 44 expression clones have been constructed with the Gateway™ cloning system (Invitrogen, The Netherlands). Of these, 35 clones were expressed as recombinant proteins in Escherichia coli strain BL21 (DE3)-pLysS, of which 12 were soluble and four have been purified to homogeneity. Crystallization conditions were screened for the purified proteins in 96-well plates under oil. After further refinement with the same device or by the hanging-drop method, crystals were grown, with needle, plate and prism shapes. A 2.12 Å data set was collected for protein NCC27. The results provide insights into the high-throughput target selection, cloning, expression and crystallization of human genomic proteins. [ABSTRACT FROM AUTHOR]

We construct a fluorescent supramolecular system (TPE-Q4⊂ DSP5) of excellent tolerance to a wide range of pH by the facile self-assembly of a new pillar[5]arene bearing disulfonated arms (DSP5) with an AIE-active tetraphenylethene-based tetratopic guest bearing four quaternary ammonium binding sites (TPE-Q4), which exhibits strong blue emission even in dilute aqueous solutions along with much higher quantum yield and longer fluorescence lifetime than TPE-Q4 itself. This appreciable property can be attributed to the supramolecular assembly-induced emission (SAIE) mechanism endowed by the host-guest inclusion complexation based on synthetic macrocycles. Remarkably, the enhanced fluorescence of the supramolecular assembly is quenched efficiently and exclusively by ferric ions in water with a high Stern–Volmer formula constant of 1.3 × 105 mol-1, demonstrating the excellent cation selectivity and visualized responsiveness in ion sensing and detection.

The q-deformation of the infinite-dimensional n-algebras is investigated. Based on the structure of the q-deformed Virasoro–Witt algebra, we derive a nontrivial q-deformed Virasoro–Witt n-algebra which is nothing but a sh-n-Lie algebra. Furthermore in terms of the pseud-differential operators, we construct the (co)sine n-algebra and the q-deformed SDiff(T2) n-algebra. We find that they are the sh-n-Lie algebras for the n even case. In terms of the magnetic translation operators, an explicit physical realization of the (co)sine n-algebra is given.

BACKGROUND:The autoantigen of anti-glomerular basement membrane (GBM) disease has been identified as the non-collagenous domain 1 of α3 chain of type IV collagen, α3(IV)NC1. Our previous study revealed a peptide on α3(IV)NC1 as a major linear epitope for B cells and potentially nephrogenic, designated as P14 (α3129-150). This peptide has also been proven to be the epitope of auto-reactive T cells in anti-GBM patients. This study was aimed to further characterize the critical motif of P14. METHODS:16 patients with anti-GBM disease and positive anti-P14 antibodies were enrolled. A set of truncated and alanine substituted peptides derived from P14 were synthesized. Circulating antibodies against the peptides were detected by enzyme linked immunosorbent assay (ELISA). RESULTS:We found that all sera with anti-P14 antibodies reacted with the 13-mer sequence in the C-terminus of P14 (P14c) exclusively. The level of antibodies against P14 was highly correlated with the level of antibodies against P14c (r=0.970, P

Linear deposition of IgG and complement 3 (C3) along glomerular basement membrane (GBM) is generally revealed in the kidneys of human anti-GBM disease. Our recent studies demonstrated the pathogenic role of complement activation in renal damage of this disease. However, the pathways of complement activation were still paradoxical. In this study, renal biopsy tissues from 10 patients with anti-GBM disease were used to investigate the pathways of complement activation by detecting the deposition of various complement components, including C1q, factor B, factor P (properdin), mannose-binding lectin (MBL), C3d, C4d and C5b-9, using immunohistochemistry and immunofluorescence. We found that C1q, factor B, properdin, C3d, C4d and C5b-9 were detected in all the glomeruli of our patients, along GBM with a linear and/or granular staining pattern. Furthermore, C1q, factor B and properdin co-localized well with C5b-9. The properdin also co-localized well with C3d. However, the deposition of MBL was diffusive in mesangium, GBM, Bowman's capsule and within crescents and was not co-localized with C5b-9 but partially co-localized with C4d. The intensity of factor B deposition (3.3 vs. 1.2, P

In the title compound, C30H24N4O2S, the four phenyl rings of the substituent groups make dihedral angles of 88.1 (2), 81.0 (2), 21.4 (2) and 44.6 (2)° with the triazole group. An intramolecular hydroxy–imino O—H...N hydrogen bond results in the formation of an approximately planar (r.m.s deviation = 0.0230 Å) six-membered ring.

In the title molecule, C31H26N4O2S, the phenyl ring attached to the 1,2,4-triazole ring forms dihedral angles of 65.4 (2), 63.4 (2) and 62.2 (2)° with the other three rings. The 1,2,4-triazole ring makes dihedral angles of 78.0 (2), 87.9 (2), 24.9 (2) and 62.8 (2)° with three phenyl rings and the methoxyphenyl ring.

There are two crystallographically independent molecules (A and B) in the asymmetric unit of the title compound, C25H22N4O2S, with almost identical molecular conformations. The hydroxyphenyl ring plane and the 1,2,4-triazole ring form dihedral angles of 17.1 (2) and 7.4 (2)° in A and B, respectively. The dihedral angles between 1,2,4-triazole ring and the other two phenyl rings are 89.6 (3) and 83.3 (2)° in molecule A, and 89.2 (3) and 82.2 (2)° in molecule B. One intramolecular O—H...N hydrogen bond is present in each molecule. Weak intermolecular C—H...O hydrogen bonds consolidate the crystal packing.

In the title molecule, C24H21ClN4OS, the 1,2,4-triazole ring forms dihedral angles of 37.2 (2), 71.9 (2) and 84.9 (2) ° with the three benzene rings. In the crystal, weak intermolecular N—H...S hydrogen bonds link the molecules into centrosymmetric dimers.

In the crystal structure of the title compound, C5H3Cl3N4S, two molecules related by a centre of symmetry demonstrate extremely short intermolecular S...N contacts of 2.783 (2) Å. The crystal packing also exhibits π–π interactions indicated by a short distance of 3.340 (1) Å between the centroids of the triazole rings of neighbouring molecules.

This study determined the mitochondrial genome sequence of the stonefly, Kamimuria wangi. In order to investigate the relatedness of stonefly to other members of Neoptera, a phylogenetic analysis was undertaken based on 13 protein-coding genes of mitochondrial genomes in 13 representative insects. The mitochondrial genome of the stonefly is a circular molecule consisting of 16,179 nucleotides and contains the 37 genes typically found in other insects. A 10-bp poly-T stretch was observed in the A+T-rich region of the K. wangi mitochondrial genome. Downstream of the poly-T stretch, two regions were located with potential ability to form stem-loop structures; these were designated stem-loop 1 (positions 15848-15651) and stem-loop 2 (15965-15998). The arrangement of genes and nucleotide composition of the K. wangi mitogenome are similar to those in Pteronarcys princeps, suggesting a conserved genome evolution within the Plecoptera. Phylogenetic analysis using maximum likelihood and Bayesian inference of 13 protein-coding genes supported a novel relationship between the Plecoptera and Ephemeroptera. The results contradict the existence of a monophyletic Plectoptera and Plecoptera as sister taxa to Embiidina, and thus requires further analyses with additional mitogenome sampling at the base of the Neoptera.