Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Plant-made vaccines against viral diseases in humans and farm animals.

Plants provide not only food and feed, but also herbal medicines and various raw materials for industry. Moreover, plants can be green factories producing high value bioproducts such as biopharmaceuticals and vaccines. Advantages of plant-based production platforms include easy scale-up, cost effectiveness, and high safety as plants are not hosts for human and animal pathogens. Plant cells perform many post-translational modifications that are present in humans and animals and can be essential for biological activity of produced recombinant proteins. Stimulated by progress in plant transformation technologies, substantial efforts have been made in both the public and the private sectors to develop plant-based vaccine production platforms. Recent promising examples include plant-made vaccines against COVID-19 and Ebola. The COVIFENZ® COVID-19 vaccine produced in Nicotiana benthamiana has been approved in Canada, and several plant-made influenza vaccines have undergone clinical trials. In this review, we discuss the status of vaccine production in plants and the state of the art in downstream processing according to good manufacturing practice (GMP). We discuss different production approaches, including stable transgenic plants and transient expression technologies, and review selected applications in the area of human and veterinary vaccines. We also highlight specific challenges associated with viral vaccine production for different target organisms, including lower vertebrates (e.g., farmed fish), and discuss future perspectives for the field.

Research progress on electrical impedance tomography in pulmonary perfusion / 生物医学工程学杂志

Electrical impedance tomography (EIT) is an emerging technology for real-time monitoring based on the impedance differences of different tissues and organs in the human body. It has been initially applied in clinical research as well as disease diagnosis and treatment. Lung perfusion refers to the blood flow perfusion function of lung tissue, and the occurrence and development of many diseases are closely related to lung perfusion. Therefore, real-time monitoring of lung perfusion is particularly important. The application and development of EIT further promote the monitoring of lung perfusion, and related research has made great progress. This article reviews the principles of EIT imaging, lung perfusion imaging methods, and their clinical applications in recent years, with the aim of providing assistance to clinical and scientific researchers.

Efficient cellular and humoral immune response and production of virus-neutralizing antibodies by the Hepatitis B Virus S/preS116-42 antigen.

Despite the availability of improved antiviral therapies, infection with Hepatitis B virus (HBV) remains a3 significant health issue, as a curable treatment is yet to be discovered. Current HBV vaccines relaying on the efficient expression of the small (S) envelope protein in yeast and the implementation of mass vaccination programs have clearly contributed to containment of the disease. However, the lack of an efficient immune response in up to 10% of vaccinated adults, the controversies regarding the seroprotection persistence in vaccine responders and the emergence of vaccine escape virus mutations urge for the development of better HBV immunogens. Due to the critical role played by the preS1 domain of the large (L) envelope protein in HBV infection and its ability to trigger virus neutralizing antibodies, including this protein in novel vaccine formulations has been considered a promising strategy to overcome the limitations of S only-based vaccines. In this work we aimed to combine relevant L and S epitopes in chimeric antigens, by inserting preS1 sequences within the external antigenic loop of S, followed by production in mammalian cells and detailed analysis of their antigenic and immunogenic properties. Of the newly designed antigens, the S/preS116-42 protein assembled in subviral particles (SVP) showed the highest expression and secretion levels, therefore, it was selected for further studies in vivo. Analysis of the immune response induced in mice vaccinated with S/preS116-42- and S-SVPs, respectively, demonstrated enhanced immunogenicity of the former and its ability to activate both humoral and cellular immune responses. This combined activation resulted in production of neutralizing antibodies against both wild-type and vaccine-escape HBV variants. Our results validate the design of chimeric HBV antigens and promote the novel S/preS1 protein as a potential vaccine candidate for administration in poor-responders to current HBV vaccines.

Successful Production and Ligninolytic Activity of a Bacterial Laccase, Lac51, Made in Nicotiana benthamiana via Transient Expression.

Giant panda could have bamboo as their exclusive diet for about 2 million years because of the contribution of numerous enzymes produced by their gut bacteria, for instance laccases. Laccases are blue multi-copper oxidases that catalyze the oxidation of a broad spectrum of phenolic and aromatic compounds with water as the only byproduct. As a "green enzyme," laccases have potential in industrial applications, for example, when dealing with degradation of recalcitrant biopolymers, such as lignin. In the current study, a bacterial laccase, Lac51, originating from Pseudomonas putida and identified in the gut microbiome of the giant panda's gut was transiently expressed in the non-food plant Nicotiana benthamiana and characterized. Our results show that recombinant Lac51 exhibits bacterial laccase properties, with optimal pH and temperature at 7-8 and 40°C, respectively, when using syringaldazine as substrate. Moreover, we demonstrate the functional capability of the plant expressed Lac51 to oxidize lignin using selected lignin monomers that serve as substrates of Lac51. In summary, our study demonstrates the potential of green and non-food plants as a viable enzyme production platform for bacterial laccases. This result enriches our understanding of plant-made enzymes, as, to our knowledge, Lac51 is the first functional recombinant laccase produced in plants.

Research Progress of Lipid Metabolism Reprogramming in Prostate Cancer / 肿瘤防治研究

Metabolism reprogramming plays an important role in the process of tumor occurrence and development, and provides the necessary material basis for tumor cells. It can change the metabolic patterns of amino acids, glucose and fatty acids in tumor cells, which is one of the hallmark features of tumors. At present, it is shown that most tumors tend to take advantage of glycolysis for energy resource. In contrast, studies have shown that prostate cancer cells dependent more on the fatty acid oxidation pathway for metabolic reprogramming to obtain energy substances. Therefore, it is of great significance to understand the relation between key enzymes of lipid metabolism and regulatory genes for early diagnosis, targeted treatment and better prognosis of prostate cancer.

Retrospective study on Jinghua Weikang capsule combined with Bifidobacterium in the treatment of spleen-somach damp-heat syndrome featured by helicobacter pylori infection with low count / 国际中医中药杂志

Objective:To investigate the clinical efficacy of Jinghua Weikang capsule combined with Bifidobacterium for curing patients featured by spleen-stomach damp-heat syndrome and Helicobacter pylori (Hp) infection with low DOB values.Methods:To enroll 130 cases who were admitted to the Digestion Center of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from March 2019 to March 2020. According to the treaatment protocols, the quadruple therapy group and dual therapy group, each had 65 patients. The quadruple therapy group had two different treatment protocols, 34 cases with Rabeprazole sodium enteric-coated tablet, Bismuth potassium citrate capsule, Amoxicillin capsule, and Clarithromycin, the other one had 31 cases with Rabeprazole sodium enteric-coated tablet, Bismuth potassium citrate capsule, Amoxicillin capsule, and Levofloxacin tablets. The Dual therapy group was treated with Jinghua Weikang capsule combined with Bifidobacterium. As for quadruple therapy group, 14 days was a course of treatment, while28 days was a course of treatment for dual therapy group. The two groups were treated for one course, respectively. The TCM syndromes were scored before and after treatment. After 4-weeks long drug withdrawal, all cases were reexamined via 13C-UBT. The Hp eradication rate, efficacy evaluation and adverse reactions were compared between both groups.Results:The eradication rate was 90.8% (59/65) in quadruple therapy group and 78.5% (51/65) in dual therapy group. There was no statistical difference between two groups ( χ２=3.78, P=0.052). As for quadruple therapy group, the eradication rate was 91.2% (31/34) in Protocol One and 90.3% (28/31) in Protocol Two. There was no statistical difference between two protocols ( χ２=0.01, P=0.906). After treatment, the TCM syndrome score of quadruple therapy group [(7.02±0.89) vs. (6.51±0.85), Z=-3.01], was significantly higher than that of dual therapy group ( P<0.01). The total effective rate was 93.9% (61/65) in dual therapy group and 78.5% (51/65) in quadruple therapy group. There was statistically significantly difference between two groups ( χ２=6.45, P=0.011). The adverse reactions was 24.6% (16/65) in quadruple therapy group and 6.2% (4/65) in dual therapy group. There was statistically significantly difference in two groups ( χ２=8.51, P=0.004). Conclusions:The Jinghua Weikang capsule combined with Bifidobacterium had curative effects on Hp infected patients with low DOB values. It could improve TCM Syndromes with little adverse reactions.

Corneal confocal microscopy and its application in ischemic cerebrovascular disease / 国际脑血管病杂志

Corneal confocal microscopy (CCM) is an in vivo corneal imaging technique, which can directly quantify corneal nerve fibers in real time. It has the characteristics of non-invasive, objective and high sensitivity. CCM can not only be used for the diagnosis and treatment evaluation of corneal diseases, but also plays an important role in the diagnosis and prognosis evaluation of some peripheral and central nervous system diseases, such as diabetes peripheral neuropathy and Parkinson's disease. In addition, the changes of corneal nerve fibers can indirectly reflect the severity of ischemic cerebrovascular disease, and it is expected to become a noninvasive bioimaging marker of ischemic cerebrovascular disease. This article reviews CCM and its application in ischemic cerebrovascular disease, in order to provide better means for early diagnosis and prognosis evaluation of ischemic cerebrovascular disease.

Establish a diagnosis differential model for IgA nephropathy and non-IgA nephropathy by machine learning / 中华检验医学杂志

Objective:To establish a differential diagnosis model for IgA nephropathy and non-IgA nephropathy based on machine learning algorithms.Methods:Retrospective study adopted,from 2019 to 2020,260 patients were referred to the Department of Nephrology at the First Affiliated Hospital of Kunming Medical University, the First People′s Hospital in Yunnan province, and Yan′an Hospital of Kunming city. All patients were diagnosed by renal pathology, 130 cases of primary IgA nephropathy, the 130 cases of non-IgA nephropathy. Collection of materials, including gender and age, 28 clinical data, and routine laboratory test results,the sex ratio of IgA nephropathy group and non-IgA nephropathy group were 59∶71 and 64∶66 respectively, the ages were 37.20 (21.89, 53.78) and 43.30 (27.77, 59.18) years, respectively. 260 patients were divided into a training set (70%, 182 cases) and a test set (30%, 78 cases). Using the decision tree, random forests, support vector machine, extreme gradient boosting to establish a differential diagnosis model for IgA nephropathy and non-IgA nephropathy. Based on the true positive rate, true negative rate, false-positive rate, false-negative rate, accuracy, subjects features work area under the curve(AUC), the precision ratio, recall ratio, and F1 score, comprehensively evaluate the performance of each model, finally, the best performance of the model was chosen. Using SPSS 25.0 to analyze the data, P<0.05 was considered to be statistically significant. Results:The accuracy of the decision tree, support vector machine, random forests and extreme gradient boosting establish differential diagnosis model was 67.95%, 70.51%, 80.77% and 83.33%, respectively; AUC values was 0.74, 0.76, 0.80 and 0.83; Judgment for primary IgA nephropathy F1 score was 0.73, 0.72, 0.80 and 0.83, respectively. The efficiency of the extreme gradient boosting model based on the above evaluation indicators is the highest, its diagnosis of IgA nephropathy of the sensitivity and specificity respectively 89% and 79%. The variable importance from high to low was blood albumin, IgA/C3, serum creatinine, age, urine protein, urine albumin, high-density lipoprotein cholesterol, urea.Conclusion:The differential diagnosis model for IgA nephropathy was established successfully and non-IgA nephropathy and the efficiency performance of the extreme gradient boosting algorithm was the best.

Challenges and Prospects of Plant-Derived Oral Vaccines against Hepatitis B and C Viruses.

Hepatitis B and C viruses chronically affect approximately 3.5% of the global population, causing more than 800,000 deaths yearly due to severe liver pathogenesis. Current HBV vaccines have significantly contributed to the reduction of chronic HBV infections, supporting the notion that virus eradication is a feasible public health objective in the near future. In contrast to HBV, a prophylactic vaccine against HCV infection is not available yet; however, intense research efforts within the last decade have significantly advanced the field and several vaccine candidates are shortlisted for clinical trials. A successful vaccine against an infectious disease of global importance must not only be efficient and safe, but also easy to produce, distribute, administer, and economically affordable to ensure appropriate coverage. Some of these requirements could be fulfilled by oral vaccines that could complement traditional immunization strategies. In this review, we discuss the potential of edible plant-based oral vaccines in assisting the worldwide fight against hepatitis B and C infections. We highlight the latest research efforts to reveal the potential of oral vaccines, discuss novel antigen designs and delivery strategies, as well as the limitations and controversies of oral administration that remain to be addressed to make this approach successful.

Plant-Produced Vaccines: Future Applications in Aquaculture.

Aquaculture has undergone rapid development in the past decades. It provides a large part of high-quality protein food for humans, and thus, a sustainable aquaculture industry is of great importance for the worldwide food supply and economy. Along with the quick expansion of aquaculture, the high fish densities employed in fish farming increase the risks of outbreaks of a variety of aquatic diseases. Such diseases not only cause huge economic losses, but also lead to ecological hazards in terms of pathogen spread to marine ecosystems causing infection of wild fish and polluting the environment. Thus, fish health is essential for the aquaculture industry to be environmentally sustainable and a prerequisite for intensive aquaculture production globally. The wide use of antibiotics and drug residues has caused intensive pollution along with risks for food safety and increasing antimicrobial resistance. Vaccination is the most effective and environmentally friendly approach to battle infectious diseases in aquaculture with minimal ecological impact and is applicable to most species of farmed fish. However, there are only 34 fish vaccines commercially available globally to date, showing the urgent need for further development of fish vaccines to manage fish health and ensure food safety. Plant genetic engineering has been utilized to produce genetically modified crops with desirable characteristics and has also been used for vaccine production, with several advantages including cost-effectiveness, safety when compared with live virus vaccines, and plants being capable of carrying out posttranslational modifications that are similar to naturally occurring systems. So far, plant-derived vaccines, antibodies, and therapeutic proteins have been produced for human and animal health. However, the development of plant-made vaccines for animals, especially fish, is still lagging behind the development of human vaccines. The present review summarizes the development of fish vaccines currently utilized and the suitability of the plant-production platform for fish vaccine and then addresses considerations regarding fish vaccine production in plants. Developing fish vaccines by way of plant biotechnology are significant for the aquaculture industry, fish health management, food safety, and human health.

Degradation of difenoconazole in water and soil: Kinetics, degradation pathways, transformation products identification and ecotoxicity assessment.

Difenoconazole is a widely used triazole fungicide that has been frequently detected in the environment, but comprehensive study about its environmental fate and toxicity of potential transformation products (TPs) is still lacking. Here, laboratory experiments were conducted to investigate the degradation kinetics, pathways, and toxicity of transformation products of difenoconazole. 12, 4 and 4 TPs generated by photolysis, hydrolysis and soil degradation were identified via UHPLC-QTOF/MS and the UNIFI software. Four intermediates TP295, TP295A, TP354A and TP387A reported for the first time were confirmed by purchase or synthesis of their standards, and they were further quantified using UHPLC-MS/MS in all tested samples. The main transformation reactions observed for difenoconazole were oxidation, dechlorination and hydroxylation in the environment. ECOSAR prediction and laboratory tests showed that the acute toxicities of four novel TPs on Brachydanio rerio, Daphnia magna and Selenastrum capricornutum are substantially lower than that of difenoconazole, while all the TPs except for TP277C were predicted chronically very toxic to fish, which may pose a potential threat to aquatic ecosystems. The results are important for elucidating the environmental fate of difenoconazole and assessing the environmental risks, and further provide guidance for scientific and reasonable use.

Pollution by Antibiotics and Antimicrobial Resistance in LiveStock and Poultry Manure in China, and Countermeasures.

The demand for animal protein has increased considerably worldwide, especially in China, where large numbers of livestock and poultry are produced. Antibiotics have been widely applied to promote growth and prevent diseases. However, the overuse of antibiotics in animal feed has caused serious environmental and health risks, especially the wide spread of antimicrobial resistance (AMR), which seriously affects animal and human health, food safety, ecosystems, and the sustainable future development of animal protein production. Unfortunately, AMR has already become a worldwide challenge, so international cooperation is becoming more important for combatting it. China's efforts and determination to restrict antibiotic usage through law enforcement and effective management are of significance. In this review, we address the pollution problems of antibiotics; in particular, the AMR in water, soil, and plants caused by livestock and poultry manure in China. The negative impact of widespread and intensive use of antibiotics in livestock production is discussed. To reduce and mitigate AMR problems, we emphasize in this review the development of antibiotic substitutes for the era of antibiotic prohibition.

Propionate induces intestinal oxidative stress via Sod2 propionylation in zebrafish.

Propionate and propionyl-CoA accumulation have been associated with the development of mitochondrial dysfunction. In this study, we show that propionate induces intestinal damage in zebrafish when fed a high-fat diet (HFD). The intestinal damage was associated with oxidative stress owing to compromised superoxide dismutase 2 (Sod2) activity. Global lysine propionylation analysis of the intestinal samples showed that Sod2 was propionylated at lysine 132 (K132), and further biochemical assays demonstrated that K132 propionylation suppressed Sod2 activity. In addition, sirtuin 3 (Sirt3) played an important role in regulating Sod2 activity via modulating de-propionylation. Finally, we revealed that intestinal oxidative stress resulting from Sod2 propionylation contributed to compositional change of gut microbiota. Collectively, our results in this study show that there is a link between Sod2 propionylation and oxidative stress in zebrafish intestines and highlight the potential mechanism of intestinal problems associated with high propionate levels.

The impact of lymph node dissection on survival in patients with clinical early-stage ovarian cancer / 부인종양

Objective@#To estimate the impact of lymph node dissection on survival in patients with apparent early-stage epithelial ovarian cancer (EOC). @*Methods@#We conducted a retrospective review of patients with clinical stage I–II EOC. All patients underwent primary surgery at Sun Yat-sen University Cancer Center between January 2003 and December 2015. Demographic features and clinicopathological information as well as perioperative adverse events were investigated, and survival analyses were performed. @*Results@#A total of 400 ovarian cancer patients were enrolled, and patients were divided into 2 groups: 81 patients did not undergo lymph node resection (group A), and 319 patients underwent lymph node dissection (group B). In group B, the median number of removed nodes per patient was 25 (21 pelvic and 4 para-aortic nodes). In groups A and B, respectively, the 5-year progression-free survival (PFS) rates were 83.3% and 82.1% (p=0.305), and the 5-year overall survival (OS) rates were 93.1% and 90.9% (p=0.645). The recurrence rate in the retroperitoneal lymph nodes was not associated with lymph node dissection (p=0.121).The median operating time was markedly longer in group B than in group A (220 minutes vs. 155 minutes, p<0.001), and group B had a significantly higher incidence of lymph cysts at discharge (32.9% vs. 0.0%, p<0.001). @*Conclusion@#In patients with early-stage ovarian cancer, lymph node dissection was not associated with a gain in OS or PFS and was associated with an increased incidence of perioperative adverse events.

Effects of abdominal obesity on cognitive status in patients with moderate to severe of obstructive sleep apnea syndrome / 中华老年医学杂志

Objective:To observe the effects of abdominal obesity on cognitive status in patients with obstructive sleep apnea syndrome(OSAS).Methods:150 cases with moderate to severe OSAS patients were enrolled in this prospective case-control study in the Department of Neurology of Beijing Luhe Hospital Affiliated to Capital Medical University from June 2016 to September 2020.According to whether abdominal obesity was complicated, the patients were divided into non-abdominal obesity group(n=31)and abdominal obesity group(n=119). The cognitive function of the patients was evaluated by Montreal Cognitive Assessment(Mo-CA)scale and Symbol Digit Modalities Test(SDMT)in the two groups, and the independent influencing factors of each cognitive function were determined by linear regression.Two factors Analysis of Variance(ANOVA)was used to analyze the main effects and interactions of Apnea Hypopnea Index(AHI)and abdominal obesity on various cognitive functions.Results:Compared with the non-abdominal obesity group, the body mass index, neck circumference, waist circumference, hip circumference, AHI, minimum oxygen saturation and oxygen de-saturation index(ODI)were significantly higher in the abdominal obesity group(all P<0.01). Before correction for any factors, the total score of Mo-CA, visual space and executive score and language score were lower in abdominal obesity group than in non-abdominal obesity group( P<0.01). After adjusting for gender, age, years of education, smoking history, drinking history, AHI and other factors, there were still significant differences in visual space, executive score and language score between the two groups( P<0.05), but there was no significant difference in the total score of Mo-Ca( P>0.05). The correct number of SDMT(40.4±14.5)was lower in non-abdominal obesity group than in abdominal obesity group(44.4±9.0), but the difference was not statistically significant( t=1.887, P>0.05). After adjusting for gender, age, years of education, smoking history, and drinking history, there was still no significant difference in AHI and other factors between the two groups( P>0.05). Regression analysis results showed that independent influencing factors of the total Mo-CA score were age, education, abdominal obesity, and AHI>30( β=-0.174, 0.213, 0.011, 0.158, respectively all P<0.05); the independent influencing factors of visual space and execution ability were the years of education and the abdominal obesity( β=0.182, -0.038, P<0.01); the independent influence factors of naming were gender( β=-0.176, P<0.01); independent influencing factors of attention were age( β=-0.159, P<0.01); independent influencing factors of language were abdominal obesity( β=-0.203, P<0.01); independent influences factors for abstract thinking ability were the length of education( β=0.204, P<0.01); independent influencing factors for delay recall were age, years of education and AHI>30(βvalues were -0.206, -0.125, and -0.174, respectively, all P<0.05, respectively); independent influencing factors for SDMT correct number were age, years of education(β values were -0.177, 0.153, respectively, all P<0.01, respectively). Interaction analysis results showed that there was an interaction between AHI and abdominal obesity in language score( P<0.05). Conclusions:Abdominal obesity can impair the visuospatial and executive abilities as well as language ability in moderate to severe obstructive sleep apnea patients.And there is an interaction between apnea-hypopnea index and MO-CA scores in language ability.

Application effect of family integrated care combined with intelligent health education platform in health education of elderly patients with stroke / 中华健康管理学杂志

Objective:To explore the effect of family integrated care (FIC) combined with intelligent health education platform in health education for elderly patients with stroke.Methods:Eighty patients with stroke were included from the Department of Neurology of the Second Affiliated Hospital of Chongqing Medical University from June 2019 to May 2020. They were divided into the experimental group and the control group ( n=40, respectively) by the random number table method. Patients in the control group received routine FIC in the Department of Neurology. Additional intelligent health education platform was provided for the experimental group to carry out intensive education. The modified Barthel index scale, self-care compliance scale and hospital anxiety and depression scale (HADS) were used before and after the intervention to evaluate patient′s self-care ability, self-care compliance and the degree of anxiety and depression. Results:Finally, 39 patients in the experimental group (1 case lost to followed-up) and 37 patients in the control group (3 cases lost to followed-up) completed the study. After the intervention, the scores of the modified Barthel index and self-care compliance scale of the experimental group were significantly higher than those of the control group [(65.9±12.6) vs (60.1±11.9) points, (78.2±13.6) vs (71.4±14.6) points], the HADS score was significantly lower than the control group [(15.18±2.46) vs (19.46±2.40) points] (all P<0.05). The scores of the modified Barthel index scale and self-care compliance scale of the experimental group after the intervention were significantly higher than those before the intervention [(65.9±12.6) vs (40.8±12.5) points, (78.2±13.6) vs (54.6±15.9) points] (all P<0.05), the HADS score was significantly lower than before the intervention [(15.18±2.46) vs (21.74±3.52) points] (all P<0.05). Similarly,the scores of the modified Barthel index and self-care compliance scale of the control group after the intervention were significantly higher than before the intervention [(60.1±11.9) vs (41.6±9.72) points, (71.4±14.6) vs (54.3±14.8) points], the HADS score was significantly lower than before the intervention [(19.46±2.40) vs (21.38±3.09) points] (all P<0.05). Conclusion:FIC combined with intelligent health education platform can significantly improve the self-care ability and self-nursing compliance of elderly stroke patients, and markedly improve the degree of depression and anxiety.

Transcriptome profiling and in silico detection of the antimicrobial peptides of red king crab Paralithodes camtschaticus.

Endogenous antimicrobial peptides (AMPs) are evolutionarily ancient factors of innate immunity, which are produced by all multicellular organisms and play a key role in their protection against infection. Red king crab (Paralithodes camtschaticus), also called Kamchatka crab, is widely distributed and the best known species of all king crabs belonging to the family Lithodidae. Despite their economic importance, the genetic resources of king crabs are scarcely known and no full-genome sequences are available to date. Therefore, analysis of the red king crab transcriptome and identification and characterization of its AMPs could potentially contribute to the development of novel antimicrobial drug candidates when antibiotic resistance has become a global health threat. In this study, we sequenced the P. camtschaticus transcriptomes from carapace, tail flap and leg tissues using an Illumina NGS platform. Libraries were systematically analyzed for gene expression profiles along with AMP prediction. By an in silico approach using public databases we defined 49 cDNAs encoding for AMP candidates belonging to diverse families and functional classes, including buforins, crustins, paralithocins, and ALFs (anti-lipopolysaccharide factors). We analyzed expression patterns of 27 AMP genes. The highest expression was found for Paralithocin 1 and Crustin 3, with more than 8,000 reads. Other paralithocins, ALFs, crustins and ubiquicidins were among medium expressed genes. This transcriptome data set and AMPs provide a solid baseline for further functional analysis in P. camtschaticus. Results from the current study contribute also to the future application of red king crab as a bio-resource in addition to its being a known seafood delicacy.

Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response.

Diseases caused by viruses threaten the production industry and food safety of aquaculture which is a great animal protein source. Grass carp reovirus (GCRV) has caused tremendous loss, and the molecular function of viral proteins during infection needs further research, as for most aquatic viruses. In this study, interaction between GCRV major outer capsid protein VP4 and RIG-I, a critical viral RNA sensor, was screened out by GST pull-down, endogenous immunoprecipitation and subsequent LC-MS/MS, and then verified by co-IP and an advanced far-red fluorescence complementation system. VP4 was proved to bind to the CARD and RD domains of RIG-I and promoted K48-linked ubiquitination of RIG-I to degrade RIG-I. VP4 reduced mRNA and promoter activities of key genes of RLR pathway and sequential IFN production. As a consequence, antiviral effectors were suppressed and GCRV replication increased, resulting in intensified cytopathic effect. Furthermore, results of transcriptome sequencing of VP4 stably expressed CIK (C. idella kidney) cells indicated that VP4 activated the MyD88-dependent TLR pathway. Knockdown of VP4 obtained opposite effects. These results collectively revealed that VP4 interacts with RIG-I to restrain interferon response and assist GCRV invasion. This study lays the foundation for anti-dsRNA virus molecular function research in teleost and provides a novel insight into the strategy of immune evasion for aquatic virus.

Elevated serum IgM levels indicate poor outcome in patients with coronavirus disease 2019 pneumonia: A retrospective case-control study

BackgroundThe coronavirus disease 2019 (COVID-19) pneumonia outbreak began in Wuhan and pandemics tend to occur. Although SARS-CoV-2-specific immunoglobulins have been detected in serum of COVID-19 patients, their dynamics and association with outcomes have not been characterized. MethodsA total of 116 hospitalized patients with confirmed COVID-19 pneumonia and SARS-CoV-2-specific immunoglobulins tested in Tongji hospital were retrospectively investigated. Clinical, laboratory, radiological characteristics and outcomes data were compared between mild-moderate group and died group. Further, a paired case-control study was conducted where each deceased case was matched to three mild-moderate patients of similar age. FindingsAmong 116 subjects included, 101 mild-moderate patients survived and 15 cases died. SARS-CoV-2-specific IgM levels peaked in forth week after onset of COVID-19 pneumonia, while serum IgG levels increased over 8 weeks. Serum IgM levels were higher in deceased patients than mild-moderate patients (P = 0.024), but not IgG. Serum IgM levels were negatively correlated with clinical outcome, eosinophil count and albumin levels (r = -0.269, P = 0.003; r = -0.188, P = 0.043; and r = -0.198, P = 0.033, resp.). The area under the ROC curve (AUC) for IgM antibody was 0.681 (95% CI: 0.517-0.845, P = 0.024). In case-control study paired by age, serum IgM was higher in deceased patients than mild-moderate patients (P = 0.019), positively correlated with leucocyte count (r = 0.260, P = 0.045), while negatively correlated with clinical outcome and albumin levels (r = -0.337, P = 0.008; r = -0.265, P = 0.041). AUC for IgM levels was 0.704 (95% CI: 0.534-0.873, P = 0.019). InterpretationThese results indicate that dynamics of SARS-CoV-2 specific IgM and IgG antibodies was similar with that of SARS-CoV, while elevated serum IgM levels indicate poor outcome in patients with COVID-19 pneumonia.