PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Deactivation of SARS-CoV-2 surrogate porcine epidemic diarrhea virus with electron beam irradiation under the cold chain transportation condition

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prevailed all over the world and emerged as a significant public health emergency. The rapid outbreak of SARS-CoV-2 is largely due to its high transmission capacity. Studies implied that the cold chain logistics would be a potential route for the spread of SARS-CoV-2. The low temperature condition of the cold chain is conducive to survival and transmission of virus. Thus, the virus disinfection in cold chain should not be neglected for controlling COVID-19. However, due to the low temperature feature of the cold-chain, the virus disinfecting methods suitable in cold chain are limited. Here the high-energy electron beam irradiation is proposed to disinfect the SARS-CoV-2 in cold chain logistics. We evaluated the impact of high-energy electron beam irradiation on porcine epidemic diarrhea virus (PEDV), an enveloped virus surrogate for SARS-CoV-2, and explored the possible mechanism of the action of high-energy electron beam irradiation on PEDV. The irradiation dose of 10 kGy inactivated 98.1 % PEDV on the both top and bottom surfaces of various packaging materials under cold chain frozen condition. High-energy electron beam inactivated PEDV by inducing damages on viral genome or even capsid.

A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates

A safe, efficacious and deployable vaccine is urgently needed to control COVID-19 pandemic. We report here the preclinical development of a COVID-19 vaccine candidate, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and NHPs, and also elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 g or 50 g ZF2001 prevented infection with SARS-CoV-2 in lung, trachea and bronchi, with milder lung lesions. No evidence of disease enhancement is observed in both models. ZF2001 is being evaluated in the ongoing international multi-center Phase 3 trials (NCT04646590) and has been approved for emergency use in Uzbekistan.

A non-competing pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design. One Sentence SummaryA pair of human neutralizing monoclonal antibodies against COVID-19 compete cellular receptor binding but with different epitopes, and with post-exposure viral load reduction activity.

Effects of isoorientin on autophagy of gastric cancer cell / 中国生化药物杂志

Objective To explore effect of isoorientin on gastric cancer cell autophagy.Methods Isoorientin and autophagy activator and effect of inhibitors on proliferation of human gastric cancer cell line SGC-7901 by MTT assay.Cell apoptosis was detected by flow cytometry.Production of autophagy lysosomal in gastric cancer SGC-7901 cells was obseroved by AO and MDC staining.Characteristic expression of autophagy protein was analysed by Western blot.Results MTT assay indicated that isoorientin could inhibit gastric cancer cell growth, RAP has the same effects, but 3-MA inhibition of apoptosis.Flow cytometry was used to detect the apoptosis rate of isoorientin and RAP could promote cell apoptosis , while 3-MA had the opposite effect.In AO staining, the red light appeared in the cells, and the green fluorescence appeared in the cells of MDC staining, which showed that there was an autophagy in the cells.Western blot test found the isoorientin was cell autophagy specific protein LC-3II, Beclin-1 expression increased, 3-MA suppressed the expression of the two proteins, and RAP had the opposite effect.Conclusion Isoorientin could induce apoptosis in gastric cancer SGC-7901 cells, autophagy is involved in the process of death.

The injection on myocardial protection and prognosis of acute organophosphorus pesticide with Salvia miltiorrhiza / 国际中医中药杂志

Objective To investigate the effects of hemodynamic,prognostic effect and myocardial protection of Salvia injection on patients with acute organophosphorus pesticide poisoning. Methods 68 cases of patients with acute organophosphate were divided into observation group(n=34)and control group(n=34) from January 2012 to December 2013.The control group were given with atropine detoxification (dose:5-10mg), Tiopronin (0.2 g/d, 1 times/d) liver treatment, Pioneer will(2 g/second,1/d).The observed group received the foundation treatment and Salvia injection(30ml, 1/d), 7d course of treatment. The myocardial enzymes and hemodynamic parameters of two groups were observed before and after treatment. Results The survival rate and died rate of observation group were 94.12%(32 cases ), 5.88%(2 cases ). The survival rate and died rate of control group were 79.41%(27cases )and 20.59%(7cases). The survival rate and died rate of two groups were significant difference (χ2=5.123, P<0.05). The myocardial enzymes (AST, CK, CK-MB, LDH, HBDH) of observation groupafter 2d each index[were(58.6±22.7)U/L, (412.6±156.9)U/L, (78.6± 35.2)U/L, (489.3 ± 112.3)U/L, (412.8 ± 259.6)U/L] and blood rheology (ESR, FIB, LBV, HBV)each index[were(14.36±4.19) mm/h before , (259.3±23.14)g/L, (7.17±1.12)mPa?s, (4.12±0.81)mPa?s]were lower than in the same group therapy [myocardial enzymes indexes were (131.3±32.5)U/L, (1324.5± 345.2)U/L, (187.5 ± 72.2)U/L, (914.5 ± 312.2)U/L, (812.3 ± 312.2)U/L; hemorheology indexes were (23.29±3.49)mm/h, (389.57±34.24) g/L, (10.4±1.3)mPa?s, (6.3±1.2)mPa?s]. 5 d after treatment control group myocardial enzymes(AST, CK, CK-MB, LDH, HBDH)each index[were(85.3±22.8)U/L, (486.3± 78.9)U/L, (67.8±11.2)U/L, (542.3±78.6)U/L, (225.9±112.4)U/L]and hemorheology indexes[were(17.7± 4.6)mm/h, (289.4±32.5)g/L, (8.9±1.2)mPa?s, (5.6±1.3)mPa?s] was significantly lower than in the same group before treatment[myocardial enzymes indexes were(128.3±29.3)U/L, (1298.6±329.4)U/L, (182.6± 70.6)U/L, (902.3±286.3)U/L, (803.6±293.6)U/L;hemorheology indexes were (23.9±3.5)mm/h, (382.6± 32.5)g/L, (10.3±1.1)mPa?s, (6.2±1.1)mPa?s, P<0.05]. Conclusion Salvia injection can effectively improve the hemodynamic indicators of acute organophosphorus pesticide poisoning patients , reduce myocardial damage, promote patient prognosis.

Kunjin virus replicon--a novel viral vector / 生物工程学报

Viral replicon is a kind of self-replicating viral RNA sourced from viral genome, which contains viral non-structural genes that are critical for viral genome replication with structural proteins deleted or replaced by foreign genes. Kunjin virus is a member of the Flavivirida family, Flavivirus genus, and Kunjin virus replicon is the first and the clearly defined flavivirus replicon. Kunjun virus replicon has been regarded as an excellent viral vector on account of its high expression, lower cytotoxicity and genetic stability. These unique characteristics of kunjin virus replicons make them suitable for the study of viral genome replication, recombinant proteins production, vaccine development and gene therapy. In this article, recent progress in the development, properties and applications of kunjin virus replicon system was briefly reviewed.

Adult male circumcision for military men: history and future / 中华男科学杂志

Adult male circumcision (MC) has been shown to reduce the transmission of HPV, HSV, and HIV significantly during vaginal intercourse. However, the benefits of adult MC for men in military service have been poorly documented. Soldiers in war time have additional challenges in maintaining good penile hygiene, rendering uncircumcised men vulnerable to inflammation and infection; these maladies not only negatively impact these individuals, but also undermine the overall military strength. Adult MC can provide some long-term benefits for these military service men. Many African countries have already taken a special interest in adult MC for their military forces, resulting in increased numbers of these surgeries among this special population of men. In this review, we discuss the history of adult MC in the military along with the current trends and economic significance.

Practical research in ability training of community nurses in community practice base / 中国实用护理杂志

Objective To improve the comprehensive nursing abilities in the practice process in the practice base, to adapt to the needs of the development of community nursing. Methods Convenient sampling was adopted, 83 nurses were divided into the experimental group (43 nurses) and the control group (40 nurses),who interned in the practice base in the years 2008 and 2009, the control group received con-ventional teachings, and the experimental group was given the teaching method and modes which were targeted at and focusing on the training of ability. The practice result was compared between the two groups.- Results Based on the teachers, the assessment and mixed capability were higher in the experimental group, by the employers' evaluation, all of the indicators were higher than the control group, and it is statistically significant. Conclusions It can improve various nursing abilities of the community nurses by the teaching method and modes which are targeted and focusing on the training of capability.

Interventianal therapy of acute myocardial infarction complicated with ventricular septal rapture / 中华老年医学杂志

Objective To evaluate the feasibility and safety of the treatment for ventricular septal rupture (VSR) by transcatheter interventional therapy coordinated with percutaneous coronary intervention (PCI) or percutaneous transluminal coronary angioplasty (PTCA).Methods Six patients who suffered from cardiogenic shock due to acute myocardial infarction (AMI) and VSR were given intra-aortic balloon pump (IABP) and mechanical ventilation support. After three weeks, they underwent transcatheter closure of ventricular septal rupture with Amplatzer ventricular septal occluder, and at the same time PCI and PTCA were performed. Results All the patients successfully underwent ventricular septal defect occlusion, including two cases of residual shunt. Segmental stenosis of the middle of anterior descending branch and circumflex artery were noted in three patients, and then stent implantation was used. The other three cases had multi-vessel lesion but were without stent implantation. All the patients with stent implantation survived and discharged. Conclusions It is safe and feasible to apply transcatheter closure of ventricular septal rupture with Amplatzer ventricular septal occluder, coordinated with PCI and PTCA for patients with acute myocardial infarction complicated with ventricular septal rupture.

Application of peer education in guiding community diabetic patients to adopt diet therapy using food exchange method / 中国实用护理杂志

Objective To use peer education to guide community diabetic patients to adopt diet therapy using food exchange method in order to explore effective method for diet therapy of diabetes mellitus. Meth-ods 91 diabetic patients were selected using simple sampling method and randomly divided into the peer ed-ucation(45 cases) and the common education group(46 cases), the two groups adopted food exchange method for diet therapy for 1 year. The blood glucose, blood lipid, glycosylated hemoglobin and body weight index were compared between the two groups using t test. Results The blood glucose, blood lipid, glycosylated hemoglobin and body weight index all decreased in the two groups after intervention, but the the decreased de-gree in the peer education group was more obvious. The fasting blood glucose, 2 hour postprandial blood glu-cose, glycosylated hemoglobin, triglyceride, low-donordensity lipid protein and body weight index in the peer education were lower thanthose of the common education group, but HDL-C was higher. Conclusions Peer education is more effective in health education of food exchange method.

[No-scalpel vasectomy]. / Vasectomía sin bisturí.

No scalpel vasectomy (NSV) is a new and refined technique with advantages over the conventional incisional technique. It requires no incision, no stitches; it is faster to perform and with less complications, and is equally effective. We present our experience in 100 patients submitted to NSV. The technique is described herein, as well as the anesthetic procedure and the instruments required for NSV.

PIP: The procedure for no-scalpel vasectomy is explained and diagrammed, and the results of a series of 100 operations performed in Barcelona are presented. No-scalpel vasectomy was developed in 1974 in Sichuan, China. The technique gained international attention after a 1985 visit by a group of international experts to Sichuan, and it is now being introduced into Europe. The technique requires two specially designed types of scissors, which are pictured and described. The remaining tools are all commonly employed in minor urologic surgery. The nerve structure of the scrotum and deferens are explained and the necessary anesthesia for each is described. The procedure for fixing and exteriorizing the deferent is then described. Any of the commonly used occlusive techniques may be used. A telephone survey about immediate postoperative problems and the activities undertaken in the first three days after vasectomy was conducted among 100 men who underwent no-scalpel vasectomy in Barcelona. No hematomas or infections were reported. The time required for no-scalpel vasectomy in the most recent 100 operations ranged from five to twelve minutes and averaged eight minutes. No-scalpel vasectomy involves new techniques and new surgical methods, and thus requires training. But its greater speed, simplicity, and freedom from side effects constitute advantages over traditional incisional techniques.