基于新型冠状病毒S蛋白结构及入胞机制的抗体与药物研发

新型冠状病毒肺炎,世界卫生组织命名为"2019冠状病毒病"(corona virus disease 2019,COVID-19),是一种由2019新型冠状病毒(2019-nCov)感染导致的肺炎.目前新冠肺炎在全球广泛流行,且疫情尚未得到全部控制.由于新型冠状病毒表面的刺突蛋白(spike protein,S)介导病...     

Hepatitis E Virus: An emerging enigmatic and underestimated pathogen

Hepatitis E virus (HEV) is an RNA virus causing hepatitis E disease. The virus is of one serotype but has diverse genotypes infecting both humans and animals. Based on evidence from seroprevalence studies, about 2 billion people are estimated to have been infected with HEV globally. HEV, therefore, poses a significant public health and economic challenge worldwide. HEV was discovered in the 1980s and was traced back to the 1955 – 1956 outbreak of hepatitis that occurred in India. Subsequently, several HEV epidemics involving thousands of individuals have occurred nearly annually in different countries in Asia and Africa. Initially, the virus was thought to be only enterically transmitted, and endemic in developing countries. Due to the environmental hygiene and sanitation challenges in those parts of the world. However, recent studies have suggested otherwise with the report of autochthonous cases in industrialised countries with no history of travel to the so-called endemic countries. Thus, suggesting that HEV has a global distribution with endemicity in both developing and industrialised nations. Studies have also revealed that HEV has multiple risk factors, and modes of transmission as well as zoonotic potentials. Additionally, recent findings have shown that HEV leads to severe disease, particularly among pregnant women. In contrast to the previous narration of a strictly mild and self-limiting infection. Studies have likewise demonstrated chronic HEV infection among immunocompromised persons. Consequent to these recent discoveries, this pathogen is considered a re – emerging virus, particularly in the developed nations. However, despite the growing public health challenges of this pathogen, the burden is still underestimated. The underestimation is often attributed to poor awareness among clinicians and a lack of routine checks for the disease in the hospitals. Thus, leading to misdiagnosis and underdiagnosis. Hence, this review provides a concise overview of epidemiology, diagnosis, and prevention of hepatitis E.     

A picture of tuberculosis in young Portuguese people in the early 20th century: a multidisciplinary study of the skeletal and historical evidence

The aim of this study was to examine the evidence, and consider the differential diagnosis, for tuberculosis (TB) in juvenile individuals from early 20th century documented skeletons. There are 66 male and female juvenile individuals in the Coimbra Identified Skeletal Collection (CISC) with an age at death ranging from 7-21 years. The individuals died between 1904-1936 in different areas of Coimbra, Portugal. Eighteen of these individuals died from TB affecting different parts of the body. Thirteen (72.2%) showed skeletal lesions that may be related to this infection. Of the 48 individuals with a non-tuberculous cause of death, only 2 (4.2%) had skeletal changes that could be attributed to TB. The distribution of skeletal manifestations caused by the types of TB under study, based on macroscopic and radiological findings, is described and discussed. In addition, the medical records from 6 tuberculous individuals who died in Coimbra University Hospital (CUH) were analysed, and the information, including their diet and access to treatment, is presented. This work, based on data arising before antibiotics became available for treatment, can contribute to the future diagnosis of TB in non-documented skeletal material, and will facilitate a more reliable diagnosis of TB in juvenile individuals.     

Predictive margins with survey data

In the analysis of covariance, the display of adjusted treatment means allows one to compare mean (treatment) group outcomes controlling for different covariate distributions in the groups. Predictive margins are a generalization of adjusted treatment means to nonlinear models. The predictive margin for group r represents the average predicted response if everyone in the sample had been in group r. This paper discusses the use of predictive margins with complex survey data, where an important consideration is the choice of covariate distribution used to standardize the predictive margin. It is suggested that the textbook formula for the standard error of an adjusted treatment mean from the analysis of covariance may be inappropriate for applications involving survey data. Applications are given using data from the 1992 National Health Interview Survey (NHIS) and the Epidemiologic Followup Study to the first National Health and Nutrition Examination Survey (NHANES I).     

Towards developing a diagnostic regimen for the treatment follow-up of Trypanosoma brucei gambiense

BALB/c mice infected with a high virulent strain of Trypanosoma brucei gambiense IL3707 were treated intraperitoneally (i.p.) with either Melarsoprol (Mel-B) or PSG(+) buffer as controls. The mice were subsequently monitored regularly for parasites by direct microscopic examination of their tail blood or buffy coat and by polymerase chain reaction (PCR). Mel-B was found to be an effective drug for treatment against T.b. gambiense because at the end of the first treatment schedule, all treated mice were negative for parasites even by PCR, while all the control animals were positive. Three of the five Mel-B treated mice, while parasitologically negative, were PCR positive between 53 and 80 days post infection (DPI), indicating that they still harbored an infection. All treated mice were subsequently negative for parasites even by PCR at 88 DPI. A combination of conventional microscopic examination and PCR offers a good prediction of cure following treatment of trypanosomosis.     

Barotolerance is inducible by preincubation under hydrostatic pressure, cold-, osmotic- and acid-stress conditions in Lactobacillus sanfranciscensis DSM 20451T

AIMS: This study addresses the inducibility of barotolerance by preincubation of Lactobacillus sanfranciscensis DSM 20451T under various sublethal stress conditions. METHODS AND RESULTS: Stress conditions which reduce the growth rate of L. sanfranciscensis DSM 20451T to 10% of its maximum were determined. These conditions were met at 43, 12.5 degrees C, a pH value of 3.7, 1.9% NaCl, or 80 MPa respectively. In contrast to heat preincubation, other prestresses, including salt, cold and pressure led to an increase of barotolerance by hydrostatic pressure of 300 MPa for 30 min. Stationary-phase cells also showed an increased barotolerance. Sublethal pressure leads to enhanced heat tolerance. CONCLUSIONS: Stress response to salt, low temperature and acidic pH as well as starvation overlap with that one to high pressure by inducing barotolerance. SIGNIFICANCE AND IMPACT OF THE STUDY: Inactivation of bacteria by high pressure treatment is influenced by their history which modulates barotolerance. Mechanisms of barotolerance appear different from heat shock defence.     

Millimeter wave-induced suppression of B16 F10 melanoma growth in mice: involvement of endogenous opioids

Millimeter wave treatment (MMWT) is widely used in Eastern European countries, but is virtually unknown in Western medicine. Among reported MMWT effects is suppression of tumor growth. The main aim of the present "blind" and dosimetrically controlled experiments was to evaluate quantitatively the ability of MMWT to influence tumor growth and to assess whether endogenous opioids are involved. The murine experimental model of B16 F10 melanoma subcutaneous growth was used. MMWT characteristics were: frequency, 61.22 GHz; average incident power density, 13.3 x 10(-3) W/cm2; single exposure duration, 15 min; and exposure area, nose. Naloxone (1 mg/kg, intraperitoneally, 30 min prior to MMWT) was used as a nonspecific blocker of opioid receptors. Five daily MMW exposures, if applied starting at the fifth day following B16 melanoma cell injection, suppressed subcutaneous tumor growth. Pretreatment with naloxone completely abolished the MMWT-induced suppression of melanoma growth. The same course of 5 MMW treatments, if started on day 1 or day 10 following tumor inoculations, was ineffective. We concluded that MMWT has an anticancer therapeutic potential and that endogenous opioids are involved in MMWT-induced suppression of melanoma growth in mice. However, appropriate indications and contraindications have to be developed experimentally before recommending MMWT for clinical usage.     

Quantification of<Emphasis Type="Italic">Bacillus</Emphasis> species in a wastewater treatment system by the molecular analyses

Bacillus species were observed and quantified by molecular approaches, using the 165 rDNA primers/probes, in a wastewater treatment plant designed for the purpose of stimulating the growth ofBacillus species. The plant has been operating as a test plant since 1997 in the city of Ina, Japan, with excellent treatment performance. Observations byin situ hybridization, usingBacillus-specific probes, indicated thatBacillus strains were inhabited in the plant and their numbers decreased during the treatment process. Similar results were obtained from a quantitative PCR analysis using aBacillus-specific primer set, and the amount of DNA originating from variousBacillus species was maximally 1.91% of the total DNA in the wastewater treatment tank. Clone library analysis using theBacillus-specific primers suggested that, while the population was noticeably increased, the phylogenetic diversity of the increasingBacillus species was very low.     

Behavior of microbial communities developed in the presence/reduced level of soluble microbial products

Soluble microbial products (SMP) are organics produced by microorganisms as they degrade substrates. The available literature does not reveal how SMP affect and regulate microbial activities. In this study, we monitored variations in pH, dissolved oxygen concentration, soluble biological and chemical oxygen demands (sBOD₅ and sCOD) as a measure of microbial activity in synthetic wastewater. Aerobic degradation tests were carried out under the following conditions: aeration, 1,500 cm³ /min; initial sBOD₅, 515±5 mg/l; initial sCOD, 859±6 mg/l; initial biomass concentration (defined as mixed liquor suspended solids), 1,200±25 mg/l; sludge retention time, 24 h; and temperature, 20±1°C. The study involved non-acclimated biomass (R0 flora), biomass developed in the presence of SMP (R1 flora), and biomass developed in reduced level of SMP (R2 flora). We also determined which of these flora produced more refractory SMP. The results showed that R2 flora utilized the synthetic feed more quickly, and produced less refractory organic matter than R0 and R1 flora. The production of more refractory organics by R0 and R1 flora shows that not all the biomass was active. R1 flora degraded the substrates irregularly, suggesting that some microbes were dependent on the metabolic products of those that could utilize the feed components. These results show that production of SMP also depends on the prior substrates and on the ability of the flora to respond to changes in substrate composition.     

Bioremediation of petroleum hydrocarbons through landfarming: Are simplicity and cost-effectiveness the only advantages?

The biological removal of petroleum products using landfarming has been applied commercially in large scale with relative success. The technology has been widely used due to its simplicity and cost-effectiveness. However, together with these advantages, there are physical, chemical and biological aspects of the technology that can hamper the remediation process. The dominant pollutant removal mechanisms involved in landfarming are volatilisation of low molecular weight volatile compounds during the early days of contamination or treatment, biodegradation and adsorption. However, volatilisation, leaching of the petroleum products and the remaining recalcitrant hydrocarbon residues present both health and environmental challenges to the rehabilitation practitioners when designing the landfarming technology. Bioaugmentation and biostimulation are promising bioremediation approaches involving landfarming. However, due to the inherent problems related to bioaugmentation such as poor survival of augmented strains, biostimulation should be preferred in contaminated sites with indigenous pollutant-degrading bacteria. Although simplicity and cost-effectiveness are the major advantages for using landfarming, other factors generally regarded as disadvantageous to implementing the technology can be addressed. These includes requirements for large land area for treatment, availability of the pollutant degrading bacteria, effectiveness of the technology at high constituent concentration (more than 50,000 ppm), improved concentration reductions in cases requiring more than 95% of pollution reduction and the flexibility of the technology in integrating the removal of petroleum hydrocarbons with other contaminants that may occur with the petroleum products.