COVID-19 acts like a stress test, uncovering the vulnerable part of the human body: a retrospective study of 1640 cases in China.

BACKGROUND: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits multi-organ damage with diverse complications, the correlation between age, gender, medical history and clinical manifestations of novel coronavirus disease 2019 (COVID-19) patients was investigated. METHODS: 1640 patients who were infected with SARS-CoV-2 and hospitalized at the First Affiliated Hospital of Ningbo University from 22 December 2022 to 1 March 2023 were categorized and analysed. Normal distribution test and variance homogeneity test were performed. Based on the test results, one-way analysis of variance, Pearson's chi-squared test and logistic regression analysis were conducted in the study. RESULTS: According to the ANOVA, there was a significant difference in the age distribution (P = .001) between different clinical presentations, while gender did not (P = .06). And regression analysis showed that age, hypertension, atherosclerosis and cancer were significant hazard factors for the development of predominant clinical manifestations in patients hospitalized with novel COVID-19. Additionally, infection with SARS-CoV-2 has the potential to exacerbate the burden on specific diseased or related organs. CONCLUSION: The elderly who are infected with SARS-CoV-2 ought to be treated with emphasis not only on antiviral therapy but also on individualized treatment that takes their medical history and comorbidities into account.

Lipid metabolism: the potential targets for toxoplasmosis treatment.

Toxoplasmosis is a zoonosis caused by Toxoplasma gondii (T. gondii). The current treatment for toxoplasmosis remains constrained due to the absence of pharmaceutical interventions. Thus, the pursuit of more efficient targets is of great importance. Lipid metabolism in T. gondii, including fatty acid metabolism, phospholipid metabolism, and neutral lipid metabolism, assumes a crucial function in T. gondii because those pathways are largely involved in the formation of the membranous structure and cellular processes such as division, invasion, egress, replication, and apoptosis. The inhibitors of T. gondii's lipid metabolism can directly lead to the disturbance of various lipid component levels and serious destruction of membrane structure, ultimately leading to the death of the parasites. In this review, the specific lipid metabolism pathways, correlative enzymes, and inhibitors of lipid metabolism of T. gondii are elaborated in detail to generate novel ideas for the development of anti-T. gondii drugs that target the parasites' lipid metabolism.

Monoterpenoid indole alkaloids from Alstonia scholaris and their Toxoplasma gondii inhibitory activity.

Nine previously unreported various types of monoterpenoid indole alkaloids, together with seven known analogues were isolated from the stem barks of Alstonia scholaris through a silica gel free methodology. The structures of 1-9 were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compound 1 is a modified echitamine-type alkaloid with a novel 6/5/5/7/6/6 hetero hexacyclic bridged ring system, and 8 and 9 exist as a zwitterion and trifluoroacetate salt, respectively. The anti-Toxoplasma activity of all isolates on infected Vero cells were evaluated, which revealed that compound 14 at 0.24 µM displayed potent activity. This study expanded the structural diversity of alkaloids of A. scholaris, and presented their potential application in anti-Toxoplasma drug development.

Protective Immunity Induced by TgMIC5 and TgMIC16 DNA Vaccines Against Toxoplasmosis.

Toxoplasma gondii is an obligate intracellular parasite, which is responsible for a widely distributed zoonosis. Effective vaccines against toxoplasmosis are necessary to protect the public health. The aim of this study is to evaluate the immune efficacy of DNA vaccines encoding TgMIC5 and TgMIC16 genes against T. gondii infection. The recombinant plasmid pVAX-MIC5 and pVAX-MIC16 were constructed and injected intramuscularly in mice. The specific immune responses and protection against challenge with T. gondii RH tachyzoites were evaluated by measuring the cytokine levels, serum antibody concentrations, lymphocyte proliferation, lymphocyte populations, and the survival time. The protection against challenge with the T. gondii RH tchyzoites and PRU cysts was examined by evaluation of the reduction in the brain cyst burden. The results indicated that immunized mice showed significantly increased levels of IgG, IFN-γ, IL-2, IL-12p70, and IL-12p40 and percentages of CD4+ and CD8+ T cells. Additionally, vaccination prolonged the mouse survival time and reduced brain cysts compared with controls. Mouse groups immunized with a two-gene cocktail of pVAX-MIC5 + pVAX-MIC16 were more protected than mouse groups immunized with a single gene of pVAX-MIC5 or pVAX-MIC16. These results demonstrate that TgMIC5 and TgMIC16 induce effective immunity against toxoplasmosis and may serve as a good vaccine candidate against T. gondii infection.

New life for an old drug: In vitro and in vivo effects of the anthelmintic drug niclosamide against Toxoplasma gondii RH strain.

Toxoplasma gondii is the causative agent of toxoplasmosis and causes serious public health problems. However, the current treatment drugs have many limitations, such as serious side effects. Niclosamide is a salicylanilide drug commonly used to treat worm infections. Herein, the effectiveness of niclosamide for the treatment of T. gondii infection was demonstrated. This study was to evaluate the in vitro and in vivo activities of niclosamide against T. gondii and to explore its mechanism of action. The in vitro cytotoxicity of niclosamide on human foreskin fibroblast cells was evaluated by MTT test. Niclosamide displayed low host toxicity and its 50% inhibitory concentration was 8.3 µg/mL. The in vitro anti-proliferation and anti-invasion effects of niclosamide on T. gondii were determined by quantitative PCR and Giemsa staining. Niclosamide also inhibited T. gondii tachyzoite proliferation, with a 50% effective concentration of 45.3 ng/mL, and reduced the invasion of cells by tachyzoites (17.8% for the parasite control versus 1.9% for the niclosamide group treated with 100 ng/mL). A model was established by infecting BALB/c mice with the virulent RH strain of T. gondii and used to determine the in vivo effects of niclosamide on acute infection. The mice infected with tachyzoites and treated with 160, 200 or 240 mg/kg·bw niclosamide for 7 days exhibited 20%, 40% and 50% survival, respectively. In addition, niclosamide reduced the parasite burden in the blood and tissues of acutely infected mice, and niclosamide induced decreases in the mitochondrial membrane potential (ΔΨm) and adenosine triphosphate (ATP) levels in extracellular tachyzoites, as assessed by laser confocal microscopy and a multilabel reader. These findings indicated that the mechanism of action of niclosamide might be associated with T. gondii mitochondria oxidative phosphorylation. In conclusion, our results support the efficacy of niclosamide as a potential compound for the treatment of T. gondii infection.

High prevalence of fasciolosis and evaluation of the efficacy of anthelmintics against Fasciola hepatica in buffaloes in Guangxi, China.

Fasciola hepatica is a common parasite of grazing livestock in Guangxi Zhuang Autonomous Region in China, but its prevalence has not been studied. While triclabendazole is commonly used to treat F. hepatica infection in China, oxyclozanide has never been used. This study investigated the prevalence of F. hepatica infections in buffaloes in the Guangxi and evaluated the efficacy of oxyclozanide and triclabendazole as treatments. In the prevalence study, a total of 767 individual faecal samples were obtained from 58 farms in Guangxi to detect the prevalence of F. hepatica, and the total rate of infection was 87.35%. A subset of 277 infected buffaloes from these farms were randomly divided into 3 groups. Group 1 (n = 101) was treated with oxyclozanide at 10 mg/kg.bw; group 2 (n = 94) was treated with triclabendazole (12 mg/kg.bw); and group 3 (n = 82) was untreated. Faecal samples were taken on days 0, 7, 14, 21 and 28. Whole blood and serum were collected on days 0 and 14. Anthelmintic efficacy was assessed using faecal egg count reduction (FECR), buffaloes positive by coprology reduction (BPCR) as well as post-treatment improvement in biochemical and haematological indicators. After 28 days treatment, group 1 and 2 showed FECR% values above 98%, and BPCR% values of 97.03% and 77.66%, respectively. In addition, the biochemical indicators and haematological parameters were improved at 14 days post-treatment compared with those before treatment. These results indicate a high prevalence of F. hepatica in Guangxi, demonstrate that oxyclozanide and triclabendazole are effective against F. hepatica infection in buffaloes, and indicate that oxyclozanide could be used in China as an alternative drug.

[Lightning-caused fire, its affecting factors and prediction: a review].

Lightning-caused fire is the most important natural fire source. Its induced forest fire brings enormous losses to human beings and ecological environment. Many countries have paid great attention to the prediction of lightning-caused fire. From the viewpoint of the main factors affecting the formation of lightning-caused fire, this paper emphatically analyzed the effects and action mechanisms of cloud-to-ground lightning, fuel, meteorology, and terrain on the formation and development process of lightning-caused fire, and, on the basis of this, summarized and reviewed the logistic model, K-function, and other mathematical methods widely used in prediction research of lightning-caused fire. The prediction methods and processes of lightning-caused fire in America and Canada were also introduced. The insufficiencies and their possible solutions for the present researches as well as the directions of further studies were proposed, aimed to provide necessary theoretical basis and literature reference for the prediction of lightning-caused fire in China.

[Fire behavior of Quercus mongolica leaf litter fuelbed under zero-slope and no-wind conditions. II. Analysis and modelling of fireline intensity, fuel consumption, and combustion efficiency].

Mongolian oak (Quercus mongolica) is an important constructive and accompanying species in mixed broadleaf-conifer forest in Northeast China, In this paper, a laboratory burning experiment was conducted under zero-slope and no-wind conditions to study the effects of fuel moisture content, loading, and thickness on the fireline intensity, fuel consumption, and combustion efficiency of the Mongolian oak leaf litter fuelbed. The fuel moisture content, loading, and thickness all had significant effects on the three fire behavior indices, and there existed interactions between these three affecting factors. Among the known models, the Byram model could be suitable for the prediction of local leaf litter fire intensity only after re-parameterization. The re-estimated alpha and beta parameters of the re-parameterized Byram model were 98.009 and 1.099, with an adjusted determination coefficient of 0.745, the rooted mean square error (RMSE) of 8.676 kW x m(-1), and the mean relative error (MRE) of 21%, respectively (R2 = 0.745). The re-estimated a and b by the burning efficiency method proposed by Albini were 0.069 and 0.169, and the re-estimated values were all higher than 93%, being mostly overestimated. The Consume model had a stronger suitability for the fuel. The R2 of the general linear models established for fireline intensity, fuel consumption, and burning efficiency was 0.82, 0.73 and 0.53, and the RMSE was 8.266 kW x m(-1) 0.081 kg x m(-2), and 0.203, respectively. In low intensity surface fires, the fine fuels could not be completely consumed, and thus, to consider the leaf litter and fine fuel in some forest ecosystems being completely consumed would overestimate the carbon release from forest fires.

[Fire behavior of ground surface fuels in Pinus koraiensis and Quercus mongolica mixed forest under no wind and zero slope condition: a prediction with extended Rothermel model].

A laboratory burning experiment was conducted to measure the fire spread speed, residual time, reaction intensity, fireline intensity, and flame length of the ground surface fuels collected from a Korean pine (Pinus koraiensis) and Mongolian oak (Quercus mongolica) mixed stand in Maoer Mountains of Northeast China under the conditions of no wind, zero slope, and different moisture content, load, and mixture ratio of the fuels. The results measured were compared with those predicted by the extended Rothermel model to test the performance of the model, especially for the effects of two different weighting methods on the fire behavior modeling of the mixed fuels. With the prediction of the model, the mean absolute errors of the fire spread speed and reaction intensity of the fuels were 0.04 m X min(-1) and 77 kW X m(-2), their mean relative errors were 16% and 22%, while the mean absolute errors of residual time, fireline intensity and flame length were 15.5 s, 17.3 kW X m(-1), and 9.7 cm, and their mean relative errors were 55.5%, 48.7%, and 24%, respectively, indicating that the predicted values of residual time, fireline intensity, and flame length were lower than the observed ones. These errors could be regarded as the lower limits for the application of the extended Rothermel model in predicting the fire behavior of similar fuel types, and provide valuable information for using the model to predict the fire behavior under the similar field conditions. As a whole, the two different weighting methods did not show significant difference in predicting the fire behavior of the mixed fuels by extended Rothermel model. When the proportion of Korean pine fuels was lower, the predicted values of spread speed and reaction intensity obtained by surface area weighting method and those of fireline intensity and flame length obtained by load weighting method were higher; when the proportion of Korean pine needles was higher, the contrary results were obtained.

[Fire behavior of Mongolian oak leaves fuel-bed under no-wind and zero-slope conditions. I. Factors affecting fire spread rate and modeling].

Aimed to understand the fire behavior of Mongolian oak leaves fuel-bed under field condition, the leaves of a secondary Mongolian oak forest in Northeast Forestry University experimental forest farm were collected and brought into laboratory to construct fuel-beds with varied loading, height, and moisture content, and a total of 100 experimental fires were burned under no-wind and zero-slope conditions. It was observed that the fire spread rate of the fuel-beds was less than 0.5 m x min(-1). Fuel-bed loading, height, and moisture contents all had significant effects on the fire spread rate. The effect of fuel-bed moisture content on the fire spread had no significant correlations with fuel-bed loading and height, but the effect of fuel-bed height was related to the fuel-bed loading. The packing ratio of fuel-beds had less effect on the fire spread rate. Taking the fuel-bed loading, height, and moisture content as predictive variables, a prediction model for the fire spread rate of Mongolian oak leaves fuel-bed was established, which could explain 83% of the variance of the fire spread rate, with a mean absolute error 0.04 m x min(-1) and a mean relative error less than 17%.

[Fire behavior of Mongolian oak leaves fuel bed under no-wind and zero-slope conditions. II. Analysis of the factors affecting flame length and residence time and related prediction models].

Taking fuel moisture content, fuel loading, and fuel bed depth as controlling factors, the fuel beds of Mongolian oak leaves in Maoershan region of Northeast China in field were simulated, and a total of one hundred experimental burnings under no-wind and zero-slope conditions were conducted in laboratory, with the effects of the fuel moisture content, fuel loading, and fuel bed depth on the flame length and its residence time analyzed and the multivariate linear prediction models constructed. The results indicated that fuel moisture content had a significant negative liner correlation with flame length, but less correlation with flame residence time. Both the fuel loading and the fuel bed depth were significantly positively correlated with flame length and its residence time. The interactions of fuel bed depth with fuel moisture content and fuel loading had significant effects on the flame length, while the interactions of fuel moisture content with fuel loading and fuel bed depth affected the flame residence time significantly. The prediction model of flame length had better prediction effect, which could explain 83.3% of variance, with a mean absolute error of 7.8 cm and a mean relative error of 16.2%, while the prediction model of flame residence time was not good enough, which could only explain 54% of variance, with a mean absolute error of 9.2 s and a mean relative error of 18.6%.