Engineered phage with cell-penetrating peptides for intracellular bacterial infections.

IMPORTANCE: Salmonella infection is a significant threat to global public health, and the increasing prevalence of antibiotic resistance exacerbates the situation. Therefore, finding new and effective ways to combat this pathogen is essential. Phages are natural predators of bacteria and can be used as an alternative to antibiotics to kill specific bacteria, including drug-resistant strains. One significant limitation of using phages as antimicrobial agents is their low cellular uptake, which limits their effectiveness against intracellular bacterial infections. Therefore, finding ways to enhance phage uptake is crucial. Our study provides a straightforward strategy for displaying cell-penetrating peptides on non-model phages, offering a promising novel and effective therapeutic approach for treating intracellular and drug-resistant bacteria. This approach has the potential to address the global challenge of antibiotic resistance and improve public health outcomes.

Clinical diagnosis of severe COVID-19: A derivation and validation of a prediction rule.

BACKGROUND: The widespread coronavirus disease 2019 (COVID-19) has led to high morbidity and mortality. Therefore, early risk identification of critically ill patients remains crucial. AIM: To develop predictive rules at the time of admission to identify COVID-19 patients who might require intensive care unit (ICU) care. METHODS: This retrospective study included a total of 361 patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction between January 19, 2020, and March 14, 2020 in Shenzhen Third People's Hospital. Multivariate logistic regression was applied to develop the predictive model. The performance of the predictive model was externally validated and evaluated based on a dataset involving 126 patients from the Wuhan Asia General Hospital between December 2019 and March 2020, by area under the receiver operating curve (AUROC), goodness-of-fit and the performance matrix including the sensitivity, specificity, and precision. A nomogram was also used to visualize the model. RESULTS: Among the patients in the derivation and validation datasets, 38 and 9 participants (10.5% and 2.54%, respectively) developed severe COVID-19, respectively. In univariate analysis, 21 parameters such as age, sex (male), smoker, body mass index (BMI), time from onset to admission (> 5 d), asthenia, dry cough, expectoration, shortness of breath, asthenia, and Rox index < 18 (pulse oxygen saturation, SpO2)/(FiO2 × respiratory rate, RR) showed positive correlations with severe COVID-19. In multivariate logistic regression analysis, only six parameters including BMI [odds ratio (OR) 3.939; 95% confidence interval (CI): 1.409-11.015; P = 0.009], time from onset to admission (≥ 5 d) (OR 7.107; 95%CI: 1.449-34.849; P = 0.016), fever (OR 6.794; 95%CI: 1.401-32.951; P = 0.017), Charlson index (OR 2.917; 95%CI: 1.279-6.654; P = 0.011), PaO2/FiO2 ratio (OR 17.570; 95%CI: 1.117-276.383; P = 0.041), and neutrophil/lymphocyte ratio (OR 3.574; 95%CI: 1.048-12.191; P = 0.042) were found to be independent predictors of COVID-19. These factors were found to be significant risk factors for severe patients confirmed with COVID-19. The AUROC was 0.941 (95%CI: 0.901-0.981) and 0.936 (95%CI: 0.886-0.987) in both datasets. The calibration properties were good. CONCLUSION: The proposed predictive model had great potential in severity prediction of COVID-19 in the ICU. It assisted the ICU clinicians in making timely decisions for the target population.

[Characteristics of rain season atmospheric PM2.5 concentration and its water-soluble ions contents in forest parks along an urban-rural gradient in Guangzhou City of South China].

During the rainy season (April-September) of 2012, the atmospheric particulate matter with a diameter less than 2.5 mm (PM2.5) were sampled from the forest parks in the urban area, suburban area, and rural area of Guangzhou City. The mass concentration of PM2.5 and its water-soluble ions (SO4(2-), NO3-, NO2-, Cl-, F-, Na+, NH4+, Ca2+, K+, and Mg2+) contents were also measured. In the forest parks in the urban area, suburban area, and rural area, the diurnal variation of PM2.5 mass concentration was 21.8-161.7, 19.4-156.3, and 17.2-66.5 microg x m(-3), with an arithmetic average being 55.9, 49.8, and 44.4 microg x m(-3), respectively. SO4(2-), Na+, and NH4+ were the main components of water-soluble ions in the PM2.5, and the SO4(2-) had the highest content and decreased gradually from urban to rural forest parks. The contribution of the SO2 and NOx in the PM2.5 from coal combustion to the forest parks was larger than that from vehicle exhaust, but presented a decreasing trend from urban to rural forest parks, indicating that vehicle exhaust had a greater contribution to the atmospheric SO2 and NOx in the urban forest park. In the sampling period, the contribution of sea salt to the water soluble fractions (especially K+) of the PM2.5 was greater for the suburban forest park than for the other two parks. The equivalent concentration of the NH4+ in the PM2.5 was far less than those of the SO4(2-) and NO3-, with a neutralization ratio being much lower than 1.0, which suggested that the PM2.5 had a higher acidity. The PM2.5 acidity had an increasing trend from rural to urban forest parks.

[Effect of tanshinone II A on the calcineurin activity in proliferating vascular smooth muscle cells of rats].

OBJECTIVE: To study the effect of tanshinone II A (TSN) on angiotensin II (Ang II) induced proliferation of vascular smooth muscle cells (VSMCs). METHODS: VSMCs were cultured by explant attached method, and induced to proliferative cell model with Ang II. The effect of TSN in different concentrations on calcineurin (CaN) activity was detected by enzyme reaction phosphorus measurement; the CaN mRNA expression was detected by RT-PCR; and the expression of proliferating cell nuclear antigen (PCNA) were observed by immunocytochemical method. RESULTS: Compared with the normal control group, Ang II could significantly stimulate the proliferation of VSMCs, showing obviously elevated degree of proliferation activity (P <0. 01). After being treated with TSN, all the indexes, including CaN activity, CaN mRNA expression and PCNA expression, were obviously reduced in a dose-dependent manner (P<0.05, P<0.01). CONCLUSION: VSMCs proliferation can be inhibited by TSN in a dose-dependent manner and the inhibiting mechanism may be related to the down-regulation of CaN activities and the inhibition on CaN mRNA and PCNA expressions.