A novel multivariate logistic model for predicting risk factors of failed treatment with carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia.

Background: This study aimed to explore the risk factors for failed treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia (CRAB-VAP) with tigecycline and to establish a predictive model to predict the incidence of failed treatment and the prognosis of CRAB-VAP. Methods: A total of 189 CRAB-VAP patients were included in the safety analysis set from two Grade 3 A national-level hospitals between 1 January 2022 and 31 December 2022. The risk factors for failed treatment with CRAB-VAP were identified using univariate analysis, multivariate logistic analysis, and an independent nomogram to show the results. Results: Of the 189 patients, 106 (56.1%) patients were in the successful treatment group, and 83 (43.9%) patients were in the failed treatment group. The multivariate logistic model analysis showed that age (OR = 1.04, 95% CI: 1.02, 1.07, p = 0.001), yes. of hypoproteinemia (OR = 2.43, 95% CI: 1.20, 4.90, p = 0.013), the daily dose of 200 mg (OR = 2.31, 95% CI: 1.07, 5.00, p = 0.034), yes. of medication within 14 days prior to surgical intervention (OR = 2.98, 95% CI: 1.19, 7.44, p = 0.019), and no. of microbial clearance (OR = 0.31, 95% CI: 0.14, 0.70, p = 0.005) were risk factors for the failure of tigecycline treatment. Receiver operating characteristic (ROC) analysis showed that the AUC area of the prediction model was 0.745 (0.675-0.815), and the decision curve analysis (DCA) showed that the model was effective in clinical practice. Conclusion: Age, hypoproteinemia, daily dose, medication within 14 days prior to surgical intervention, and microbial clearance are all significant risk factors for failed treatment with CRAB-VAP, with the nomogram model indicating that high age was the most important factor. Because the failure rate of CRAB-VAP treatment with tigecycline was high, this prediction model can help doctors correct or avoid risk factors during clinical treatment.

Random forest regression on joint role of meteorological variables, demographic factors, and policy response measures in COVID-19 daily cases: global analysis in different climate zones.

Different sources of factors in environment can affect the spread of COVID-19 by influencing the diffusion of the virus transmission, but the collective influence of which has hardly been considered. This study aimed to utilize a machine learning algorithm to assess the joint effects of meteorological variables, demographic factors, and government response measures on COVID-19 daily cases globally at city level. Random forest regression models showed that population density was the most crucial determinant for COVID-19 transmission, followed by meteorological variables and response measures. Ultraviolet radiation and temperature dominated meteorological factors, but the associations with daily cases varied across different climate zones. Policy response measures have lag effect in containing the epidemic development, and the pandemic was more effectively contained with stricter response measures implemented, but the generalized measures might not be applicable to all climate conditions. This study explored the roles of demographic factors, meteorological variables, and policy response measures in the transmission of COVID-19, and provided evidence for policymakers that the design of appropriate policies for prevention and preparedness of future pandemics should be based on local climate conditions, population characteristics, and social activity characteristics. Future work should focus on discerning the interactions between numerous factors affecting COVID-19 transmission.

Association between meteorological factors and COVID-19 transmission in low- and middle-income countries: A time-stratified case-crossover study.

BACKGROUND: Evidence is limited regarding the association between meteorological factors and COVID-19 transmission in low- and middle-income countries (LMICs). OBJECTIVE: To investigate the independent and interactive effects of temperature, relative humidity (RH), and ultraviolet (UV) radiation on the spread of COVID-19 in LMICs. METHODS: We collected daily data on COVID-19 confirmed cases, meteorological factors and non-pharmaceutical interventions (NPIs) in 2143 city- and district-level sites from 6 LMICs during 2020. We applied a time-stratified case-crossover design with distributed lag nonlinear model to evaluate the independent and interactive effects of meteorological factors on COVID-19 transmission after controlling NPIs. We generated an overall estimate through pooling site-specific relative risks (RR) using a multivariate meta-regression model. RESULTS: There was a positive, non-linear, association between temperature and COVID-19 confirmed cases in all study sites, while RH and UV showed negative non-linear associations. RR of the 90th percentile temperature (28.1 °C) was 1.14 [95% confidence interval (CI): 1.02, 1.28] compared with the 50th percentile temperature (24.4 °C). RR of the10th percentile UV was 1.41 (95% CI: 1.29, 1.54). High temperature and high RH were associated with increased risks in temperate climate but decreased risks in tropical climate, while UV exhibited a consistent, negative association across climate zones. Temperature, RH, and UV interacted to affect COVID-19 transmission. Temperature and RH also showed higher risks in low NPIs sites. CONCLUSION: Temperature, RH, and UV appeared to independently and interactively affect the transmission of COVID-19 in LMICs but such associations varied with climate zones. Our results suggest that more attention should be paid to meteorological variation when the transmission of COVID-19 is still rampant in LMICs.

Neglected Aspects of SARS-CoV-2 Aerosol Transmission in Bathrooms of Multistory and High-Rise Buildings - Beijing Municipality, China, October 2022.

What is already known about this topic?: There is a toilet flush-soil stack-floor drain pathway of aerosol transmission in multistory and high-rise buildings, but the influencing factors are not completely clear. What is added by this report?: The poor airtightness of the connecting parts of the floor drain, as well as pressure fluctuations in the sewage pipe during toilet flushing caused by blockage of the soil stack vent, may lead to the cross-floor transmission of viral aerosols through the soil stack and floor drains. What are the implications for public health practice?: In multistory and high-rise buildings, the bathroom floor drains should be kept sealed, and floor drain connecting parts should be airtight. Furthermore, the soil stack vent should not be blocked. In this way, the cross-floor transmission of viral aerosols can be effectively reduced.

Independent and Interactive Effects of Environmental Conditions on Aerosolized Surrogate SARS-CoV-2 - Beijing, China, June to September 2020.

What is already known about this topic?: Environmental factors such as temperature and humidity play important roles in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via droplets/aerosols. What is added by this report?: Higher relative humidity (61%-80%), longer spreading time (120 min), and greater dispersal distance (1 m) significantly reduced SARS-CoV-2 pseudovirus loads. There was an interaction effect between relative humidity and spreading time. What are the implications for public health practice?: The findings contribute to our understanding of the impact of environmental factors on the transmission of SARS-CoV-2 via airborne droplets/aerosols.

AGEs/RAGE Promote Osteogenic Differentiation in Rat Bone Marrow-Derived Endothelial Progenitor Cells via MAPK Signaling.

Systemic vascular impairment is the most common complication of diabetes. Advanced glycation end products (AGEs) can exacerbate diabetes-related vascular damage by affecting the intima and media through a variety of mechanisms. In the study, we demonstrated that AGEs and their membrane receptor RAGE could induce the differentiation of EPCs into osteoblasts under certain circumstances, thereby promoting accelerated atherosclerosis. Differentiation into osteoblasts was confirmed by positive staining for DiI-acetylated fluorescently labeled low-density lipoprotein and FITC-conjugated Ulex europaeus agglutinin. During differentiation, expression of receptor for AGE (RAGE) was significantly upregulated. This upregulation was attenuated by transfection with RAGE-targeting small interfering (si)RNA. siRNA-mediated knockdown of RAGE expression significantly inhibited the upregulation of AGE-induced calcification-related proteins, such as runt-related transcription factor 2 (RUNX2) and osteoprotegerin (OPG). Additional experiments showed that AGE induction of EPCs significantly induced ERK, p38MAPK, and JNK activation. The AGE-induced upregulation of osteoblast proteins (RUNX2 and OPG) was suppressed by treatment with a p38MAPK inhibitor (SB203580) or JNK inhibitor (SP600125), but not by treatment with an ERK inhibitor (PD98059), which indicated that AGE-induced osteoblast differentiation from EPCs may be mediated by p38MAPK and JNK signaling, but not by ERK signaling. These data suggested that AGEs may bind to RAGE on the EPC membrane to trigger differentiation into osteoblasts. The underlying mechanism appears to involve the p38MAPK and JNK1/2 pathways, but not the ERK1/2 pathway.

A narrative review on the role of temperature and humidity in COVID-19: Transmission, persistence, and epidemiological evidence.

Since December 2019, the 2019 coronavirus disease (COVID-19) outbreak has become a global pandemic. Understanding the role of environmental conditions is important in impeding the spread of COVID-19. Given that airborne spread and contact transmission are considered the main pathways for the spread of COVID-19, this narrative review first summarized the role of temperature and humidity in the airborne trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Meanwhile, we reviewed the persistence of the virus in aerosols and on inert surfaces and summarized how the persistence of SARS-CoV-2 is affected by temperature and humidity. We also examined the existing epidemiological evidence and addressed the limitations of these epidemiological studies. Although uncertainty remains, more evidence may support the idea that high temperature is slightly and negatively associated with COVID-19 growth, while the conclusion for humidity is still conflicting. Nonetheless, the spread of COVID-19 appears to have been controlled primarily by government interventions rather than environmental factors.

AGEs promote calcification of HASMCs by mediating Pi3k/AKT-GSK3ß signaling.

This study aimed to investigate the effects of advanced glycation end products (AGEs) on the calcification of human arterial smooth muscle cells (HASMCs) and to explore whether AGEs can promote the calcification of HASMCs by activating the phosphoinositide 3-kinase (PI3K)/AKT-glycogen synthase kinase 3 beta (GSK3-ß) axis. Cultured HASMCs were divided into five groups: blank control group, dimethyl sulfoxide (vehicle) group, AGEs group, LY294002 (AKT inhibitor) group, and TWS119 (GSK3-ß inhibitor) group. Cells were pretreated with either vehicle, LY294002, or TWS119 for 2 hours followed by incubation with AGEs (25 µg/mL) for 5 days, and the expression levels of proteins in each group were analyzed by western blotting. AGE treatment promoted HASMC calcification, which coincided with increased expression of p-AKT and p-GSK3-ß (serine 9). Also, AGEs upregulated the expression of osteoprotegerin and bone morphogenetic protein, and these effects were suppressed by LY294002 but enhanced by TWS119. In conclusion, AGEs promote calcification of HASMCs, and this effect is ameliorated by inhibition of AKT activity but potentiated by inhibition of GSK3-ß activity. Hence, AGEs trigger HASMC calcification by regulating PI3K/AKT-GSK3-ß signaling.

Controllable Phosphorylation of Thioesters: Selective Synthesis of Aryl and Benzyl Phosphoryl Compounds.

The controllable phosphorylations of thioesters were developed. When the reaction was catalyzed by a palladium catalyst, aryl or alkenyl phosphoryl compounds were generated through decarbonylative coupling, while the benzyl phosphoryl compounds were produced through deoxygenative coupling when the reaction was carried out in the presence of only a base.

Advanced Glycation End Products Induce Proliferation and Migration of Human Aortic Smooth Muscle Cells through PI3K/AKT Pathway.

Advanced glycation end products (AGEs) have been widely regarded as an important inducing factor in the pathogenesis of diabetic arteriosclerosis, and the proliferation and migration of vascular smooth muscle cells (VSMCs) are also involved in this process. However, it is not clear whether AGEs promote atherosclerosis by inducing the proliferation and migration of VSMCs. To figure out this question, this study investigated the effects of AGEs on the proliferation and migration of human aorta vascular smooth muscle cells (HASMCs) and the underlying mechanisms. This study evaluated the effects of different concentrations of AGEs on cell proliferation and migration. CCK8, transwell, and western blotting assays demonstrated that AGEs significantly increased cell proliferation and migration in a concentration-dependent manner and that the optimal proproliferative and promigratory concentrations of AGEs were 10 mg/L and 20 mg/L, respectively. AGE-induced cell proliferation, migration, and expression of filament actin (F-actin) were markedly attenuated by a PI3K inhibitor (LY2940002). Additionally, the phosphorylation of AKT was reduced when the receptor of advanced glycation end product (RAGE) gene was silenced by lentivirus transfection, which led to a concomitant reduction of the expression of proliferation and migration-related proteins. These data indicate that AGEs may activate the PI3K/AKT pathway through RAGE and thus facilitate the proliferation and migration of HASMCs.

Palladium-Catalyzed N-Acylation of Tertiary Amines by Carboxylic Acids: A Method for the Synthesis of Amides.

A palladium-catalyzed N-acylation of tertiary amines by carboxylic acids was achieved through C-N cleavage. This reaction showed a wide substrate scope. Both aromatic and aliphatic acids served well as the acylating reagents and coupled with tertiary amines to produce the corresponding amides in good to excellent yields. With the strategy, bioactive carboxylic acids were also efficiently modified, highlighting the synthetic value of the process in organic synthesis.

Purification and characterization of Inonotus hispidus exopolysaccharide and its protective effect on acute alcoholic liver injury in mice.

This study characterized the Inonotus hispidus extracellular exopolysaccharide (IHEPS) from fermentation broth and investigated its liver protective effect on acute alcoholic liver injury in mice. The characterization of IHEPS was analyzed by HPLC, UV-vis and FT-IR. To determine the liver protective effect of IHEPS, mice were administered with IHEPS once daily for 3 weeks, before ethanol induced acute alcoholic liver injury. Biochemical parameters of liver function, histopathological sections, mRNA and protein expression of related antioxidant enzymes were compared between with or without IHEPS administrated mice. As a result, IHEPS could extend the duration of righting reflex, shorten the durations of the recovery, and decrease the liver index in acute alcoholic liver mice. At the same time, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) levels were decreased in IHEPS mice. Moreover, increased alcohol dehydrogenase (ADH), catalase (CAT) and superoxide dismutase (SOD) levels were also found in IHEPS mice. Furthermore, IHEPS activated Nrf2 signaling pathway and increased the expression of downstream related antioxidant enzymes, such as NQO1, CAT and Cu-Zn SOD.

Extraction, characterization and antioxidant activity analysis of the polysaccharide from the solid-state fermentation substrate of Inonotus hispidus.

A polysaccharide from Inonotus hispidus was prepared by solid-state fermentation (SSF), and an efficient ultrasound-assisted extraction method was used to optimize the extraction process of Inonotus hispidus solid-state fermentation polysaccharide (IHSFP). The optimal extraction parameters were as follows: solid-liquid ratio of 1:40, ultrasound time of 34 min, ultrasound power of 350 W and ultrasound temperature of 70 °C. The yield of IHSFP was 51.06 ±â€¯0.34% under the optimal conditions. Two types of polysaccharide fractions (IHSFP-1 and IHSFP-2) were isolated by DEAE-52 and Sephadex G-200 columns. IHSFP-2 had stronger antioxidant activity than IHSFP-1, and it can reduce H2O2-induced oxidative damage to cells in vitro. Therefore, the properties of IHSFP-2 were further characterized. The results showed that the molecular weight of IHSFP-2 was 14.44 kDa, it was composed of glucose (Glc), mannose (Man), galactose (Gal), glucuronic acid (GlcUA), galactosamine (GalN), arabinose (Ara) and ribose (Rib), and the contents of these monosaccharides were 51%, 21%, 20%, 3%, 2%, 2% and 1%, respectively. The results of this study may contribute to the efficient production of the polysaccharide of Inonotus hispidus, and provide new ideas for its application in functional foods and cosmetics.