Physicochemical code for quinary protein interactions in Escherichia coli

This study shows that the diffusive motions of proteins in live cells are by no means without control but follow simplistic physical−chemical rules that can be quantified and optimized through surface composition. Most strikingly, human proteins are observed to stick to the “foreign” environment of bacterial cells, whereas the bacterial analogue moves around freely. Even so, the human proteins can predictably be transformed to bacterial behavior with a few structurally benign surface mutations, and, conversely, the bacterial protein can be made to stick. The findings have not only fundamental implications for how protein function is controlled at the physical−chemical level but can also be used to adjust protein motion in Escherichia coli at will

Microenvironment Restruction of Emerging 2D Materials and their Roles in Therapeutic and Diagnostic Nano-Bio-Platforms

Engineering advanced therapeutic and diagnostic nano-bio-platforms (NBPFs) have emerged as rapidly-developed pathways against a wide range of challenges in antitumor, antipathogen, tissue regeneration, bioimaging, and biosensing applications. Emerged 2D materials have attracted extensive scientific interest as fundamental building blocks or nanostructures among material scientists, chemists, biologists, and doctors due to their advantageous physicochemical and biological properties. This timely review provides a comprehensive summary of creating advanced NBPFs via emerging 2D materials (2D-NBPFs) with unique insights into the corresponding molecularly restructured microenvironments and biofunctionalities. First, it is focused on an up-to-date overview of the synthetic strategies for designing 2D-NBPFs with a cross-comparison of their advantages and disadvantages. After that, the recent key achievements are summarized in tuning the biofunctionalities of 2D-NBPFs via molecularly programmed microenvironments, including physiological stability, biocompatibility, bio-adhesiveness, specific binding to pathogens, broad-spectrum pathogen inhibitors, stimuli-responsive systems, and enzyme-mimetics. Moreover, the representative therapeutic and diagnostic applications of 2D-NBPFs are also discussed with detailed disclosure of their critical design principles and parameters. Finally, current challenges and future research directions are also discussed. Overall, this review will provide cutting-edge and multidisciplinary guidance for accelerating future developments and therapeutic/diagnostic applications of 2D-NBPFs

Effectiveness of decision support tools on reducing antibiotic use for respiratory tract infections: a systematic review and meta-analysis

Background: Clinical decision support tools (CDSs) have been demonstrated to enhance the accuracy of antibiotic prescribing among physicians. However, their effectiveness in reducing inappropriate antibiotic use for respiratory tract infections (RTI) is controversial.Methods: A literature search in 3 international databases (Medline, Web of science and Embase) was conducted before 31 May 2023. Relative risk (RR) and corresponding 95% confidence intervals (CI) were pooled to evaluate the effectiveness of intervention. Summary effect sizes were calculated using a random-effects model due to the expected heterogeneity (I2 over 50%).Results: A total of 11 cluster randomized clinical trials (RCTs) and 5 before-after studies were included in this meta-analysis, involving 900,804 patients met full inclusion criteria. Among these studies, 11 reported positive effects, 1 reported negative results, and 4 reported non-significant findings. Overall, the pooled effect size revealed that CDSs significantly reduced antibiotic use for RTIs (RR = 0.90, 95% CI = 0.85 to 0.95, I2 = 96.10%). Subgroup analysis indicated that the intervention duration may serve as a potential source of heterogeneity. Studies with interventions duration more than 2 years were found to have non-significant effects (RR = 1.00, 95% CI = 0.96 to 1.04, I2 = 0.00%). Egger’s test results indicated no evidence of potential publication bias (p = 0.287).Conclusion: This study suggests that CDSs effectively reduce inappropriate antibiotic use for RTIs among physicians. However, subgroup analysis revealed that interventions lasting more than 2 years did not yield significant effects. These findings highlight the importance of considering intervention duration when implementing CDSs.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432584, Identifier: PROSPERO (CRD42023432584)

Evaluation of the impact of the COVID-19 pandemic on health service utilization in China: A study using auto-regressive integrated moving average model

BackgroundThe outbreak of COVID-19 in early 2020 presented a major challenge to the healthcare system in China. This study aimed to quantitatively evaluate the impact of COVID-19 on health services utilization in China in 2020.MethodsHealth service-related data for this study were extracted from the China Health Statistical Yearbook. The Auto-Regressive Integrated Moving Average model (ARIMA) was used to forecast the data for the year 2020 based on trends observed between 2010 and 2019. The differences between the actual 2020 values reported in the statistical yearbook and the forecast values from the ARIMA model were used to assess the impact of COVID-19 on health services utilization.ResultsIn 2020, the number of admissions and outpatient visits in China declined by 17.74 and 14.37%, respectively, compared to the ARIMA model’s forecast values. Notably, public hospitals experienced the largest decrease in outpatient visits and admissions, of 18.55 and 19.64%, respectively. Among all departments, the pediatrics department had the greatest decrease in outpatient visits (35.15%). Regarding geographical distribution, Beijing and Heilongjiang were the regions most affected by the decline in outpatient visits (29.96%) and admissions (43.20%) respectively.ConclusionThe study’s findings suggest that during the first year of the COVID-19 pandemic, one in seven outpatient services and one in six admissions were affected in China. Therefore, there is an urgent need to establish a green channel for seeking medical treatment without spatial and institutional barriers during epidemic prevention and control periods

A role for two-pore potassium (K2P) channels in endometrial epithelial function.

The human endometrial epithelium is pivotal to menstrual cycle progression, implantation and early pregnancy. Endometrial function is directly regulated by local factors that include pH, oxygen tension and ion concentrations to generate an environment conducive to fertilization. A superfamily of potassium channels characterized by two-pore domains (K2P) and encoded by KCNK genes is implicated in the control of the cell resting membrane potential through the generation of leak currents and modulation by various physicochemical stimuli. The aims of the study were to determine the expression and function of K2P channel subtypes in proliferative and secretory phase endometrium obtained from normo-ovulatory women and in an endometrial cancer cell line. Using immunochemical methods, real-time qRT-PCR proliferation assays and electrophysiology. Our results demonstrate mRNA for several K2P channel subtypes in human endometrium with molecular expression of TREK-1 shown to be higher in proliferative than secretory phase endometrium (P < 0.001). The K2P channel blockers methanandamide, lidocaine, zinc and curcumin had antiproliferative effects (P < 0.01) in an endometrial epithelial cancer cell line indicating a role for TASK and TREK-1 channels in proliferation. Tetraethylammonium- and 4-aminopyridine-insensitive outwards currents were inhibited at all voltages by reducing extracellular pH from 7.4 to 6.6. Higher expression of TREK-1 expression in proliferative phase endometrium may, in part, underlie linked to increased cell division. The effects of pH and a lack of effect of non-specific channel blockers of voltage-gated potassium channels imply a role for K2P channels in the regulation of human endometrial function

Accelerated apoptotic death and <i>in vivo</i> turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2

The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk−/−) and corresponding wild-type mice (msk+/+). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk−/− and msk+/+ mice, but reticulocyte count was significantly increased in msk−/− mice. Cell membrane PS exposure was similar in untreated msk−/− and msk+/+ erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk−/− erythrocytes than in msk+/+ erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk−/− erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk−/− mice. The spleens from msk−/− mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk+/+ mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice

Photoelectric Emission from Interstellar Dust: Grain Charging and Gas Heating

We model the photoelectric emission from and charging of interstellar dust and obtain photoelectric gas heating efficiencies as a function of grain size and the relevant ambient conditions. Using realistic grain size distributions, we evaluate the net gas heating rate for various interstellar environments, and find less heating for dense regions characterized by R_V=5.5 than for diffuse regions with R_V=3.1. We provide fitting functions which reproduce our numerical results for photoelectric heating and recombination cooling for a wide range of interstellar conditions. In a separate paper we will examine the implications of these results for the thermal structure of the interstellar medium. Finally, we investigate the potential importance of photoelectric heating in H II regions, including the warm ionized medium. We find that photoelectric heating could be comparable to or exceed heating due to photoionization of H for high ratios of the radiation intensity to the gas density. We also find that photoelectric heating by dust can account for the observed variation of temperature with distance from the galactic midplane in the warm ionized medium.Comment: 50 pages, including 18 figures; corrected title and abstract field

Primary cilia-associated protein IFT172 in ciliopathies

Cilium is a highly conserved antenna-like structure protruding from the surface of the cell membrane, which is widely distributed on most mammalian cells. Two types of cilia have been described so far which include motile cilia and immotile cilia and the latter are also known as primary cilia. Dysfunctional primary cilia are commonly associated with a variety of congenital diseases called ciliopathies with multifaceted presentations such as retinopathy, congenital kidney disease, intellectual disability, cancer, polycystic kidney, obesity, Bardet Biedl syndrome (BBS), etc. Intraflagellar transport (IFT) is a bi-directional transportation process that helps maintain a balanced flow of proteins or signaling molecules essential for the communication between cilia and cytoplasm. Disrupted IFT contributes to the abnormal structure or function of cilia and frequently promotes the occurrence of ciliopathies. Intraflagellar transport 172 (IFT172) is a newly identified member of IFT proteins closely involved in some rare ciliopathies such as Mainzer-Saldino syndrome (MZSDS) and BBS, though the underpinning causal mechanisms remain largely elusive. In this review, we summarize the key findings on the genetic and protein characteristic of IFT172, as well as its function in intraflagellar transport, to provide comprehensive insights to understand IFT172-related ciliopathies

Different Physical Activity Subtypes and Risk of Metabolic Syndrome in Middle-Aged and Older Chinese People

Background: The prevalence of metabolic syndrome (MetS) is growing rapidly in China. Tai chi and dancing are common types of exercise among middle-aged and elderly Chinese. It remains unclear whether these activities are associated with a lower risk of MetS. Methodology/Principal Findings A total of 15,514 individuals (6,952 men, 8,562 women) aged 50 to 70 years from the Dongfeng-Tongji Cohort in Shiyan, China participated in a cross-sectional study. Physical activity and other lifestyle factors were assessed with semi-structured questionnaires during face-to-face interviews. MetS was defined by the current National Cholesterol Education Program/Adult treatment Panel III criteria for Asian Americans. The prevalence of MetS was 33.2% in the study population. In the multivariable-adjusted logistic regression analyses, total physical activity levels were monotonically associated with a lower odds of MetS [OR 0.75 comparing extreme quintiles, 95% confidence interval (CI) 0.66–0.86, P<0.001]. Compared with non-exercisers in a specific exercise type, jogging (OR 0.82, 95% CI 0.68–1.00, P = 0.046), tai chi (OR 0.72, 95% CI 0.60–0.88, P<0.001), and dancing (OR 0.56, 95% CI 0.47–0.67, P<0.001) were associated with significantly lower odds of MetS. Furthermore, each 1–h/week increment in tai chi and dancing was associated with a 5% (95% CI 2%–9%) and a 9% (95% CI 6%, 12%) lower risk of MetS. Conclusions/Significance: Jogging, tai chi and dancing are associated with a significantly lower risk of having MetS in middle-aged and older Chinese. Future intervention studies should consider the role of jogging, tai chi and dancing in preventing MetS