Culture and political regimes: How have they influenced the effectiveness of COVID-19 response policy?

This study investigates the efficacy of national emergency response policies in addressing the COVID-19 pandemic and their interactions with cultural and political factors. Employing the synthetic control method, we analyze data from countries on five continents that implemented such policies in early 2020. Our results indicate the overall effectiveness of these policies in mitigating the impact of COVID-19 yet reveal significant variability in their outcomes among countries. Notably, we identify a negative association between policy effectiveness and a culture characterized by individualism. Additionally, we observe that the impact of COVID-19 response measures is more prominent in countries with lower levels of democracy. These findings offer valuable insights into the intricate interplay between COVID-19 response policies, cultural dynamics, and political regimes, with potential implications for future policy decisions and research endeavors.

Cyclic GMP-AMP synthase recognizes the physical features of DNA.

Cyclic GMP-AMP synthase (cGAS) is a major cytosolic DNA sensor that plays a significant role in innate immunity. Upon binding to double stranded DNA (dsDNA), cGAS utilizes GTP and ATP to synthesize the second messenger cyclic GMP-AMP (cGAMP). The cGAMP then binds to the adapter protein stimulator of interferon genes (STING) in the endoplasmic reticulum, resulting in the activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent induction of type I interferon. An important question is how cGAS distinguishes between self and non-self DNA. While cGAS binds to the phosphate backbone of DNA without discrimination, its activation is influenced by physical features such as DNA length, inter-DNA distance, and mechanical flexibility. This suggests that the recognition of DNA by cGAS may depend on these physical features. In this article we summarize the recent progress in research on cGAS-STING pathway involved in antiviral defense, cellular senescence and anti-tumor response, and focus on DNA recognition mechanisms based on the physical features.

Combined alkali-photocatalytic stimulation enables click microbial domestication for boosted ammonia nitrogen removal.

Microbe-driven ammonia nitrogen removal plays a crucial role in the nitrogen cycle and wastewater treatment. However, the rational methods and mechanisms for boosting nitrogen conversion through microbial domestication are still limited. Herein, a combined alkali-photocatalytic stimulation strategy was developed to activate the Halomonas shizuishanensis DWK9 for efficient ammonia nitrogen removal. The strain DWK9 selected from saline-alkaline soil in Northwestern China possessed strong resistance to stress of saline-alkaline environment and free radicals, and was abundant in nitrogen conversion genes, thus is an ideal model for advanced microbial domestication. Bacterial in the combined alkali-photocatalytic stimulation group achieved a high ammonia nitrogen conversion rate of 67.5 %, 10 times outperforming the non-stimulated and single alkali/photocatalytic stimulation control groups. Morphology analysis revealed that the bacteria in the alkali-photocatalytic stimulated group formed a favorable structure for bioelectric transfer. Remarkably, the domesticated bacteria demonstrated improved electrochemical properties, including increased current capacity and lower overpotentials and impedance. Prokaryotic transcription genetic analysis together with qPCR analysis showed upregulation of denitrification-related metabolic pathway genes. A novel FAD dependent and NAD(P)H independent energy mode has been proposed. The universality and effectiveness of the as-developed combined alkali-photocatalytic microbial domestication strategy were further validated through indicator fish survival experiments. This work provides unprecedented degrees of freedom for the exploration of rational microbial engineering for optimized and controllable biogeochemical conversion.

Phosphorus fertilization enhanced overwintering, root system and forage yield of late-seeded alfalfa in sodic soils.

Sowing date and soil fertility are very important factors in the overwintering and production performance of alfalfa (Medicago sativa L.), yet there's a knowledge gap in knowledge on how late-seeded alfalfa responds to phosphorus (P) fertilization. A field study was conducted in Inner Mongolia from 2020 to 2022 using a split-plot design. The main plots consisted of five sowing dates (31 July, 8, 16, and 24 August, and 1 September), while the subplots involved five P application rates (0, 40, 70, 100, and 130 kg P2O5 ha-1). Throughout the growing seasons, the overwintering rate, root traits, forage yield, and yield components were measured. The results revealed a consistent decrease in overwintering ability and productivity with the delayed sowing. This reduction in overwintering rate was mainly due to diminished root traits, while the decrease in forage yield was largely associated with a reduction in plants per square meter. However, P fertilizer application to late-seeded alfalfa demonstrated potential in enhancing the diameter of both the crown and taproot, thus strengthening the root system and improving the overwintering rate, the rate of increase ranges from 11.6 to 49%. This adjustment could also improve the shoots per square meter and mass per shoot, increasing by 9.4-31.3% and 15.0-27.1% respectively in 2 years, which can offset the decline in forage yield caused by late sowing and might even increase the forage yield. Regression and path analysis indicated that alfalfa forage yield is primarily affected by mass per shoot rather than shoots per square meter. This study recommended that the sowing of alfalfa in similar regions of Inner Mongolia should not be later than mid-August. Moreover, applying P fertilizer (P2O5) at 70.6-85.9 kg ha-1 can enhance the forage yield and persistence of late-seeded alfalfa. Therefore, appropriate late sowing combined with the application of P fertilizer can be used as an efficient cultivation strategy for alfalfa cultivation after a short-season crop harvest in arid and cold regions.

A nomogram model for predicting postoperative prognosis in patients with aneurysmal subarachnoid hemorrhage using preoperative biochemical indices.

OBJECTIVE: The nutritional status and inflammatory responses of patients with aneurysmal subarachnoid hemorrhage (aSAH) play a vital prognostic role. We investigated the relationship between preoperative prognostic nutritional index (PNI)、neutrophil/albumin ratio (NAR)、platelet/albumin ratio (PAR) and other factors and the clinical prognosis of patients who underwent clipping for aSAH and its predictive model. METHODS: The clinical data of 212 patients with aSAH who underwent neurosurgery at Nanyang Central Hospital between 2018 and 2023 were retrospectively analyzed. Based on the Glasgow Outcome Scale (GOS) score at 6 months postoperatively, the patients were categorized into two groups: poor (GOSI-III) and good (GOSIV-V) prognosis groups. Multivariate logistic regression analysis was performed to determine the predictive value of preoperative PNI、NAR、PAR、hyperlipidemia and Glasgow Coma Scale (GCS) for prognosis. Furthermore, nomograms and prognostic prediction models were constructed. Receiver operating characteristic curves and area under the curve (AUC) were utilized to determine the predictive values. RESULTS: Multivariate logistic regression analysis revealed that PNI (OR = 1.250, 95%CI 1.060 ~ 1.475, P = 0.008), NAR (OR = 0.000, 95%CI 0.000 ~ 0.004, P = 0.000), PAR(OR = 0.515, 95%CI 0.283 ~ 0.937, P = 0.030), hyperlipidemia (OR = 4.627, 95%CI 1.166 ~ 18.367, P = 0.029), and GCS(OR = 1.446, 95%CI 1.041 ~ 2.008, P = 0.028) are independent risk factors for poor postoperative prognosis. The total score of the nomogram was 200, and the AUC value was 0.972. CONCLUSIONS: PNI and NAR can reflect the nutritional status and inflammatory responses of patients.They are significantly associated with the postoperative prognosis of patients with aSAH. Comprehensively analyzing PNI and NAR combined with other clinical indicators can more effectively guide treatment and help predict prognosis.

Novel insight into the feed conversion ratio in laying hens and construction of its prediction model.

Feed efficiency (FE) is an important economic factor in poultry production, and feed conversion ratio (FCR) is one of the most widely used measures of FE. Factors associated with FCR include genetics, the environment, and other factors. However, the mechanisms responsible for FCR in chickens are still less well appreciated. In this study, we examined the pattern changes of FCR, then delved into understanding the mechanisms behind these variations from both genetic and environmental perspectives. Most interestingly, the FCR at the front section of henhouse exhibited the lowest value. Further investigation revealed that laying rate in the high FCR (HFCR) group was lower than that in the low FCR (LFCR) group (P < 0.05). Cortisol, total antioxidant capacity (TAOC), and IgG levels in the LFCR group were significantly lower than those in the HFCR group (P < 0.05), while BUN level was significantly higher than that in the HFCR group (P < 0.05). We identified a total of 67 and 10 differentially expressed genes (DEGs) associated with FCR in ovarian and small intestine tissues, respectively. Functional enrichment analysis of DEGs revealed that they might affect FCR by modulating genes associated with salivary secretion, ferroptosis, and mineral absorption. Moreover, values for relative humidity (RH), air velocity (AV), PM2.5, ammonia (NH3), and carbon dioxide (CO2) in the LFCR group were significantly lower than those in the HFCR group (P < 0.05). Conversely, value for light intensity (LI) in the LFCR group was significantly higher than that in the HFCR group (P < 0.05). Correlation analysis revealed a positive correlation between FCR and RH, AV, PM2.5, NH3, and CO2, and a negative correlation with LI. Finally, the FCR prediction model was successfully constructed based on multiple environmental variables using the random forest algorithm, providing a valuable tool for predicting FCR in chickens.

Feasibility of noninvasive near-infrared spectroscopy monitoring in predicting the prognosis of spontaneous intracerebral hemorrhage.

Objective: This study aimed to assess the impact of multimodal monitoring on predicting the prognosis of patients with spontaneous intracerebral hemorrhage (SICH) and to examine the feasibility of using noninvasive near-infrared spectroscopy (NIRS) for monitoring clinical prognosis. Methods: Clinical data of 38 patients with SICH who underwent surgery in the Department of Neurosurgery of Shaanxi Provincial People's Hospital from May 2022 to December 2022 were retrospectively analyzed. The patients were categorized into two groups based on the Glasgow Outcome Scale (GOS) 3 months after operation: poor outcome group (GOSI-III) and good outcome group (GOSIV and V). Multimodal monitoring included invasive intracranial pressure (ICP), brain temperature (BT), internal jugular venous oxygen saturation (SjvO2), and noninvasive NIRS. NIRS monitoring comprised the assessment of brain tissue oxygen saturation (StO2), blood volume index (BVI), and tissue hemoglobin index (THI). The prognostic differences between the two groups were compared. The predictive values were evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: ICP, BT, BVI, and THI in the good prognosis group were lower than those in the poor prognosis group. The SjvO2 and StO2 in the group with a good prognosis were higher than those in the group with a poor prognosis. Conclusion: The levels of ICP, BT, SjvO2, StO2, BVI, and THI reflect the changes in brain function and cerebral blood flow and significantly correlate with the prognosis of patients with SICH. NIRS monitoring has a high clinical utility in assessing the prognosis.

Enhancing therapeutic potential: Human adipose-derived mesenchymal stem cells modified with recombinant adeno-associated virus expressing VEGF165 gene for peripheral nerve injury.

This study aimed to investigate the therapeutic potential of human adipose-derived mesenchymal stem cells (hADSCs) modified with recombinant adeno-associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate-buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control-hADSCs group), or rAAV VEGF165 vector (VEGF165-hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium-binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165-hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV-VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.

Multi-Sensor-Assisted Low-Cost Indoor Non-Visual Semantic Map Construction and Localization for Modern Vehicles.

With the transformation and development of the automotive industry, low-cost and seamless indoor and outdoor positioning has become a research hotspot for modern vehicles equipped with in-vehicle infotainment systems, Internet of Vehicles, or other intelligent systems (such as Telematics Box, Autopilot, etc.). This paper analyzes modern vehicles in different configurations and proposes a low-cost, versatile indoor non-visual semantic mapping and localization solution based on low-cost sensors. Firstly, the sliding window-based semantic landmark detection method is designed to identify non-visual semantic landmarks (e.g., entrance/exit, ramp entrance/exit, road node). Then, we construct an indoor non-visual semantic map that includes the vehicle trajectory waypoints, non-visual semantic landmarks, and Wi-Fi fingerprints of RSS features. Furthermore, to estimate the position of modern vehicles in the constructed semantic maps, we proposed a graph-optimized localization method based on landmark matching that exploits the correlation between non-visual semantic landmarks. Finally, field experiments are conducted in two shopping mall scenes with different underground parking layouts to verify the proposed non-visual semantic mapping and localization method. The results show that the proposed method achieves a high accuracy of 98.1% in non-visual semantic landmark detection and a low localization error of 1.31 m.

Influence of hypocalcemia on the prognosis of patients with multiple trauma.

BACKGROUND: Hypocalcemia is highly common in hospitalized patients, especially in those with trauma, On the other hand, abnormal calcium metabolism is an important metabolic challenge; however, it is often neglected and untreated, and certain factors may induce serious neurological and cardiovascular complications. AIM: To retrospectively analyze the impact of hypocalcemia on the prognosis of patients with multiple traumas. METHODS: The study was conducted from January 2020 to December 2021. Ninety-nine patients with multiple injuries were treated at the critical care medicine department of Fuyang People's Hospital. The selected indicators included sex, age, and blood calcium and hematocrit levels. Many indicators were observed, including within 24 h of hospitalization, and the prognosis was collected after 28 d. Based on the blood calcium levels, the patients were divided into the following two groups: Normocalcemia and hypocalcemia. Of the 99 patients included, 81 had normocalcemia, and 18 had hypocalcemia. Separate experiments were conducted for these two groups. RESULTS: There was an association between serum calcium levels and the prognosis of patients with polytrauma. CONCLUSION: Clinically, the prognosis of patients with multiple traumas can be preliminarily evaluated based on serum calcium levels.

Utilizing deep learning algorithms for automated oil spill detection in medium resolution optical imagery.

This study evaluates the performance of three typical convolutional neural network based deep learning algorithms for oil spill detection using medium-resolution optical satellite imagery from Sentinel-2 MSI, Landsat-8 OLI, and Landsat-9 OLI2. Oil slick training and validation dataset were created through a semi-automatic labeling approach, based on chronic and accidental oil spill cases reported worldwide. The research enhances UNet, BiSeNetV2, and DeepLabV3+ architectures by integrating attention mechanisms including the Squeeze-and-Excitation module (SE), Convolutional Block Attention Module (CBAM), and a Simple, parameter-free Attention Module (SimAM), analyzing the optimal model for oil spill detection. Notably, UNet integrated with CBAM, especially with sun glint as a feature, significantly outperformed others, achieving a micro-average F1 score of 88.8 %. This research highlights deep learning's potential in optical remote sensing for oil spill detection, stressing its escalating relevance with the growing deployment of medium- to high-resolution optical satellites.

Dynamic Features of Body Mass Index in Late Life Predict Cognitive Trajectories and Alzheimer's Disease: A Longitudinal Study.

Background: The causal relationships of late-life body mass index (BMI) with Alzheimer's disease (AD) remains debated. Objective: We aimed to assess the associations of dynamic BMI features (ΔBMIs) with cognitive trajectories, AD biomarkers, and incident AD risk. Methods: We analyzed an 8-year cohort of 542 non-demented individuals who were aged ≥65 years at baseline and had BMI measurements over the first 4 years. ΔBMIs were defined as changing extent (change ≤ or >5%), variability (standard deviation), and trajectories over the first 4 years measured using latent class trajectory modeling. Linear mixed-effect models were utilized to examine the influence of ΔBMIs on changing rates of AD pathology biomarkers, hippocampus volume, and cognitive functions. Cox proportional hazards models were used to test the associations with AD risk. Stratified analyzes were conducted by the baseline BMI group and age. Results: Over the 4-year period, compared to those with stable BMI, individuals who experienced BMI decreases demonstrated accelerated declined memory function (p = 0.006) and amyloid-ß deposition (p = 0.034) while BMI increases were associated with accelerated hippocampal atrophy (p = 0.036). Three BMI dynamic features, including stable BMI, low BMI variability, and persistently high BMI, were associated with lower risk of incident AD (p < 0.005). The associations were validated over the 8-year period after excluding incident AD over the first 4 years. No stratified effects were revealed by the BMI group and age. Conclusions: High and stable BMI in late life could predict better cognitive trajectory and lower risk of AD.

Vitamin D and Atherosclerosis: Unraveling the Impact on Macrophage Function.

Vitamin D plays a crucial role in preventing atherosclerosis and in the regulation of macrophage function. This review aims to provide a comprehensive summary of the clinical evidence regarding the impact of vitamin D on atherosclerotic cardiovascular disease, atherosclerotic cerebrovascular disease, peripheral arterial disease, and associated risk factors. Additionally, it explores the mechanistic studies investigating the influence of vitamin D on macrophage function in atherosclerosis. Numerous findings indicate that vitamin D inhibits monocyte or macrophage recruitment, macrophage cholesterol uptake, and esterification. Moreover, it induces autophagy of lipid droplets in macrophages, promotes cholesterol efflux from macrophages, and regulates macrophage polarization. This review particularly focuses on analyzing the molecular mechanisms and signaling pathways through which vitamin D modulates macrophage function in atherosclerosis. It claims that vitamin D has a direct inhibitory effect on the formation, adhesion, and migration of lipid-loaded monocytes, thus exerting anti-atherosclerotic effects. Therefore, this review emphasizes the crucial role of vitamin D in regulating macrophage function and preventing the development of atherosclerosis.

Concentration-resistance relationship and PK/PD evaluation of danofloxacin against emergence of resistant Pasteurella multocida in an in vitro dynamic model.

AIMS: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. METHODS AND RESULTS: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.

Seasonal and Genetic Characteristics of Human Metapneumovirus Circulating - Henan Province, China, 2017-2023.

Introduction: This study examines the seasonal and genetic characteristics of human metapneumovirus (HMPV) in Henan from 2017 to 2023. Methods: Samples from patients with acute respiratory infection (ARI) testing positive for HMPV were subjected to real-time reverse transcription polymerase chain reaction The G gene was amplified and sequenced from these samples for epidemiological and phylogenetic analysis. Results: We enrolled 2,707 ARI patients from October 2017 to March 2023, finding an HMPV positivity rate of 6.17% (167/2,707). Children under five exhibited the highest infection rate at 7.78% (138/1,774). The 2018 and 2019 HMPV outbreaks predominantly occurred in spring (March to May), with peak positivity rates of 31.11% in May 2018 and 19.57% in May 2019. A notable increase occurred in November 2020, when positivity reached a historic high of 42.11%, continuing until January 2021. From February 2021 through March 2023, no significant seasonal peaks were observed, with rates ranging from 0% to 8.70%. Out of 81 G gene sequences analyzed, 46.91% (38/81) were identified as subtype A (A2c: 45.67%, 37/81; A2b: 1.23%, 1/81) and 53.09% (43/81) as subtype B (B1: 9.88%, 8/81; B2: 43.21%, 35/81). Notably, an AAABBA switch pattern was observed in HMPV subtypes. The dominant strains were A2c111nt-dup in subtype A and B2 in subtype B. Conclusions: Six years of surveillance in Henan Province has detailed the seasonal and genetic dynamics of HMPV, contributing valuable insights for the control and prevention of HMPV infections in China. These findings support the development of targeted HMPV vaccines and immunization strategies.

Exploring the therapeutic mechanisms of resveratrol for treating arecoline-induced malignant transformation in oral epithelial cells: insights into hub targets.

BACKGROUND: Betel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non-flavonoid polyphenol, possesses anti-cancer properties. It has been shown to inhibit arecoline-induced oral malignant cells in preliminary experiments but the underlying mechanism remains unclear. This research therefore aimed to explore the potential therapeutic targets of resveratrol in treating arecoline-induced oral cancer. METHODS: Data mining identified common targets and hub targets of resveratrol in arecoline-induced oral cancer. Gene set variation analysis (GSVA) was used to score and validate the expression and clinical significance of these hub targets in head and neck cancer (HNC) tissues. Molecular docking analysis was conducted on the hub targets. The effect of resveratrol intervention on hub targets was verified by experiments. RESULTS: Sixty-one common targets and 15 hub targets were identified. Hub targets were highly expressed in HNC and were associated with unfavorable prognoses. They played a role in HNC metastasis, epithelial-mesenchymal transition, and invasion. Their expression also affected immune cell infiltration and correlated negatively with sensitivity to chemotherapeutic agents such as bleomycin and docetaxel. Experiments demonstrated that resveratrol down-regulated the expression of the hub targets, inhibited their proliferation and invasion, and induced apoptosis. CONCLUSION: Resveratrol inhibits the arecoline-induced malignant phenotype of oral epithelial cells by regulating the expression of some target genes, suggesting that resveratrol may be used not only as an adjuvant treatment for oral cancer, but also as an adjuvant for oral cancer prevention due to its low toxicity and high efficacy. © 2024 Society of Chemical Industry.

The effect of extracellular polymeric substances on MICP solidifying rare earth slags and stabilizing Th and U.

Microbially induced carbonate precipitation (MICP) has been used to cure rare earth slags (RES) containing radionuclides (e.g. Th and U) and heavy metals with favorable results. However, the role of microbial extracellular polymeric substances (EPS) in MICP curing RES remains unclear. In this study, the EPS of Lysinibacillus sphaericus K-1 was extracted for the experiments of adsorption, inducing calcium carbonate (CaCO3) precipitation and curing of RES. The role of EPS in in MICP curing RES and stabilizing radionuclides and heavy metals was analyzed by evaluating the concentration and morphological distribution of radionuclides and heavy metals, and the compressive strength of the cured body. The results indicate that the adsorption efficiencies of EPS for Th (IV), U (VI), Cu2+, Pb2+, Zn2+, and Cd2+ were 44.83%, 45.83%, 53.7%, 61.3%, 42.1%, and 77.85%, respectively. The addition of EPS solution resulted in the formation of nanoscale spherical particles on the microorganism surface, which could act as an accumulating skeleton to facilitate the formation of CaCO3. After adding 20 mL of EPS solution during the curing process (Treat group), the maximum unconfined compressive strength (UCS) of the cured body reached 1.922 MPa, which was 12.13% higher than the CK group. The contents of exchangeable Th (IV) and U (VI) in the cured bodies of the Treat group decreased by 3.35% and 4.93%, respectively, compared with the CK group. Therefore, EPS enhances the effect of MICP curing RES and reduces the potential environmental problems that may be caused by radionuclides and heavy metals during the long-term sequestration of RES.

The small-molecule drug homoharringtonine targets HSF1 to suppress pancreatic cancer progression.

Heat shock factor 1 (HSF1), an essential transcription factor for stress response, is exploited by various tumors to facilitate their initiation, progression, invasion, and migration. Amplification of HSF1 is widely regarded as an indicator in predicting cancer severity, the likelihood of treatment failure and reduced patient survival. Notably, HSF1 is markedly amplified in 40% of pancreatic cancer (PC), which typically have limited treatment options. HSF1 has been proven to be a promising therapeutic target for multiple cancers. However, a direct small molecule HSF1 inhibitor with sufficient bioactivity and reliable safety has not been developed clinically. In this study, we successfully established a high-throughput screening system utilizing luciferase reporter assay specifically designed for HSF1, which leads to the discovery of a potent small molecule inhibitor targeting HSF1. Homoharringtonine (HHT) selectively inhibited PC cell viability with high HSF1 expression and induced a markedly stronger tumor regression effect in the subcutaneous xenograft model than the comparator drug KRIBB11, known for its direct action on HSF1. Moreover, HHT shows promise in countering the resistance encountered with HSP90 inhibitors, which have been observed to increase heat shock response intensity in clinical trials. Mechanistically, HHT directly bound to HSF1, suppressing its expression and thereby inhibiting transcription of HSF1 target genes. In conclusion, our work presents a preclinical discovery and validation for HHT as a HSF1 inhibitor for PC treatment.

P3N-PIPO but not P3 is the avirulence determinant in melon carrying the Wmr resistance against watermelon mosaic virus, although they contain a common genetic determinant.

Viruses employ a series of diverse translational strategies to expand their coding capacity, which produces viral proteins with common domains and entangles virus-host interactions. P3N-PIPO, which is a transcriptional slippage product from the P3 cistron, is a potyviral protein dedicated to intercellular movement. Here, we show that P3N-PIPO from watermelon mosaic virus (WMV) triggers cell death when transiently expressed in Cucumis melo accession PI 414723 carrying the Wmr resistance gene. Surprisingly, expression of the P3N domain, shared by both P3N-PIPO and P3, can alone induce cell death, whereas expression of P3 fails to activate cell death in PI 414723. Confocal microscopy analysis revealed that P3N-PIPO targets plasmodesmata (PD) and P3N associates with PD, while P3 localizes in endoplasmic reticulum in melon cells. We also found that mutations in residues L35, L38, P41, and I43 of the P3N domain individually disrupt the cell death induced by P3N-PIPO, but do not affect the PD localization of P3N-PIPO. Furthermore, WMV mutants with L35A or I43A can systemically infect PI 414723 plants. These key residues guide us to discover some WMV isolates potentially breaking the Wmr resistance. Through searching the NCBI database, we discovered some WMV isolates with variations in these key sites, and one naturally occurring I43V variation enables WMV to systemically infect PI 414723 plants. Taken together, these results demonstrate that P3N-PIPO, but not P3, is the avirulence determinant recognized by Wmr, although the shared N terminal P3N domain can alone trigger cell death.IMPORTANCEThis work reveals a novel viral avirulence (Avr) gene recognized by a resistance (R) gene. This novel viral Avr gene is special because it is a transcriptional slippage product from another virus gene, which means that their encoding proteins share the common N-terminal domain but have distinct C-terminal domains. Amazingly, we found that it is the common N-terminal domain that determines the Avr-R recognition, but only one of the viral proteins can be recognized by the R protein to induce cell death. Next, we found that these two viral proteins target different subcellular compartments. In addition, we discovered some virus isolates with variations in the common N-terminal domain and one naturally occurring variation that enables the virus to overcome the resistance. These results show how viral proteins with common domains interact with a host resistance protein and provide new evidence for the arms race between plants and viruses.

Risk Factors for Postoperative Complications of Laparoscopic Right Colectomy: A Post Hoc Analysis of the RELARC Trial.

BACKGROUND: There is concern regarding the possibility of postoperative complications for laparoscopic right colectomy. OBJECTIVE: To evaluate the risk factors for postoperative complications for patients undergoing laparoscopic right colectomy. DESIGN: This was an observational study. SETTINGS: This was a post hoc analysis of a prospective, multicenter, randomized controlled trial (RELARC trial, NCT02619942). PATIENTS: Patients included in the modified intention-to-treat analysis in the RELARC trial were all enrolled in this study. MAIN OUTCOME MEASURES: Risk factors for postoperative complications were identified using univariate and multivariable logistic regression analysis. RESULTS: Of 995 patients, 206 (20.7%) had postoperative complications. Comorbidity ( p = 0.02; OR: 1.544; 95% CI, 1.077-2.212) and operative time >180 minutes ( p = 0.03; OR: 1.453; 95% CI, 1.032-2.044) were independent risk factors for postoperative complications, whereas female sex ( p = 0.04; OR: 0.704; 95% CI, 0.506-0.980) and extracorporeal anastomosis ( p < 0.001; OR: 0.251; 95% CI, 0.166-0.378) were protective factors. Eighty patients (8.0%) had overall surgical site infection, 53 (5.3%) had incisional surgical site infection, and 33 (3.3%) had organ/space surgical site infection. Side-to-side anastomosis was a risk factor for overall surgical site infection ( p < 0.001; OR: 1.912; 95% CI, 1.118-3.268) and organ/space surgical site infection ( p = 0.005; OR: 3.579; 95% CI, 1.455-8.805). The extracorporeal anastomosis was associated with a reduced risk of overall surgical site infection ( p < 0.001; OR: 0.239; 95% CI, 0.138-0.413), organ/space surgical site infection ( p = 0.002; OR: 0.296; 95% CI, 0.136-0.646), and incisional surgical site infection ( p < 0.001; OR: 0.179; 95% CI, 0.099-0.322). Diabetes ( p = 0.039; OR: 2.090; 95% CI, 1.039-4.205) and conversion to open surgery ( p = 0.013; OR: 5.403; 95% CI, 1.437-20.319) were risk factors for incisional surgical site infection. LIMITATIONS: Due to the retrospective nature, the key limitation is the lack of prospective documentation and standardization regarding the perioperative management of these patients, such as preoperative optimization, bowel preparation regimens, and antibiotic regimens, which may be confounder factors of complications. All surgeries were performed by experienced surgeons, and the patients enrolled were relatively young, generally healthy, and without obesity. It is unclear whether the results will be generalizable to obese and other populations worldwide. CONCLUSIONS: Male sex, comorbidity, prolonged operative time, and intracorporeal anastomosis were independent risk factors for postoperative complications of laparoscopic right colectomy. Side-to-side anastomosis was associated with an increased risk of organ/space surgical site infection. Extracorporeal anastomosis could reduce the incidence of overall surgical site infection. Diabetes and conversion to open surgery were associated with an increased risk of incisional surgical site infection. See Video Abstract . CLINICALTRIALSGOV IDENTIFIER: NCT02619942. FACTORES DE RIESGO DE COMPLICACIONES POSOPERATORIAS EN COLECTOMA DERECHA LAPAROSCPICA UN ANLISIS POST HOC DEL ENSAYO RELARC: ANTECEDENTES:Existe preocupación con respecto a la posibilidad de complicaciones postoperatorias en colectomía derecha laparoscópica.OBJETIVO:Evaluar los factores de riesgo de complicaciones postoperatorias en pacientes sometidos a colectomía derecha laparoscópica.DISEÑO:Este fue un estudio observacional.ENTORNO CLINICO:Este fue un análisis post hoc de un ensayo controlado aleatorio, multicéntrico y prospectivo: ensayo RELARC (NCT02619942).PACIENTES:Todos los pacientes incluidos en el análisis de intención de tratar modificado en el ensayo RELARC fueron inscritos en este estudio.PRINCIPALES MEDIDAS DE RESULTADO:Los factores de riesgo de complicaciones posoperatorias se identificaron mediante análisis de regresión logística univariante y multivariable.RESULTADOS:De 995 pacientes, 206 (20,7%) tuvieron complicaciones postoperatorias. La comorbilidad ( p = 0,02, OR: 1,544, IC 95%: 1,077-2,212) y el tiempo operatorio >180 min ( p = 0,03, OR: 1,453, IC 95%: 1,032-2,044) fueron factores de riesgo independientes de complicaciones postoperatorias. Mientras que el sexo femenino ( p = 0,04, OR: 0,704, IC 95%: 0,506-0,980) y la anastomosis extracorpórea ( p < 0,001, OR: 0,251, IC 95%: 0,166-0,378) fueron factores protectores. 80 (8,0%) tenían infección general del sitio quirúrgico (ISQ), 53 (5,3%) tenían ISQ incisional y 33 (3,3%) tenían ISQ de órgano/espacio. Anastomosis latero-lateral fue un factor de riesgo para la ISQ general ( p < 0,001, OR: 1,912, IC 95%: 1,118-3,268) y ISQ órgano/espacio ( p = 0,005, OR: 3,579, IC 95%: 1,455-8.805). La anastomosis extracorpórea se asoció con un riesgo reducido de ISQ general ( p < 0,001, OR: 0,239, IC 95%: 0,138-0,413), ISQ órgano/espacio ( p = 0,002, OR: 0,296, IC 95%: 0,136-0,646), e ISQ incisional ( p < 0,001, OR: 0,179, IC 95%: 0,099-0,322). Diabetes ( p = 0,039, OR: 2,090, IC 95%: 1,039-4,205) y la conversión a cirugía abierta ( p = 0,013, OR: 5,403, IC 95%: 1,437-20,319) fueron factores de riesgo para ISQ incisional.LIMITACIONES:Debido a la naturaleza retrospectiva, la limitación clave es la falta de documentación prospectiva y estandarización sobre el manejo perioperatorio de estos pacientes, como la optimización preoperatoria, los regímenes de preparación intestinal y los regímenes de antibióticos, que pueden ser factores de confusión de las complicaciones. Todas las cirugías fueron realizadas por cirujanos experimentados y los pacientes inscritos eran relativamente jóvenes, generalmente sanos y no obesos. No está claro si los resultados serán generalizables a las poblaciones obesas y de otro tipo en todo el mundo.CONCLUSIONES:Sexo masculino, comorbilidad, el tiempo operatorio prolongado y anastomosis intracorpórea fueron factores de riesgo independientes de complicaciones postoperatorias de la colectomía derecha laparoscópica. Anastomosis latero-lateral se asoció con un mayor riesgo de SSI de órgano/espacio. La anastomosis extracorpórea podría reducir la incidencia de ISQ general. La diabetes y la conversión a cirugía abierta se asociaron con un mayor riesgo de ISQ incisional. (Traducción- Dr. Francisco M. Abarca-Rendon ).