A methodological framework for estimating ambient PM2.5 particulate matter concentrations in the UK.

Scientific evidence sustains PM2.5 particles' inhalation may generate harmful impacts on human beings' health; therefore, their monitoring in ambient air is of paramount relevance in terms of public health. Due to the limited number of fixed stations within the air quality monitoring networks, development of methodological frameworks to model ambient air PM2.5 particles is primordial to providing additional information on PM2.5 exposure and its trends. In this sense, this work aims to offer a global easily-applicable tool to estimate ambient air PM2.5 as a function of meteorological conditions using a multivariate analysis. Daily PM2.5 data measured by 84 fixed monitoring stations and meteorological data from ERA5 (ECMWF Reanalysis v5) reanalysis daily based data between 2000 and 2021 across the United Kingdom were attended to develop the suggested approach. Data from January 2017 to December 2020 were employed to build a mathematical expression that related the dependent variable (PM2.5) to predictor ones (sea-level pressure, planetary boundary layer height, temperature, precipitation, wind direction and speed), while 2021 data tested the model. Evaluation indicators evidenced a good performance of model (maximum values of RMSE, MAE and MAPE: 1.80 µg/m3, 3.24 µg/m3, and 20.63%, respectively), compiling the current legislation's requirements for modelling ambient air PM2.5 concentrations. A retrospective analysis of meteorological features allowed estimating ambient air PM2.5 concentrations from 2000 to 2021. The highest PM2.5 concentrations relapsed in the Mid- and Southlands, while Northlands sustained the lowest concentrations.

Unveiling the structural influence of nematic mesogens on customizable temperature and spectral responses.

Rapid and accurate detection and visualization of temperature variations near the human body hold significant importance. This study presents thermochromic colloids capable of adjusting the detectable temperature range and reflection wavelength over a wide spectrum. The systematic investigation focuses on understanding the influence of the molecular structure of nematic mesogens on the morphological dynamics of cholesteric liquid crystal droplets and their associated thermochromic behaviors. A tunable colorimetric temperature range (i.e., from 10 to 40 °C) and high sensitivity (i.e., Δλ ΔT-1 > 100nm °C-1) are realized through precise modulation of the alkyl chain lengths in cyanobiphenyls molecules, combined with a cholesteryl oleyl carbonate as a chiral dopant. We demonstrate the efficiency of a binary mixture of different mesogens, enabling customized structural colors with desired temperature responses. Finally, inspired by the ability of the octopus to camouflage through the elongation or contraction of its pigment cells, thermochromic droplets are embedded within a polymer matrix, resulting in a portable skin patch that offers quick, reversible, and direct temperature visualization of the human body.

Effect of cationized guar gum on stability and bioaccessibility of curcumin-loaded Pickering emulsion stabilized by starch nanoparticles.

To enhance stability and bioaccessibility of curcumin in Pickering emulsions stabilized by starch nanoparticles (SNP), cationized guar gum (CGG) was incorporated into the emulsion. Zeta potential results revealed that SNP and CGG formed electrostatic interactions, resulting in stable interfacial layer with higher hydrophobicity. Adding 0.4 % CGG maintained a homogeneous phase without significant droplet size change for up to one month. The emulsion with 0.4 % CGG demonstrated stable storage under varying pH (4-10), ionic strength (0-10 mM NaCl), and freeze-thaw cycles (up to 3). When optimized Pickering emulsion system was applied to curcumin encapsulation, curcumin-loaded emulsions were stably maintained for up to one month. The curcumin retained approximately 100 % stability under thermal (90 °C) and UV (12h) treatments. In the optimized emulsion, starch components resisted digestion in oral and gastroenteric phases but were primarily digested in small intestine, resulting in an increasing bioaccessibility from 88.23 to 96.92 %.

Comparative analysis of the oncologic outcomes and risk factors for open conversion in laparoscopic surgery for non-metastatic colorectal cancer: A retrospective multicenter study.

PURPOSE: Laparoscopic colon surgery is now commonly used for colorectal cancer (CRC) resection. The objective of this study was to compare the oncologic outcomes between open conversion and laparoscopic surgery, and to identify risk factors for open conversion. METHODS: We retrospectively reviewed the medical records of patients who underwent curative resection for stage 0-III CRC at five Hallym University-affiliated hospitals between January 2011 and June 2021. The patients were divided into the conversion and laparoscopic groups according to whether laparoscopic surgery was completed. RESULTS: Out of 2231 patients, laparoscopic surgery was completed in 2131 patients and 100 (4.5 %) converted to open surgery. The operation time (P = 0.028) and postoperative hospital stay (P = 0.036) were longer in the conversion group than in the laparoscopic group. Overall (P = 0.022) and severe (Clavien-Dindo classification grade ≥3) (P = 0.048) complications were more frequent in the conversion group than in the laparoscopic group. The 5-year recurrence-free survival (RFS) rate was worse in the conversion group than in the laparoscopic group (P = 0.002). In the multivariable analysis, open conversion was not a prognostic factor for RFS (P = 0.082). Abdominal surgery history (P = 0.021), obstruction (P < 0.001), and T4 stage (P < 0.001) were independently associated with open conversion. CONCLUSION: The conversion group had worse perioperative and oncologic outcomes. History of abdominal surgery, obstruction, and T4 stage were associated with open conversion. However, conversion itself was not associated with RFS.

Targeting uridine diphosphate glucuronosyltransferase 1A1 in liver disease: Current research and future directions.

The current letter to the editor pertains to the manuscript entitled 'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'. Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress, oxidative stress, and dysregulated lipid metabolism, impeding hepatocyte apoptosis and necroptosis.

Electrostatic spraying for fine-tuning particle dimensions to enhance oral bioavailability of poorly water-soluble drugs.

While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs, the outcomes often exhibit suboptimal particle size distribution and large particle sizes, limiting their effectiveness. In this study, we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs, enabling the fabrication of nanoparticles with fine and uniform particle size distribution. Regorafenib (1 g), as a model drug, copovidone (5 g), and sodium dodecyl sulfate (0.1 g) were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer. The electrostatic spray-dried nanoparticles (ESDN) showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles (CSDN). ESDN demonstrated significantly enhanced solubility and rapid release in water. In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent, exhibiting superior cytotoxicity compared to CSDN. Furthermore, ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN. These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs, effectively addressing the limitations associated with CSD methods.

Recent progress in cancer vaccines and nanovaccines.

Vaccine science, nanotechnology, and immunotherapy are at the forefront of cancer treatment strategies, each offering significant potential for enhancing tumor-specific immunity and establishing long-lasting immune memory to prevent tumor recurrence. Despite the promise of these personalized and precision-based anti-cancer approaches, challenges such as immunosuppression, suboptimal immune activation, and T-cell exhaustion continue to hinder their effectiveness. The limited clinical success of cancer vaccines often stems from difficulties in identifying effective antigens, efficiently targeting immune cells, lymphoid organs, and the tumor microenvironment, overcoming immune evasion, enhancing immunogenicity, and avoiding lysosomal degradation. However, numerous studies have demonstrated that integrating nanotechnology with immunotherapeutic strategies in vaccine development can overcome these challenges, leading to potent antitumor immune responses and significant progress in the field. This review highlights the critical components of cancer vaccine and nanovaccine strategies for immunomodulatory antitumor therapy. It covers general vaccine strategies, types of vaccines, antigen forms, nanovaccine platforms, challenges faced, potential solutions, and key findings from preclinical and clinical studies, along with future perspectives. To fully unlock the potential of cancer vaccines and nanovaccines, precise immunological monitoring during early-phase trials is essential. This approach will help identify and address obstacles, ultimately expanding the available options for patients who are resistant to conventional cancer immunotherapies.

Interactions that define the arrangement of sugar-binding sites in BDCA-2 and dectin-2 dimers.

The sugar-binding receptors dectin-2 and blood dendritic cell antigen 2 (BDCA-2) bind oligosaccharide ligands through extracellular carbohydrate-recognition domains (CRDs) and initiate intracellular signaling through Fc receptor γ adapters (FcRγ). Dectin-2 stimulates macrophages in response to pathogen binding while BDCA-2 modulates cytokine production in plasmacytoid dendritic cells. The oligomeric states of these receptors and the orientations of their CRDs have been investigated by analysis of a naturally occurring disulfide-bonded variant of BDCA-2 and by replacement of transmembrane domains with N-terminal dimerization domains to create extracellular domain dimers of both dectin-2 and BDCA-2. Analysis of these constructs, as well as previously described crystal structures of the CRDs from these proteins and a novel structure of an extended version of the extracellular domain of dectin-2, showed that there is only limited interaction of the CRDs in the dimers, but interactions can be stabilized by the presence of the neck region. The resulting orientation of sugar-binding sites in the dimers would favor crosslinking of multiple dimers by oligosaccharide ligands, causing clustering of FcRγ to initiate signaling.

Effect of Endurance Exercise Training on Gut Microbiota and ER Stress.

Regular exercise as part of one's lifestyle is well-recognized for its beneficial effect on several diseases such as cardiovascular disease and obesity; however, many questions remain unanswered regarding the effects of exercise on the gut environment. This study aimed to investigate the impact of long-term endurance exercise on modulating inflammation and endoplasmic reticulum (ER) stress. Fifteen-week-old male Sprague-Dawley (SD) rats were subjected to six months of endurance treadmill training, while age-matched controls remained sedentary. Results showed that IL-6 mRNA levels in colon tissues were significantly higher in the exercise group compared to the sedentary group. Exercise activated a significant ER stress-induced survival pathway by increasing BiP and phosphorylation of eIF2α (p-eIF2α) expressions in the liver and colon, while decreasing CHOP in the liver. Gene expressions of MUC2, Occludin, and Claudin-2 were increased in the colon of the exercise group, indicating enhanced intestinal integrity. Furthermore, the data showed a positive correlation between microbiota α-diversity and BiP (r = 0.464~0.677, p < 0.05). Populations of Desulfovibrio C21 c20 were significantly greater in the exercise group than the sedentary group. Additionally, predicted functions of the gut microbial community in terms of enzymes and pathways supported the enhancement of fatty-acid-related processes by exercise. These findings suggest that prolonged endurance exercise can affect the colon environment, which is likely related to changes in inflammation, ER stress, mucin layers and tight junctions, associated with modifications in the gut microbiome.

Analysis of Inverter Efficiency Using Photovoltaic Power Generation Element Parameters.

Photovoltaic power generation is influenced not only by variable environmental factors, such as solar radiation, temperature, and humidity, but also by the condition of equipment, including solar modules and inverters. In order to preserve energy production, it is essential to maintain and operate the equipment in optimal condition, which makes it crucial to determine the condition of the equipment in advance. This paper proposes a method of determining a degradation of efficiency by focusing on photovoltaic equipment, especially inverters, using LSTM (Long Short-Term Memory) for maintenance. The deterioration in the efficiency of the inverter is set based on the power generation predicted through the LSTM model. To this end, a correlation analysis and a linear analysis were performed between the power generation data collected at the power plant to learn the power generation prediction model and the data collected by the environmental sensor. With this analysis, a model was trained using solar radiation data and power data that are highly correlated with power generation. The results of the evaluation of the model's performance show that it achieves a MAPE of 7.36, an RMSE of 27.91, a MAE of 18.43, and an R2 of 0.97. The verified model is applied to the power generation data of the selected inverters for the years 2020, 2021, and 2022. Through statistical analysis, it was determined that the error rate in 2022, the third year of its operation, increased by 159.55W on average from the error rate of the power generation forecast in 2020, the first year of operation. This indicates a 0.75% decrease in the inverter's efficiency compared to the inverter's power generation capacity. Therefore, it is judged that it can be applied effectively to analyses of inverter efficiency in the operation of photovoltaic plants.

Silibinin Suppresses Inflammatory Responses Induced by Exposure to Asian Sand Dust.

Asian sand dust (ASD), generated from the deserts of China and Mongolia, affects Korea and Japan during spring and autumn, causing harmful effects on various bio-organs, including the respiratory system, due to its irritants such as fine dust, chemicals, and toxic materials. Here, we investigated the therapeutic effects of silibinin against ASD-induced airway inflammation using mouse macrophage-like cell line RAW264.7 and a murine model. ASD was intranasally administered to mice three times a week and silibinin was administered for 6 days by oral gavage. In ASD-stimulated RAW264.7 cells, silibinin treatment decreased tumor necrosis factor-α production and reduced the expression of p-p65NF-κB, p-p38, and cyclooxygenase (COX)-2, while increasing heme oxygenase (HO)-1 expression. In ASD-exposed mice, silibinin administration reduced inflammatory cell count and cytokines in bronchoalveolar lavage fluid and decreased inflammatory cell infiltration in lung tissue. Additionally, silibinin lowered oxidative stress, as evidenced by decreased 8-hydroxy-2'-deoxyguanosin (8-OHdG) expression and increased HO-1 expression. The expression of inflammatory-related proteins, including p-p65NF-κB, COX-2, and p-p38, was markedly reduced by silibinin administration. Overall, silibinin treatment reduced the expression of p-p65NF-κB, COX-2, and p-p38 in response to ASD exposure, while increasing HO-1 expression both in vitro and in vivo. These findings suggest that silibinin mitigates pulmonary inflammation caused by ASD exposure by reducing inflammatory signaling and oxidative stress, indicating its potential as a therapeutic agent for ASD-induced pulmonary inflammation.

Safety Assessment of Camelid-Derived Single-Domain Antibody as Feed Additive for Juvenile Whiteleg Shrimp (Litopenaeus vannamei) Against White Spot Syndrome Virus.

A six-week feeding trial was conducted to assess the safety of single-domain antibodies (sdAbs) derived from camelids against the white spot syndrome virus (WSSV) (WSSVvp28 was used as the antigen), focusing on the whole-organism responses and molecular-level changes in juvenile whiteleg shrimp (Litopenaeus vannamei). Five experimental diets with varying levels of sdAbs were formulated: CON (no sdAb supplementation); SDA8.2 (8.20% of sdAbs); SDA16.4 (16.40% of sdAbs); SDA24.6 (24.60% of sdAbs); and SDA32.8 (32.80% of sdAbs). In the CON diet, 450 mL of water per kg of diet (45%) was used to form a feed dough, while sdAbs were used to replace the water in the treatment diets. A total of 450 shrimp, with an initial body weight of 3.27 ± 0.02 g (mean ± SEM), were randomly distributed in 15 tanks (30 shrimp per tank; three tanks per treatment). Each tank was filled with 30 L of seawater (77 L capacity) in an indoor semi-recirculating system with a constant water flow rate of 1.2 L min-1. The photoperiod was maintained at 12 h of light and 12 h of dark. The water temperature, pH, salinity, and dissolved oxygen were 27.3 ± 0.1 °C, 7.61 ± 0.01, 34 ± 1 ppt, and 5.94 ± 0.04 mg L-1, respectively. During the feeding trial, the shrimp were fed the experimental diet (40% protein and 11% lipid) three times a day for six weeks. Following the feeding trial, an acute cold-water-temperature stress test was conducted by abruptly exposing the shrimp from each treatment to 15 °C for 4 h, down from 27 °C. The results showed no significant differences in the growth performance (weight gain, feed utilization efficiency, survival, etc.), plasma metabolites (aspartate aminotransferase activity, alanine aminotransferase activity, total protein, and glucose), or antioxidant enzymes (superoxide dismutase and glutathione peroxidase) among all the experimental diets (p > 0.05). In the acute cold-temperature stress test, there was no significant interaction between sdAb supplementation and temperature stress, nor any main effect from either factor, except for the main effect of temperature stress on the glucose levels, which was significantly higher in shrimp exposed to cold-temperature stress (p < 0.05). The next-generation sequencing of differentially expressed genes (DEGs) in the hepatopancreases of shrimp fed the CON, SDA16.4, and SDA32.8 diets, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, indicated that DEGs were significantly enriched in signaling pathways associated with growth, cold stress, and antioxidant systems. Overall, the results from conventional measurements suggest that the use of sdAbs against the WSSV may be safe for juvenile whiteleg shrimp. However, findings from the sophisticated analysis indicate that further research is needed to understand the molecular mechanisms underlying the observed changes, and to evaluate the long-term effects of sdAb supplementation in shrimp diets.

Single-cell transcriptomic analysis reveals dynamic activation of cellular signaling pathways regulating beige adipogenesis.

PDGFRA+ cells have been identified as adipocyte stem cells (ASCs) that differentiate into beige adipocytes in white adipose tissue (WAT) following thermogenic stimuli. To elucidate the molecular heterogeneity of ASCs, we conducted single-cell transcriptomic profiling of PDGFRA+ cells isolated from the inguinal WAT (iWAT) of mice treated with the beta3 adrenergic receptor agonist CL316243. Single-cell RNA-seq revealed nine major clusters, which were categorized into four groups: resting, proliferating, differentiating, and adipogenic factor-expressing cells (AFECs). Trajectory analysis revealed sequential activation of molecular pathways, including the Hedgehog and Notch signaling pathways, during beige adipogenesis. AFECs expressed Dpp4 and did not differentiate into adipocytes in culture or after transplantation. Furthermore, genetic lineage tracing studies indicated that DPP4+ cells did not differentiate into adipocytes in iWAT during CL316243-induced beige adipogenesis. However, high-fat diet feeding led to the recruitment of adipocytes from DPP4+ cells in iWAT. Overall, this study improved our understanding of the dynamic molecular basis of beige adipogenesis and the potential contribution of DPP4+ adipocyte lineages to the pathological expansion of WAT during diet-induced obesity.

Genetic and Epigenetic Alterations in Aging and Rejuvenation of Human.

All the information essential for life is encoded within our genome and epigenome, which orchestrates diverse cellular states spatially and temporally. In particular, the epigenome interacts with internal and external stimuli, encoding and preserving cellular experiences, and it serves as the regulatory base of the transcriptome across diverse cell types. The emergence of single-cell transcriptomic and epigenomic data collection has revealed unique omics signatures in diverse tissues, highlighting cellular heterogeneity. Recent research has documented age-related epigenetic changes at the single-cell level, alongside the validation of cellular rejuvenation through partial reprogramming, which involves simultaneous epigenetic modifications. These dynamic shifts, primarily fueled by stem cell plasticity, have catalyzed significant interest and cross-disciplinary research endeavors. This review explores the genomic and epigenomic alterations with aging, elucidating their reciprocal interactions. Additionally, it seeks to discuss the evolving landscape of rejuvenation research, with a particular emphasis on dissecting stem cell behavior through the lens of single-cell analysis. Moreover, it proposes potential research methodologies for future studies.

Giant Decrease in Interfacial Energy of Liquid Metals by Native Oxides.

Native oxides form on the surface of many metals. Here, using gallium-based liquid metal alloys, Johnson-Kendall-Roberts (JKR) measurements are employed to show that native oxide dramatically lower the tension of the metal interface from 724 to 10 mN m-1. Like conventional surfactants, the oxide has asymmetry between the composition of its internal and external interfaces. Yet, in comparison to conventional surfactants, oxides are an order of magnitude more effective at lowering tension and do not need to be added externally to the liquid (i.e., oxides form naturally on metals). This surfactant-like asymmetry explains the adhesion of oxide-coated metals to surfaces. The resulting low interfacial energy between the metal and the interior of the oxide helps stabilize non-spherical liquid metal structures. In addition, at small enough macroscopic contact angles, the finite tension of the liquid within the oxide can drive fluid instabilities that are useful for separating the oxide from the metal to form oxide-encased bubbles or deposit thin oxide films (1-5 nm) on surfaces. Since oxides form on many metals, this work can have implications for a wide range of metals and metal oxides in addition to explaining the physical behavior of liquid metal.

Prognosis of Proximal and Distal Vertebrobasilar Artery Stent Placement.

BACKGROUND AND PURPOSE: Vertebrobasilar artery stent placement (VBS) is potentially effective in preventing recurrent posterior circulation strokes; however, the incidences of in-stent restenosis and stented-territory ischemic events based on the location of stent placement have rarely been investigated. We aimed to investigate the characteristics and prognosis of VBS between intracranial and extracranial. MATERIALS AND METHODS: This study was single-center retrospective cohort study, and we obtained medical records of patients who underwent VBS. We compared clinical and periprocedural factors between extracranial and intracranial VBS. The primary outcomes included the incidence of in-stent restenosis (>50% reduction in lumen diameter) and stented-territory ischemic events. We compared the incidence of in-stent restenosis and stented-territory ischemic events by using Kaplan-Meier curves. RESULTS: Of the 105 patients, 41 (39.0%) underwent extracranial VBS, and 64 (61.0%) underwent intracranial VBS. During the follow-up, the incidences of in-stent restenosis and stented-territory ischemic events were 15.2% and 22.9%, respectively. The procedure time was longer (47.7 ± 19.5 minutes versus 74.5 ± 35.2 minutes, P < .001), and the rate of residual stenosis (≥30%) just after VBS was higher (2 [4.9%] versus 24 [37.5%], P < .001) in intracranial VBS than in extracranial VBS. Also, the incidences of in-stent restenosis were significantly higher in intracranial VBS than in extracranial VBS (4.9% versus 21.9%, P = .037). On the other hand, the incidences of stented-territory ischemic events (7.3% versus 32.8%, P < .001) were significantly higher in intracranial VBS than in extracranial VBS. The main mechanisms of stroke were artery-to-artery embolism (2 [66.7%]) in extracranial VBS, and artery-to-artery embolism (9 [42.9%]) and branch atheromatous disease (8 [38.1%]) in intracranial VBS. The Kaplan-Meier curve demonstrated a higher incidence of in-stent restenosis and stented-territory ischemic events in intracranial VBS than in extracranial VBS (P = .008 and P = .002, respectively). CONCLUSIONS: During the follow-up, the incidence of in-stent restenosis and stented-territory ischemic events was higher in patients with intracranial VBS than in those with extracranial VBS. The higher rates of postprocedural residual stenosis might have contributed to the increased risk of in-stent restenosis. Furthermore, prolonged procedure time and additional stroke mechanism, including branch atheromatous disease, might be associated with a higher risk of stented-territory ischemic events in intracranial VBS.

Mutation of a RING E3 ligase, OsDIRH2, enhances drought tolerance in rice with low stomata density.

Drought is a major environmental stress factor that negatively affects rice growth and yield. From a forward genetic perspective, we selected a drought-insensitive TILLING line (ditl4) from a gamma-ray-induced core mutant population (M10). Under drought conditions, ditl4 exhibited greater fresh weight, survival rate, chlorophyll, proline, and soluble sugar contents, and lower H2O2 and MDA levels than wild-type (WT). In addition, the activities of antioxidant enzymes, such as superoxide dismutase, catalase, and peroxidase, were higher in ditl4 than in the WT. In the relative water loss assay, dilt4 showed significantly decreased leaf curling and water loss compared to WT. Also, the ratio of "closed" stomata aperture was increased in ditl4 under drought stress, suggesting reduced transpiration to prevent water loss. The ditl4 mutant showed decreased stomatal conductance, transpiration, and CO2 assimilation and increased water use efficiency due to the low density of stomata. Whole-genome resequencing analysis of dilt4 identified a single nucleotide polymorphism (SNP) in OsDIRH2 (LOC_Os11g39640), annotated as a RING-H2 type E3 ligase, resulting in a premature stop codon. CRISPR/Cas9-mediated knock-out mutants (OsDIRH2a and OsDIRH2b) enhanced drought tolerance by lowering stomatal density compared to empty vector control plants. These findings suggested that ditl4 with low stomatal density would be useful as a genetic resource for a drought-tolerant breeding program to improve water-use efficiency.

YAP Overcomes Mechanical Barriers to Induce Mitotic Rounding and Adult Cardiomyocyte Division.

BACKGROUND: Many specialized cells in adult organs acquire a state of cell cycle arrest and quiescence through unknown mechanisms. Our limited understanding of mammalian cell cycle arrest is derived primarily from cell culture models. Adult mammalian cardiomyocytes, a classic example of cell cycle arrested cells, exit the cell cycle postnatally and remain in an arrested state for the life of the organism. Cardiomyocytes can be induced to re-enter the cell cycle by YAP5SA, an active form of the Hippo signaling pathway effector YAP. METHODS: We performed clonal analyses to determine the cell kinetics of YAP5SA cardiomyocytes. We also performed single-cell RNA sequencing, marker gene analysis, and functional studies to examine how YAP5SA cardiomyocytes progress through the cell cycle. RESULTS: We discovered that YAP5SA-expressing cardiomyocytes divided efficiently, with >20% of YAP5SA cardiomyocyte clones containing ≥2 cardiomyocytes. YAP5SA cardiomyocytes re-entered cell cycle at the G1/S transition and had an S phase lasting ≈48 hours. Sarcomere disassembly is required for cardiomyocyte progression from S to G2 phase and the induction of mitotic rounding. Although oscillatory Cdk expression was induced in YAP5SA cardiomyocytes, these cells inefficiently progressed through G2 phase. This is improved by inhibiting P21 function, implicating checkpoint activity as an additional barrier to YAP5SA-induced cardiomyocyte division. CONCLUSIONS: Our data reveal that YAP5SA overcomes the mechanically constrained myocardial microenvironment to induce mitotic rounding with cardiomyocyte division, thus providing new insights into the in vivo mechanisms that maintain cell cycle quiescence in adult mammals.

Occurrence of human infection with Salmonella Typhi in sub-Saharan Africa.

Typhoid fever, caused by Salmonella enterica serovar Typhi, results in over 1.2 million cases and 29 thousand deaths annually from sub-Saharan Africa. Combating this disease requires various intervention approaches, such as typhoid conjugate vaccines and improving water, sanitation, and hygiene. Enhancing the effectiveness of these strategies necessitates a deeper understanding of the variation of the typhoid fever across the target region. Although the magnitude and variation of typhoid fever at the country level have been studied globally, sub-national variation remains underexplored. To address this gap, we collected data from 229 published reports on typhoid fever occurrences in sub-Saharan Africa between January 2000 and December 2020. The dataset includes information on the year and geographical location of observation, diagnostic tests used, and the type of studies in which typhoid fever was reported. By analyzing this dataset, we can gain insights into the sub-national heterogeneity of typhoid fever's burden in the region. This knowledge will be instrumental in designing more effective intervention strategies to combat the disease.

Antibacterial activity of recombinant liver-expressed antimicrobial peptide-2 derived from olive flounder, Paralichthys olivaceus.

Liver-expressed antimicrobial peptide-2 (LEAP-2) is a cysteine-rich peptide that plays a crucial role in the innate immune system of fish. To investigate the molecular function of LEAP-2 from olive flounder, Paralichthys olivaceus, we cloned the gene encoding LEAP-2 using PCR and expressed it in Escherichia coli. Analysis of LEAP-2 expression revealed predominant transcripts in the liver and lower levels in the intestine of olive flounder, whereas their expression levels in the liver and head kidney increased, during the initial stage of infection with the aquapathogenic bacterium Edwardsiella piscicida. Recombinant LEAP-2 (rOfLEAP-2) purified from E. coli exhibited antimicrobial activity, as demonstrated by the ultrasensitive radial diffusion assay, against both Gram-positive (Bacillus subtilis, Streptococcus parauberis, and Lactococcus garvieae) and Gram-negative (Vibrio harveyi and E. coli) bacteria, with minimum inhibitory concentrations ranging from 25 to 100 µg/mL depending on the species tested. The antibacterial activity of rOfLEAP-2 was attributed to its ability to disrupt bacterial membranes, validated by the N-phenylnaphthalen-1-amine uptake assays and scanning electron microscope analysis against E. coli, V. harveyi, B. subtilis, and L. garvieae treated with rOfLEAP-2. Furthermore, a synergistic enhancement of antibacterial activity was observed when rOfLEAP-2 was combined with ampicillin or synthetic LEAP-1 peptide, suggesting a distinct mechanism of action from those of other antimicrobial agents. These findings provide evidence for the antibacterial efficacy of LEAP-2 from olive flounder, highlighting its potential therapeutic application against pathogenic bacteria.