Identification of DNase I hypersensitive sites in the human genome by multiple sequence descriptors.

DNase I hypersensitive sites (DHSs) are chromatin regions highly sensitive to DNase I enzymes. Studying DHSs is crucial for understanding complex transcriptional regulation mechanisms and localizing cis-regulatory elements (CREs). Numerous studies have indicated that disease-related loci are often enriched in DHSs regions, underscoring the importance of identifying DHSs. Although wet experiments exist for DHSs identification, they are often labor-intensive. Therefore, there is a strong need to develop computational methods for this purpose. In this study, we used experimental data to construct a benchmark dataset. Seven feature extraction methods were employed to capture information about human DHSs. The F-score was applied to filter the features. By comparing the prediction performance of various classification algorithms through five-fold cross-validation, random forest was proposed to perform the final model construction. The model could produce an overall prediction accuracy of 0.859 with an AUC value of 0.837. We hope that this model can assist scholars conducting DNase research in identifying these sites.

A Novel Hydrated Iron Vanadate Cathode Material for Advanced Aqueous Nickel-Ion Batteries.

Aqueous nickel-ion batteries (ANIBs) as an emerging energy storage device attracted much attention owing to their multielectron redox reaction and dendrite-free Ni anode, yet their development is hindered by the divalent properties of Ni2+ and the lack of suitable cathode materials. Herein, a hydrated iron vanadate (Fe2V3O10.5∙1.5H2O, FOH) with a preferred orientation along the (200) plane is innovatively proposed and used as cathode material for ANIBs. The FOH cathode exhibits a remarkable capacity of 129.3 mAh g-1 at 50 mA g-1 and a super-high capacity retention of 95% at 500 mA g-1 after 700 cycles. The desirable Ni2+ storage capacity of FOH can be attributed to the preferentially oriented and tunnel structures, which offer abundant reaction active planes and a broad Ni2+ diffusion path, the abundant vacancies and high specific surface area further increase ion storage sites and accelerate ion diffusion in the FOH lattice. Furthermore, the Ni2+ storage mechanism and structural evolution in the FOH cathode are explored through ex situ XRD, ex situ Raman, ex situ XPS and other ex situ characteristics. This work opens a new way for designing novel cathode materials to promote the development of ANIBs.

Is conventional functional liver remnant volume higher than 40% still sufficient to prevent post-hepatectomy liver failure in jaundiced patients with hilar cholangiocarcinoma? A single-center experience in China.

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.

A bibliometric analysis from 2013 to 2023 reveals research hotspots and trends in the connection between sport and regenerative medicine.

The field of regenerative medicine for sports injuries has grown significantly in the 21st century. This study attempted to provide an overview of the current state of research and key findings regarding the relationship between sport and regenerative medicine in general, identifying trends and hotspots in research topics. We gathered the literature from the Web of Science (WOS) database covering the last 10 years (2013-2023) pertaining to regenerative medicine for sporter and applied Citespace to assess the knowledge mapping. The findings demonstrated that there were 572, with a faster increase after 2018. The country, institution, and author with the most publications are the USA, Harvard University, and Maffulli Nicola. In addition, the most co-cited reference is J Acad Nutr Diet (2016) (199). Adipose tissue, high tibial osteotomy, and bone marrow are the hot spots in this field in the next few years.

Phthalate exposure and markers of biological aging: The mediating role of inflammation and moderating role of dietary nutrient intake.

Limited evidence has suggested a relationship between phthalate exposure and biological aging. This study investigated the association between phthalate exposure and biological aging, focusing on the mediating role of inflammation and the interaction with dietary nutrient intake. Data were analyzed from a nationwide cross-sectional survey comprising 12,994 participants aged 18 and above. Eight phthalate metabolites were detected in spot urine samples. Biological aging was assessed using the Klemera-Doubal method-biological age (KDM-BA) acceleration, phenotypic age (PA) acceleration, and homeostatic dysregulation (HD). The systemic immune-inflammation index (SII) evaluated systemic inflammation. The individual and combined associations between phthalate exposure and biological aging were assessed using linear regression, weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp). The participants had a mean age of 47 years, with 50.7 % male and 44.8 % non-Hispanic white. Most phthalate metabolites were positively correlated with KDM-BA acceleration (ß = 0.306-0.584), PA acceleration (ß = 0.081-0.281), and HD (ß = 0.016-0.026). Subgroup analysis indicated that men, older individuals, and non-Hispanic whites are particularly sensitive populations. WQS regression and qgcomp analyses consistently indicated a positive association between mixed phthalate exposure and HD, highlighting MEHHP as the most significant contributing metabolite. Mediation analyses showed inflammation partially mediated the association between phthalate metabolites and biological aging. Significant interactions regarding biological aging were found between specific phthalate metabolites and dietary nutrients (carotenoids, vitamins A, B1, B2, B6, B12, niacin, and selenium) intake. These findings indicated that the association between phthalate exposure and biological aging was mediated by inflammation, with nutrient intake mitigating this effect.

Dectin-1 induces TRPV1 sensitization and contributes to visceral hypersensitivity of irritable bowel syndrome in male mice.

BACKGROUND: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). METHODS: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 µg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a-/-) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. RESULTS: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. CONCLUSIONS: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. SIGNIFICANCE STATEMENT: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.

Distribution, risk evaluation, and source allocation of cesium and strontium in surface soil in a mining city.

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.

A mitochondria-related genes associated neuroblastoma signature - based on bulk and single-cell transcriptome sequencing data analysis, and experimental validation.

Background: Neuroblastoma (NB), characterized by its marked heterogeneity, is the most common extracranial solid tumor in children. The status and functionality of mitochondria are crucial in regulating NB cell behavior. While the significance of mitochondria-related genes (MRGs) in NB is still missing in key knowledge. Materials and methods: This study leverages consensus clustering and machine learning algorithms to construct and validate an MRGs-related signature in NB. Single-cell data analysis and experimental validation were employed to characterize the pivotal role of FEN1 within NB cells. Results: MRGs facilitated the classification of NB patients into 2 distinct clusters with considerable differences. The constructed MRGs-related signature and its quantitative indicators, mtScore and mtRisk, effectively characterize the MRGs-related patient clusters. Notably, the MRGs-related signature outperformed MYCN in predicting NB patient prognosis and was adept at representing the tumor microenvironment (TME), tumor cell stemness, and sensitivity to the chemotherapeutic agents Cisplatin, Topotecan, and Irinotecan. FEN1, identified as the most contributory gene within the MRGs-related signature, was found to play a crucial role in the communication between NB cells and the TME, and in the developmental trajectory of NB cells. Experimental validations confirmed FEN1's significant influence on NB cell proliferation, apoptosis, cell cycle, and invasiveness. Conclusion: The MRGs-related signature developed in this study offers a novel predictive tool for assessing NB patient prognosis, immune infiltration, stemness, and chemotherapeutic sensitivity. Our findings unveil the critical function of FEN1 in NB, suggesting its potential as a therapeutic target.

Anlotinib destabilizes PAX3-FOXO1 to induce rhabdomyosarcoma cell death via upregulating NEK2.

BACKGROUND: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas in children and adolescents, in which PAX3-FOXO1 fusion gene positive patients have very poor prognosis. PAX3-FOXO1 has been identified as an independent prognostic predictor in RMS, with no currently available targeted therapeutic intervention. The novel tyrosine kinase inhibitor anlotinib exhibits a wide range of anticancer effects in multiple types of cancers; however, there have been no relevant studies regarding its application in RMS. MATERIALS AND METHODS: We investigated the effects of PAX3-FOXO1 on the therapeutic efficacy of anlotinib using the CCK-8 assay, flow cytometry, invasion assay, wound healing assay, western blotting, quantitative polymerase chain reaction(qPCR), and xenograft experiments. RNA-seq and co-immunoprecipitation assays were conducted to determine the specific mechanism by which anlotinib regulates PAX3-FOXO1 expression. RESULTS: Anlotinib effectively inhibited RMS cell proliferation and promoted apoptosis and G2/M phase arrest while impeding tumor growth in vivo. Downregulation of PAX3-FOXO1 enhances the antitumor effects of anlotinib. Anlotinib upregulates protein kinase NEK2 and increases the degradation of PAX3-FOXO1 via the ubiquitin-proteasome pathway, leading to a reduction in PAX3-FOXO1 protein levels. CONCLUSION: Anlotinib effectively inhibited the malignant progression of RMS and promoted degradation of the fusion protein PAX3-FOXO1. Anlotinib could be a targeted therapeutic approach to treat PAX3-FOXO1 fusion-positive RMS.

Combining multimodal diffusion-weighted imaging and morphological parameters for detecting lymph node metastasis in cervical cancer.

BACKGROUND: Accurate detection of lymph node metastasis (LNM) is crucial for determining the tumor stage, selecting optimal treatment, and estimating the prognosis for cervical cancer. This study aimed to assess the diagnostic efficacy of multimodal diffusion-weighted imaging (DWI) and morphological parameters alone or in combination, for detecting LNM in cervical cancer. METHODS: In this prospective study, we enrolled consecutive cervical cancer patients who received multimodal DWI (conventional DWI, intravoxel incoherent motion DWI, and diffusion kurtosis imaging) before treatment from June 2022 to June 2023. The largest lymph node (LN) observed on each side on imaging was matched with that detected on pathology to improve the accuracy of LN matching. Comparison of the diffusion and morphological parameters of LNs and the primary tumor between the positive and negative LN groups. A combined diagnostic model was constructed using multivariate logistic regression, and the diagnostic performance was evaluated using receiver operating characteristic curves. RESULTS: A total of 93 cervical cancer patients were enrolled: 35 with LNM (48 positive LNs were collected), and 58 without LNM (116 negative LNs were collected). The area under the curve (AUC) values for the apparent diffusion coefficient, diffusion coefficient, mean diffusivity, mean kurtosis, long-axis diameter, short-axis diameter of LNs, and the largest primary tumor diameter were 0.716, 0.720, 0.716, 0.723, 0.726, 0.798, and 0.744, respectively. Independent risk factors included the diffusion coefficient, mean kurtosis, short-axis diameter of LNs, and the largest primary tumor diameter. The AUC value of the combined model based on the independent risk factors was 0.920, superior to the AUC values of all the parameters mentioned above. CONCLUSION: Combining multimodal DWI and morphological parameters improved the diagnostic efficacy for detecting cervical cancer LNM than using either alone.

Assessment of the influence of levees along Yangtze River on Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

BACKGROUND: Oncomelania hupensis is the exclusive intermediate host of Schistosoma japonicum in China. Snail control is an essential component of schistosomiasis elimination programme. With 70 years of continuous efforts, the range of O. hupensis had reduced significantly, but slowed down in last decades. A large number of levees against flooding were constructed along Yangtze River and its affiliated lakes in the middle and lower reaches, which influenced the hydrology and ecology in the alluvial plains. The purpose of this study was to assess the impact of levees on the distribution of O. hupensis in the middle and lower reaches of the Yangtze River. METHODS: The snail habitats were digitalised by hand-held GPS system. The years for discovery and elimination of snail habitats were extracted from historical records. The accumulated snail-infested range for each habitat was calculated on the basis of annual reports. The current distribution of O. hupensis was determined by systematic and environmental sampling. The geographical distribution of levees was obtained from satellite imagery. To assess the impact of levees, the data pertaining to O. hupensis were divided into two parts: inside and outside the Yangtze River. Joinpoint regression was utilised to divide the study time span and further characterise the regression in each period. The 5-year-period moving averages of eliminated area infested by snails were calculated for the habitats inside and outside Yangtze River. The moving routes of corresponding geographical median centres were simulated in ArcGIS. Hotspot analysis was used to determine the areas with statistical significance clustering of O. hupensis density. RESULTS: Three periods were identified according to Joinpoint regression both inside and outside Yangtze River. The area infested by O. hupensis increased in the first two periods. It decreased rapidly outside Yangtze River year over year after 1970, while that inside the Yangtze River did not change significantly. Furthermore, the latter was significantly higher than the former. It was observed that the present density of O. hupensis inside Yangtze River was lower than outside the Yangtze River. The median centre for eliminated ranges inside Yangtze River wavered between the east (lower reach) and the west (middle reach). In contrast, the median centre for eliminated ranges continuously moved from the east to the west. CONCLUSIONS: Our findings indicated that the levees had a considerable negative impact on the distribution of O. hupensis outside Yangtze River. Some hotspots observed in the irrigation areas need a sluice system at the inlet of branch for snail control. The major distribution of O. hupensis located in Hubei might be caused by severe waterlogging. The intensive surveillance should be implemented there. The biggest two freshwater lakes, the major endemic regions historically, were identified as cold spots. The long-term impact of Three Gorges Dam on the distribution of O. hupensis in the lakes should be monitored and evaluated.

[Retracted] Tumor suppressor miR­613 induces cisplatin sensitivity in non­small cell lung cancer cells by targeting GJA1.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the colony formation assay data shown in Fig. 2F, the tumor images in Fig. 3A, the "NC" experiment for the Ki67 immunohistochemical staining experiment shown in Fig. 3E and the migration assay data in Fig. 4D were strikingly similar to data appearing in different form in other papers by different authors at different research institutes that had either already been published, or were under consideration for publication at around the same time. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 23: 385, 2021; DOI: 10.3892/mmr.2021.12024].

Fluoranthene slow down sulfamethazine migration in soil via π-π interaction to increase the abundance of antibiotic resistance genes.

Sulfonamide antibiotics and polycyclic aromatic hydrocarbons (PAHs) often coexist in soil, leading to compound pollution through various pathways. This study focuses on sulfamethazine (SMZ) and PAHs (fluoranthene) as the subject for compound pollution research. Using a soil-groundwater simulation system, we investigated the migration characteristics of SMZ under coexistence with fluoranthene (Fla) and observed variations in the abundance of antibiotic resistance genes (ARGs). Through molecular docking simulations and isothermal adsorption experiments, we discovered that Fla bound with SMZ via π-π interactions, resulting in a 20.9% increase in the SMZ soil-water partition coefficient. Under compound conditions, the concentration of SMZ in surface soil could reach 1.4 times that of SMZ added alone, with an 13.4% extension in SMZ half-life. The deceleration of SMZ's vertical migration rate placed additional stress on surface soil microbiota, leading to a proliferation of ARGs by 66.3%-125.8%. Moreover, under compound pollution, certain potential hosts like Comamonadaceae and Gemmatimonas exhibited a significant positive correlation with resistance genes such as sul 1 and sul 2. These findings shed light on the impact of PAHs on sulfonamide antibiotic migration and the abundance of ARGs. They also provide theoretical insights for the development of technologies aimed at mitigating compound pollution in soil.

Reduction of Beany Flavor and Improvement of Nutritional Quality in Fermented Pea Milk: Based on Novel Bifidobacterium animalis subsp. lactis 80.

Peas (Pisum sativum L.) serve as a significant source of plant-based protein, garnering consumer attention due to their high nutritional value and non-GMO modified nature; however, the beany flavor limits its applicability. In this study, the effects of Bifidobacterium animalis subsp. Lactis 80 (Bla80) fermentation on the physicochemical characteristics, particle size distribution, rheological properties, and volatile flavor compounds of pea milk was investigated. After fermentation by Bla80, the pH of pea milk decreased from 6.64 ± 0.01 to 5.14 ± 0.01, and the (D4,3) distribution decreased from 142.4 ± 0.47 µm to 122.7 ± 0.55 µm. In addition, Lactic acid bacteria (LAB) fermentation significantly reduced the particle size distribution of pea milk, which was conducive to improving the taste of pea milk and also indicated that Bla80 had the probiotic potential of utilizing pea milk as a fermentation substrate. According to GC-MS analysis, 64 volatile compounds were identified in fermented pea milk and included aldehydes, alcohols, esters, ketones, acids, and furans. Specifically, aldehydes in treated samples decreased by 27.36% compared to untreated samples, while esters, ketones, and alcohols increased by 11.07%, 10.96%, and 5.19%, respectively. These results demonstrated that Bla80 fermentation can significantly decrease the unpleasant beany flavor, such as aldehydes and furans, and increase fruity or floral aromas in treated pea milk. Therefore, Bla80 fermentation provides a new method to improve physicochemical properties and consumer acceptance of fermented pea milk, eliminating undesirable aromas for the application of pea lactic acid bacteria beverage.

Screening of environmental stimuli for the positive regulation of stomatal aperture in centipedegrass.

Grasslands, the largest carbon pool in China, possess enormous potential for carbon sequestration. Increasing the stomatal aperture to increase the CO2 absorption capacity is a potential method to improve plant photosynthetic efficiency and ultimately enhance the carbon sequestration capacity of grass plants. Research on stomatal aperture regulation has focused mostly on Arabidopsis or crops, while research on grass plants in these areas is scarce, which seriously restricts the implementation of this grassland carbon sequestration strategy. Here, a widely used ecological grass, centipedegrass, was used as the experimental material. First, a convenient method for observing the stomatal aperture was developed. The leaves were floated in a potassium ion-containing open solution (67 mM KCl, pH 6.0) with the adaxial surface rather than the abaxial surface in contact with the solution and were cultivated under light for 1.5 h. Then, nail polish was applied on the adaxial surface, and a large number of open stomata were imprinted. Second, with the help of this improved method, the concentration‒response characteristics of the stomatal aperture to eleven environmental stimuli were tested. The stomatal aperture is dependent on these environmental stimuli in a concentration-dependent manner. The addition of 100 µM brassinolide led to the maximal stomatal aperture. This study provided a technical basis for manipulating stomatal opening to increase the carbon sequestration capacity of centipedegrass.

Pharmacokinetic assessment of low dose decitabine in combination therapies: Development and validation of a sensitive UHPLC-MS/MS method for murine plasma analysis.

Decitabine is a DNA methyltransferase inhibitor used in the treatment of acute myeloid leukemia and myelodysplastic syndrome. The notion that ongoing trials are presently exploring the combined use of decitabine, with or without the cytidine deaminase inhibitor cedazuridine, and other antileukemic drugs necessitates a comprehensive understanding of pharmacokinetic properties and an evaluation of drug-drug interaction liabilities. We report here the development and validation of a sensitive UHPLC-MS/MS method for quantifying decitabine in mouse plasma, which should be useful for such studies. The method involved a one-step protein precipitation extraction, and chromatographic separation on an XBridge HILIC column using gradient elution. The method was found to be robust, accurate, precise, and sufficiently sensitive (lower limit of quantitation, 0.4 ng/mL) to determine decitabine concentrations in microvolumes of plasma from mice receiving the agent orally or intravenously in the presence or absence of cedazuridine.

Increased capacity to maintain glucose homeostasis in a transgenic mouse expressing human but not mouse growth hormone with developing high-fat diet-related insulin resistance, hepatic steatosis and adipose dysfunction.

The objective was to assess the potential differential effects of human versus mouse growth hormone in vivo, given that human unlike mouse growth hormone can bind prolactin as well as the growth hormone receptor. To this end, a transgenic CD-1 mouse expressing human but not mouse growth hormone was generated, and the phenotypes of male mice fed with a regular chow or high-fat diet were assessed. Pancreas and epididymal white adipose tissue gene expression and/or related function were targeted as the pancreas responds to both prolactin and growth hormone receptor signaling, and catabolic effects like lipolytic activity are more directly attributable to growth hormone and growth hormone receptor signaling. The resulting human growth hormone-expressing mice are smaller than wild-type CD-1 mice, despite higher body fat and larger adipocytes, but both mouse types grow at the same rate with similar bone densities. Unlike wild-type mice, there was no significant delay in glucose clearance in human growth hormone-expressing mice when assessed at 8 versus 24 weeks on a high-fat diet. However, both mouse types showed signs of hepatic steatosis that correlated with elevated prolactin but not growth hormone RNA levels. The larger adipocytes in human growth hormone-expressing mice were associated with modified leptin (higher) and adiponectin (lower) RNA levels. Thus, while limited to observations in the male, the human growth hormone-expressing mice exhibit signs of growth hormone insufficiency and adipocyte dysfunction as well as an initial resistance to the negative effects of high-fat diet on glucose clearance.

Liver-based inter-organ communication: A disease perspective.

Inter-organ communication through hormones, cytokines and extracellular vesicles (EVs) has emerged to contribute to the physiological states and pathological processes of the human body. Notably, the liver coordinates multiple tissues and organs to maintain homeostasis and maximize energy utilization, with the underlying mechanisms being unraveled in recent studies. Particularly, liver-derived EVs have been found to play a key role in regulating health and disease. As an endocrine organ, the liver has also been found to perform functions via the secretion of hepatokines. Investigating the multi-organ communication centered on the liver, especially in the manner of EVs and hepatokines, is of great importance to the diagnosis and treatment of liver-related diseases. This review summarizes the crosstalk between the liver and distant organs, including the brain, the bone, the adipose tissue and the intestine in noticeable situations. The discussion of these contents will add to a new dimension of organismal homeostasis and shed light on novel theranostics of pathologies.

Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study.

Purpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA). Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine (group ED, n=76), 0.5-µg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications. Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P <0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P<0.0001). Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.

Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.

Performance of Pit Latrines and Their Herd Protection Against Diarrhea: A Longitudinal Cohort Study in Rural Ethiopia.

In sanitation policies, "improved sanitation" is often broadly described as a goal with little rationale for the minimum standard required. We conducted a secondary analysis of data collected as part of a cluster randomized controlled trial in rural Ethiopia. We compared the performance of well-constructed and poorly constructed pit latrines in reducing child diarrhea. In addition, we explored whether having a well-constructed household latrine provides indirect protection to neighbors if cluster-level coverage reaches a certain threshold. We followed up children aged younger than 5 years (U5C) of 906 households in rural areas of the Gurage zone, Ethiopia, for 10 months after community-led total sanitation interventions. A study-improved latrine was defined as having all the following: pit of ≥2 m depth, slab of any material, drop-hole cover, wall, roof, door, and handwashing facilities (water and soap observed). U5C in households with a study-improved latrine had 54% lower odds of contracting diarrhea than those living in households with a latrine missing 1 or more of the characteristics (adjusted odds ratio [aOR]=0.46; 95% confidence interval [CI]=0.27, 0.81; P=.006). Analyses were adjusted for child age and sex, presence of improved water for drinking, and self-reported handwashing at 4 critical times. The odds of having diarrhea among those with an improved latrine based on the World Health Organization/UNICEF Joint Monitoring Program (JMP) definition (i.e., pit latrines with slabs) were not substantially different from those with a JMP-unimproved latrine (aOR=0.99; 95% CI=0.56, 1.79; P=.99). Of U5C living in households without a latrine or with a study-unimproved latrine, those in the high-coverage villages were less likely to contract diarrhea than those in low-coverage villages (aOR=0.55; 95% CI=0.35, 0.86; P=.008). We recommend that academic studies and routine program monitoring and evaluation should measure more latrine characteristics and evaluate multiple latrine categories instead of making binary comparisons only.