Comparison of modified Furlow palatoplasty using small double-opposing Z-plasty and conventional Furlow palatoplasty: A long-term outcome study.

BACKGROUND: The aim of palatoplasty is to create a functional palate to achieve normal speech, while minimizing post-operative complications. This study aimed to compare the long-term outcomes of modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ) and conventional Furlow palatoplasty (conventional-DOZ) performed in a single center. METHODS: A retrospective review of consecutive patients who underwent Furlow palatoplasty between May 2007 and March 2014 was executed. Non-syndromic patients subjected to palatoplasty prior to 24 months of age and followed-up until at least 9 years of age were included. RESULTS: A total of 196 small-DOZ and 280 conventional-DOZ palatoplasty patients were included in this study. Overall, 14 patients (2.9%) developed oronasal fistula, and 40 patients (8.4%) received velopharyngeal insufficiency (VPI) surgery. In comparisons, oronasal fistula rate was significantly higher in conventional-DOZ (0.5% vs. 4.6%, p = 0.01), and the VPI prevalence was not significantly different (9.2% vs. 7.9%, p = 0.62). Patients who developed fistula had a significantly higher likelihood of developing VPI than patients without oronasal fistula (50.0% vs. 7.1%, respectively; p < 0.01), with an odds ratio of 13.0. CONCLUSION: Both modalities of palatoplasty yielded commendable velopharyngeal function in the long-term follow-up. The small-DOZ with reduced tension lowered the risk of oronasal fistula.

Circulating Levels of T-Cell Traits and the Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

Amyotrophic lateral sclerosis (ALS) represents a rare and potentially fatal neurodegenerative disease. Diverse T-cell subsets could potentially exert diametrically opposite impacts upon ALS development. A two-sample Mendelian randomization (MR) analysis was performed to investigate the correlation between 244 T-cell subsets and ALS risk. Genetic instrumental variables were procured from a standard genome-wide association study (GWAS) that encompassed 244 T-cell subsets in 3757 individuals of European lineage. ALS-related data were collected from a GWAS comprising 20,806 ALS instances and 59,804 European control participants. Multiple sensitivity analyses were performed to verify the robustness of the significant results. Reverse MR analysis was used for delineating the effects of ALS on the characteristics of T-cells. After multiple comparison corrections, 24 out of the 244 subtypes demonstrated a potential association with ALS risk. Significantly, 75% of these associations encompassed the expression of the CD3 on diverse T-cell subtypes, revealing a highly consistent inverse relation to ALS risk. The proportion of T regulatory cells (Tregs) in CD4+ T cells and secreting Tregs in CD4+ T cells demonstrated negative associations with the risk of ALS. CCR7 expression on naive CD4+ T cells and CCR7 expression on naive CD8+ T cells showed positive associations with ALS risk. Certain T-cell subsets, particularly those identified by CD3 expression on terminally differentiated CD8+ T cells, proportions of Tregs, and CCR7 expression, indicated an association with ALS risk. These findings harmonize with and extend previous observational studies investigating the involvement of T lymphocyte subset-induced immunological processes in ALS.

SVEN_5003 is a Major Developmental Regulator in Streptomyces venezuelae.

Many regulatory genes that affect cellular development in Streptomyces, such as the canonical bld genes, have already been identified. However, in this study, we identified sven_5003 in Streptomyces venezuelae as a major new developmental regulatory gene, the deletion of which leads to a bald phenotype, typical of bld mutants, under multiple growth conditions. Our data indicated that disruption of sven_5003 also has a differential impact on the production of the two antibiotics jadomycin and chloramphenicol. Enhanced production of jadomycin but reduced production of chloramphenicol were detected in our sven_5003 mutant strain (S. venezuelae D5003). RNA-Seq analysis indicated that SVEN_5003 impacts expression of hundreds of genes, including genes involved in development, primary and secondary metabolism, and genes of unknown function, a finding confirmed by real-time PCR analysis. Transcriptional analysis indicated that sven_5003 is an auto-regulatory gene, repressing its own expression. Despite the evidence indicating that SVEN_5003 is a regulatory factor, a putative DNA-binding domain was not predicted from its primary amino acid sequence, implying an unknown regulatory mechanism by SVEN_5003. Our findings revealed that SVEN_5003 is a pleiotropic regulator with a critical role in morphological development in S. venezuelae.

Stability between single and segmental maxillary osteotomies in bimaxillary surgery for cleft-associated class III deformity: a CBCT study.

OBJECTIVE: Segmental Le Fort I osteotomy through the cleft is a common strategy to narrow the alveolar cleft in adults. This study compared skeletal stability between single and segmental Le Fort I osteotomies in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: This retrospective analysis examined 45 adults with complete UCLP-associated class III deformities who underwent bimaxillary surgery with either single (n = 30) or segmental (n = 15) Le Fort I advancement. Cone beam computed tomography (CBCT) scans of the facial skeleton were acquired before surgery, 1-week postsurgery, and at follow-up. Measures of landmarks from the CBCT images for the two treatment groups were compared for translation (left/right, posterior/anterior, superior/inferior) and rotation (yaw, roll, pitch). RESULTS: Postsurgery, the downward movement of the maxilla was larger in the segmental group than the single group. At follow-up, the maxilla moved backward in both groups, and upward in the segmental group. The mandible moved forward and upward and rotated upward in both groups. The amount of upward movement and rotation was larger in the segmental group than the single group. CONCLUSIONS: Two years after bimaxillary surgery in patients with UCLP-associated class III deformity, greater relapse was found after segmental Le Fort I osteotomies in vertical translation of the maxilla and mandible, and pitch rotation of the mandible compared with single Le Fort I osteotomies. CLINICAL RELEVANCE: The vertical relapse of the maxilla was larger after segmental Le Fort I advancement compared with single Le Fort I advancement in clefts.

Reg3A Overexpression Facilitates Hepatic Metastasis by Altering Cell Adhesion in LoVo Colon Cancer Cells.

Reg3A is upregulated in various cancers and considered a potential target for antitumor treatments. However, the effect of Reg3A in metastasis has been elusive. This study aims to disclose the role of Reg3A overexpression in hepatic metastasis of LoVo colon cancer cells. A stable cell line of LoVo cells overexpressing Reg3A (LoVo-luc-Reg3A), labeled with luc reporter gene, was constructed. Cell proliferation, apoptosis, migration, and invasion were determined using MTT, EdU, Hoechst's staining, flow cytometry, and transwell assays, respectively. Hepatic metastasis of LoVo-luc-Reg3A cells was investigated in BALB/c nude mice. Living bioluminescence imaging, histological examination, and mRNA sequencing (mRNA-seq) were performed to assess the metastatic efficiency and gene expression alteration. Reg3A content was determined by Western blotting and Enzyme-Linked Immunosorbent Assay. Cell attachment capacity was determined in the Matrigel culture. Reg3A overexpression did not promote LoVo cell proliferation or apoptosis, but facilitated cell migration and invasion. In the hepatic metastasis model, Reg3A overexpression increased the number of metastatic colonies. The result of mRNA-seq suggested 349 differentially expressed genes (DEGs) by Reg3A upregulation, many of which were related to colon adenocarcinoma tumorigenesis compared to normal colon tissue. Gene ontology enrichment assay indicated that the DEGs are mainly associated with cell adhesion, leukocyte regulation, extracellular matrix (ECM) remodeling, integrin binding, and STAT protein binding. Reg3A overexpression led to an enrichment of Reg3A protein in local tumor tissue of liver metastasis and ECM/intracellular space in ex vivo cultured cells. However, Reg3A concentration in serum and culture medium was relatively low. Reg3A overexpression also resulted in an increased number of cells that attach to Matrigel, which was attenuated by treatments of siRNA-Reg3A and single-chain variable fragment against Reg3A. Endogenous Reg3A overexpression facilitates hepatic metastasis of LoVo colon cancer cells. The prometastatic effect could be contributed by Reg3A enrichment in ECM, which alters the cell adhesion behavior.

Exposure to resorcinol bis (diphenyl phosphate) induces colonization of alien microorganisms with potential impacts on the gut microbiota and metabolic disruption in male zebrafish.

Organophosphate esters (OPEs) have been demonstrated to induce various forms of toxicity in aquatic organisms. However, a scarcity of evidence impedes the conclusive determination of whether OPEs manifest sex-dependent toxic effects. Here, we investigated the effects of tris (1-chloro-2-propyl) phosphate (TCPP) and resorcinol bis (diphenyl phosphate) (RDP) on the intestines of both female and male zebrafish. The results indicated that, in comparison to TCPP, RDP induced more pronounced intestinal microstructural damage and oxidative stress, particularly in male zebrafish. 16S rRNA sequencing and metabolomics revealed significant alterations in the species richness and oxidative stress-related metabolites in the intestinal microbiota of zebrafish under exposure to both TCPP and RDP, manifesting gender-specific effects. Based on differential species analysis, we defined invasive species and applied invasion theory to analyze the reasons for changes in the male fish intestinal community. Correlation analysis demonstrated that alien species may have potential effects on metabolism. Overall, this study reveals a pronounced gender-dependent impact on both the intestinal microbiota and metabolic disruptions of zebrafish due to OPEs exposure and offers a novel perspective on the influence of pollutants on intestinal microbial communities and metabolism.

The role of exosome derived miRNAs in inter-cell crosstalk among insulin-related organs in type 2 diabetes mellitus.

Exosomes are small extracellular vesicles secreted by almost all cell types, and carry diverse cargo including RNA, and other substances. Recent studies have focused exosomal microRNAs (miRNAs) on various human diseases, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (METS) which accompany the occurrence of insulin resistance. The regulation of insulin signaling has connected with some miRNA expression which play a significant regulatory character in insulin targeted cells or organs, such as fat, muscle, and liver. The miRNAs carried by exosomes, through the circulation in the body fluids, mediate all kinds of physiological and pathological process involved in the human body. Studies have found that exosome derived miRNAs are abnormally expressed and cross-talked with insulin targeted cells or organs to affect insulin pathways. Further investigations of the mechanisms of exosomal miRNAs in T2DM will be valuable for the diagnostic biomarkers and therapeutic targets of T2DM. This review will summarize the molecular mechanism of action of the miRNAs carried by exosomes which are secreted from insulin signaling related cells, and elucidate the pathogenesis of insulin resistance to provide a new strategy for the potential diagnostic biomarkers and therapeutic targets for the type 2 diabetes.

Deep learning assisted fluid volume calculation for assessing anti-vascular endothelial growth factor effect in diabetic macular edema.

Objective: To develop an algorithm using deep learning methods to calculate the volume of intraretinal and subretinal fluid in optical coherence tomography (OCT) images for assessing diabetic macular edema (DME) patients' condition changes. Design: Cross-sectional study. Participants: Treatment-naive patients diagnosed with DME recruited from April 2020 to November 2021. Methods: The deep learning network, which was built for autonomous segmentation utilizing an encoder-decoder network based on the U-Net architecture, was used to calculate the volume of intraretinal fluid (IRF) and subretinal fluid (SRF). The alterations of retinal vessel density and thickness, and the correlation between best-corrected visual acuity (BCVA) and OCT parameters were analyzed. Results: 2,955 OCT images of fourteen eyes from DME patients with IRF and SRF who received anti-vascular endothelial growth factor (VEGF) agents were obtained. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the algorithm was 0.993 for IRF and 0.998 for SRF. The volumes of IRF and SRF were significantly decreased from 1.93 ± 0.58 /1.14 ± 0.25 mm3 (baseline) to 0.26 ± 0.13 /0.26 ± 0.18 mm3 (post-injection), respectively (p = 0.0170 for IRF, and p = 0.0004 for SRF). The Spearman correlation demonstrated that the reduction of IRF volume was negatively correlated with age (coefficient = -0.698, p = 0.006). Conclusion: We developed a deep learning assisted fluid volume calculation algorithm with high sensitivity and specificity for assessing the volume of IRF and SRF in DME patients. Key words: deep learning; diabetic macular edema; optical coherence tomography.

Synthesis of polyethylene glycol-grafted magnetic nanoparticles for the fast and efficient extraction of anabolic substances from human urine.

Anabolic steroids and ß-agonists are commonly prohibited substances found in doping control studies; therefore, the determination of anabolic substances in biological samples is crucial. To analyze the anabolic compounds in urine, an adsorbent, polyethylene glycol (PEG)-grafted magnetic nanoparticle material (Fe3O4@SiO2-PEG), with low toxicity and strong biocompatibility was prepared in this investigation. Compared to those of Fe3O4 and Fe3O4@SiO2, the grafted PEG chains (approximately 5.4 wt.%) on the magnetic nanoparticles improved the extraction efficiencies by factors of 3.9-17.0 and 2.5-2.9, respectively, likely due to the electrostatic attraction and hydrogen bonding. To achieve maximum extraction efficiency, several extraction parameters were optimized, including the kind and volume of desorption solvent, pH, and the extraction and desorption time. The standard curves were linear within the range of 0.5-20 µg/L for methyltestosterone and trenbolone, and 0.02-5 µg/L for clenbuterol. The limits of detection for the three drugs were 0.01-0.12 µg/L. The limits of quantification were 0.02-0.40 µg/L. The levels of precision of the optimized method were assessed based on the respective intra- and inter-day and batch-to-batch relative standard deviations in the ranges of 3.2-5.2 % (n = 5), 5.9-11.3 % (n = 4), and 6.7-9.2 % (n = 3). The Fe3O4@SiO2-PEG nanoparticles could exclude urine matrix interferences (matrix effect of 91.8-98.1 %) and achieve satisfactory recoveries (75.5-116.1 %), affording sensitive and accurate determination of trace anabolic substances in urine.

Incidence of surgical site infection in minimally invasive colorectal surgery.

BACKGROUND: Surgical site infection (SSI) is a common complication of colorectal surgery. Minimally invasive surgery notably reduces the incidence of SSI. This study aimed to compare the incidences of SSI after robot-assisted colorectal surgery (RACS) vs that after laparoscopic assisted colorectal surgery (LACS) and to analyze associated risk factors for SSI in minimally invasive colorectal surgery. AIM: To compare the incidences of SSI after RACS and LACS, and to analyze the risk factors associated with SSI after minimally invasive colorectal surgery. METHODS: Clinical data derived from patients who underwent minimally invasive colorectal surgery between October 2020 and October 2022 at the First Affiliated Hospital of Soochow University were collated. Differences in clinical characteristics and surgeryrelated information associated with RACS and LACS were compared, and possible risk factors for SSI were identified. RESULTS: A total of 246 patients (112 LACS and 134 RACS) were included in the study. Fortythree (17.5%) developed SSI. The proportions of patients who developed SSI were similar in the two groups (17.9% vs 17.2%, P = 0.887). Diabetes mellitus, intraoperative blood loss ≥ 100 mL, and incision length were independent risk factors for SSI. Possible additional risk factors included neoadjuvant therapy, lesion site, and operation time. CONCLUSION: There was no difference in SSI incidence in the RACS and LACS groups. Diabetes mellitus, intraoperative blood loss ≥ 100 mL, and incision length were independent risk factors for postoperative SSI.

miR-743b-3p promotes hepatic lipogenesis via branched-chain amino acids (BCAA) metabolism by targeting PPM1K in aged mice.

BACKGROUND: Lipid metabolism disorders appear to play an important role in the ageing process, thus understanding the cellular and molecular mechanisms underlying the association of ageing with elevated vulnerability to lipid metabolism related diseases is crucial towards promoting quality of life in old age. MicroRNAs (miRNAs) have emerged as crucial regulators of lipid metabolism, and some miRNAs have key roles in ageing. METHODS: In this study, we investigated changes in liver lipid metabolism of ageing mice and the mechanisms of the altered expression of miRNAs in the ageing liver which contributes to the age-dependent increase in lipid synthesis. Here we found that miR-743b-3p was higher expressed in the liver tissues of ageing mice through the small RNA sequencing and bioinformatics analysis, and its target PPM1K was predicted and confirmed the target relationship of miR-743b-3p with PPM1K in the aged mouse liver tissues and the cultured senescent hepatocytes in vitro. Moreover, using the transfected miR-743b-3p mimics/inhibitors into the senescent hepatocyte AML12. RESULTS: We found that miR-743b-3p inhibition reversed the hepatocyte senescence, and finally decreased the expression of genes involved in lipid synthesis(Chrebp, Fabp4, Acly and Pparγ) through increasing the target gene expression of PPM1K which regulated the expression of branched-chain amino acids (BCAA) metabolism-related genes (Bckdhα, Bckdk, Bcat2, Dbt). CONCLUSIONS: These results identify that age-induced expression of miR-743b-3p inhibits its target PPM1K which induces BCAA metabolic disorder and regulates hepatocyte lipid accumulation during ageing.

Association between ACE1 and missed abortion: ACE1 promotes H2O2-induced trophoblast cell injury in vitro†.

The aim of this study was to evaluate the role of angiotensin-converting enzyme 1 (ACE1) in H2O2-induced trophoblast cell injury and the potential molecular mechanisms. Oxidative stress was modeled by exposing HTR-8/SVneo cells to 200 µM H2O2. Western blot and real-time quantitative PCR methods were used to detect protein and mRNA expression level of ACE1 in chorionic villus tissue and trophoblast HTR-8/SVneo cell. Inhibition of ACE1 expression was achieved by transfection with small interfering RNA. Then flow cytometry, Cell Counting Kit-8, and Transwell assay was used to assess apoptosis, viability, and migration ability of the cells. Reactive oxygen species (ROS) were detected by fluorescent probes, and malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) activities were determined by corresponding detection kits. Angiotensin-converting enzyme 1 expression was upregulated in chorionic villus tissue of patients with missed abortion (MA) compared with individuals with normal early pregnancy abortion. H2O2 induced elevated ACE1 expression in HTR-8/SVneo cells, promoted apoptosis, and inhibited cell viability and migration. Knockdown of ACE1 expression inhibited H2O2-induced effects to enhance cell viability and migration and suppress apoptosis. Additionally, H2O2 stimulation caused increased levels of ROS and MDA and decreased SOD and GSH activity in the cells, whereas knockdown of ACE1 expression led to opposite changes of these oxidative stress indicators. Moreover, knockdown of ACE1 attenuated the inhibitory effect of H2O2 on the Nrf2/HO-1 pathway. Angiotensin-converting enzyme 1 was associated with MA, and it promoted H2O2-induced injury of trophoblast cells through inhibiting the Nrf2 pathway. Therefore, ACE1 may serve as a potential therapeutic target for MA.

Preclinical Evaluation of Off-The-Shelf PD-L1+ Human Natural Killer Cells Secreting IL15 to Treat Non-Small Cell Lung Cancer.

We described previously a human natural killer (NK) cell population that upregulates PD-L1 expression upon recognizing and reacting to tumor cells or exposure to a combination of IL12, IL18 and IL15. Here, to investigate the safety and efficacy of tumor-reactive and cytokine-activated (TRACK) NK cells, human NK cells from umbilical cord blood were expanded, transduced with a retroviral vector encoding soluble (s) IL15, and further cytokine activated to induce PD-L1 expression. Our results show cryopreserved and thawed sIL15_TRACK NK cells had significantly improved cytotoxicity against non-small cell lung cancer (NSCLC) in vitro when compared to non-transduced (NT) NK cells, PD-L1+ NK cells lacking sIL15 expression (NT_TRACK NK), or NK cells expressing sIL15 without further cytokine activation (sIL15 NK cells). Intravenous injection of sIL15_TRACK NK cells into immunodeficient mice with NSCLC significantly slowed tumor growth and improved survival when compared to NT NK and sIL15 NK cells. The addition of the anti-PD-L1 atezolizumab further improved control of NSCLC growth by sIL15_TRACK NK cells in vivo. Moreover, a dose-dependent efficacy was assessed for sIL15_TRACK NK cells without observed toxicity. These experiments indicate that the administration of frozen, off-the-shelf allogeneic sIL15_TRACK NK cells is safe in preclinical models of human NSCLC and has potent antitumor activity without and with the administration of atezolizumab. A Phase I clinical trial modeled after this preclinical study using sIL15_TRACK NK cells alone or with atezolizumab for relapsed or refractory NSCLC is currently underway (NCT05334329).

Heterointerface regulation of covalent organic framework-anchored graphene via a solvent-free strategy for high-performance supercapacitor and hybrid capacitive deionization electrodes.

Covalent organic frameworks (COFs) with customizable geometry and redox centers are an ideal candidate for supercapacitors and hybrid capacitive deionization (HCDI). However, their poor intrinsic conductivity and micropore-dominated pore structures severely impair their electrochemical performance, and the synthesis process using organic solvents brings serious environmental and cost issues. Herein, a 2D redox-active pyrazine-based COF (BAHC-COF) was anchored on the surface of graphene in a solvent-free strategy for heterointerface regulation. The as-prepared BAHC-COF/graphene (BAHCGO) nanohybrid materials possess high-speed charge transport offered by the graphene carrier and accelerated electrolyte ion migration within the BAHC-COF, allowing ions to effectively occupy ion storage sites inside BAHC. As a result, the BAHCGO//activated carbon asymmetric supercapacitor achieves a high energy output of 61.2 W h kg-1 and a satisfactory long-term cycling life. More importantly, BAHCGO-based HCDI possesses a high salt adsorption capacity (SAC) of 67.5 mg g-1 and excellent long-term desalination/regeneration stability. This work accelerates the application of COF-based materials in the fields of energy storage and water treatment.

Emergence of Orchestrated and Dynamic Metabolism of Saccharomyces cerevisiae.

Microbial metabolism is a fundamental cellular process that involves many biochemical events and is distinguished by its emergent properties. While the molecular details of individual reactions have been increasingly elucidated, it is not well understood how these reactions are quantitatively orchestrated to produce collective cellular behaviors. Here we developed a coarse-grained, systems, and dynamic mathematical framework, which integrates metabolic reactions with signal transduction and gene regulation to dissect the emergent metabolic traits of Saccharomyces cerevisiae. Our framework mechanistically captures a set of characteristic cellular behaviors, including the Crabtree effect, diauxic shift, diauxic lag time, and differential growth under nutrient-altered environments. It also allows modular expansion for zooming in on specific pathways for detailed metabolic profiles. This study provides a systems mathematical framework for yeast metabolic behaviors, providing insights into yeast physiology and metabolic engineering.

Increasing and sustaining discharges by noon - a multi-year process improvement project.

High hospital occupancy degrades emergency department performance by increasing wait times, decreasing patient satisfaction, and increasing patient morbidity and mortality. Late discharges contribute to high hospital occupancy by increasing emergency department (ED) patient length of stay (LOS). We share our experience with increasing and sustaining early discharges at a 650-bed academic medical center in the United States. Our process improvement project followed the Institute of Medicine Model for Improvement of successive Plan‒Do‒Study‒Act cycles. We implemented multiple iterative interventions over 41 months. As a result, the proportion of discharge orders before 10 am increased from 8.7% at baseline to 22.2% (p < 0.001), and the proportion of discharges by noon (DBN) increased from 9.5% to 26.8% (p < 0.001). There was no increase in balancing metrics because of our interventions. RA-LOS (Risk Adjusted Length Of Stay) decreased from 1.16 to 1.09 (p = 0.01), RA-Mortality decreased from 0.65 to 0.61 (p = 0.62) and RA-Readmissions decreased from 0.92 to 0.74 (p < 0.001). Our study provides a roadmap to large academic facilities to increase and sustain the proportion of patients discharged by noon without negatively impacting LOS, 30-day readmissions, and mortality. Continuous performance evaluation, adaptability to changing resources, multidisciplinary engagement, and institutional buy-in were crucial drivers of our success.

The ATF4-RPS19BP1 axis modulates ribosome biogenesis to promote erythropoiesis.

Hematopoietic differentiation is controlled by intrinsic regulators and the extrinsic hematopoietic niche. Activating transcription factor 4 (ATF4) plays a crucial role in the function of fetal and adult hematopoietic stem cell maintenance; however, the precise function of ATF4 in the bone marrow niche and the mechanism by which ATF4 regulates adult hematopoiesis remain largely unknown. Here, we employ four cell-type-specific mouse Cre lines to achieve conditional knockout of Atf4 in Cdh5+ endothelial cells, Prx1+ bone marrow stromal cells, Osx+ osteo-progenitor cells, and Mx1+ hematopoietic cells, and uncover the role of Atf4 in niche cells and hematopoiesis. Intriguingly, depletion of Atf4 in niche cells does not affect hematopoiesis; however, Atf4-deficient hematopoietic cells exhibit erythroid differentiation defects, leading to hypoplastic anemia. Mechanistically, ATF4 mediates direct regulation of Rps19bp1 transcription, which is, in turn, involved in 40S ribosomal subunit assembly to coordinate ribosome biogenesis and promote erythropoiesis. Finally, we demonstrate that under conditions of 5-fluorouracil-induced stress, Atf4 depletion impedes the recovery of hematopoietic lineages, which requires efficient ribosome biogenesis. Taken together, our findings highlight the indispensable role of the ATF4-RPS19BP1 axis in the regulation of erythropoiesis.

Molecular Mechanisms and Roles of MiR-136-5p in Human Cancer and Other Disorders.

BACKGROUND: MiR-136-5p plays a vital function in regulating developmental processes as well as in the pathophysiology of diseases, with a notable record in tumor suppression. METHODS: This article summarizes the latest findings on the physiological and pathophysiological processes of miR-136-5p in diseases. We searched for relevant studies and selected research articles from the last five years on PubMed with miR-136-5p as the keyword. RESULTS: MiR-136-5p represents a class of microRNAs (miRNAs) that are involved in various human maladies, encompassing cancers, cardio-cerebrovascular disease, diabetes, inflammatory disease, tuberous sclerosis, idiopathic pulmonary fibrosis, and polycystic ovary syndrome. Altered expression of miR-136-5p in specific ailments results in downstream gene expression imbalance, influencing cellular behaviors, such as migration, proliferation, and invasion. Furthermore, miR-136-5p is implicated in five signaling pathways, where it is critical in the onset and advancement of a number of illnesses. Additionally, it has the potential to promote drug resistance to a variety of medications. CONCLUSION: The current review aims to elucidate the role of miR-136-5p in both cancer progression and non-cancerous disorders, emphasizing dysregulated signaling pathways. It also sheds light on the potential of this miRNA as a prognostic biomarker in cancer, offering valuable insights and directions for future research.

Extracellular volume fraction can predict the treatment response and survival outcome of colorectal cancer liver metastases.

OBJECTIVE: To assess the prognostic value of pre- and post-therapeutic changes in extracellular volume (ECV) fraction of liver metastases (LMs) for treatment response (TR) and survival outcomes in colorectal cancer liver metastases (CRLM). METHODS: 186 LMs were confirmed by pathology or follow-up (Training: 130; Test: 56). We analyzed the changes in ECV fraction of LMs before and after 2 cycles of chemotherapy combined with bevacizumab. After 12 cycles, we evaluated the TR on LMs based on the RECIST v1.1. Relative changes in ECV fraction and Hounsfield Units (HU), defined as ΔECV and ΔHU, were associated with progression-free survival (PFS), overall survival (OS), and TR. We identified TR predictors with multivariate logistic regression and PFS, OS risk factors with COX analysis. RESULTS: 186 LMs were classified as TR lesions (TR+: 84) and non-TR lesions (TR-:102). ΔECV, ΔHUA-E, and texture could distinguish the TR of LMs in training and test set (P < 0.05). ΔECV [Odds ratio (OR): 1.03; 95% Confidence interval (CI): 1.02-1.05, P < 0.01] was an independent predictor of TR-. Area under the curve (AUC), sensitivity and specificity of TR model in training and test set were 0.87, 0.84, 90.14%, 90.32%, 72.88%, 64.00%, respectively. High CRD_score indicates that patients have shorter PFS [Hazard ratio (HR): 2.01; 95%CI: 1.02-3.98, P = 0.045)] and OS (HR: 1.89, 95%CI: 1.04-3.42, P = 0.038). CONCLUSION: ΔECV can be used as an independent predictor of TR of CRLM chemotherapy combined with bevacizumab.