Prognostic implication of consolidation-to-tumor ratio in early lung adenocarcinoma: a retrospective cross-sectional study.

Background: The threshold value of consolidation-to-tumor ratio (CTR) for distinguishing between ground-glass opacity (GGO)-predominant and solid-predominant ground-glass nodules (GGNs) needs to be clarified, as the lack of clarity has caused the prognostic implications to remain ambiguous. This study aimed to determine the threshold value of CTR for distinguishing between GGO-predominant GGNs and solid-predominant GGNs and elucidate the prognostic implications of the solid-predominant GGNs categorized by CTR on c-stage IA lung adenocarcinoma. Methods: Between January 2016 and October 2018, 764 c-stage IA lung adenocarcinoma cases were assembled from the First Affiliated Hospital of Chongqing Medical University. Of the 764 lesions, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were solid nodules (SNs) on thin-section computed tomography (CT). We evaluated the correlation of the 3-dimensional (3D) consolidation component volume ratio with CTR based on the coefficient of determination, r. After receiver operating characteristic (ROC) analysis of 515 GGNs, we defined the nodule with CTR >0.750 as solid-predominant GGN and the nodule with CTR ≤0.750 as GGO-predominant GGN. Subsequently, the prognosis of 439 patients who had follow-up registration was evaluated. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was employed to compare survival rates among different groups. Cox proportional hazard regression models were applied to evaluate the independent risk factors for recurrence-free survival (RFS). Results: Among 764 patients, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were SNs on thin-section CT. For 515 GGNs, the 3D consolidation component volume ratio correlated well with CTR (r=0.888). CTR tended to be slightly larger than the 3D consolidation component volume ratio. A 3D consolidation component volume ratio >50% was best predicted by CTR >0.750, followed by CTR >0.549. CTR >0.750 and CTR >0.549 predicted 3D consolidation component volume ratio >50% with 85% and 99.2% sensitivity and 91.6% and 57.2% specificity, respectively. The 5-year RFS and overall survival (OS) of patients with 0.750< CTR <1 were worse than those of patients with 0≤ CTR ≤0.750 (P<0.001 and P<0.001, respectively) but better than those of patients with CTR =1 (P=0.002 and P=0.03, respectively). Carcinoembryonic antigen (CEA) >2.1 [hazard ratio (HR) =12.516, 95% confidence interval (CI): 1.729-90.598], CTR >0.750 (HR =13.934, 95% CI: 3.341-58.123), larger consolidation component size with diameter more than 20 mm (HR =1.855, 95% CI: 1.242-2.770), poorly differentiated (HR =1.622, 95% CI: 1.056-2.491), lymph node metastasis (HR =2.473, 95% CI: 1.601-3.821), and sublobar resection (HR =2.596, 95% CI: 1.701-3.962) could predict the poor prognosis. Patients with 0≤ CTR ≤0.750 receiving sublobar resection had prognoses comparable to those receiving lobar resection, whether the tumor size ≤2 cm or consolidation component size ≤3 cm. Lobar resection was superior to sublobar resection for non-small cell lung cancer (NSCLC) ≤2 cm with CTR >0.750. Conclusions: Compared to CTR =0.5, the 2-dimensional (2D) CTR =0.750 found using the 3D consolidation component volume ratio as the gold standard better differentiated between solid-predominant GGNs and GGO-predominant GGNs. CTR >0.750 was an independent risk factor associated with the poor prognosis of patients with c-stage IA lung adenocarcinoma. Sublobar resection should be cautiously adopted in GGNs with 0.750< CTR ≤1.

Early enteral nutrition with exclusive donor milk instead of formula milk affects the time of full enteral feeding for very low birth weight infants.

This study investigated the effects of exclusive donor milk or formula in the first 7 days after birth, on the time to full enteral feeding, growth, and morbidity of adverse events related to premature infants. This was a retrospective study carried out from July 2014 to December 2019 at the Department of Neonatology of Shanghai Children's Hospital. All infants with a birth weight < 1,500 g and a gestational age ≤ 32 who received exclusive donor milk or formula in the first 7 days after birth were included in this study. The time to full enteral feeding (defined as 150 mL/kg) in the donor milk group was significantly shorter than in the formula group (18 vs. 22 days, p = 0.01). Donated breast milk was also associated with a lower incidence of NEC (4.4 vs. 7%, p < 0.01), ROP (3.8 vs. 13.2%, p < 0.01), and culture-confirmed sepsis (11 vs. 22.6%, p < 0.01). Using donated breast milk instead of current formula milk for early enteral nutrition can shorten the time to full enteral feeding and reduce the incidence of NEC, ROP, and sepsis.

Evaluating the Effectiveness of Radiofrequency Therapy and Manual Pelvic Fascial Release in Treating Myofascial Pelvic Pain.

INTRODUCTION AND HYPOTHESIS: Myofascial pelvic pain (MFPP), characterized by sensitive trigger points in the pelvic floor muscles, leads to chronic pain and affects various aspects of life. Despite the availability of different treatment modalities, there is limited comparative research on their effectiveness. This study compares radiofrequency (RF) therapy and myofascial manual therapy (MMT) in treating MFPP. We aimed to evaluate pelvic floor muscle strength changes, clinical symptoms, and patient comfort during treatment. METHODS: The study involved 176 participants, divided equally into RF and MMT groups. We assessed pelvic floor pain using the Visual Analogue Scale (VAS), muscle strength using the Modified Oxford Scale (MOS) and surface electromyography (sEMG), clinical symptom improvement through questionnaires, and patient discomfort during treatment. RESULTS: Both RF and MMT groups significantly reduced pelvic floor and paraurethral muscle pain (VAS scores, p < 0.001). RF treatment significantly decreased vaginal laxity in its group (p < 0.001), with no notable change in the MMT group (p = 0.818). RF therapy also resulted in greater patient comfort than MMT (p < 0.001). Although both treatments improved clinical symptoms, there was no significant difference between the two (p = 0.692). MOS scores and pelvic floor sEMG values showed no significant differences between the groups before and after treatment (p > 0.05). CONCLUSIONS: Both RF and MMT effectively alleviate pelvic floor pain and improve clinical symptoms in MFPP patients. RF therapy, however, offers additional benefits in reducing vaginal laxity and enhancing treatment comfort.

Cardioprotective effects of curcumin against Diabetic Cardiomyopathies: A systematic review and meta-analysis of preclinical studies.

BACKGROUND: As a common complication of diabetes, diabetic cardiomyopathy (DCM) often leads to further damage to the heart muscle. Curcumin has been proven to have a variety of cardioprotective effects, however, the protective effect against DCM has not been systematically reviewed. PURPOSE: In this study, we aimed to analyze the preclinical (animal model) evidence of curcumin's therapeutic effects in DCM. METHODS: Eight databases and two registry systems were searched from the time of library construction to 1 November 2023. We performed rigorous data extraction and quality assessment. The included studies' methodological quality was appraised using the SYRCLE RoB tool, statistical analyses were carried out using RevMan 5.4 software, and Funnel plots and Egger's test were performed using Stata 17.0 software to assess publication bias. RESULTS: This study included 32 trials with a total of 681 animals. Meta-analysis showed that curcumin significantly improved cardiac function indices (LVEF, LVFS, and LVSd) (p < 0.01), decreased markers of myocardial injury, HW/BW ratio, and randomized blood glucose compared to the control group, in addition to showing beneficial effects on mechanistic indices of myocardial oxidation, inflammation, apoptosis, and autophagy (p < 0.05). CONCLUSIONS: Curcumin may exert cardioprotective effects in DCM through its antioxidant, anti-inflammatory, autophagy-enhancing, and anti-apoptotic effects. Its protective effect is proportional to the dose, and the efficacy may be further increased at a concentration of more than 200 mg/kg, and further validation is needed.

Cross-Linking CdSO4-Type Nets with Hexafluorosilicate Anions to Form an Ultramicroporous Material for Efficient C2H2/CO2 and C2H2/C2H4 Separation.

A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.

Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway.

Neuropeptide substance P (SP) belongs to a family of bioactive peptides and regulates many human diseases. This study aims to investigate the role and underlying mechanisms of SP in colitis. Here, activated SP-positive neurons and increased SP expression were observed in dextran sodium sulfate (DSS)-induced colitis lesions in mice. Administration of exogenous SP efficiently ameliorated the clinical symptoms, impaired intestinal barrier function, and inflammatory response. Mechanistically, SP protected mitochondria from damage caused by DSS or TNF-α exposure, preventing mitochondrial DNA (mtDNA) leakage into the cytoplasm, thereby inhibiting the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. SP can also directly prevent STING phosphorylation through the neurokinin-1 receptor (NK1R), thereby inhibiting the activation of the TBK1-IRF3 signaling pathway. Further studies revealed that SP alleviated the DSS or TNF-α-induced ferroptosis process, which was associated with repressing the cGAS-STING signaling pathway. Notably, we identified that the NK1R inhibition reversed the effects of SP on inflammation and ferroptosis via the cGAS-STING pathway. Collectively, we unveil that SP attenuates inflammation and ferroptosis via suppressing the mtDNA-cGAS-STING or directly acting on the STING pathway, contributing to improving colitis in an NK1R-dependent manner. These findings provide a novel mechanism of SP regulating ulcerative colitis (UC) disease.

Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.

Oral vitamin A supplements to prevent acute upper respiratory tract infections in children up to seven years of age.

BACKGROUND: According to global prevalence analysis studies, acute upper respiratory tract infections (URTIs) are the most common acute infectious disease in children, especially in preschool children. Acute URTIs lead to an economic burden on families and society. Vitamin A refers to the fat-soluble compound all-trans-retinol and also represents retinol and its active metabolites. Vitamin A interacts with both the innate immune system and the adaptive immune system and improves the host's defences against infections. Correlation studies show that serum retinol deficiency was associated with a higher risk of respiratory tract infections. Therefore, vitamin A supplementation may be important in preventing acute URTIs. OBJECTIVES: To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding. Primary outcomes Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence). Secondary outcomes Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.

Evolutionary game analysis of data sharing among large and medium-sized enterprises in the perspective of platform empowerment.

With the swift advancement of the global digital economy, data has emerged as a critical component in fostering the integration of large enterprises with small and medium-sized enterprises (SMEs). Nevertheless, due to disparities in resources and capabilities between these entities, there is a deficiency in the willingness to share data, hindering the full actualization of data's potential value. Hence, it is imperative to facilitate a novel cooperative development paradigm wherein platforms enable data sharing among large enterprises and SMEs. In this paper, we construct a tripartite evolutionary game model encompassing large enterprises, SMEs, and digital platforms, examine the evolutionary stable strategies adopted by these entities in the data sharing, and use numerical simulation to explore the system's evolutionary stability under various influencing factors. Contrasting with prior research, this study considers the heterogeneity of enterprise scale and delves into the data sharing dynamics between large enterprises and SMEs. Simultaneously, it positions the digital platform as a player in the game, examining its impact on data sharing among the enterprises. Findings indicate that: (1) SMEs exhibit greater eagerness for data sharing compared to large enterprises, which display a U-shaped influence during the process; (2) Digital platforms are particularly sensitive to costs, with the platform's initiative and the service quality will affect enterprises strategic choices; (3) Government subsidies positively encourage tripartite cooperation, and robust data security governance framework is crucial for enterprises. Finally, based on the results of the study and combining with the current situation of digital economy development, it puts forward the suggestions for promoting platforms to empower large enterprises and SMEs to realize data sharing and the prospects for future research.

Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression.

BACKGROUND: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. METHODS: Analysis of multi-omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co-immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual-luciferase reporter, chromatin immunoprecipitation, western blotting and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log-rank test. RESULTS: c-Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate-aspartate shuttle (MAS) in NB cells. Mechanistically, c-Myc directly promoted the expression of glutamyl-prolyl-tRNA synthetase (EPRS) and leucyl-tRNA synthetase (LARS), resulting in translational up-regulation of glutamic-oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c-Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre-clinically, lobeline was discovered as a LMNA-binding compound to facilitate its interaction with c-Myc, which inhibited aminoacyl-tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c-Myc knock-in mice. Low levels of LMNA or elevated expression of c-Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. CONCLUSIONS: These results suggest that targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.

Two-component system RstAB promotes the pathogenicity of adherent-invasive Escherichia coli in response to acidic conditions within macrophages.

Adherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn's disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.

A Fruit-Expressed MYB Transcription Factor Regulates Anthocyanin Biosynthesis in Atropa belladonna.

Anthocyanins are water-soluble flavonoid pigments that play a crucial role in plant growth and metabolism. They serve as attractants for animals by providing plants with red, blue, and purple pigments, facilitating pollination and seed dispersal. The fruits of solanaceous plants, tomato (Solanum lycopersicum) and eggplant (Solanum melongena), primarily accumulate anthocyanins in the fruit peels, while the ripe fruits of Atropa belladonna (Ab) have a dark purple flesh due to anthocyanin accumulation. In this study, an R2R3-MYB transcription factor (TF), AbMYB1, was identified through association analysis of gene expression and anthocyanin accumulation in different tissues of A. belladonna. Its role in regulating anthocyanin biosynthesis was investigated through gene overexpression and RNA interference (RNAi). Overexpression of AbMYB1 significantly enhanced the expression of anthocyanin biosynthesis genes, such as AbF3H, AbF3'5'H, AbDFR, AbANS, and Ab3GT, leading to increased anthocyanin production. Conversely, RNAi-mediated suppression of AbMYB1 resulted in decreased expression of most anthocyanin biosynthesis genes, as well as reduced anthocyanin contents in A. belladonna. Overall, AbMYB1 was identified as a fruit-expressed R2R3-MYB TF that positively regulated anthocyanin biosynthesis in A. belladonna. This study provides valuable insights into the regulation of anthocyanin biosynthesis in Solanaceae plants, laying the foundation for understanding anthocyanin accumulation especially in the whole fruits of solanaceous plants.

Versatile morphology transition of nano-assemblies via ultrasonics/microwave assisted aqueous polymerization-induced self-assembly based on host-guest interaction.

Nano-assemblies have wide applications in biomedicine, functional coatings, Pickering emulsifiers, hydrogels, and so forth. The preparation of assemblies mainly utilizes the polymerization-induced self-assembly (PISA) method, which can produce high-concentration nanoscale assemblies in one step. However, the initiation processes of most reported PISA are limited to thermal initiation. Here, we reported two green and efficient methods for synthesizing nano-assemblies with various morphologies using ultrasound (20 kHz)/ microwave (500 W) assisted aqueous-phase RAFT-PISA in 3 h and 1 h. Cyclodextrin (CD) and styrene (St) nucleating monomer were complexed in a 1:1 ratio. Then, using Poly (ethylene glycol) methyl ether as the macromolecular reversible addition-fragmentation chain transfer (RAFT) agent (PEG-CTA) to control the CD/St complexes, the conversion rate of St monomer was respectively 27 %-60 %, 20 %-30 % within 3 h and 1 h under ultrasonics/microwave assisted PISA. Results showed that the morphologies of the assemblies are not only related to the length of PS block, but also to the assistance types and the remaining monomer concentration. The results showed that only PEG45-b-PS90 and PEG45-b-PS241 assemblies prepared by ultrasonics assisted PISA form evolved lamellaes and vesicles (100 nm), which break through the limitation of kinetic freezing. But the ultrasonic reaction on morphology of assemblies is not all favourable. For one thing, it can promote the movement of particles; for another, it makes reverse morphology transformation and sphere is preferred morphology. Therefore, the main reason of morphology evolution is the remaining monomer concentration of PEG45-b-PS90 and PEG45-b-PS241 assemblies reaches to 55 %-65 %, which promoting the segment movement. The results showed that the morphology of the assemblies prepared by microwave assisted PISA changed from spherical micelles to short rods, and finally to vesicles (120-140 nm) as the length of hydrophobic PS block increases. The kinetic freezing problem was solved in microwave-assisted PISA due to the action of microwaves and more remaining monomer concentration. Both them can boost particles movement.

miR-133a and miR-135a Regulate All-Trans Retinoic Acid-Mediated Differentiation in Pediatric Acute Myeloid Leukemia by Inhibiting CDX2 Translation and Serve as Prognostic Biomarkers.

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.

The relationship between mean corpuscular hemoglobin concentration and mortality in hypertensive individuals: A population-based cohort study.

INTRODUCTION: Hematology is an essential field for investigating the prognostic outcomes of cardiovascular diseases (CVDs). Recent research has suggested that mean corpuscular hemoglobin concentration (MCHC) is associated with a poor prognosis in several CVDs. There is no evidence of a correlation between MCHC and hypertension. Therefore, our study aimed to analyze the association of MCHC with all-cause and cardiovascular mortality in hypertensive patients. METHODS: We used cohort data from U.S. adults who participated in the National Health and Nutrition Examination Survey from 1999-2014. COX regression was applied to analyze the relationship between MCHC and all-cause and cardiovascular mortality. In addition, three models were adjusted to reduce confounding factors. We reanalyzed the data after propensity score matching (PSM) to inspect the stability of the results. Stratified analysis was additionally adopted to investigate the results of each subgroup. RESULTS: Our research included 15,154 individuals. During a mean follow-up period of 129 months, 30.6% of the hypertensive population succumbed to mortality. Based on previous studies, we categorized patients with MCHC ≤33mg/dl as the hypochromia group and those with >33mg/dl as the non-hypochromia group. After PSM, the hypochromia group had higher all-cause mortality (adjusted hazard ratio [HR]:1.26, 95% confidence interval [95%CI]:1.11-1.43) and cardiovascular mortality (adjusted HR:1.42, 95%CI:1.12-1.80) than the non-hypochromia group. The results of the COX regression remain stable after matching. Stratified analyses before PSM revealed an interaction of anemia in the relationship between MCHC and mortality, whereas there was no significant interaction after matching. CONCLUSION: In hypertensive individuals, low MCHC was correlated with a poor prognosis. Further studies on MCHC are necessary to analyze the potential mechanisms of its poor prognosis in hypertensive populations.

Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

Focus on brain-lung crosstalk: preventing or treating the pathological vicious circle between the brain and the lung.

Recently, there has been increasing attention to bidirectional information exchange between the brain and lungs. Typical physiological data is communicated by channels like the circulation and sympathetic nervous system. However, communication between the brain and lungs can also occur in pathological conditions. Studies have shown that severe traumatic brain injury(TBI), cerebral hemorrhage, subarachnoid hemorrhage(SAH), and other brain diseases can lead to lung damage. Conversely, severe lung diseases such as acute respiratory distress syndrome(ARDS), pneumonia, and respiratory failure can exacerbate neuroinflammatory responses, aggravate brain damage, deteriorate neurological function, and result in poor prognosis. A brain or lung injury can have adverse effects on another organ through various pathways, including inflammation, immunity, oxidative stress, neurosecretory factors, microbiome and oxygen. Researchers have increasingly concentrated on possible links between the brain and lungs. However, there has been little attention given to how the interaction between the brain and lungs affects the development of brain or lung disorders, which can lead to clinical states that are susceptible to alterations and can directly affect treatment results. This review described the relationships between the brain and lung in both physiological and pathological conditions, detailing the various pathways of communication such as neurological, inflammatory, immunological, endocrine, and microbiological pathways. Meanwhile, this review provides a comprehensive summary of both pharmacological and non-pharmacological interventions for diseases related to the brain and lungs. It aims to support clinical endeavors in preventing and treating such ailments and serve as a reference for the development of relevant medications.

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice.

As of December 2022, 2,603 cases laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we constructed two vaccine candidates of DNA and replicating Vaccinia Tian Tan (VTT) vector that carried the MERS-CoV Spike (S) protein. Compared with homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The mice immunized generated robust binding antibodies and broader neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8+ T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates but also proposes a heterologous sequential immunization strategy worthy of further development.

Five undescribed meroterpenoids from Ganoderma lucidum and their inhibitory activities against renal fibrosis.

Five undescribed meroterpenoids, baosglucidnes A - E (1-5), were isolated from the fruiting bodies of Ganoderma lucidum. Among them, baosglucidne B (2) as a racemic mixture was obtained. Chiral HPLC was employed to separate a pair of enantiomers (+)-2 and (-)-2. The structures and stereochemical features of these substances were characterized by utilizing spectroscopic data and ECD calculations. Finally, the results of anti-renal fibrosis activity evaluation showed that baosglucidne E (5) could inhibit the expression of collagen I in TGF-ß1-induced rat kidney proximal tubular cells at 20 µM.

Central nervous system anomalies in 41 Chinese children incontinentia pigmenti.

INTRODUCTION: Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase. MATERIALS AND METHODS: This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi'an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data. RESULTS: Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 109), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 109). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration. CONCLUSION: Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.