FOXO3 polymorphisms influence the risk and prognosis of rhabdomyosarcoma in children.

Background: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children. Methods: Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3. Results: We found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA. Conclusions: This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.

Nucleus-targeted carbon dots as peroxidase nanozyme for photoacoustic imaging and phototherapy of tumor.

High-purity carbon dots (CDs) with a highly π-conjugated sp2-hybridized graphite structure were prepared by the pulse electrolysis method using the graphite plate as raw material. Photoacoustic signal together with photothermal effect was found in the CDs-dispersed suspensions under near-infrared (NIR) irradiation. For the suspension with the CDs concentration of 500 µg/mL, the photothermal conversion efficiency is high up 64.3% and the solution's temperature can be increased to 82.2 °C under NIR irradiation. Moreover, CDs can be effectively endocytosed by human hepatoma (HepG2) cells with a few hours, act as peroxidase nanozyme to decompose H2O2 and facilitate the production of reactive oxygen species. Under NIR irradiation, CDs exhibit an outstanding apoptosis-inducing effect on HepG2 cells by the photothermal effect. In addition, in vivo experiments show that CDs can be used in photoacoustic imaging (PAI) and guiding the tumor treatment. As a result, the nucleus-targeted CDs with an unique combination of PAI and photothermal effect have potential in cancer diagnosis and treatment.

Pain control and neonatal outcomes in 211 women under epidural anesthesia during childbirth at high altitude in Qinghai, China.

Background: High altitudes are characterized by low-pressure oxygen deprivation. This is further exacerbated with increasing altitude. High altitudes can be associated with reduced oxygenation, which in turn, can affect labor, as well as maternal and fetal outcomes. Epidural anesthesia can significantly relieve labor pain. This study aimed to assess the effects of elevation gradient changes at high altitude on the analgesic effect of epidural anesthesia, labor duration, and neonatal outcomes. Methods: We divided 211 women who received epidural anesthesia into groups according to varying elevation of their residence (76 in Xining City, mean altitude 2,200 m; 63 in Haibei Prefecture, mean altitude 3,655 m; and 72 in Yushu Prefecture, mean altitude 4,493 m). The analgesic effect was assessed using a visual analog scale (VAS). Labor duration was objectively recorded. The neonatal outcome was assessed using Apgar scores and fetal umbilical artery blood pH. Results: VAS scores among the three groups did not differ significantly (p > 0.05). The neonatal Apgar scores in descending order were: Xining group > Haibei group > Yushu group (p < 0.05). The stage of labor was similar among the three groups (p > 0.05). Fetal umbilical artery blood pH in descending order were: Xining group > Haibei group > Yushu group (p < 0.05). Conclusion: Elevation gradient changes in highland areas did not affect the efficacy of epidural anesthesia or labor duration. However, neonatal outcomes were affected.

Obtaining giant Rashba-Dresselhaus spin splitting in two-dimensional chiral metal-organic frameworks.

Two-dimensional (2D) nonmagnetic semiconductors with large Rashba-Dresselhaus (R-D) spin splitting at valence or conduction bands are attractive for magnetic-field-free spintronic applications. However, so far, the number of 2D R-D inorganic semiconductors has been quite limited, and the factors that determine R-D spin splitting as well as rational design of giant spin splitting, remain unclear. For this purpose, by exploiting 2D chiral metal-organic frameworks (CMOFs) as a platform, we theoretically develop a three-step screening method to obtain a series of candidate 2D R-D semiconductors with valence band spin splitting up to 97.2 meV and corresponding R-D coupling constants up to 1.37 eV Å. Interestingly, the valence band spin texture is reversible by flipping the chirality of CMOFs. Furthermore, five keys for obtaining giant R-D spin splitting in 2D CMOFs are successfully identified: (i) chirality, (ii) large spin-orbit coupling, (iii) narrow band gap, (iv) valence and conduction bands having the same symmetry at the Γ point, and (v) strong ligand field.

Atom-Modified gDNA Enhances Cleavage Activity of TtAgo Enabling Ultra-Sensitive Nucleic Acid Testing.

The DNA-guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2'-fluorine (2'F)-modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2'F-nucleotides at the 3'-end (2'F-gDNA) can promote the assembly of the TtAgo-guide-target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40-fold activity enhancement and decreasing minimum reaction temperature from 65 to 60°C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2'F-gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G-quadruplex and Thioflavin T, the FAST assay achieves one-pot real-time fluorescence analysis with ultra-sensitivity, providing a limit of detection up to 5 copies (20 µL reaction mixture) for miR-21 detection. In summary, an atom-modification-based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo-based nucleic acid testing technology with ultra-sensitivity and high-specificity.

Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine.

Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mycobacterium tuberculosis (M. tuberculosis), but the underlying mechanism remains unknown. Here, we report that L-alanine interacts with PRSS1 and unfreezes the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzes L-alanine and reduces the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associates with TAK1 and disruptes the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disables PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene ß-defensin 4 (Defb4) impairs the virulence by Rv2780 during infection in mice. Both L-alanine and the Rv2780 inhibitor, GWP-042, exhibits excellent inhibitory activity against M. tuberculosis infection in vivo. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis.

Perioperative complications of en bloc resection and anterior column reconstruction for thoracic and lumbar spinal tumors.

PURPOSE: To evaluate the perioperative clinical outcomes of en bloc resection and anterior column reconstruction for thoracolumbar spinal tumors. METHODS: This study conducted a retrospective analysis of prospective data collection of 86 consecutive patients, including 40 males and 46 females, with an average age of 39 years (ranged from 10 to 71 years). There were 35 cases of a malignant primary tumor,42 cases of an aggressive benign tumor, and nine cases of metastases. The main lesions were located in 65 cases of thoracic spine, 17 cases of lumbar spine, and 4 cases of thoracolumbar spine. Tumors involved one level in 45 patients, two levels in 12 patients, three levels in 21 patients, four levels in five patients, five levels in two patients, and six levels in one patient. RESULTS: According to the Weinstein-Boriani-Biagini surgical staging system, all patients achieved en bloc resections, including 74 cases of total en bloc spondylectomy and 12 cases of sagittal resections. The mean surgical time was 559 min (210-1208 min), and the mean total blood loss was 1528 ml (260-5500 ml). A total of 122 complications were observed in 62(72.1%) patients, of which 18(20.9%) patients had 25 major complications and one patient (1.2%) died of complications. The combined approach (P = 0.002), total blood loss (P = 0.003), staged surgery (P = 0.004), previous surgical history (P = 0.045), the number of involved vertebrae (P = 0.021) and lumbar location (P = 0.012) were statistically significant risk factors for major complication. When all above risk factors were incorporated in multivariate analysis, only the combined approach (P = 0.052) still remained significant. CONCLUSIONS: En bloc resection and anterior column reconstruction is accompanied by a high incidence of complications, especially when a combined approach is necessary.

Liver Involvement is Associated with Higher Risk of Rapidly Progressive Interstitial Lung Disease and Mortality in Anti-Melanoma Differentiation-Associated Gene 5 Antibody- Positive Dermatomyositis.

Purpose: This study aimed to assess liver involvement and investigate its correlation with rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 positive) DM patients. Patients and Methods: This retrospective study included 159 patients diagnosed with anti-MDA5 positive DM or anti-synthetase syndrome (ASyS). Clinical features and laboratory findings were compared between patients with anti-MDA5 positive DM and patients with ASyS. In the anti-MDA5 positive DM cohort, clinical features and laboratory findings between patients with liver involvement and without liver involvement were further compared. The effects of liver involvement on the overall survival (OS) and development of RP-ILD were also analyzed using Kaplan-Meier method and Cox regression analysis. Results: Levels of serum aspartate aminotransferase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γGT) and alkaline phosphatase (ALP) were all significantly higher in patients with anti-MDA5 positive DM than those in patients with ASyS. In our cohort of anti-MDA5 positive DM patents, 31 patients (34.4%) were complicated with liver involvement. Survival analysis revealed that serum ferritin >1030.0 ng/mL (p<0.001), ALT >103.0 U/l (p<0.001), AST >49.0 U/l (p<0.001), γGT >82.0 U/l (p<0.001), ALP >133.0 U/l (p<0.001), lactate dehydrogenase (LDH)>474.0 U/l (p<0.001), plasma albumin (ALB) <35.7 g/l (p<0.001) and direct bilirubin (DBIL) >2.80 µmol/l (p=0.002) predicted poor prognosis. The incidence of RP-ILD increased remarkably in patients with liver involvement compared to patients without liver involvement (58.1% vs 22.0%, p=0.001). Multivariate analysis revealed that elevated serum ALT level was an independent risk factor for mortality (HR 6.0, 95% CI 2.3, 16.2, p<0.001) and RP-ILD (HR 5.9, 95% CI 2.2, 15.9, p<0.001) in anti-MDA5 positive DM patents. Conclusion: Liver involvement is common in patients with anti-MDA5 positive DM. Elevated serum ALT level was an independent risk factor for RP-ILD and mortality in patients with anti-MDA5 positive DM.

Photothermal conditions and upwelling enhance very short-lived brominated halocarbons emissions in the western tropical Pacific Ocean.

Sea-to-air emissions of very short-lived brominated halocarbons (VSLBrHs) are known to contribute to 30 % of stratospheric and tropospheric ozone depletion. However, empirical data on their occurrence in open ocean are scarce, which makes it difficult to estimate the significant contribution of open ocean releases to the global budget of halocarbons. This study was conducted in 2022 to explore the spatial variations of VSLBrHs and their controlling factors in the western tropical Pacific Ocean (WTPO). The findings highlighted that high biological productivity and the resulting dissolved organic matter (DOM) as well as upwelling dynamics significantly influenced the distribution and production of VSLBrHs in seawater, with atmospheric levels primarily governed by oceanic emissions. Based on the simultaneous observation of seawater and atmospheric concentrations, the mean sea-to-air fluxes of CH2Br2, CHBr3, CHBrCl2, and CHBr2Cl were estimated to be 1.01, 6.65, 9.31, and 7.25 nmol m-2 d-1, respectively. Sea-to-air fluxes of these gases in the upwelling regions were 9.0, 4.6, 2.9, and 6.8 times those in the non-upwelling regions, respectively. Additionally, in-situ incubation experiments revealed that the enzymatic mediated biosynthesis pathways of VSLBrHs were enhanced under temperature and light-induced stress and in waters rich in humus-like substances. Therefore, we tentatively concluded that abundant photothermal conditions and the existence of upwelling in the WTPO made it a potential hotspot for the emission of VSLBrHs. This study offers critical insights into the environmental dynamics of VSLBrHs emissions and underscores the importance of regional oceanic conditions in influencing atmospheric greenhouse gas compositions.

Zhibai dihuang pill (ZBDH) exhibits therapeutic effects on idiopathic central sexual precocity in rats by modulating the gut microflora.

To reveal the role of gut microbiota (GM) in the occurrence and development of idiopathic central precocious puberty (ICPP) using 16S rDNA sequencing and bioinformatics analysis. The Danazol-induced ICPP model was successfully constructed in this study. ZBDH and GnRHa treatments could effectively inhibit ICPP in rats, as manifested by the delayed vaginal opening time, reduced weight, decreased uterine organ coefficient, and decreased uterine wall thickness and corpus luteum number, as well as remarkably reduced serum hormone (LH, FSH, and E2) levels. According to 16S rDNA sequencing analysis results, there was no significant difference in the GM community diversity across different groups; however, the composition of the microbial community and the abundance of the dominant microbial community were dramatically different among groups. ZBDH and GnRHa treatments could effectively reduce the abundance of Muribaculateae and Lactobacillus and promote Prevotella abundance. ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats.

Variation in neuroimaging and outcomes in patients with Sturge Weber syndrome Type III.

OBJECTIVES: Sturge Weber syndrome (SWS) is a neurovascular condition with an estimated incidence of 1 in 20,000 to 50,000 live births. SWS Types I and II involve cutaneous and ophthalmological findings, with neurological involvement in Type I. SWS Type III is exclusive to brain stigmata. Our study aims to describe the characteristics of brain MRI findings and report neuroradiological features with seizure and cognitive outcomes in patients with SWS Type III. METHODS: This is a retrospective case series examining the clinical, radiological, and cognitive characteristics of patients with SWS Type III referred to the SWS Clinic at Boston Children's Hospital. We analyzed brain MRI findings based on vascular and parenchymal features. Clinical and cognitive outcomes were based on a validated assessment tool in this population (Neuroscore). RESULTS: This dedicated case series of patients with Type III SWS from a single center identified ten patients. All patients had classic stigmata indicative of SWS. Two distinct radiological phenotypes were found, one characterized by more pronounced deep venous enlargement, and the other, with more pronounced parenchymal abnormalities. There was heterogeneity in seizure presentation and outcome. Earlier age of onset and seizures predict more severe outcomes, as seen in classic SWS. CONCLUSION: We could not find significant divergence in outcomes between patients with differing neuroimaging phenotypes. These results raise the question of whether the two distinct radiological phenotypes found in SWS Type III are reflective of different disease entities, with underlying genetic heterogeneity. These results suggest the need for larger, multi-center natural history studies.

Associations of obesity with chronic inflammatory airway diseases and mortality in adults: a population-based investigation.

BACKGROUND: The association between obesity and respiratory diseases has been confirmed. However, few studies have reported the relationship between obesity and the risk and mortality of chronic inflammatory airway disease (CIAD). The aim of this study was to reveal the association between obesity and the risk of CIAD, and mortality in patients with CIAD. METHODS: The study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 among adults aged 20 years and above. All participants were grouped according to body mass index (BMI) and waist circumference (WC) levels to study the relationship between obesity and CIAD. Multivariate logistic regression analysis was utilized to examine the connection between CIAD and obesity in a cross-sectional study. The association between obesity and all-cause mortality in individuals with CIAD was examined using multiple cox regression models and smooth curve fitting in a prospective cohort study. RESULTS: When stratified based on BMI in comparison to the normal weight group, the ORs with 95%CIs of CIAD for underweight and obesity were 1.39 (1.01-1.93) and 1.42 (1.27-1.58), respectively. The OR with 95%CI of CIAD for obesity was 1.20 (1.09-1.31) when stratified according to WC. Additionally, underweight was associated with a higher mortality (HR = 2.44, 95% CI = 1.31-4.55), whereas overweight (HR = 0.58,95% CI = 0.39-0.87) and obesity (HR = 0.59,95% CI = 0.4-0.87) were associated with a lower mortality (P for trend < 0.05). There was a non-linear association between BMI and all-cause mortality (P for non-linear = 0.001). An analysis of a segmentation regression model between BMI and all-cause mortality revealed a BMI turning point value of 32.4 kg/m2. The mortality of CIAD patients was lowest when BMI was 32.4 kg/m2. When BMI ≤ 32.4 kg/m2, BMI was inversely associated with all-cause mortality in patients with CIAD (HR: 0.92, 95%CI:0.88-0.97). However, when BMI > 32.4 kg/m2, there was no association between BMI and all-cause mortality (HR:1.02, 95%CI:0.97-1.06). CONCLUSION: Compared to normal weight, underweight and obesity were associated with the increased risk of CIAD. Underweight was associated with increased all-cause mortality, while overweight was associated with reduced all-cause mortality. There was a non-linear association between BMI and all-cause mortality in patients with CIAD. The all-cause mortality was lowest when BMI was 32.4 kg/m2.

How mesenchymal stem cells transform into adipocytes: Overview of the current understanding of adipogenic differentiation.

Mesenchymal stem cells (MSCs) are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts, chondrocytes and adipocytes. The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes, in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes. Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis. However, the mechanism underlying the adipogenic differentiation of MSCs is not fully understood. Here, the current knowledge of adipogenic differentiation in MSCs is reviewed, focusing on signaling pathways, noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation. Finally, the relationship between maladipogenic differentiation and diseases is briefly discussed. We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

Association between physical activity and depression in adult prescription opioid users: A cross-sectional analysis based on NHANES 2007-2018.

OBJECTIVE: This study was designed to examine the association between physical activity (PA) and depression among adult prescription opioid users. METHOD: Data of adults who recently took prescription opioids were collected from NHANES 2007-2018. Participants were divided into two groups according to whether PA in each domain was ≥600 MET-min/week. According to weekly activity frequency, recreational physical activity (RPA) was divided into inactivity, insufficient activity, weekend warrior (WW), and regular activity. PHQ-9 scores ≥10 were identified as depression. RESULTS: RPA of ≥600 MET-min/week was associated with a 40% (OR: 0.60, 95%CI: 0.38-0.96, P = 0.032) reduction in the risk of depression. Restricted Cubic Spline plots found a nonlinear dose-response relationship between RPA and depression (P = 0.045), and the turning point of depression risk was around 600 MET-min/week. There was no significant difference in the risk of depression between the WW and inactivity groups (OR: 0.65, 95%CI: 0.25-1.72, P = 0.382). The regular activity group had an 45% (OR: 0.55, 95%CI: 0.31-0.99, P = 0.046)lower risk for depression than the inactivity group. CONCLUSION: Only regular RPA is associated with a reduced risk of depression, and RPA showed a nonlinear dose-response relationship. The antidepressant effect of the WW is not significant.

High-dose vitamin C improves norepinephrine level in patients with septic shock: A single-center, prospective, randomized controlled trial.

BACKGROUND: The effects of vitamin C supplementation on patients with septic shock remain controversial. We aimed to evaluate the effects of different vitamin C dosages on norepinephrine (NE) synthesis in adult patients with septic shock. METHODS: A total of 58 patients with septic shock admitted to our intensive care unit (ICU) between July 2021 and December 2022 were included. Patients were randomly divided into 3 groups: high-dose vitamin C (150 mg/kg/d, group A), low-dose vitamin C (50 mg/kg/d, group B), and placebo (group C). NE synthesis-related indicators (dopamine-ß-hydroxylase [DßH], tyrosine hydroxylase [TH], tetrahydrobiopterin [BH4], and dopamine [DA]), plasma NE, and vitamin C levels were measured every 24 hours and analyzed. All-cause mortality within 28 days and other clinical outcomes (including Acute Physiology and Chronic Health Evaluation [APACHE], Sequential Organ Failure Assessment [SOFA], and Multiple-Organ Dysfunction Syndrome [MODS] scores) were compared. RESULTS: Changes in TH, BH4, and DßH levels at 96 hours in groups A and B were greater than those in group C. These differences became more pronounced over the course of the intravenous vitamin C administration. Significant differences between groups A and C were detected at 96-hours TH, 72-hours BH4, 96-hours BH4, 96-hours DA, and DßH levels every 24 hours. The 96-hours TH, 96-hours BH4, and 48-hours DßH in group B were significantly higher than those in group C. The NE levels every 24 hours in groups A and B were higher than those in group C, group A and group C had a statistically significant difference. The 96-hours exogenous NE dosage in groups A and B was significantly lower than that in group C. No significant reductions in APACHE, SOFA, or MODS scores were observed in the vitamin C group, including the duration of ICU stay and mechanical ventilation. The 28-days mortality was lower in groups A and B than in group C (0%, 10%, and 16.67%, P = .187), but the difference was not significant. CONCLUSION: For patients with septic shock, treatment with vitamin C significantly increased TH, BH4, and DßH levels and reduced the exogenous NE dosage, but did not significantly improve clinical outcomes.

The EIN3 transcription factor GmEIL1 improves soybean resistance to Phytophthora sojae.

Phytophthora root and stem rot of soybean (Glycine max), caused by the oomycete Phytophthora sojae, is an extremely destructive disease worldwide. In this study, we identified GmEIL1, which encodes an ethylene-insensitive3 (EIN3) transcription factor. GmEIL1 was significantly induced following P. sojae infection of soybean plants. Compared to wild-type soybean plants, transgenic soybean plants overexpressing GmEIL1 showed enhanced resistance to P. sojae and GmEIL1-silenced RNA-interference lines showed more severe symptoms when infected with P. sojae. We screened for target genes of GmEIL1 and confirmed that GmEIL1 bound directly to the GmERF113 promoter and regulated GmERF113 expression. Moreover, GmEIL1 positively regulated the expression of the pathogenesis-related gene GmPR1. The GmEIL1-regulated defence response to P. sojae involved both ethylene biosynthesis and the ethylene signalling pathway. These findings suggest that the GmEIL1-GmERF113 module plays an important role in P. sojae resistance via the ethylene signalling pathway.

Loss of ZNF451 mediates fibroblast activation and promotes lung fibrosis.

BACKGROUND: No effective therapies for pulmonary fibrosis (PF) exist because of the unclear molecular pathogenesis and the lack of effective therapeutic targets. Zinc finger protein 451 (ZNF451), a transcriptional regulator, plays crucial roles in the pathogenesis of several diseases. However, its expression pattern and function in PF remain unknown. This study was designed to investigate the role of ZNF451 in the pathogenesis of lung fibrosis. METHODS: GEO dataset analysis, RT‒PCR, and immunoblot assays were used to examine the expression of ZNF451 in PF; ZNF451 knockout mice and ZNF451-overexpressing lentivirus were used to determine the importance of ZNF451 in PF progression; and migration assays, immunofluorescence staining, and RNA-seq analysis were used for mechanistic studies. RESULTS: ZNF451 is downregulated and negatively associated with disease severity in PF. Compared with wild-type (WT) mice, ZNF451 knockout mice exhibited much more serious PF changes. However, ZNF451 overexpression protects mice from BLM-induced pulmonary fibrosis. Mechanistically, ZNF451 downregulation triggers fibroblast activation by increasing the expression of PDGFB and subsequently activating PI3K/Akt signaling. CONCLUSION: These findings uncover a critical role of ZNF451 in PF progression and introduce a novel regulatory mechanism of ZNF451 in fibroblast activation. Our study suggests that ZNF451 serves as a potential therapeutic target for PF and that strategies aimed at increasing ZNF451 expression may be promising therapeutic approaches for PF.

Peroxiredoxin 1 promotes proliferation and inhibits differentiation of MC3T3-E1 cells via AKT1 / NF-κB signaling pathway.

OBJECTIVES: Osteoporosis is the most common metabolic bone disease worldwide. The decrease in bone mass is primarily accompanied by a decrease in the number and activity of osteoblasts. Peroxiredoxins (PRDXs) are proteins that detect extremely low peroxide levels and act as sensors that regulate oxidation signals, thereby regulating various cellular functions. This study aimed to evaluate the effects of PRDX1 and estrogen on the biological behavior of osteoblasts, including their proliferation and differentiation. METHODS: Ovariectomized (OVX) mice were used to establish a model of osteoporosis and perform morphological and immunohistochemical analyses. Prdx1 gene knockout and overexpression were performed in mouse MC3T3-E1 pre-osteoblasts to assess proliferation and osteogenic differentiation using the cell counting kit-8, quantitative reverse transcription polymerase chain reaction, western blotting (WB), Alizarin Red S staining, etc. RESULTS: The OVX mice exhibited osteoporosis and PRDX1 expression increased. In vitro experiments showed that during the osteogenic differentiation of osteoblasts, PRDX1 expression decreased, while the expression of COL1 and RUNX2 increased. After Prdx1 knockout, the proliferation of osteoblasts decreased; expression of Runx2, ALP, and COL1 increased; and mineralization increased. However, after Prdx1 overexpression, osteoblast proliferation was enhanced, whereas osteogenic differentiation and mineralization were inhibited. Estrogen inhibits the H2O2-induced decrease in osteoblastic differentiation and increase in PRDX1 expression. WB revealed that when LY294002 inhibited the AKT signaling pathway, the levels of p-AKT1, p-P65, and PRDX1 protein in MC3T3-E1 cells decreased. However, when pyrrolidine dithiocarbamate (PDTC) inhibited the NF-κB signaling pathway, the expression of p-AKT1 and PRDX1 did not change except for a significant reduction of p-P65 expression. Furthermore, PDTC reversed the decreased expression of RUNX2, ALP, and COL1 caused by PRDX1 overexpression. CONCLUSIONS: PRDX1 promotes the proliferation of osteoblasts and inhibits osteogenic differentiation. Estrogen regulated osteoblastic differentiation by affecting the expression of PRDX1 in osteoblasts, and the effect is related to the AKT1/NF-κB signaling pathway.

Enhancing Colonoscopy Preparation in Elderly Constipation Patients: A Personalized Approach with PEG and Exercise - A Case Study.

This study aimed to optimize bowel preparation efficacy for colonoscopy in elderly constipation patients. A 71-year-old patient with chronic constipation and a history of poor bowel preparation. To address these challenges, we implemented a personalized strategy combining of PEG administration and walking exercise. The PEG was administered according to a protocol, with intermittent exercise breaks of 10 minute. Bowel cleanliness was assessed using the Boston Bowel Preparation Scale (BBPS). Adverse reactions and tolerance were closely monitored throughout the intervention. The patient's BBPS score improved from 3 to 8 post-intervention. The exercise intervention was well-tolerated (rating I), and mild nausea was observed only after the first PEG dose. No severe adverse reactions occurred. Subsequent Follow-up revealed symptom relief. The personalized approach combining (PEG and exercise intervention) successfully improved bowel preparation quality in the elderly constipation patient undergoing colonoscopy. This approach considers age-related changes in gastrointestinal function and activity level, offering an effective strategy to improve patient tolerance and reduce adverse reactions during bowel preparation. The findings underscore the importance of tailoring interventions for elderly constipation patients to optimize the colonoscopy experience.

Determination of the FABP5 expression profile in skin lesions of an IMQ-induced psoriasis mouse model using flow cytometry.

The fatty acid-binding protein 5 (FABP5) is a key player in psoriasis development. Therefore, characterizing the expression profile of FABP5 in various cell types within both layers of psoriatic skin is important. Here, we present a protocol that describes steps for an imiquimod-induced psoriasis mouse model and preparation of epidermal and dermal single-cell suspensions. We then detail procedures to detect the FABP5 expression profile in skin keratinocytes and immune cells using intracellular flow cytometry staining. For complete details on the use and execution of this protocol, please refer to Hao et al.1.