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1.
Molecules ; 29(12)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38930992

ABSTRACT

In this study, RM (red mud) was acidified with sulfuric acid, and the acidified ARM (acidified red mud) was utilized as an innovative adsorption material for treating antibiotic-containing wastewater. The adsorption conditions, kinetics, isotherms, thermodynamics, and mechanism of ARM for CIP (ciprofloxacin) were investigated. The characterization of the ARM involved techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), X-ray fluorescence (XRF), thermogravimetric analysis (TGA), and NH3-TPD analysis. Adsorption studies employed a response surface methodology (RSM) for the experimental design. The results showed that ARM can absorb CIP effectively. The RSM optimal experiment indicated that the most significant model terms influencing adsorption capacity were solution pH, CIP initial concentration, and ARM dosage, under which the predicted maximum adsorption capacity achieved 7.30 mg/g. The adsorption kinetics adhered to a pseudo-second-order model, while equilibrium data fitted the Langmuir-Freundlich isotherm, yielding maximum capacity values of 7.35 mg/g. The adsorption process occurred spontaneously and absorbed heat, evidenced by ΔGθ values between -83.05 and -91.50 kJ/mol, ΔSθ at 281.6 J/mol/K, and ΔHθ at 0.86 kJ/mol. Analysis using attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) indicated a complex reaction between the Al-O in the ARM and the ester group -COO in CIP. The C=O bond in CIP was likely to undergo a slight electrostatic interaction or be bound to the internal spherical surface of the ARM. The findings indicate that ARM is a promising and efficient adsorbent for CIP removal from wastewater.


Subject(s)
Ciprofloxacin , Thermodynamics , Water Pollutants, Chemical , Water Purification , Adsorption , Ciprofloxacin/chemistry , Water Pollutants, Chemical/chemistry , Kinetics , Water Purification/methods , Hydrogen-Ion Concentration , Wastewater/chemistry , Anti-Bacterial Agents/chemistry
2.
Mech Ageing Dev ; 220: 111955, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38852746

ABSTRACT

While high-fat diet (HFD)-induced obesity is a major threat to global public health, the effect of HFD on cognition and insulin signaling during ageing remains controversial. The aim of this study was to characterize the dynamic alterations in cognition and cerebral insulin signaling during 6-month HFD consumption, and to investigate the potential therapeutic target and optimal timing to rescue obesity-related cognitive deficits. In the present study, impaired memory retention induced by 2-month HFD was recovered after 4 months on HFD. Prolonged (6-month) HFD did not further enhance tau hyperphosphorylation and ß-amyloid deposition, which was consistent with the alleviation of memory retention. In brain insulin signaling, 2-month HFD increased IRS-1 and p-IRS-1(Ser307)/IRS-1, while decreasing pAKT(Ser473)/AKT, PI3K and mTOR; 4-month HFD decreased IRS-1 and pAKT(Ser473)/AKT, while increasing AKT; 6-month HFD increased IRS-1, pAKT(Ser473)/AKT, and mTOR, while decreasing p-IRS-1(Ser307)/IRS-1, PI3K and AKT. Notably, bioinformatic analysis revealed a rhythmic process presented only in 4-month HFD group, with Srebf1 emerging as a link between circadian rhythms and insulin signaling pathway. These results suggest that prolonged HFD prevents further cognitive decline and the progression of Alzheimer's disease (AD)-related pathologies during ageing. Moreover, there may be a window for recovery, in which Srebf1 acts as a self-recovery switch to address obesity-related cognitive disorders in elders.

3.
Int J Mol Sci ; 25(11)2024 May 26.
Article in English | MEDLINE | ID: mdl-38891991

ABSTRACT

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.


Subject(s)
Spermatogenesis , Testis , Humans , Male , Testis/metabolism , Testis/growth & development , Animals , Follicle Stimulating Hormone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Androgens/metabolism , Testosterone/metabolism
4.
J Cancer Res Clin Oncol ; 150(6): 317, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38914670

ABSTRACT

INTRODUCTION: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer. METHODOLOGY: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting. RESULTS: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression. CONCLUSIONS: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.


Subject(s)
Breast Neoplasms , CD24 Antigen , Cell Proliferation , Disease Progression , MicroRNAs , RNA, Long Noncoding , Humans , CD24 Antigen/genetics , CD24 Antigen/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Female , MicroRNAs/genetics , Animals , Mice , RNA, Long Noncoding/genetics , Mice, Nude , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Transcription Factors/genetics , Transcription Factors/metabolism , Cell Movement/genetics , Mice, Inbred BALB C , Prognosis
5.
J Sex Marital Ther ; : 1-18, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853443

ABSTRACT

We investigated the effectiveness of online Sensate Focus exercises, delivered online as a series of 11 animation videos, in improving participants' sexual functioning and enhancing intimacy, relationship and sexual satisfaction. We studied 35 Chinese heterosexual couples, assessed them at pretest, post-test, and a three-month follow-up. Compared to the waitlist control group, the experimental group showed improvement in orgasm in women, and this was maintained at follow-up. Also, for those with a lower function at pretest, the intervention was possibly effective in improving erectile function among men, as well as overall sexual function and pain among women. These improvements were maintained at follow-up as well. Findings from the current study suggest that online Sensate Focus intervention has potential in treating sexual dysfunction of Chinese heterosexual couples. It may also serve as the first part of a stepped care approach or be integrated with other medication or cognitive behavioral therapy treatment.

6.
Neuropharmacology ; 257: 110032, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38852839

ABSTRACT

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

7.
Ageing Res Rev ; 99: 102363, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838785

ABSTRACT

The basolateral amygdala (BLA) is the subregion of the amygdala located in the medial of the temporal lobe, which is connected with a wide range of brain regions to achieve diverse functions. Recently, an increasing number of studies have focused on the participation of the BLA in many neuropsychiatric disorders from the neural circuit perspective, aided by the rapid development of viral tracing methods and increasingly specific neural modulation technologies. However, how to translate this circuit-level preclinical intervention into clinical treatment using noninvasive or minor invasive manipulations to benefit patients struggling with neuropsychiatric disorders is still an inevitable question to be considered. In this review, we summarized the role of BLA-involved circuits in neuropsychiatric disorders including Alzheimer's disease, perioperative neurocognitive disorders, schizophrenia, anxiety disorders, depressive disorders, posttraumatic stress disorders, autism spectrum disorders, and pain-associative affective states and cognitive dysfunctions. Additionally, we provide insights into future directions and challenges for clinical translation.

8.
J Hazard Mater ; 476: 135024, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38943882

ABSTRACT

The particle size distribution in tailings notably influences their physical properties and behavior. Despite this, our understanding of how the distribution of tailings particle sizes impacts in situ pollution and ecological remediation in in-situ environment remains limited. In this study, an iron tailings reservoir was sampled along a particle flow path to compare the pollution characteristic and microbial communities across regions with different particle sizes. The results revealed a gradual reduction in tailings particle size along the flow direction. The predominant mineral composition shifts from minerals such as albite and quartz to layered minerals. Total nitrogen, total organic carbon, and total metal concentrations increased, whereas the acid-generating potential decreased. The region with the finest tailings particle size exhibited the highest microbial diversity, featuring metal-resistant microorganisms such as KD4-96, Micrococcaceae, and Acidimicrobiia. Significant discrepancies were observed in tailings pollution and ecological risks across different particle sizes. Consequently, it is necessary to assess tailings reservoirs pollution in the early stages of remediation before determining appropriate remediation methods. These findings underscore that tailings particle distribution is a critical factor in shaping geochemical characteristics. The responsive nature of the microbial community further validated these outcomes and offered novel insights into the ecological remediation of tailings.

9.
Adv Healthc Mater ; : e2401649, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38938121

ABSTRACT

Immune checkpoint blockade (ICB) has significantly improved the prognosis of patients with cancer, although the majority of such patients achieve low response rates; consequently, new therapeutic approaches are urgently needed. The upregulation of sialic acid-containing glycans is a common characteristic of cancer-related glycosylation, which drives disease progression and immune escape via numerous pathways. Herein, the development of self-assembled core-shell nanoscale coordination polymer nanoparticles loaded with a sialyltransferase inhibitor, referred to as NCP-STI which effectively stripped diverse sialoglycans from cancer cells, providing an antibody-independent pattern to disrupt the emerging Siglec-sialic acid glyco-immune checkpoint is reported. Furthermore, NCP-STI inhibits sialylation of the concentrated nucleoside transporter 1 (CNT1), promotes the intracellular accumulation of anticancer agent gemcitabine (Gem), and enhances Gem-induced immunogenic cell death (ICD). As a result, the combination of NCP-STI and Gem (NCP-STI/Gem) evokes a robust antitumor immune response and exhibits superior efficacy in restraining the growth of multiple murine tumors and pulmonary metastasis. Collectively, the findings demonstrate a novel form of small molecule-based chemo-immunotherapy approach which features sialic acids blockade that enables cooperative effects of cancer cell chemosensitivity and antitumor immune responses for cancer treatment.

10.
Anal Chim Acta ; 1312: 342751, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38834265

ABSTRACT

BACKGROUND: The abuse of the Phencyclidine-type substances, especially ketamine is a serious problem worldwide, and retrospective analysis are important for both the analysis and the identification of forms of drug abuse. The current major analytical methods, while all excellent in terms of accuracy, are time- and reagent-consuming. This depletion is made even more unfortunate by the fact that a large number of samples are negative in retrospective analyses. It is clear that a set of methods that can be analyzed both accurately and quickly need to be developed and applied to the screening and analysis of large quantities of samples. RESULTS: We described a urine test based on acoustic ejection mass spectrometry, which allows precise injection at very low volumes and near 1 ejection s-1 and data acquisition. The confidence in identification was increased by the characterization of the abundance ratio of the two pairs of ions. Urine samples could be diluted with water and loaded into a 384-well plate for sampling without complicated sample preparation. The sample in the transparent 384-well plate was pre-scanned by the laser, and then 20 nL droplets were ejected into the ion source for targeted analysis of 2 ion transitions per droplet totaling 9 targeted analytes in the sequence of acquisition methods. It took 90 min to screen 250 samples in this approach, yielding 10 ng mL-1 detection limits. Positive samples were further analyzed by UHPLC-MS/MS for confirmation and quantification of up to 36 analytes. SIGNIFICANCE: This was the first fast screening method for phencyclidine-type substances based on acoustic ejection mass spectrometry, which greatly reduces the analytical time, and can accomplish in 1.5 h what UHPLC-MS/MS needs 3 days to complete. And the samples can be analyzed without complicated sample preparation, and also can obtain good detectability. It was applied to a short-term retrospective analysis in Shanghai, and its accuracy was also extremely high.


Subject(s)
High-Throughput Screening Assays , Phencyclidine , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Phencyclidine/urine , Humans , Substance Abuse Detection/methods , Acoustics
11.
Dalton Trans ; 53(20): 8803-8811, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38716557

ABSTRACT

Two photochromic Cd(II)-CPs were obtained based on the viologen ligand using different synthetic routes, named {[Cd4(p-BDC)4(CPB)2(H2O)2]·2H2O·EtOH}n (1) and {[Cd(p-BDC)(CPB)(H2O)]·(L)·DMF}n (2) (p-H2BDC = 1,4-benzene-dicarboxylate, HCPB·Cl = 1-(4-carboxyphenyl)-4,4'-bipyridinium·Cl, L = 2,4-dinitrochlorobenzene, and DMF = N,N-dimethylformamide), respectively. Due to different coordination modes, the two Cd(II)-CPs show different structures. Compound 1 exhibits a three-dimensional (3D) framework with bimetallic nodes, while compound 2 displays a 2-fold interpenetrated (4,4) net topology. Notably, the two Cd(II)-CPs exhibit substantial disparities in photo/thermochromism, which can be attributed to variations in donor-acceptor (D-A) distances arising from structural differences. Compound 1 showed visually sensitive photo- and thermochromic behavior due to multi-pathway electron transfer and short D-A distances, which is relatively rare in electron-transfer type photochromic systems. In contrast, 2 only demonstrates insensitive photochromic behavior, with a slight deepening of the color observed after 2 hours of UV light, which is due to the mono-pathway electron transfer and long D-A distance. Moreover, we first combined Cd(II)-viologen CPs with polydimethylsiloxane (PDMS) to prepare a 1@PDMS flexible UV imaging film. 1@PDMS exhibits excellent bendability and stretchability and maintains good photochromic properties after 100 bending cycles. To demonstrate the rapid color response and distinct color contrast of 1, its application in anti-counterfeiting is also demonstrated.

12.
bioRxiv ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38712109

ABSTRACT

Background: The understanding of how varying radiation beam parameter settings affect the induction and magnitude of the FLASH effect remains limited. Purpose: We sought to evaluate how the magnitude of radiation-induced gastrointestinal (GI) toxicity (RIGIT) depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP). Methods: C57BL/6J mice were subjected to total abdominal irradiation (11-14 Gy single fraction) under conventional irradiation (low DPP and low MDR, CONV) and various combinations of DPP and MDR up to ultra-high-dose-rate (UHDR) beam conditions. The effects of DPP were evaluated for DPPs of 1-6 Gy while the total dose and MDR were kept constant; the effects of MDR were evaluated for the range 0.3- 1440 Gy/s while the total dose and DPP were kept constant. RIGIT was quantified in non-tumor-bearing mice through the regenerating crypt assay and survival assessment. Tumor response was evaluated through tumor growth delay. Results: Within each tested total dose using a constant MDR (>100 Gy/s), increasing DPP led to better sparing of regenerating crypts, with a more prominent effect seen at 12 and 14 Gy TAI. However, at fixed DPPs >4 Gy, similar sparing of crypts was demonstrated irrespective of MDR (from 0.3 to 1440 Gy/s). At a fixed high DPP of 4.7 Gy, survival was equivalently improved relative to CONV for all MDRs from 0.3 Gy/s to 104 Gy/s, but at a lower DPP of 0.93 Gy, increasing MDR produced a greater survival effect. We also confirmed that high DPP, regardless of MDR, produced the same magnitude of tumor growth delay relative to CONV using a clinically relevant melanoma mouse model. Conclusions: This study demonstrates the strong influence that the beam parameter settings have on the magnitude of the FLASH effect. Both high DPP and UHDR appeared independently sufficient to produce FLASH sparing of GI toxicity, while isoeffective tumor response was maintained across all conditions.

13.
Forensic Sci Int ; 360: 112067, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38821023

ABSTRACT

Nitrous oxide (N2O), also known as laughing gas, has a euphoric effect and is becoming increasingly popular as a recreational inhalant drug. Deaths caused by recreational nitrous oxide abuse are rare, but may still occur. Although some methods for the quantification of N2O by GC-MS have been reported, elimination of carbon dioxide interference and the choice of a suitable internal standard remain current limitations to accurate N2O quantification. Here, a validated method using headspace-gas chromatography-mass spectrometry (HS-GC-MS) is described that allows the quantification of N2O in human blood samples: sodium hydroxide is used to remove carbon dioxide, and n-pentane is chosen as a suitable internal standard. Collectively, the validation results show a good linear relationship of N2O in blood within the concentration range of 0.02 ∼ 0.5 mL/mL and an LOD of 0.005 mL/mL. Subsequent application of the validated method to two real mortality cases due to N2O intoxication provided reference values for blood concentrations in forensic cases. Other biological specimens (gaseous samples and tissues) of the deceased were also analyzed to demonstrate that the deaths were caused by asphyxia due to the inhalation of N2O.


Subject(s)
Forensic Toxicology , Gas Chromatography-Mass Spectrometry , Nitrous Oxide , Humans , Nitrous Oxide/poisoning , Nitrous Oxide/blood , Forensic Toxicology/methods , Male , Asphyxia/blood , Adult , Limit of Detection
14.
PLoS Pathog ; 20(5): e1012227, 2024 May.
Article in English | MEDLINE | ID: mdl-38739631

ABSTRACT

IFN regulatory factor 3 (IRF3) is the transcription factor crucial for the production of type I IFN in viral defence and inflammatory responses. The activity of IRF3 is strictly modulated by post-translational modifications (PTMs) to effectively protect the host from infection while avoiding excessive immunopathology. Here, we report that zebrafish myosin-regulated light chain interacting protein b (mylipb) inhibits virus-induced type I IFN production via two synergistic mechanisms: induction of autophagic degradation of irf3 and reduction of irf3 phosphorylation. In vivo, mylipb-null zebrafish exhibit reduced lethality and viral mRNA levels compared to controls. At the cellular level, overexpression of mylipb significantly reduces cellular antiviral capacity, and promotes viral proliferation. Mechanistically, mylipb associates with irf3 and targets Lys 352 to increase K6-linked polyubiquitination, dependent on its E3 ubiquitin ligase activity, leading to autophagic degradation of irf3. Meanwhile, mylipb acts as a decoy substrate for the phosphokinase tbk1 to attenuate irf3 phosphorylation and cellular antiviral responses independent of its enzymatic activity. These findings support a critical role for zebrafish mylipb in the limitation of antiviral innate immunity through two synergistic mechanisms targeting irf3.


Subject(s)
Immunity, Innate , Interferon Regulatory Factor-3 , Zebrafish Proteins , Zebrafish , Animals , Interferon Regulatory Factor-3/metabolism , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Rhabdoviridae Infections/immunology , Phosphorylation , Ubiquitination , Humans , Autophagy/immunology
15.
World J Clin Cases ; 12(15): 2568-2577, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38817233

ABSTRACT

BACKGROUND: The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated. AIM: To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality. METHODS: This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors. RESULTS: Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort. CONCLUSION: In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

16.
Gene ; 923: 148590, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-38772516

ABSTRACT

Long noncoding RNAs (lncRNAs) are implicated in a number of regulatory functions in eukaryotic genomes. In humans, KCNQ1OT1 is a 91 kb imprinted lncRNA that inhibits multiple surrounding genes in cis. Among them, CDKN1C is closely related to KCNQ1OT1 and is involved in multiple epigenetic disorders. Here, we found that pigs also had a relatively conserved paternal allele expressing KCNQ1OT1 and had a shorter 5' end (∼27 kb) compared to human KCNQ1OT1. Knockdown of KCNQ1OT1 using antisense oligonucleotides (ASO) showed that upregulation of CDKN1C expression in pigs. However, porcine KCNQ1OT1 did not affect the DNA methylation status of the CpG islands in the promoters of KCNQ1OT1 and CDKN1C. Inhibition of DNA methyltransferase using Decitabine treatment resulted in a significant increase in both KCNQ1OT1 and CDKN1C expression, suggesting that the regulation between KCNQ1OT1 and CDKN1C may not be dependent on RNA interference. Further use of chromosome conformation capture and reverse transcription-associated trap detection in the region where CDKN1C was located revealed that KCNQ1OT1 bound to the CDKN1C promoter and affected chromosome folding. Phenotypically, inhibition of KCNQ1OT1 at the cumulus-oocyte complex promoted cumulus cell transformation, and to upregulated the expression of ALPL at the early stage of osteogenic differentiation of porcine bone marrow mesenchymal stem cells. Our results confirm that the expression of KCNQ1OT1 imprinting in pigs as well as porcine KCNQ1OT1 regulates the expression of CDKN1C through direct promoter binding and chromatin folding alteration. And this regulatory mechanism played an important role in cell differentiation.


Subject(s)
Chromatin , Cyclin-Dependent Kinase Inhibitor p57 , DNA Methylation , Genomic Imprinting , Promoter Regions, Genetic , RNA, Long Noncoding , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Swine , Cyclin-Dependent Kinase Inhibitor p57/genetics , Cyclin-Dependent Kinase Inhibitor p57/metabolism , Chromatin/genetics , Chromatin/metabolism , Potassium Channels, Voltage-Gated/genetics , Potassium Channels, Voltage-Gated/metabolism , CpG Islands , Gene Expression Regulation
17.
Sci Rep ; 14(1): 10633, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724550

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) technology has been widely used to study the differences in gene expression at the single cell level, providing insights into the research of cell development, differentiation, and functional heterogeneity. Various pipelines and workflows of scRNA-seq analysis have been developed but few considered multi-timepoint data specifically. In this study, we develop CASi, a comprehensive framework for analyzing multiple timepoints' scRNA-seq data, which provides users with: (1) cross-timepoint cell annotation, (2) detection of potentially novel cell types emerged over time, (3) visualization of cell population evolution, and (4) identification of temporal differentially expressed genes (tDEGs). Through comprehensive simulation studies and applications to a real multi-timepoint single cell dataset, we demonstrate the robust and favorable performance of the proposal versus existing methods serving similar purposes.


Subject(s)
Sequence Analysis, RNA , Single-Cell Analysis , Single-Cell Analysis/methods , Sequence Analysis, RNA/methods , Humans , Gene Expression Profiling/methods , Software , Computational Biology/methods
18.
AEM Educ Train ; 8(3): e10987, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38765712

ABSTRACT

Objective: The core content of emergency medicine (EM) residency training includes the management of oncologic emergencies; however, documented knowledge gaps continue to exist in this subtopic. This study represents a targeted needs assessment as indicated by Step 2 of Kern's curriculum design to determine the specific training gaps to be addressed within the oncologic EM curriculum. Methods: A multi-institutional cross-sectional survey of oncologists (surgical and medical) and emergency physicians (attendings and residents) was conducted during 2023 at five institutions. The voluntary survey consisted of general and specialty-specific questions exploring gaps in oncologic emergency-specific training/education topics. Descriptive statistics reported responses as frequencies and percentages. Results: Of the 833 surveys sent across the five sites, 302 (36.3%) were accessed by link; of these, 271 (89.7%) surveys were completed. There were no differences in the responses between early and later respondents and no differences in the characteristics of respondents between sites. A vast majority of the oncologist and EM groups (91.2% and 83.0%, respectively) reported a belief that emergency physicians would benefit from additional oncologic emergency training. Our survey identified 16 important topics for inclusion in an oncologic EM curriculum, including five topics not present on the 2022 Model of Clinical Practice of Emergency Medicine. Conclusions: Based on this needs assessment, an oncologic EM curriculum should include the topics listed under oncologic emergencies in the 2022 Model of the Clinical Practice of Emergency Medicine along with our respondent-identified topics of radiation therapy adverse effects, stem cell transplant complications, and the management of cancer-specific postsurgical complications, pain, and common diseases in patients with cancer.

19.
World J Diabetes ; 15(5): 1011-1020, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38766432

ABSTRACT

BACKGROUND: Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. AIM: To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS: Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. RESULTS: The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. CONCLUSION: This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

20.
Micromachines (Basel) ; 15(5)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38793151

ABSTRACT

To reduce the power consumption of a TDC in high-speed applications, a TDC architecture applied to SS ADC is proposed to reduce redundant counting. This structure can remove the identical part between two rows of pixel signals in a CMOS image sensor by adjusting the start and stop signal of the TDC, which will reduce the number of flipping of D flip-flops in the TDC. This structure requires the simultaneous readout of two rows of pixels in the high-speed CMOS image sensor. In the 110 nm CMOS process, simulation results show that the designed 5-bit TDC achieves an effective number of bits (ENOB) at 4.72 bits and a figure-of-merit (FOM) at 104.7-162.3 fJ/step, with a power consumption ranging from 60 µW to 93 µW. Compared with traditional counting methods, the proposed TDC can reduce counting power consumption by 30%.

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