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1.
Talanta ; 282: 127000, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39378764

ABSTRACT

Timely and facile monitoring of Mycobacterium tuberculosis (M. tuberculosis) plays an important role for preventing and controlling tuberculosis infection. Mycobacterium smegmatis (M. smegmatis) has long been employed as a safe surrogate for the investigation of M. tuberculosis. In this work, an aqueous soluble tail protein derived from our previously isolated mycobacteriophage was prepared with a recombinant expression technique and noted as GP89, which shows noticeable binding capacity to Mycobacterium genus. GP89 was sprayed as a capture agent onto a nitrocellulose membrane for forming the test line of a lateral flow assay (LFA) strip. Moreover, an aptamer binding M. tuberculosis and M. smegmatis was labeled with fluorescent microspheres to act as the signal tracer of the LFA method. With the GP89 based LFA, M. tuberculosis and M. smegmatis can be detected with the aid of a handheld UV flashlight or a portable fluorescent strip reader within 10 min. The concentration range for quantitating M. tuberculosis and M. smegmatis are both 1.0 × 102 CFU mL-1 - 1.0 × 106 CFU mL-1, and the detection limits for the two mycobacteria are 2.0 and 24 CFU mL-1 (S/N = 3), respectively. The test strip was applied to detect M. tuberculosis and M. smegmatis in different samples such as physiological salt solution, urine, and saliva. This study offers a promising screening tool for diagnosing M. tuberculosis infection in resource-limited institutes.

2.
JMIR Res Protoc ; 13: e64216, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39365658

ABSTRACT

BACKGROUND: Early neurodevelopmental risks, compounded with traumatic medical experiences, contribute to emotional and behavioral challenges in as many as 1 in 2 children with congenital heart disease (CHD). Parents report a strong need for supports; yet, there remains a lack of accessible, evidence-based behavioral interventions available for children with CHD and their families. I-InTERACT-North is a web-based stepped-care mental health program designed to support family well-being and reduce behavioral concerns through positive parenting for children with early medical complexity. In previous pilot studies, the program was effective in increasing positive parenting skills and decreasing child behavior problems, with high parent-reported acceptability. This paper presents the protocol for the first randomized study of stepped-care parent support for families of children with CHD. OBJECTIVE: This study will involve a single-site, 2-arm, single-blind randomized controlled trial to evaluate (1) the feasibility and acceptability of a web-based stepped-care parent support program (I-InTERACT-North) and (2) the effectiveness of the program in enhancing positive parenting skills and reducing behavioral concerns among families of children with CHD. METHODS: Families will be randomized (1:1) to either receive treatment or continue with care as usual for 12 months. Randomization will be stratified by child's sex assigned at birth and baseline parent-reported child behavior intensity. Primary outcomes include positive parenting skills and child behavior at baseline, 3 months, 6 months, and 12 months. Secondary outcomes include parental mental health, quality of life, service usage, and feasibility including program reach and adherence. A sample size of 244 families will provide >95% power to detect an effect size of d=0.64. Based on attrition data from pilot studies, a target of 382 families will be enrolled. Parent reports of acceptability, adoption, and suggested adaptability of the program will be examined using cross-case thematic analyses. Primary efficacy analysis will be conducted using an intent-to-treat approach. Generalized estimating equations will be used to examine changes in positive parenting. Child behavior, quality of life, and parent mental health will be tested with repeated-measures analyses. Additional sensitivity and replication analyses will also be carried out. RESULTS: Recruitment began in February 2024, and recruitment and follow-up will continue until January 2029. We anticipate results in late 2029. CONCLUSIONS: This study aims to test the effectiveness of I-InTERACT-North web-based stepped-care parent support in improving positive parenting skills and reducing child behavior problems in families of children with CHD compared with a care as usual control group. Results will inform future clinical implementation and expansion of this program among families of children with early medical conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06075251; https://clinicaltrials.gov/study/NCT06075251. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64216.


Subject(s)
Heart Defects, Congenital , Parents , Humans , Heart Defects, Congenital/psychology , Heart Defects, Congenital/therapy , Parents/education , Parents/psychology , Child , Female , Male , Internet-Based Intervention , Single-Blind Method , Adult , Parenting/psychology , Child, Preschool
3.
ACS Appl Bio Mater ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39365689

ABSTRACT

PEG-enzyme nanocomplexes are prepared and stabilized in an oil-in-water-type emulsion for Pickering interfacial biocatalysis, and these nanocomplexes function as catalysts and emulsifiers at the emulsion interface. The nanocomplexes are self-assembled by cross-linking mPEG-ALD with lipase, without complicated synthesis steps, toxic chemical reagents, and external carriers. Moreover, the mild cross-linking process preserves the original structure of the enzyme, the retention rate of enzyme activity is 82.1%, and the nanocomplexes are used to emulsify biphasic aqueous-organic solution into Pickering emulsion. The system exhibits excellent reusability, with enzyme activity remaining at 86.05% after five cycles, providing a desirable eco-friendly platform for carrier-free Pickering interfacial biocatalysis.

4.
Int J Biol Macromol ; 281(Pt 1): 136289, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39368585

ABSTRACT

In the background of severe water pollution, adsorption is a charming technique for heavy metal remediation. In this work, NiFe2O4 decorated chitosan-graphene oxide (NFCG) was prepared by simple hydrothermal method for Co(II) remediation application. Adsorption mechanism was elaborately elucidated based on multiple evidences extracted from adsorption fitting (isotherms, thermodynamics and kinetics), spectroscopic test (XPS, UV-Vis absorption, fluorescent emission and Raman spectra) and the hard-soft acid-base (HSAB) theory inspection. Result shows, for Co(II) with initial concentration 200 mg·L-1, NFCG with dosage 500 mg·L-1 reaches adsorption equilibrium in 24 min, rendering removal percentage and adsorption amount 96.87 % and 387.48 mg·g-1, respectively. Owing to the efficient recovery enabled by paramagnetism, NFCG keeps adsorption amount 311.01 mg·g-1 for Co(II) after six consecutive cycles. Moreover, NFCG exhibits selectivity towards Co(II) under the coexistence of common interfering substances. Adsorption fitting suggests chemical adsorption based on heterogeneous affinity. Spectroscopic analysis discloses, CO, CO, -C(=O)NH-, OH and aromatic part contribute to Co(II) adsorption via electron donation, forming CoO bond. This atomic scale adsorption mechanism was substantiated by HSAB theory calculation. In brief, this work provides basic knowledge and technical support for fabricating high efficiency magnetic bio adsorbent.

5.
Biomolecules ; 14(9)2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39334927

ABSTRACT

Dendritic cells (DCs) are antigen-presenting cells that play a crucial role in initiating immune responses by cross-presenting relevant antigens to initial T cells. The activation of DCs is a crucial step in inducing anti-tumor immunity. Upon recognition and uptake of tumor antigens, activated DCs present these antigens to naive T cells, thereby stimulating T cell-mediated immune responses and enhancing their ability to attack tumors. It is particularly noted that DCs are able to cross-present foreign antigens to major histocompatibility complex class I (MHC-I) molecules, prompting CD8+ T cells to proliferate and differentiate into cytotoxic T cells. In the malignant progression of hepatocellular carcinoma (HCC), the inactivation of DCs plays an important role, and the activation of DCs is particularly important in anti-HCC immunotherapy. In this review, we summarize the mechanisms of DCs activation in HCC, the involved regulatory factors and strategies to activate DCs in HCC immunotherapy. It provides a basis for the study of HCC immunotherapy through DCs activation.


Subject(s)
Carcinoma, Hepatocellular , Dendritic Cells , Liver Neoplasms , Tumor Microenvironment , Dendritic Cells/immunology , Humans , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Tumor Microenvironment/immunology , Immunotherapy , Animals
6.
Curr Dev Nutr ; 8(9): 104431, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39263224

ABSTRACT

Background: Superior mesenteric ischemia/reperfusion (I/R) causes barrier dysfunction and facilitates bacterial translocation (BT) in the small intestine, which can even lead to systemic sepsis. Our previous research showed that luminal administration of glucose and its anaerobic glycolytic metabolites exerted cytoprotective effects on epithelial cells and ameliorated I/R-induced BT in the liver and spleen. Notably, the reduction of BT occurs over the whole intestinal tract, not only restricted in the ligated glucose-containing loop. Objectives: In this study, we hypothesized that local jejunal glucose-contacting might confer on the remote intestinal epithelium regeneration potential, fortify their barrier function and goblet cell secretory activity. Methods: Two 10-cm jejunal segments were isolated in Wistar rats. One segment was ligatured at both ends and infused with Krebs buffer containing 0- or 50-mM glucose (local loop), whereas the adjacent segment was left unaltered and not exposed to glucose (remote loop). The rats then underwent either a sham operation or I/R challenge by occlusion of the superior mesenteric artery for 20 min, followed by reperfusion for 1 h. Results: Enteral addition of glucose in the local jejunum loop alleviated ischemia-induced barrier defects, histopathological scores, cell death, and mucosal inflammation (myeloperoxidase and inflammatory cytokine production) in the remote jejunum. After ischemia, goblet cells in the remote jejunum showed cavitation of mucin granules and low MUC2 expression. Local addition of glucose enhanced MUC2 synthesis and stimulated a jet-like mucus secretion in the remote jejunum, which was accompanied by the restoration of crypt activity. Conclusions: Our results showed local enteral glucose effectively mitigates I/R-induced barrier dysfunction, suggesting that local glucose-stimulated mucus secretion by remote goblet cells may serve to mitigate mucosal inflammation and BT. We provide a more precise barrier protection role of enteral glucose upon I/R challenge, presenting new opportunities for future therapeutic potential.

8.
J Org Chem ; 89(18): 13678-13690, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39240699

ABSTRACT

Herein, a visible-light-promoted radical cascade cyclization of heterocyclic ketene aminals (HKAs) and thiocyanates was developed to access functionalized fused 2-iminothiazolines. This novel cascade reaction can be realized under only visible-light irradiation without the help of external photocatalysts, oxidants, and additives. These multicomponent cascade reactions demonstrate excellent selectivity for the Z-isomers and ensure the formation of the products only in their isomeric form. Preliminary mechanism investigations demonstrated that HKAs and thiocyanates can form electron donor-acceptor complexes for harvesting the energy of visible light to activate substrates and generate reactive radicals. This protocol can be used for synthesizing various natural-like products such as fused 2-iminothiazolines. This approach demonstrates multiple advantages such as commercially available substrates, convenient operation, environmentally friendly, mild conditions, and an efficient multicomponent reaction (2A + B).

9.
J Pediatr ; 276: 114271, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39218208

ABSTRACT

OBJECTIVE: To examine sex differences in neurodevelopmental outcomes and brain development from early life to 8 years in males and females born preterm. STUDY DESIGN: This was a prospective cohort study of infants born very preterm (24-32 weeks of gestation) and followed to 8 years with standardized measures of neurodevelopment. Brain magnetic resonance imaging scans were performed soon after birth, term-equivalent age, and 8 years. The relationship between sex, severe brain injury, early pain exposure, fractional anisotropy, and neurodevelopmental outcomes were assessed using multivariable generalized estimating equations. RESULTS: Males (n = 78) and females (n = 66) were similar in clinical risk factors. Male sex was associated with lower cognitive scores (ß = -3.8, P = .02) and greater motor impairment (OR, 1.8; P = .04) across time. Male sex was associated with lower superior white matter fractional anisotropy across time (ß = -0.01; P = .04). Sex moderated the association between severe brain injury, early pain, and neurodevelopmental outcomes. With severe brain injury, males had lower cognitive scores at 3 years of age (P < .001). With increasing pain, females had lower cognitive scores at 8 years of age (P = .008), and males had greater motor impairment at 4.5 years of age (P = .001) and 8 years of age (P = .05). CONCLUSIONS: Males born preterm had lower cognitive scores and greater motor impairment compared with females, which may relate to differences in white matter maturation. The association between severe brain injury, early pain exposure, and neurodevelopmental outcomes was moderated by sex, indicating a differential response to early-life adversity in males and females born preterm.

10.
Sci Total Environ ; 953: 175990, 2024 Nov 25.
Article in English | MEDLINE | ID: mdl-39245378

ABSTRACT

The rare earth element lanthanum (La(III)) has been found to effectively enhance crop yields and improve plant growth and development. Arsenic (As), as a class of toxic metals widely found in the environment, poses a serious threat to both ecological and human health. Research on the application of La(III) in phytoremediation to enhance remediation efficiency is currently lacking. This study examined the impact of La(III) on physiological and biochemical indicators of Solanum nigrum L. (S. nigrum) exposed to Sodium hydrogen arsenate (SA) and Roxarsone (ROX) treatments under hydroponic conditions. Results indicated that La(III) treatment increased S. nigrum's aboveground As transport capacity by 58.68 %-213 % compared to no La(III) application. Additionally, foliar spraying of La(III) significantly inhibited the expression of toxic metabolites in the root system of S. nigrum, reducing Benzamide by 99.79 % under SA treatment and ZON by 87.72 % under ROX treatment. La(III) is likely to promote the transport of toxins and nutrients within and out of cells by activating ABC transporters, thereby enhancing S. nigrum's arsenic tolerance and metabolic activity. These findings provide molecular-scale insights into La(III) enhancement of the resilience of hyper-enriched plants and the remediation potential of contaminated sites.


Subject(s)
Arsenates , Lanthanum , Roxarsone , Soil Pollutants , Solanum nigrum , Solanum nigrum/metabolism , Solanum nigrum/drug effects , Arsenates/metabolism , Arsenates/toxicity , Roxarsone/metabolism , Soil Pollutants/metabolism , Biodegradation, Environmental , Metabolomics
11.
Adv Sci (Weinh) ; : e2403389, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264289

ABSTRACT

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress-related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome-related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte-specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive-like behaviors by inhibiting lysosomal exocytosis-mediated adenosine 5'-triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive-like behaviors induced by astrocyte-specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress-sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants.

12.
Gels ; 10(8)2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39195032

ABSTRACT

The "sol-gel method" was used to prepare spherical chitosan-modified bentonite (SCB) hydrogels in this study. The SCB hydrogels were characterized and used as sorbents to remove tetracycline (TC) from aqueous solutions. The adsorbents were characterized by SEM, XRD, FTIR, TG, and BET techniques. Various characterization results showed that the SCB adsorbent had fewer surface pores and a specific surface area that was 96.6% lower than the powder, but the layered mesoporous structure of bentonite remained unchanged. The adsorption process fit to both the Freundlich model and the pseudo-second-order kinetic model showed that it was a non-monolayer chemical adsorption process affected by intra-particle diffusion. The maximum monolayer adsorption capacity determined by the Langmuir model was 39.49 mg/g. Thermodynamic parameters indicated that adsorption was a spontaneous, endothermic, and entropy-increasing process. In addition, solid-liquid separation was easy with the SCB adsorbent, providing important reference information for the synthesis of SCB as a novel and promising adsorbent for the removal of antibiotics from wastewater at the industrial level.

13.
Anal Chem ; 96(37): 15074-15080, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39215695

ABSTRACT

Multimodal immunochromatographic sensors (ICSs) have acquired extensive attention since they not only provide reliable results by comparing the different output signals but also flexibly respond to various application environments. Herein, an ICS with triple signal outputs including colorimetry, temperature, and pressure was developed for sensitive detection of chlorothalonil. The multivalent Pt/Ti3C2Tx nanoparticles as signal tags were facilely synthesized by loading PtNPs onto single-layer Ti3C2Tx nanosheets with high surface area. The acquired Pt/Ti3C2TxNPs accelerated the rate-limiting step of the aerogenesis reaction of H2O2 for producing intensive pressure signals due to their significant catalase-mimic activity. Meanwhile, they showed desirable photothermal conversion efficiency in the near-infrared region for producing significant temperature signals. Furthermore, their deep color also allowed facile colorimetry by using the naked eye. Based on a competitive immunoassay, chlorothalonil was detected as a model analyte on this trimodal ICS platform. The detection limits for pressure, temperature, and colorimetric modes were 0.04, 0.09, and 5 ng mL-1, respectively. The recoveries for detecting chlorothalonil supplemented in Astragalus and Honeysuckle with pressure mode were 84.0-110% and 108-114%, respectively. Therefore, the ICS presented a portable, sensitive, accurate, and flexible multimodal strategy suitable for point-of-care testing.


Subject(s)
Colorimetry , Nanocomposites , Nitriles , Platinum , Temperature , Nanocomposites/chemistry , Platinum/chemistry , Immunoassay/methods , Nitriles/chemistry , Pressure , Titanium/chemistry , Limit of Detection
14.
Transl Oncol ; 49: 102088, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39167956

ABSTRACT

This study investigates the expression and functional roles of SUGT1 in ovarian cancer, utilizing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Our analyses reveal that SUGT1 is significantly upregulated in ovarian cancer tissues compared to normal controls. We further explore the prognostic value of SUGT1, where elevated expression correlates with poorer patient outcomes, particularly in ovarian cancer. The functional implications of SUGT1 in cancer biology were assessed through in vitro and in vivo experiments. Gene Set Enrichment Analysis (GSEA) indicates a significant association between high SUGT1 expression and the activation of glycolytic pathways, suggesting a potential role in metabolic reprogramming. Inhibition of SUGT1 via siRNA in ovarian cancer cell lines results in decreased proliferation and increased apoptosis, along with reduced migration and invasion capabilities. Additionally, our study identifies the transcription factor ELF1 as a significant regulator of SUGT1 expression. Through promoter analysis and chromatin immunoprecipitation, we demonstrate that ELF1 directly binds to the SUGT1 promoter, enhancing its transcription. This regulatory mechanism underscores the importance of transcriptional control in cancer metabolism, providing insights into potential therapeutic targets. Our findings establish SUGT1 as a crucial player in the oncogenic processes of ovarian cancer, influencing both metabolic pathways and transcriptional regulation. This highlights its potential as a biomarker and therapeutic target in managing ovarian cancer.

15.
Oncogene ; 43(38): 2850-2867, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39155295

ABSTRACT

Chemoresistance is an important cause of treatment failure in bladder cancer, and identifying genes that confer drug resistance is an important step toward developing new therapeutic strategies to improve treatment outcomes. In the present study, we show that gemcitabine plus cisplatin (GEM/DDP) therapy induces NF-κB signaling, which promotes p65-mediated transcriptional activation of OIP5. OIP5 recruits the E3 ubiquitin ligase TRIP12 to bind to and degrade the phosphatase PPP1CB, thereby enhancing the transcription factor activity of YBX1. This in turn upregulates drug-resistance-related genes under the transcriptional control of YBX1, leading to chemoresistance. Moreover, PPP1CB degradation can enhance the phosphorylation activity of IKKß, triggering the NF-κB signaling cascade, which further stimulates OIP5 gene expression, thus forming a negative feedback regulatory loop. Consistently, elevated OIP5 expression was associated with chemoresistance and poor prognosis in patients with bladder cancer. Furthermore, we used a CRISPR/Cas9-based engineered gene circuit, which can monitor the progression of chemoresistance in real-time, to induce OIP5 knockout upon detection of increased NF-κB signaling. The gene circuit significantly inhibited tumor cell growth in vivo, underscoring the potential for synergy between gene therapy and chemotherapy in the treatment of cancer.


Subject(s)
Drug Resistance, Neoplasm , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Humans , Drug Resistance, Neoplasm/genetics , Animals , Mice , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Cell Line, Tumor , NF-kappa B/metabolism , NF-kappa B/genetics , Signal Transduction/drug effects , Signal Transduction/genetics , Gene Expression Regulation, Neoplastic/drug effects , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Gemcitabine , Cisplatin/pharmacology , Cisplatin/therapeutic use , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Mice, Nude , Xenograft Model Antitumor Assays , Transcription Factors/genetics , Transcription Factors/metabolism , Y-Box-Binding Protein 1
16.
Sci Total Environ ; 950: 175324, 2024 Nov 10.
Article in English | MEDLINE | ID: mdl-39127202

ABSTRACT

The excessive and frequent use of insecticides has led to serious problems with insecticide residues, impacting nontarget organisms such as the parasitoid Encarsia formosa. This study examined the growth, development, and enzyme activity of E. formosa exposed to spirotetramat at LC10, LC30, and LC50. The regression equation for the toxicity of spirotetramat toward E. formosa was Y = 5.25X-11.07. After exposure to spirotetramat, the survival rates of E. formosa sharply decreased, which occurred earlier than those in the control batch. Although the maximum daily parasitism quantity of E. formosa increased and the average parasitism number, enumerated from the 1st to the 5th day, was 53.97 after being exposed to spirotetramat at LC10, the life span of its F1 generation adults was only 8.47 days, which was significantly shorter than that in the control batch. After being exposed to spirotetramat at LC50, the average parasitism number of E. formosa was 63.30, and the developmental time of its F1 generation, enumerated from the 1st to the 5th day after exposure to spirotetramat, was significantly longer than that of the control batch. The activities of mixed function oxidase, acetylcholinesterase, carboxylesterase, and catalase increased significantly, and the rate of increase in enzyme activity was directly proportional to the increase in the concentration of spirotetramat. These results revealed that the parasitic ability of E. formosa decreased after exposure to spirotetramat at LC10, LC30, and LC50. This leads to a change in parasitoid control of pests, revealing the potential environmental threat of insecticide residues to nontarget organisms.


Subject(s)
Aza Compounds , Hemiptera , Insecticides , Spiro Compounds , Wasps , Animals , Spiro Compounds/toxicity , Hemiptera/drug effects , Aza Compounds/toxicity , Insecticides/toxicity , Wasps/drug effects , Wasps/physiology , Insect Control
17.
Article in English | MEDLINE | ID: mdl-39116913

ABSTRACT

OBJECTIVE: The hippocampus plays a critical role in cognitive networks. The anterior hippocampus is vulnerable to early-life stress and socioeconomic status (SES) with alterations persisting beyond childhood. How SES modifies the relationship between early hippocampal development and cognition remains poorly understood. This study examined associations between SES, structural and functional development of neonatal hippocampus, and 18-month cognition in very preterm neonates. METHODS: In total, 179 preterm neonates were followed prospectively. Structural and resting-state functional MRI were obtained early-in-life and at term-equivalent age (median 32.9 and 41.1 weeks post-menstrual age) to calculate anterior and posterior hippocampal volumes and hippocampal functional connectivity strength. Eighteen-month cognition was assessed via Bayley-III. Longitudinal statistical analysis using generalized estimating equations, accounting for birth gestational age, post-menstrual age at scan, sex, and motion, was performed. RESULTS: SES, measured as maternal education level, modified associations between anterior but not posterior hippocampal volumes and 18-month cognition (interaction term p = 0.005), and between hippocampal connectivity and cognition (interaction term p = 0.05). Greater anterior hippocampal volumes and hippocampal connectivity were associated with higher cognitive scores only in the lowest SES group. Maternal education alone did not predict neonatal hippocampal volume from early-in-life and term. INTERPRETATION: SES modified the relationship between neonatal hippocampal development and 18-month cognition in very preterm neonates. The lack of direct association between maternal education and neonatal hippocampal volumes indicates that socio-environmental factors beyond the neonatal period contribute to modifying the relationship between hippocampal development and cognition. These findings point toward opportunities to more equitably promote optimal neurodevelopmental outcomes in very preterm infants.

18.
J Exp Clin Cancer Res ; 43(1): 235, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39164728

ABSTRACT

BACKGROUND: Ubiquitin-specific protease 15 (USP15) exhibits amplifications in various tumors, including gastric cancer (GC), yet its biological function and mechanisms in GC progression remain elusive. METHODS: Here, we established stable USP15 knockdown or overexpression GC cell lines and explored the potential mechanism of USP15 in GC. Besides, we also identified interacting targets of USP15. RESULTS: USP15 knockdown significantly impeded cell proliferation, invasion, epithelial-mesenchymal transition, and distal colonization in xenograft models, while enhancing oxaliplatin's antitumor effect. USP15 was involved in ubiquitination modification of glycolytic regulators. Silencing of USP15 suppressed glycolytic activity and impaired mitochondrial functions. Interference with USP15 expression reversed tumor progression and distal colonization in vivo. HKDC1 and IGF2BP3 were found as core interacting targets of USP15, and HKDC1 was identified as a substrate for ubiquitination modification by USP15, whereby USP15 regulated glucose metabolism activity by inhibiting the ubiquitination degradation of HKDC1. CONCLUSIONS: Our study unveiled aberrantly high expression of USP15 in GC tissues, correlating with malignant progression and nonresponse to neoadjuvant therapy. USP15 inhibitors, if developed, could be effective in promoting chemotherapy through glucose metabolism remodeling.


Subject(s)
Disease Progression , Glucose , Stomach Neoplasms , Ubiquitin-Specific Proteases , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/genetics , Mice , Animals , Ubiquitin-Specific Proteases/metabolism , Ubiquitin-Specific Proteases/genetics , Glucose/metabolism , Cell Line, Tumor , Cell Proliferation , Male , Ubiquitination , Female , Epithelial-Mesenchymal Transition , Mice, Nude , Xenograft Model Antitumor Assays
19.
Virology ; 598: 110196, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39098183

ABSTRACT

Reovirus (Reo) has shown promising potential in specifically killing tumor cells, and offering new possibilities for ovarian cancer (OC) treatment. However, neutralizing antibodies in the ascites from OC patients greatly limit the further application of Reo. In this study, we employed cationic liposomes (Lipo) to deliver Reo, significantly enhancing its ability to enter OC cells and its effectiveness in killing these cells under ascitic conditions. Pre-treatment with the MßCD inhibitor notably decreased Reo-mediated tumor cell death, indicating that Lipo primarily enables Reo's cellular uptake through caveolin-mediated endocytosis. Our results demonstrate that Lipo effectively facilitates the entry of Reo into the cytoplasm and triggers cell apoptosis. The above findings provide a new strategy to overcome the obstacle of neutralizing antibodies in the clinical application of Reo.


Subject(s)
Antibodies, Neutralizing , Liposomes , Ovarian Neoplasms , Reoviridae , Female , Humans , Ovarian Neoplasms/immunology , Antibodies, Neutralizing/immunology , Reoviridae/immunology , Reoviridae/physiology , Cell Line, Tumor , Oncolytic Virotherapy/methods , Apoptosis , Animals , Cations , Oncolytic Viruses/immunology , Mice
20.
New Microbiol ; 47(2): 186-189, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39023530

ABSTRACT

Stephanoascus ciferrii, a conditional pathogenic fungus prevalent in nature, is more frequently encountered in patients with compromised immunity. However, the literature rarely reports infections caused by Stephanoascus ciferrii in peritoneal dialysis patients. Here, we detail the case of a 66-year-old female suffering from renal failure who experienced catheter-related infection during peritoneal dialysis. Dialysate turbidity prompted the detection of Stephanoascus ciferrii in both peritoneal dialysate and tubes through microbiological cultures. Subsequent treatment involved antifungal drugs and a transition to hemodialysis, resulting in the disappearance of peritonitis symptoms and the patient's discharge. In recent years, fungal infections, particularly dialysis-related infections, are on the rise. This marks the first reported case of catheter-related peritonitis infection caused by Stephanoascus ciferrii. Compared to bacterial infections, fungal infections pose challenges due to limited drug options, significant side effects, and prolonged treatment durations. Hence, prompt pathogen diagnosis and drug sensitivity testing are crucial for effective clinical treatment. In essence, this scientific case report underscores the uncommon occurrence of catheter-related peritonitis attributed to Stephanoascus ciferrii in a peritoneal dialysis patient with renal failure, emphasizing the distinctive management challenges and underscoring the critical significance of prompt diagnosis and suitable intervention in such instances.


Subject(s)
Mycoses , Peritoneal Dialysis , Peritonitis , Humans , Female , Aged , Peritonitis/microbiology , Peritonitis/drug therapy , Peritonitis/etiology , Peritoneal Dialysis/adverse effects , Mycoses/microbiology , Mycoses/drug therapy , Antifungal Agents/therapeutic use , Catheter-Related Infections/microbiology , Catheter-Related Infections/drug therapy , Ascomycota/isolation & purification
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