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1.
BMC Public Health ; 24(1): 1878, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010029

RESUMO

BACKGROUND: Since May 2022, mpox outbreaks have been occurring in non-mpox endemic areas, with the main population affected being men who have sex with men (MSM). Outbreak prevention and control depend not only on the effectiveness of vaccines but also on people's willingness to receive these vaccines. Currently, there is lack of synthesis on the overall rates and influence factors of MSMs' willingness to vaccinate against mpox. Therefore, we systematically reviewed studies that assessed the willingness of MSM to receive mpox vaccine. METHODS: Studies reporting mpox vaccination intentions among MSM were included by searching five databases (PubMed, Web of Science, EMBASE, CINAHL, and SCOPUS) from inception to May 12, 2024. The quality of the included literature was assessed using Joanna Briggs Institute's critical appraisal tool. The data analysis software is Stata17. The systematic review has been registered with Prospero (registration ID: CRD42023452357). RESULTS: Twenty cross-sectional studies were included in the review. Meta-analysis results showed that the pooled willingness rate of vaccinate against mpox was 77.0% (95% CI: 73-81%, I2 = 99.4%). According to subgroup analysis, study countries (P = 0.002), research sample size (P = 0.001), and whether participants were infected with HIV (P = 0.002) may be sources of heterogeneity. The results of the meta-analysis of influencing factors showed that more number of sexual partners (OR: 2.24, 95%CI: 1.86-2.69), pre-exposure prophylaxis use (OR: 6.04, 95%CI: 4.80-7.61), history of sexually transmitted infections (OR: 2.96, 95%CI: 2.33-3.76), confidence in the vaccine's effectiveness (OR: 2.79, 95%CI: 2.04-3.80) and safety (OR: 10.89, 95%CI: 5.22-22.72), fear of mpox infection (OR: 2.47, 95%CI: 2.11-2.89) and epidemics (OR: 2.87, 95%CI: 2.22-3.70), high mpox knowledge (OR: 2.35, 95%CI: 1.51-3.66), and the belief that people at high risk should be prioritized for vaccination (OR: 3.09, 95%CI: 1.40-6.84) were the facilitators of vaccine willingness. In addition, as a secondary outcome, meta-analysis results showed a pooled unwillingness rate of 16% (95% CI: 13-20%, I2 = 98.1%, 9 studies). CONCLUSION: Willingness to vaccinate mpox was high among MSM, but some participants still had negative attitudes towards vaccination. Therefore, the Ministry of Public Health should develop targeted and effective strategies against those influencing factors to prevent and manage mpox outbreaks.


Assuntos
Homossexualidade Masculina , Humanos , Masculino , Homossexualidade Masculina/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia
2.
Heliyon ; 10(11): e32454, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961944

RESUMO

Background: Septic shock is a clinical syndrome characterized by the progression of sepsis to a severe stage. Elderly patients with urosepsis in the intensive care unit (ICU) are more likely to progress to septic shock. This study aimed to establish and validate a nomogram model for predicting the risk of progression to septic shock in elderly patients with urosepsis. Methods: We extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV dataset was split into a training set for model development and an internal validation set to assess model performance. Further external validation was performed using a distinct dataset sourced from the eICU-CRD. Predictors were screened using least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analyses. The evaluation of model performance included discrimination, calibration, and clinical usefulness. Results: The study demonstrated that the Glasgow Coma Scale (GCS), white blood count (WBC), platelet, blood urea nitrogen (BUN), calcium, albumin, congestive heart failure (CHF), and invasive ventilation were closely associated with septic shock in the training cohort. Nomogram prediction, utilizing eight parameters, demonstrated strong predictive accuracy with area under the curve (AUC) values of 0.809 (95 % CI 0.786-0.834), 0.794 (95 % CI 0.756-0.831), and 0.723 (95 % CI 0.647-0.801) in the training, internal validation, and external validation sets, respectively. Additionally, the nomogram demonstrated a promising calibration performance and significant clinical usefulness in both the training and validation sets. Conclusion: The constructed nomogram is a reliable and practical tool for predicting the risk of progression to septic shock in elderly patients with urosepsis. Its implementation in clinical practice may enhance the early identification of high-risk patients, facilitate timely and targeted interventions to mitigate the risk of septic shock, and improve patient outcomes.

3.
BMC Oral Health ; 24(1): 803, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014351

RESUMO

BACKGROUND: Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients' lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. CASE PRESENTATION: Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient's dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. CONCLUSIONS: ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.


Assuntos
Deformidades Dentofaciais , Humanos , Masculino , Deformidades Dentofaciais/genética , Deformidades Dentofaciais/cirurgia , Seguimentos , Otopatias/genética , Otopatias/cirurgia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Linhagem , Orelha/anormalidades , Osteogênese por Distração/métodos , Mutação , Procedimentos Cirúrgicos Ortognáticos , China , População do Leste Asiático
4.
Small ; : e2402432, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850181

RESUMO

This paper presents a scalable and straightforward technique for the immediate patterning of liquid metal/polymer composites via multiphase 3D printing. Capitalizing on the polymer's capacity to confine liquid metal (LM) into diverse patterns. The interplay between distinctive fluidic properties of liquid metal and its self-passivating oxide layer within an oxidative environment ensures a resilient interface with the polymer matrix. This study introduces an inventive approach for achieving versatile patterns in eutectic gallium indium (EGaIn), a gallium alloy. The efficacy of pattern formation hinges on nozzle's design and internal geometry, which govern multiphase interaction. The interplay between EGaIn and polymer within the nozzle channels, regulated by variables such as traverse speed and material flow pressure, leads to periodic patterns. These patterns, when encapsulated within a dielectric polymer polyvinyl alcohol (PVA), exhibit an augmented inherent capacitance in capacitor assemblies. This discovery not only unveils the potential for cost-effective and highly sensitive capacitive pressure sensors but also underscores prospective applications of these novel patterns in precise motion detection, including heart rate monitoring, and comprehensive analysis of gait profiles. The amalgamation of advanced materials and intricate patterning techniques presents a transformative prospect in the domains of wearable sensing and comprehensive human motion analysis.

5.
J Bone Miner Res ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874138

RESUMO

Type I interferons (IFN-I) are pleiotropic factors endowed with multiple activities that play important roles in innate and adaptive immunity. Although many studies indicate IFN-I inducers exert favorable effects on broad-spectrum antivirus, immunomodulation, and anti-tumor by inducing endogenous IFN-I and IFN-stimulated genes (ISGs), their function in bone homeostasis still needs further exploration. Here, our study demonstrates two distinct IFN-I inducers, diABZI and poly(I:C), as potential therapeutics to alleviate osteolysis and osteoporosis. Firstly, IFN-I inducers suppress the genes that control osteoclast (OC) differentiation and activity in vitro. Moreover, diABZI alleviates bone loss in Ti particle-induced osteolysis and ovariectomized (OVX)-induced osteoporosis in vivo by inhibiting OC differentiation and function. In addition, the inhibitory effects of IFN-I inducers on OC differentiation are not observed in macrophages derived from Ifnar1-/- mice, which indicate that the suppressive effect of IFN-I inducers on OC is IFNAR-dependent. Mechanistically, RNAi-mediated silencing of IRF7 and IFIT3 in OC precursors impair the suppressive effect of the IFN-I inducers on OC differentiation. Taken together, these results demonstrate that IFN-I inducers play a protective role in bone turnover by limiting osteoclastogenesis and bone resorption through the induction of OC-specific mediators via the IFN-ß signaling pathway.

6.
Adv Sci (Weinh) ; : e2401634, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888507

RESUMO

Radiation enteritis is the most common complication of pelvic radiotherapy, but there is no effective prevention or treatment drug. Apoptotic T cells and their products play an important role in regulating inflammation and maintaining physiological immune homeostasis. Here it is shown that systemically infused T cell-derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines and alleviate radiation enteritis. Mechanistically, radiation elevates the synthesis of intestinal 2'3' cyclic GMP-AMP (cGAMP) and activates cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) proinflammatory pathway. After systemic infusion of ApoEVs, the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on the surface of ApoEVs hydrolyze extracellular cGAMP, resulting in inhibition of the cGAS-STING pathway activated by irradiation. Furthermore, after ApoEVs are phagocytosed by phagocytes, ENPP1 on ApoEVs hydrolyzed intracellular cGAMP, which serves as an intracellular cGAMP hydrolyzation mode, thereby alleviating radiation enteritis. The findings shed light on the intracellular and extracellular hydrolysis capacity of ApoEVs and their role in inflammation regulation.

7.
Fish Shellfish Immunol ; 149: 109574, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692379

RESUMO

B-cell lymphoma/leukemia-2 (BCL2), an anti-apoptotic factor in the mitochondrial regulatory pathway of apoptosis, is critically important in immune defenses. In this study, a novel BCL2 gene was characterized from Pteria penguin (P. penguin). The PpBCL2 was 1482 bp long, containing an open reading frame (ORF) of 588 bp encoding 195 amino acids. Four highly conserved BCL-2 homology (BH) domains were found in PpBCL2. Amino acid alignment and phylogenetic tree showed that PpBCL2 had the highest similarity with BCL2 of Crassostrea gigas at 65.24 %. Tissue expression analysis showed that PpBCL2 had high constitutive expression in gill, digestive diverticulum and mantle, and was significantly increased 72 h of Vibrio parahaemolyticus (V. parahaemolyticus) challenge in these immune tissues. Furthermore, PpBCL2 silencing significantly inhibited antimicrobial activity of hemolymph supernatant by 1.4-fold, and significantly reduced the survival rate by 51.7 % at 72 h post infection in P. penguin. These data indicated that PpBCL2 played an important role in immune response of P. penguin against V. parahaemolyticus infection.


Assuntos
Sequência de Aminoácidos , Imunidade Inata , Filogenia , Proteínas Proto-Oncogênicas c-bcl-2 , Alinhamento de Sequência , Spheniscidae , Vibrio parahaemolyticus , Animais , Vibrio parahaemolyticus/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Spheniscidae/imunologia , Spheniscidae/genética , Alinhamento de Sequência/veterinária , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Perfilação da Expressão Gênica/veterinária , Vibrioses/imunologia , Vibrioses/veterinária , Sequência de Bases
8.
Small ; : e2403130, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751304

RESUMO

Polycrystalline yttrium aluminum garnet (YAG) ceramic doped with neodymium (Nd), referred to as Nd:YAG, is widely used in solid-state lasers. However, conventional powder metallurgy methods suffer from expenses, time consumption, and limitations in customizing structures. This study introduces a novel approach for creating Nd:YAG ceramics with 3D free-form structures from micron (∼70 µm) to centimeter scales. Firstly, sol-gel synthesis is employed to form photocurable colloidal solutions. Subsequently, by utilizing a home-built micro-continuous liquid interface printing process, precursors are printed into 3D poly(acrylic acid) hydrogels containing yttrium, aluminum, and neodymium hydroxides, with a resolution of 5.8 µm pixel-1 at a speed of 10 µm s-1. After the hydrogels undergo thermal dehydration, debinding, and sintering, polycrystalline Nd:YAG ceramics featuring distinguishable grains are successfully produced. By optimizing the concentrations of the sintering aids (tetraethyl orthosilicate) and neodymium trichloride (NdCl3), the resultant samples exhibit satisfactory photoluminescence, emitting light concentrated at 1064 nm when stimulated by a 532 nm laser. Additionally, Nd:YAG ceramics with various 3D geometries (e.g., cone, spiral, and angled pillar) are printed and characterized, which demonstrates the potential for applications, such as laser and amplifier fibers, couplers, and splitters in optical circuits, as well as gain metamaterials or metasurfaces.

9.
Subst Use Misuse ; 59(10): 1455-1463, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38789408

RESUMO

BACKGROUND: Craving is a core feature of addiction. Rumination and depression play a crucial role in the process of methamphetamine addiction. The aim of this study was to examine the relationship between rumination, depression and craving in methamphetamine patients, which has not been explored yet. METHODS: A total of 778 patients with methamphetamine user disorder (MUD) at the Xinhua Drug Rehabilitation Center, located in Mianyang City, Sichuan Province, China. We used a set of self-administered questionnaires that included socio-demographic, detailed drug use history, rumination, depression and craving information. The Rumination Response Scale (RRS) was used to measure rumination, the Beck Depression Inventory (BDI) to measure depression and the Visual Analogue Scale (VAS) to measure craving. RESULTS: There was a significant positive correlation between rumination and craving, or depression, and between depression and craving. Furthermore, depression mediated between rumination and craving, with a mediation effect of 160%. CONCLUSIONS: Our findings suggest that there is a close interrelationship between rumination, craving and depression in MUD patients, and that depression may play a mediating role between rumination and craving.


This is the first study to investigate the relationship between rumination and craving during withdrawal in methamphetamine dependent patients and the mediating role of depression.Among methamphetamine patients, it was found that reflection was positively correlated with rumination and depression, depression and craving, rumination and craving, and depression plays the mediating role between rumination and craving.These findings suggest that interventions to reduce depression and rumination may also be effective for withdrawal and relapse reduction in methamphetamine patients, providing further rationale for the treatment of methamphetamine patients.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Fissura , Depressão , Metanfetamina , Ruminação Cognitiva , Humanos , Masculino , Adulto , Feminino , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Depressão/psicologia , China , Adulto Jovem , Pessoa de Meia-Idade , Inquéritos e Questionários , População do Leste Asiático
10.
JCI Insight ; 9(13)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781030

RESUMO

Acute pancreatitis (AP) is among the most common hospital gastrointestinal diagnoses; understanding the mechanisms underlying the severity of AP is critical for development of new treatment options for this disease. Here, we evaluate the biological function of phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in AP pathogenesis in 2 independent genetically engineered mouse models of AP. PFKFB3 was elevated in AP and severe AP (SAP), and KO of Pfkfb3 abrogated the severity of alcoholic SAP (FAEE-SAP). Using a combination of genetic, pharmacological, and molecular studies, we defined the interaction of PFKFB3 with inositol 1,4,5-trisphosphate receptor (IP3R) as a key event mediating this phenomenon. Further analysis demonstrated that the interaction between PFKFB3 and IP3R promotes FAEE-SAP severity by altering intracellular calcium homeostasis in acinar cells. Together, our results support a PFKFB3-driven mechanism controlling AP pathobiology and define this enzyme as a therapeutic target to ameliorate the severity of this condition.


Assuntos
Células Acinares , Cálcio , Receptores de Inositol 1,4,5-Trifosfato , Pancreatite , Fosfofrutoquinase-2 , Animais , Fosfofrutoquinase-2/metabolismo , Fosfofrutoquinase-2/genética , Camundongos , Pancreatite/metabolismo , Pancreatite/genética , Pancreatite/patologia , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Cálcio/metabolismo , Células Acinares/metabolismo , Células Acinares/patologia , Camundongos Knockout , Modelos Animais de Doenças , Índice de Gravidade de Doença , Masculino , Humanos , Sinalização do Cálcio/genética
11.
World J Gastroenterol ; 30(9): 1189-1212, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577195

RESUMO

BACKGROUND: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. AIM: To determine the role and mechanism of UGT1A1 in liver damage progression. METHODS: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. RESULTS: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. CONCLUSION: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.


Assuntos
Glucuronosiltransferase , Fígado , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Fígado/metabolismo
12.
BMC Infect Dis ; 24(1): 442, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671376

RESUMO

BACKGROUND: Urinary tract infection (UTI) is a common cause of sepsis. Elderly patients with urosepsis in intensive care unit (ICU) have more severe conditions and higher mortality rates owing to factors such as advanced age, immunosenescence, and persistent host inflammatory responses. However, comprehensive studies on nomograms to predict the in-hospital mortality risk in elderly patients with urosepsis are lacking. This study aimed to construct a nomogram predictive model to accurately assess the prognosis of elderly patients with urosepsis and provide therapeutic recommendations. METHODS: Data of elderly patients with urosepsis were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV 2.2 database. Patients were randomly divided into training and validation cohorts. A predictive nomogram model was constructed from the training set using logistic regression analysis, followed by internal validation and sensitivity analysis. RESULTS: This study included 1,251 patients. LASSO regression analysis revealed that the Glasgow Coma Scale (GCS) score, red cell distribution width (RDW), white blood count (WBC), and invasive ventilation were independent risk factors identified from a total of 43 variables studied. We then created and verified a nomogram. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) of the nomogram were superior to those of the traditional SAPS-II, APACHE-II, and SOFA scoring systems. The Hosmer-Lemeshow test results and calibration curves suggested good nomogram calibration. The IDI and NRI values showed that our nomogram scoring tool performed better than the other scoring systems. The DCA curves showed good clinical applicability of the nomogram. CONCLUSIONS: The nomogram constructed in this study is a convenient tool for accurately predicting in-hospital mortality in elderly patients with urosepsis in ICU. Improving the treatment strategies for factors related to the model could improve the in-hospital survival rates of these patients.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva , Nomogramas , Sepse , Infecções Urinárias , Humanos , Idoso , Feminino , Masculino , Infecções Urinárias/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Sepse/mortalidade , Idoso de 80 Anos ou mais , Fatores de Risco , Prognóstico , Curva ROC , Estudos Retrospectivos
13.
J Am Chem Soc ; 146(17): 12233-12242, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626786

RESUMO

Photocatalytic conversion of methane (CH4) to ethane (C2H6) has attracted extensive attention from academia and industry. Typically, the traditional oxidative coupling of CH4 (OCM) reaches a high C2H6 productivity, yet the inevitable overoxidation limits the target product selectivity. Although the traditional nonoxidative coupling of CH4 (NOCM) can improve the product selectivity, it still encounters unsatisfied activity, arising from being thermodynamically unfavorable. To break the activity-selectivity trade-off, we propose a conceptually new mechanism of H2O2-triggered CH4 coupling, where the H2O2-derived ·OH radicals are rapidly consumed for activating CH4 into ·CH3 radicals exothermically, which bypasses the endothermic steps of the direct CH4 activation by photoholes and the interaction between ·CH3 and ·OH radicals, affirmed by in situ characterization techniques, femtosecond transient absorption spectroscopy, and density-functional theory calculation. By this pathway, the designed Au-WO3 nanosheets achieve unprecedented C2H6 productivity of 76.3 mol molAu-1 h-1 with 95.2% selectivity, and TON of 1542.7 (TOF = 77.1 h-1) in a self-designed flow reactor, outperforming previously reported photocatalysts regardless of OCM and NOCM pathways. Also, under outdoor natural sunlight irradiation, the Au-WO3 nanosheets exhibit similar activity and selectivity toward C2H6 production, showing the possibility for practical applications. Interestingly, this strategy can be applied to other various photocatalysts (Au-WO3, Au-TiO2, Au-CeO2, Pd-WO3, and Ag-WO3), showing a certain universality. It is expected that the proposed mechanism adds another layer to our understanding of CH4-to-C2H6 conversion.

14.
Adv Sci (Weinh) ; 11(24): e2309725, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38647360

RESUMO

The interplay between bacteria and their host influences the homeostasis of the human immune microenvironment, and this reciprocal interaction also affects the process of tissue damage repair. A variety of immunomodulatory commensal bacteria reside in the body, capable of delivering membrane vesicles (MVs) to host cells to regulate the local immune microenvironment. This research revealed, for the initial time, the significant enhancement of mucosal and cutaneous wound healing by MVs secreted by the human commensal Lactobacillus reuteri (RMVs) through modulation of the inflammatory environment in wound tissue. Local administration of RMVs reduces the proportion of pro-inflammatory macrophages in inflamed tissues and mitigates the level of local inflammation, thereby facilitating the healing of oral mucosa and cutaneous wounds. The elevated oxidative stress levels in activated pro-inflammatory macrophages can be modulated by RMVs, resulting in phenotypic transformation of macrophages. Furthermore, 3-hydroxypropionaldehyde present in RMVs can decrease the mitochondrial permeability of macrophages and stabilize the mitochondrial membrane potential, thereby promoting the conversion of macrophages to an anti-inflammatory phenotype. This study pioneers the significance of commensal bacterial MVs in tissue injury repair and presents a novel concept for the repair of tissue damage.


Assuntos
Limosilactobacillus reuteri , Macrófagos , Mitocôndrias , Cicatrização , Macrófagos/imunologia , Macrófagos/metabolismo , Cicatrização/imunologia , Cicatrização/fisiologia , Animais , Camundongos , Mitocôndrias/metabolismo , Humanos , Modelos Animais de Doenças , Pele/microbiologia , Pele/imunologia , Pele/metabolismo
15.
Curr Med Sci ; 44(2): 426-434, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38561594

RESUMO

OBJECTIVE: Glucose-6-phosphate isomerase (GPI) deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants. This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics, often posing challenges for precise diagnoses using conventional methods. To this end, this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family. METHODS: The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis. Novel compound heterozygous variants of the GPI gene, c.174C>A (p.Asn58Lys) and c.1538G>T (p.Trp513Leu), were identified using whole-exome and Sanger sequencing. The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure. RESULTS: By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study, we found that most variants were located in exons 3, 4, 12, and 18, with a few localized in exons 8, 9, and 14. This study identified novel compound heterozygous variants associated with GPI deficiency. These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids. CONCLUSION: Early family-based sequencing analyses, especially for patients with congenital anemia, can help increase diagnostic accuracy for GPI deficiency, improve child healthcare, and enable genetic counseling.


Assuntos
Anemia Hemolítica Congênita não Esferocítica , Anemia Hemolítica , Criança , Humanos , Glucose-6-Fosfato Isomerase/genética , Glucose-6-Fosfato Isomerase/química , Anemia Hemolítica/genética , Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Anemia Hemolítica Congênita não Esferocítica/genética , Mutação de Sentido Incorreto , Éxons
16.
ACS Nano ; 18(12): 8718-8732, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38465955

RESUMO

Although stem cell therapy is proved to be a promising strategy for bone repair and regeneration, transplanted allogeneic stem cells generally suffer from unfavorable apoptosis instead of differentiation into osteocytes. How the apoptotic stem cells promote bone regeneration still needs to be uncovered. In this work, we found that apoptotic extracellular vesicles released by allogeneic stem cells are critical mediators for promoting bone regeneration. Based on the results of in vivo experiments, a mechanism of apoptotic stem cells determined autologous stem cell recruitment and enhance osteogenesis was proposed. The nanoscaled apoptotic extracellular vesicles released from transplanted stem cells were endocytosed by vascular endothelial cells and preferentially distribute at endoplasmic reticular region. The oxidized phosphatidylcholine enriched in the vesicles activated the endoplasmic reticulum stress and triggered the reflective elevation of adhesion molecules, which induced the recruitment of autologous stem cells located in the blood vessels, transported them into the defect region, and promoted osteogenesis and bone repair. These findings not only reveal the mechanism of stem cell therapy of bone defects but also provide a cue for investigation of the biological process of stem cell therapy for other diseases and develop stem cell therapeutic strategies.


Assuntos
Células Progenitoras Endoteliais , Vesículas Extracelulares , Transplante de Células-Tronco Hematopoéticas , Osteogênese , Vesículas Extracelulares/metabolismo , Diferenciação Celular
17.
J Plant Physiol ; 296: 154235, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38531181

RESUMO

Aptamers, serving as highly efficient molecular recognition and biotechnology tools, have garnered increasing interest in the realm of plant science in recent years. Aptamers are synthetic single-stranded short nucleotides or peptides, that bind targets with high specificity and affinity, triggering precise biological responses. As an alternative to antibodies, aptamers present promising avenues for advancement in biological researches. Aptamers function in a range of fields, encompassing cell signaling, drug development, biosensor technology, as well as botany, agricultural and forestry sciences. In this review, we introduce classifications and screening methods of aptamers, as well as aptamer-based technologies, highlighting their significant contributions to recent advancements. With their powerful functionality and ability to bind targets with high specificity and affinity, aptamers offer promising opportunities for breakthroughs in plant research.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Biotecnologia
18.
Cell Rep ; 43(3): 113945, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38483900

RESUMO

U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164-nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a housekeeping non-coding RNA. However, the role of U1 snRNA in regulating host antiviral immunity remains largely unexplored. Here, we find that RNVU1-18, a U1 pseudogene, is significantly upregulated in the host infected with RNA viruses, including influenza and respiratory syncytial virus. Overexpression of U1 snRNA protects cells against RNA viruses, while knockdown of U1 snRNA leads to more viral burden in vitro and in vivo. Knockout of RNVU1-18 is sufficient to impair the type I interferon-dependent antiviral innate immunity. U1 snRNA is required to fully activate the retinoic acid-inducible gene I (RIG-I)-dependent antiviral signaling, since it interacts with tripartite motif 25 (TRIM25) and enhances the RIG-I-TRIM25 interaction to trigger K63-linked ubiquitination of RIG-I. Our study reveals the important role of housekeeping U1 snRNA in regulating host antiviral innate immunity and restricting RNA virus infection.


Assuntos
Fatores de Transcrição , Ubiquitina-Proteína Ligases , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteína DEAD-box 58/metabolismo , Imunidade Inata , RNA Nuclear Pequeno , Ubiquitinação , Proteínas com Motivo Tripartido/metabolismo
19.
Thyroid ; 34(6): 753-763, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38534308

RESUMO

Background: Thyroid disorders are associated with various dietary factors and nutritional elements. The aim of this study was to investigate the relationships between dietary vitamin E intake and the prevalence of thyroid dysfunction and thyroid antibody positivity using data from the National Health and Nutrition Examination Survey (NHANES) database. Methods: Data from the NHANES database collected between 2007 and 2012 were analyzed. A total of 7,773 nonpregnant adults without preexisting thyroid diseases and possessing complete thyroid and vitamin E data were included in the study. The participants were categorized into tertiles based on their dietary vitamin E intake: the lowest group (T1: ≤4.53 mg), the intermediate group (T2: 4.54-8.10 mg), and the highest group (T3: ≥8.11 mg). We used a complex multistage probability sampling design in conjunction with R software. We compared thyroid indices, the prevalence of overt and subclinical hyperthyroidism or hypothyroidism, and the occurrence of thyroid antibody positivity among the three groups based on vitamin E intake. Weighted multinomial logistic regression was used to assess the association between dietary vitamin E intake and thyroid disorders. Restricted cubic splines (RCSs) were used to explore potential nonlinear associations. Results: The prevalence rates of subclinical hypothyroidism (SCH) were 3.63%, 3.07%, and 1.85% in T1, T2, and T3, respectively, indicating a decreasing trend (P-trend = 0.013). In the general population, high vitamin E intake (T3) was significantly associated with a lower prevalence of SCH (OR = 0.28, CI = 0.15-0.54, p < 0.001). Subgroup analysis revealed a more pronounced protective effect in males, with both moderate (T2, OR = 0.45, CI = 0.23-0.87, p = 0.020) and high (T3, OR = 0.19, CI = 0.09-0.39, p < 0.001) dietary vitamin E intake being associated with a lower prevalence of SCH. In addition, moderate (T2, OR = 0.59, CI = 0.37-0.93, p = 0.024) and high (T3, OR = 0.52, CI = 0.36-0.75, p < 0.001) dietary vitamin E intake was associated with a lower prevalence of autoimmune thyroiditis (AIT) in males. However, no significant association was observed among females. Conclusion: The findings of this study suggest that a higher intake of vitamin E is associated with lower prevalence rates of SCH and autoimmune thyroiditis among males.


Assuntos
Inquéritos Nutricionais , Tireoidite Autoimune , Vitamina E , Humanos , Vitamina E/administração & dosagem , Masculino , Feminino , Estudos Transversais , Adulto , Tireoidite Autoimune/epidemiologia , Prevalência , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Dieta , Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Autoanticorpos/sangue , Adulto Jovem , Idoso , Doenças da Glândula Tireoide/epidemiologia , Glândula Tireoide/fisiopatologia , Glândula Tireoide/imunologia
20.
Biomed Opt Express ; 15(2): 672-686, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38404332

RESUMO

Fourier ptychographic microscopy (FPM) has emerged as a new wide-field and high-resolution computational imaging technique in recent years. To ensure data redundancy for a stable convergence solution, conventional FPM requires dozens or hundreds of raw images, increasing the time cost for both data collection and computation. Here, we propose a single-shot Fourier ptychographic microscopy with isotropic lateral resolution via polarization-multiplexed LED illumination, termed SIFPM. Three LED elements covered with 0°/45°/135° polarization films, respectively, are used to provide numerical aperture-matched illumination for the sample simultaneously. Meanwhile, a polarization camera is utilized to record the light field distribution transmitted through the sample. Based on weak object transfer functions, we first obtain the amplitude and phase estimations of the sample by deconvolution, and then we use them as the initial guesses of the FPM algorithm to refine the accuracy of reconstruction. We validate the complex sample imaging performance of the proposed method on quantitative phase target, unstained and stained bio-samples. These results show that SIFPM can realize quantitative imaging for general samples with the resolution of the incoherent diffraction limit, permitting high-speed quantitative characterization for cells and tissues.

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