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1.
Environ Sci Technol ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832650

RESUMO

In the context of escalating urban heat events due to climate change, air conditioning (AC) has become a critical factor in maintaining indoor thermal comfort. Yet the usage of AC can also exacerbate outdoor heat stress and burden the electricity system, and there is little scientific knowledge regarding how to balance these conflicting goals. To address this issue, we established a coupled modeling approach, integrating the Weather Research and Forecasting model with the building energy model (WRF_BEP + BEM), and designed multiple AC usage scenarios. We selected Chongqing, China's fourth-largest megacity, as our study area due to its significant socioeconomic importance, the severity of extreme heat events, and the uniqueness of its energy infrastructure. Our analysis reveals that AC systems can substantially reduce indoor temperatures by up to 18 °C; however, it also identifies substantial nighttime warming (2-2.5 °C) and a decline in thermal comfort. Particularly for high-density neighborhoods, when we increase 2 °C indoors, the outdoor temperature can be alleviated by up to 1 °C. Besides, despite the limited capacity to regulate peak electricity demand, we identified that reducing the spatial cooled fraction, increasing targeted indoor temperature by 2 °C, and implementing temporal AC schedules can effectively lower energy consumption in high-density neighborhoods, especially the reduction of spatial cooled fraction (up to 50%). Considering the substantial demand for cooling energy, it is imperative to carefully assess the adequacy and continuity of backup energy sources. The study underscores the urgency of reassessing energy resilience and advocates for addressing the thermal equity between indoor and outdoor environments, contributing to the development of a sustainable and just urban climate strategy in an era of intensifying heat events.

2.
Sci Rep ; 14(1): 13867, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879665

RESUMO

Fever and diarrhea are key causes of malnutrition, growth and development disorders, and death among children. At present, most studies on the associated factors of fever and diarrhea in children are concentrated in African and South Asian countries, but relevant research in China is very limited. This study was aimed to analyze the two-week prevalence of fever, diarrhea, and coexisting fever and diarrhea among children aged 6-23 months in rural areas of Hunan Province and to explore the associated factors. The survey data of the Nutrition Improvement Program for Children in Poor Areas (NIPCPA) from 2016 to 2023 was used here. NIPCPA is a cross-sectional survey completed annually in Hunan to collect children's nutrition and health indicators. The two-week prevalence rates of fever, diarrhea, and coexisting fever and diarrhea among children aged 6-23 months were 12.2% (2066/16,985), 9.6% (1634/16,985), and 3.2% (542/16,985), respectively. Multivariate logistic regression analysis showed the risks of fever, diarrhea, and coexisting fever and diarrhea were higher among younger children. The high educational level of caregivers, effective consumption of Yingyangbao (a complementary food supplement containing iron, zinc, calcium, vitamins A, D, B1, B2, B12, folic acid, and other micronutrients), and complementary feeding meeting minimum dietary diversity and meeting minimum acceptable diet were protective factors against fever in children, with adjusted odds ratios (aORs) of 0.87 (95%CI: 0.78-0.98), 0.78 (0.69-0.87), 0.73 (0.65-0.82), and 0.74 (0.66-0.84), respectively. Effective consumption of Yingyangbao, and complementary feeding meeting the minimum dietary diversity and meeting minimum acceptable diet were protective factors against diarrhea in children, with aORs of 0.72 (95%CI: 0.63-0.83), 0.79 (0.70-0.91), and 0.80 (0.70-0.92), respectively. Effective consumption of Yingyangbao, and complementary feeding meeting the minimum dietary diversity and meeting minimum acceptable diet were protective factors against coexisting fever and diarrhea among children, with aORs of 0.53 (95%CI: 0.43-0.66), 0.71 (0.58-0.89), and 0.70 (0.56-0.88), respectively. Fever, diarrhea, and the coexisting fever and diarrhea affect one in eight, one in ten, and one in thirty children respectively in rural areas of Hunan. Effective interventions should be actively taken, such as improving the education level of caregivers, enhancing their scientific feeding skills for children, and promoting children's compliance with Yingyangbao consumption, to further reduce the prevalence of fever and diarrhea in children.


Assuntos
Diarreia , Febre , População Rural , Humanos , Lactente , Masculino , Feminino , Febre/epidemiologia , China/epidemiologia , Prevalência , Diarreia/epidemiologia , Estudos Transversais , Fatores de Risco
3.
Heliyon ; 10(9): e30548, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38765162

RESUMO

Urban expansion often occurs at the expense of cropland loss, posing challenges to sustainable urban growth and food security. However, detailed investigations into urban expansion and cropland loss remain limited, particularly in regions with varying levels of urbanization. Here, we take Guangdong Province, China, as a case study to exemplify how urban expansion affects cropland using remotely sensed land use products. We adopted geospatial analysis, correlation indicators, and landscape metrics to uncover their spatial relationships at 10-m spatial resolutions. Results showed that urban areas increased by 6335 km2 while cropland decreased by 3780 km2 from 2017 to 2022. Notably, 41 % of newly expanded urban areas were from croplands, and 45 % of lost croplands were converted to urban areas. Western Guangdong experienced the largest extent of urban expansion and cropland loss, emerging as a hotspot region in recent years. Additionally, our analysis observed the increasing compactness of urban areas and the growing fragmentation of cropland landscapes over time. These findings shed light on the intricate dynamics between urban expansion and cropland loss in rapidly urbanizing regions, which provide valuable insights for sustainable urban development, agricultural practice, and land management in the future.

4.
Skin Res Technol ; 30(5): e13720, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38743384

RESUMO

BACKGROUND: Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. MATERIALS AND METHODS: A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin. RESULTS: Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures. CONCLUSION: These results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.


Assuntos
Claudina-5 , Queratinócitos , MicroRNAs , Permeabilidade , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Claudina-5/genética , Claudina-5/metabolismo , Feminino , Masculino , Queratinócitos/metabolismo , Estudos Retrospectivos , Adulto , Pele/metabolismo
5.
Aging (Albany NY) ; 16(7): 6588-6612, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38604156

RESUMO

BACKGROUND: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. RESULTS: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-ß promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-ß activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFß-Smad signaling induced growth inhibition and partial EMT, whereas TGFß-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-ß was mutually restricted in LPCs. Mechanistically, we found that TGF-ß activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFß-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-ß-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-ß-induced cytostasis and partial EMT. CONCLUSION: These results suggested that TGF-ß downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-ß under fibrotic conditions and maintain partial EMT and progenitor phenotypes.


Assuntos
Transição Epitelial-Mesenquimal , Fígado , Sistema de Sinalização das MAP Quinases , Proteína Smad3 , Células-Tronco , Fator de Crescimento Transformador beta , Proteína Smad3/metabolismo , Células-Tronco/metabolismo , Animais , Fator de Crescimento Transformador beta/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Fígado/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Fosforilação , Camundongos , Transdução de Sinais
6.
ACS Cent Sci ; 10(3): 717-728, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38559297

RESUMO

Direct inhibitor of tau aggregation has been extensively studied as potential therapeutic agents for Alzheimer's disease. However, the natively unfolded structure of tau complicates the structure-based ligand design, and the relatively large surface areas that mediate tau-tau interactions in aggregation limit the potential for identifying high-affinity ligand binding sites. Herein, a group of isatin-pyrrolidinylpyridine derivative isomers (IPP1-IPP4) were designed and synthesized. They are like different forms of molecular "transformers". These isatin isomers exhibit different inhibitory effects on tau self-aggregation or even possess a depolymerizing effect. Our results revealed for the first time that the direct inhibitor of tau protein aggregation is not only determined by the previously reported conjugated structure, substituent, hydrogen bond donor, etc. but also depends more importantly on the molecular shape. In combination with molecular docking and molecular dynamics simulations, a new inhibition mechanism was proposed: like a "molecular clip", IPP1 could noncovalently bind and fix a tau polypeptide chain at a multipoint to prevent the transition from the "natively unfolded conformation" to the "aggregation competent conformation" before nucleation. At the cellular and animal levels, the effectiveness of the inhibitor of the IPP1 has been confirmed, providing an innovative design strategy as well as a lead compound for Alzheimer's disease drug development.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38596842

RESUMO

The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1ß and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.

8.
J Ethnopharmacol ; 330: 118194, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38641077

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. AIM OF THE STUDY: This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. MATERIALS AND METHODS: Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. RESULTS: The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. CONCLUSIONS: WEPUOC, obtained from the oil cakes of P. utilis, is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis.


Assuntos
Epiderme , Extratos Vegetais , Proteínas de Junções Íntimas , Regulação para Cima , Animais , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteínas de Junções Íntimas/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Regulação para Cima/efeitos dos fármacos , Água/química , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Masculino , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/genética , Permeabilidade/efeitos dos fármacos
9.
Cancer Gene Ther ; 31(4): 586-598, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38267623

RESUMO

Glutamate-NMDAR receptors (GRINs) have been reported to influence cancer immunogenicity; however, the relationship between GRIN alterations and the response to immune checkpoint inhibitors (ICIs) has not been determined. This study combined clinical characteristics and mutational profiles from multiple cohorts to form a discovery cohort (n = 901). The aim of this study was to investigate the correlation between the mutation status of the GRIN gene and the response to ICI therapy. Additionally, an independent ICI-treated cohort from the Memorial Sloan Kettering Cancer Center (MSKCC, N = 1513) was used for validation. Furthermore, this study explored the associations between GRIN2A mutations and intrinsic and extrinsic immunity using multiomics analysis. In the discovery cohort, patients with GRIN2A-MUTs had improved clinical outcomes, as indicated by a higher objective response rate (ORR: 36.8% vs 25.8%, P = 0.020), durable clinical benefit (DCB: 55.2% vs 38.7%, P = 0.005), prolonged progression-free survival (PFS: HR = 0.65; 95% CI 0.49 to 0.87; P = 0.003), and increased overall survival (OS: HR = 0.67; 95% CI 0.50 to 0.89; P = 0.006). Similar results were observed in the validation cohort, in which GRIN2A-MUT patients exhibited a significant improvement in overall survival (HR = 0.66; 95% CI = 0.49 to 0.88; P = 0.005; adjusted P = 0.045). Moreover, patients with GRIN2A-MUTs exhibited an increase in tumor mutational burden, high expression of costimulatory molecules, increased activity of antigen-processing machinery, and infiltration of various immune cells. Additionally, gene sets associated with cell cycle regulation and the interferon response were enriched in GRIN2A-mutated tumors. In conclusion, GRIN2A mutation is a novel biomarker associated with a favorable response to ICIs in multiple cancers.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Interferons , Mutação , Biomarcadores Tumorais/genética
10.
Inflammation ; 47(1): 159-172, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37740102

RESUMO

Pyroptosis is an inflammatory programmed cell death (PCD) and is reported to be associated with N6-methyladenosine (m6A) modification. This study aimed to investigate the mechanism of m6A demethylase AlkB homolog 5 (ALKBH5) in pyroptosis in the process of chronic actinic dermatitis (CAD). Changes of m6A-related genes were evaluated between CAD and normal samples using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Human keratinocytes (HaCaT cells) exposed to ultraviolet B (UVB; 10, 20, and 30 mJ/cm2), followed by evaluation of cell proliferation, cell apoptosis, inflammatory cytokines (interleukin (IL)-1ß, IL-18, and tumor necrosis factor (TNF-α)), and pyroptosis-related proteins (gasdermin D (GSDMD), Caspase-1, and Caspase-4). Small interfering RNA (siRNA) targeting ALKBH5 was transfected into HaCaT cells to assess the effect of si-ALKBH5 on CAD. A CAD mice model was induced after exposure to UVB (250 mJ/cm2 per day) to confirm the role of ALKBH5 in CAD. AKKBH5 was highly expressed in CAD patients. UVB also promoted ALKBH5 expression, increased cell apoptosis, and induced the release of inflammatory cytokines (IL-1ß, IL-18, and TNF-α) as well as pyroptosis-related proteins (GSDMD, Caspase-1, and Caspase-4). Silencing ALKBH5 repressed cell apoptosis and suppressed UVB-induced pyroptosis and inflammatory response. Meanwhile, silencing ALKBH5 attenuated UVB-induced skin damage of CAD mice, accompanied with the reduction in expression of inflammatory cytokines and pyroptosis-related proteins. This study helps to further understand the mechanism of ALKBH5 in CAD-induced pyroptosis and provides novel ideas for the research and management of CAD.


Assuntos
Transtornos de Fotossensibilidade , Piroptose , Animais , Humanos , Camundongos , Adenosina , Homólogo AlkB 5 da RNA Desmetilase , Caspase 1 , Citocinas , Interleucina-18 , Interleucina-1beta , RNA Interferente Pequeno , Fator de Necrose Tumoral alfa
11.
J Cosmet Dermatol ; 23(3): 1009-1014, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38059312

RESUMO

BACKGROUND: Sensitivity skin (SS) is a common skin disorders, which have a various of clinical manifestation. Facial erythema is common objective symptom of SS. However, the reasons for the occurrence of erythema in sensitive skin are not fully understood. AIMS: In this study, we preliminarily explain the possible factors inducing erythema of sensitive skin by evaluating facial erythematous reaction to lactic acid sting test (LAST) and capsaicin test (CAT) in subjects with sensitive skin. METHODS: A total of 197 subjects were divided into five groups, that is, normal controls (NC), LAST-positive (LAST+ ), both LAST and CAT positive (L+ C+ ), both LAST and CAT negative (L- C- ) and CAT-positive (CAT+ ). Erythema index (EI), a* value, and tissue viability imaging (TIVI) were measured before and after LAST and CAT, The ΔEI, Δa*, and ΔTIVI before and after LAST and CAT were calculated, and the correlation between the scores of CAT, EI values, a* values, and TIVI values were analyzed to clarify the causes of facial erythema. RESULTS: Our results showed that EI values and a* values were significantly higher in the L+ C+ and CAT+ group than in NC group, TIVI values were higher in the L+ C+ group than in NC group. ΔEI and Δa* values after LAST did not differ significantly among five groups. However, ΔEI values in L+ C+ group were higher than that in L- C- group, while Δa* values were higher in CAT+ group than in NC. Moreover, ΔTIVI values in L+ C+ group and CAT+ group were also significantly higher than that in NC group after capsaicin stimulation. CAT scores correlated positively with EI, a* and TIVI values. CONCLUSION: Our results suggest that sensitive skin subjects with positive CAT are more likely to experience erythema reactions, and vasodilation is more pronounced after capsaicin stimulation. Reducing vascular and neural hyperreactivity could be therapeutic target in management of facial erythema in subjects with sensitive skin.


Assuntos
Capsaicina , Eritema , Humanos , Capsaicina/efeitos adversos , Eritema/induzido quimicamente , Eritema/diagnóstico , Ácido Láctico
12.
Elife ; 122023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099574

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC, and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors along AK to cSCC progression. Immunohistochemistry (IHC)/immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration, and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.


Assuntos
Carcinoma de Células Escamosas , Ceratose Actínica , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/metabolismo , Ceratose Actínica/genética , Ceratose Actínica/metabolismo , Ceratose Actínica/patologia , Neoplasias Cutâneas/patologia , Queratinócitos/metabolismo , Transcriptoma , Microambiente Tumoral/genética
13.
Trauma Violence Abuse ; : 15248380231195888, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37706447

RESUMO

The involvement of left-behind children (LBC) in school bullying has raised concern in China. However, the susceptibility of LBC to engage in bullying is controversial, and comprehensive, representative studies covering the entire country are lacking. The purpose of this study was to evaluate the prevalence and severity of school bullying among LBC. The Chinese National Knowledge Network, WanFang, VIP, PubMed, Web of Science, EMBASE, and EBSCO databases were searched for literature on being left-behind and bullying before April 2022. The effect size was measured by odds ratio (ORs), standard mean difference (SMD), and 95% confidence interval (CI). Random-effects or fixed-effects models were selected for meta-analysis, and subgroup analysis was used to explore the sources of heterogeneity. The meta-analysis included 25 studies of school bullying among LBC and non-LBC (NLBC). The prevalence of bullying perpetration and victimization among LBC were 18.58% (95% CI [3.72%, 33.44%], p < .05) and 40.62% (95% CI [25.47%, 55.78%], p < .05), respectively. Compared with NLBC, the risk of bullying perpetration and victimization among LBC increased 1.97 times (OR = 1.97, 95% CI [1.77, 2.20], p < .05) and 2.17 times (OR = 2.17, 95% CI [1.43, 3.29], p < .05), respectively. The severity of bullying experienced by LBC was higher than that of NLBC (SMD = 0.49, 95% CI [0.20, 0.79], p < .05). The prevalence and severity of school bullying were higher in LBC than in NLBC, and left-behindness was positively associated with school bullying. LBC are a crucial population to protect when developing bullying interventions.

14.
ACS Sens ; 8(10): 3701-3712, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37738233

RESUMO

Integrin tensions are critical for cell mechanotransduction. By converting force to fluorescence, molecular tension sensors image integrin tensions in live cells with a high resolution. However, the fluorescence signal intensity results collectively from integrin tension magnitude, tension dwell time, integrin density, sensor accessibility, and so forth, making it highly challenging to specifically monitor the molecular force level of integrin tensions. Here, a ratiometric tension sensor (RTS) was developed to exclusively monitor the integrin tension magnitude. The RTS consists of two tension-sensing units that are coupled in series and always subject to the same integrin tension. These two units are activated by tension to fluoresce in separate spectra and with different activation rates. The ratio of their activation probabilities, reported by fluorescence ratiometric measurement, is solely determined by the local integrin tension magnitude. RTS responded sensitively to the variation of integrin tension magnitude in platelets and focal adhesions due to different cell plating times, actomyosin inhibition, or vinculin knockout. At last, RTS confirmed that integrin tension magnitude in platelets and focal adhesions decreases monotonically with the substrate rigidity, verifying the rigidity dependence of integrin tensions in live cells and suggesting that integrin tension magnitude could be a key biomechanical factor in cell rigidity sensing.


Assuntos
Integrinas , Mecanotransdução Celular , Integrinas/análise , Integrinas/metabolismo , Adesões Focais/metabolismo , Fenômenos Mecânicos , Citoesqueleto de Actina/metabolismo
15.
Front Psychiatry ; 14: 1139484, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37743983

RESUMO

Objective: The mental health of sexual minorities has received increasing attention, but there are few studies on the risk of psychotic-like experiences (PLEs) among sexual minorities. The purpose of this study is to explore the relationship between different sexual orientations and PLEs among college students and the moderating effect of gender. Methods: A total of 4,460 college students from seven provinces participated in this cross-sectional survey. The χ2 test and logistic regression were used to investigate the relationship between sexual orientation and PLEs. Results: Of the participants, 4.9% identified as bisexual, 1.1% as lesbian/gay, and 5.6% were questioning/unsure; 60.1% of the sample experienced at least one PLE item, 59.2% reported delusional experiences (DEs), and 20.6% had hallucinatory experiences (HEs). Compared with heterosexual college students, bisexual and questioning students showed a higher risk of PLEs, DEs, and HEs, and lesbian/gay students showed a higher risk of HEs. Stratified analysis indicated that sexual orientation was significantly associated with PLEs only for female college students. Conclusion: Sexual orientation is a predictive factor of PLEs. In particular, different sexual minority subgroups show the different effects on PLEs between male and female college students. Mental health interventions for PLEs could employ distinct strategies based on different sexual orientations and gender disparity.

16.
Photodermatol Photoimmunol Photomed ; 39(6): 598-606, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37545106

RESUMO

BACKGROUND: Chronic actinic dermatitis (CAD) is an immune-mediated photodermatosis characterized by a high eosinophil count and total immunoglobulin E (IgE) in the peripheral blood of patients. At present, however, the reasons for their elevation remain unclear. OBJECTIVE: The current study aimed to detect changes in inflammatory cytokines in CAD and explore their role in this disease. METHODS: Enzyme-linked immunosorbent assay and Luminex assay were conducted to measure inflammatory factor levels. Immunohistochemical analysis and quantitative real-time polymerase chain reaction were performed to evaluate the expression levels of interleukin-36γ (IL-36γ), IL-8, chemokine (C-C motif) ligand 17 (CCL17), and CCL18. CCK8 kits were used to assess cell proliferation. Immunofluorescence was used to detect nuclear factor κB (NF-κB) p65 nuclear translocation. Western blot analysis was performed to detect the protein expression level of phosphorylated NF-κB (p-NF-κB) p65. Hematoxylin and eosin and Masson trichrome staining were applied to observe histological changes in a chronic photo-damaged mouse model. RESULTS: Eosinophils, total IgE, IL-36γ, IL-8, tumor necrosis factor α, CCL17, and CCL18 were elevated in CAD. Of note, IL-36γ promoted the proliferation of eosinophilic cells (EOL-1) and the production of IgE in peripheral blood mononuclear cells. IL-36γ also promoted the production of IL-8 and CCL18 in immortalized human keratinocytes (HaCaT cells), while ultraviolet radiation (UVR)-induced IL-36γ via activation of the NF-κB signaling pathway. CONCLUSIONS: IL-36γ was involved in the pathogenesis of CAD and UVR contributed to the production of IL-36γ, which may provide a novel therapeutic target for CAD.


Assuntos
Transtornos de Fotossensibilidade , Raios Ultravioleta , Animais , Camundongos , Humanos , Raios Ultravioleta/efeitos adversos , NF-kappa B/metabolismo , Interleucina-8 , Leucócitos Mononucleares , Interleucinas , Fator de Necrose Tumoral alfa/farmacologia , Imunoglobulina E
17.
J Cosmet Dermatol ; 22(12): 3505-3510, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37464957

RESUMO

BACKGROUND: Although rosacea and seborrheic dermatitis share some symptoms of sensitive skin, whether they respond differently to lactic acid sting and capsaicin tests, common tests for diagnosis of sensitive skin, is unknown. OBJECTIVES: To reveal the cutaneous responses to lactic acid sting (LAST) and capsaicin test (CAT) in females with either rosacea vs. seborrheic dermatitis. METHODS: A total of 60 patients with rosacea, 20 patients with seborrheic dermatitis and 40 normal controls were enrolled in the study. Their skin sensitivity to stimuli were evaluated following topical application of either 10% lactic acid solution or 0.001% capsaicin solution. Transepidermal water loss (TEWL) rates and erythema indexes were also measured on the face. RESULTS: In comparison to normal controls, the positive rate to either LAST or CAT was significantly higher in subjects with rosacea (p < 0.001), but not in that with seborrheic dermatitis. Similarly, individuals with rosacea displayed a higher positive rate to both LAST and CAT than those with seborrheic dermatitis and normal controls (p < 0.001). In parallel, the LAST scores and CAT scores in individuals with rosacea were significantly higher than in that with either seborrheic dermatitis or normal controls (p < 0.001). The baseline TEWL rates and erythema indexes were higher in individual with rosacea than in normal controls (p < 0.001). But the baseline TEWL rates and erythema indexes did not differ significantly between subjects with rosacea and that with seborrheic dermatitis. Moreover, LAST scores and CAT scores correlated positively with TEWL (p < 0.0001). TEWL rates were higher in CAT positive than in CAT negative subjects (p < 0.0001). Finally, erythema index correlated positively with CAT scores (p < 0.0001), but not with LAST scores (p = 0.0842). CONCLUSIONS: Skin responses to LAST and CAT differ between individuals with rosacea and those with seborrheic dermatitis, possibly due to the differences in epidermal permeability barrier and the neurovascular hyperreactivity. The higher LAST and CAT scores, as well as positive rates of both LAST and CAT can be attributable to inferior permeability barrier and the neurovascular hyperreactivity in subjects with rosacea.


Assuntos
Dermatite Seborreica , Rosácea , Feminino , Humanos , Capsaicina/farmacologia , Dermatite Seborreica/diagnóstico , População do Leste Asiático , Eritema/diagnóstico , Ácido Láctico/farmacologia , Rosácea/diagnóstico , Pele , Testes Cutâneos
18.
Talanta ; 260: 124649, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37167677

RESUMO

Amyloid-ß oligomers (AßO) have been identified as core biomarkers for early diagnosis of Alzheimer's disease (AD). For the first time, a "turn-on" unlabeled colorimetric aptasensor based on aptamer-polythymine (polyT)-polyadenine (polyA)-gold nanoparticles (pA-pT-apt@AuNPs) was developed for highly sensitive and specific detection of amyloid-ß1-40 oligomers (Aß40-O). In this system, polyA sequence could preferentially anchor onto AuNPs surface as well as reduce the non-specific adsorption, and the aptamer could form upright conformation for the specific recognition of Aß40-O. The aggregation of pA-pT-apt@AuNPs was induced by MgCl2. However, the addition of Aß40-O enabled the aptamer fold adaptively upon recognition and aptamer-Aß40-O complex formed surrounding AuNPs, effectively stabilizing pA-pT-apt@AuNPs against salt-induced aggregation, therefore the color of pA-pT-apt@AuNPs solution still retained red. Based on this principle, the proposed aptasensor exhibited high sensitivity with the limit of detection of 3.03 nM and a linear detectable range from 10.00 nM to 100.0 nM. The superb sensitivity was achieved via the optimization of the length of polyA and polyT spacer. This pA-pT-apt@AuNPs based colorimetric aptasensor provides a rapid, cost-effective, highly sensitive detection method for Aß40-O, which is valuable for the early diagnosis of AD.


Assuntos
Doença de Alzheimer , Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Colorimetria/métodos , Peptídeos beta-Amiloides , Ouro , Doença de Alzheimer/diagnóstico , Técnicas Biossensoriais/métodos , Limite de Detecção
19.
Talanta ; 254: 124183, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36512973

RESUMO

Here, sulfonated polyaniline (SPAN) was decorated on the surface of copper-based metal organic frame (HKUST-1) and the composite was functionalized by luminol to construct a chemiluminescence (CL) hybrids (SPAN/HKUST-1@Luminol). The as-prepared SPAN/HKUST-1@Luminol demonstrated a great dispersion and stability performance in aqueous solution. Moreover, the resultant SPAN/HKUST-1@Luminol hybrids exhibited extremely strong CL properties, and the CL quantum yield was 136 times higher than that of luminol. In particular, it exhibited outstanding CL activity not only under alkaline conditions, but also under neutral conditions. The sensitive response of the hybrid to hydrogen peroxide was used to construct CL methods for the detection of hydrogen peroxide at a wide range of pH, with the detection limit of 60 nM at a neutral condition and 25 pM at alkaline condition. Due to strong and stable signal of the SPAN/HKUST-1@Luminol, the CL method provides a viable tool for determination of H2O2 in biological systems and enabled the monitoring of stimulated production of H2O2 released by living cells.


Assuntos
Peróxido de Hidrogênio , Luminol , Luminol/química , Peróxido de Hidrogênio/química , Cobre , Luminescência , Limite de Detecção , Medições Luminescentes/métodos , Metais , Concentração de Íons de Hidrogênio
20.
Contact Dermatitis ; 88(3): 188-200, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36461623

RESUMO

BACKGROUND: Chronic actinic dermatitis (CAD) is an immune-mediated photo-allergic skin disease. In the clinic, the treatment of this disease is hampered by the lack of proper understanding of the skin barrier dysfunction mechanism. OBJECTIVE: To illuminate the mechanism of skin barrier dysfunction in CAD. METHODS: Transcriptome sequencing and protein profiling were used to detect skin barrier injury-related genes. RNA pull down, a promoter-reporter gene assay, and chromatin isolation by RNA purification-sequencing were used to elucidate the effect of WAKMAR2 in skin barrier functionality. RESULTS: Transcriptome sequencing from patient's tissues showed a significantly decreased expression of WAKMAR2. Down-regulation of WAKMAR2 destroyed the keratinocyte barrier. Moreover, WAKMAR2 can directly bind to the c-Fos protein. This novel long non-coding RNA (LncRNA)-protein complexes were targeted to the CLDN1 promotor. Overexpression of WAKMAR2 enhanced the promoter activity of CLDN1, while the addition of AP-1 inhibitor could reverse this phenomenon. Furthermore, our in vivo results suggested that expression of WAKMAR2 was required for the repair of skin damage in mice induced by ultraviolet irradiation. CONCLUSIONS: We identified a crucial LncRNA (WAKMAR2) for the protection of the skin barrier in vitro and in vivo. Mechanically, it can specifically interact with c-Fos protein for the regulation of CLDN1, a finding which could be applied for CAD treatment.


Assuntos
Dermatite Alérgica de Contato , Dermatite Atópica , RNA Longo não Codificante , Animais , Camundongos , Dermatite Alérgica de Contato/metabolismo , Dermatite Atópica/metabolismo , Queratinócitos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/farmacologia , Humanos
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