Moderating AC Usage Can Reduce Thermal Disparity between Indoor and Outdoor Environments.

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.

MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5.

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.

GroEL triggers NLRP3 inflammasome activation through the TLR/NF-κB p-p65 axis in human periodontal ligament stem cells.

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.

Vinculin transmits high-level integrin tensions that are dispensable for focal adhesion formation.

Focal adhesions (FAs) transmit force and mediate mechanotransduction between cells and the matrix. Previous studies revealed that integrin-transmitted force is critical to regulate FA formation. As vinculin is a prominent FA protein implicated in integrin tension transmission, this work studies the relation among integrin tensions (force), vinculin (protein), and FA formation (structure) by integrin tension manipulation, force visualization and vinculin knockout (KO). Two DNA-based integrin tension tools are adopted: tension gauge tether (TGT) and integrative tension sensor (ITS), with TGT restricting integrin tensions under a designed Ttol (tension tolerance) value and ITS visualizing integrin tensions above the Ttol value by fluorescence. Results show that large FAs (area >1 µm2) were formed on the TGT surface with Ttol of 54 pN but not on those with lower Ttol values. Time-series analysis of FA formation shows that focal complexes (area <0.5 µm2) appeared on all TGT surfaces 20 min after cell plating, but only matured to large FAs on TGT with Ttol of 54 pN. Next, we tested FA formation in vinculin KO cells on TGT surfaces. Surprisingly, the Ttol value of TGT required for large FA formation is drastically decreased to 23 pN. To explore the cause, we visualized integrin tensions in both wild-type and vinculin KO cells using ITS. The results showed that integrin tensions in FAs of wild-type cells frequently activate ITS with Ttol of 54 pN. With vinculin KO, however, integrin tensions in FAs became lower and unable to activate 54 pN ITS. Force signal intensities of integrin tensions reported by 33 and 43 pN ITS were also significantly reduced with vinculin KO, suggesting that vinculin is essential to transmit high-level integrin tensions and involved in transmitting intermediate-level integrin tensions in FAs. However, the high-level integrin tensions transmitted by vinculin are not required by FA formation.

Role of interleukin-36γ induced by ultraviolet radiation in chronic actinic dermatitis.

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.

LncRNA-WAKMAR2 regulates expression of CLDN1 to affect skin barrier through recruiting c-Fos.

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.

Global COVID-19 pandemic demands joint interventions for the suppression of future waves.

Emerging evidence suggests a resurgence of COVID-19 in the coming years. It is thus critical to optimize emergency response planning from a broad, integrated perspective. We developed a mathematical model incorporating climate-driven variation in community transmissions and movement-modulated spatial diffusions of COVID-19 into various intervention scenarios. We find that an intensive 8-wk intervention targeting the reduction of local transmissibility and international travel is efficient and effective. Practically, we suggest a tiered implementation of this strategy where interventions are first implemented at locations in what we call the Global Intervention Hub, followed by timely interventions in secondary high-risk locations. We argue that thinking globally, categorizing locations in a hub-and-spoke intervention network, and acting locally, applying interventions at high-risk areas, is a functional strategy to avert the tremendous burden that would otherwise be placed on public health and society.

Drivers of foliar 15 N trends in southern China over the last century.

Foliar stable nitrogen (N) isotopes (δ15 N) generally reflect N availability to plants and have been used to infer about changes thereof. However, previous studies of temporal trends in foliar δ15 N have ignored the influence of confounding factors, leading to uncertainties on its indication to N availability. In this study, we measured foliar δ15 N of 1811 herbarium specimens from 12 plant species collected in southern China forests from 1920 to 2010. We explored how changes in atmospheric CO2 , N deposition and global warming have affected foliar δ15 N and N concentrations ([N]) and identified whether N availability decreased in southern China. Across all species, foliar δ15 N significantly decreased by 0.82‰ over the study period. However, foliar [N] did not decrease significantly, implying N homeostasis in forest trees in the region. The spatiotemporal patterns of foliar δ15 N were explained by mean annual temperature (MAT), atmospheric CO2 ( P CO 2 ), atmospheric N deposition, and foliar [N]. The spatiotemporal trends of foliar [N] were explained by MAT, temperature seasonality, P CO 2 , and N deposition. N deposition within the rates from 5.3 to 12.6 kg N ha-1  year-1 substantially contributed to the temporal decline in foliar δ15 N. The decline in foliar δ15 N was not accompanied by changes in foliar [N] and therefore does not necessarily reflect a decline in N availability. This is important to understand changes in N availability, which is essential to validate and parameterize biogeochemical cycles of N.

The relationship between pesticide exposure during critical neurodevelopment and autism spectrum disorder: A narrative review.

Agricultural pesticides have been one of the most extensively used compounds throughout the world. The main sources of contamination for humans are dietary intake and occupational exposure. The impairments caused by agricultural pesticide exposure have been a significant global public health problem. Recent studies have shown that low-level agricultural pesticide exposure during the critical period of neurodevelopment (pregnancy and lactation) is closely related to autism spectrum disorder (ASD). Inhibition of acetylcholinesterase, gut microbiota, neural dendrite morphology, synaptic function, and glial cells are targets for the effects of pesticides during nervous system development. In the present review, we summarize the associations between several highly used and frequently studied pesticides (e.g., glyphosate, chlorpyrifos, pyrethroids, and avermectins) and ASD. We also discusse future epidemiological and toxicological research directions on the relationship between pesticides and ASD.

Sporoderm-broken spores of Ganoderma lucidum alleviates liver injury induced by DBP and BaP co-exposure in rat.

Dibutyl phthalate (DBP) and Benzo(a)pyrene (BaP) are ubiquitous contaminants in environment and foodstuffs, which increase the chance of their combined exposure to humans in daily life. However, the combined effects of DBP and BaP on liver and the underlying mechanisms are still unclear. In this study, we explored the combined effects of DBP and BaP on liver and the potential mechanisms in a rat model. We found that DBP and BaP co-exposure activated the MyD88/NF-κB pathway through increasing TLR4 acetylation (TLR4ac) level, leading to the imbalance of pro-inflammatory factors (CXCL-13, IL-6 and TNF-α) and anti-inflammatory factors (IL-10), ultimately resulting in liver tissue damage and functional changes. Sporoderm-broken spores of Ganoderma lucidum (SSGL) had strong alleviating effects on liver injury induced by DBP and BaP co-exposure. Our study found that SSGL suppressed TLR4ac-regulated MyD88/NF-κB signaling to reduce the release of pro-inflammatory factors, and promote the secretion of IL-10, thus alleviating liver injury caused by DBP and BaP co-exposure. In conclusion, SSGL contributed to liver protection against DBP and BaP-induced liver injury in rats via suppressing the TLR4ac-regulated MyD88/NF-κB signaling.