Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence.

It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 ± 0.5 °C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-ß1 (TGF-ß1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial-mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated ß-galactosidase (SA-ß-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS-STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS-STING pathway followed by cellular senescence.

LRRK2 is involved in heat exposure-induced acute lung injury and alveolar type II epithelial cell dysfunction.

Heat exposure induces excessive hyperthermia associated with systemic inflammatory response that leads to multiple organ dysfunction including acute lung injury. However, how heat impairs the lung remains elusive so far. We aimed to explore the underlying mechanism by focusing on leucine-rich repeat kinase 2 (LRRK2), which was associated with lung homeostasis. Both in vivo and in vitro models were induced by heat exposure. Firstly, heat exposure exerted core temperature (Tc) disturbance, pulmonary dysfunction, atelectasis, inflammation, impaired energy metabolism, and reduced surfactant proteins in the lung of mice. In addition, decreased LRRK2 expression and increased heat shock proteins (HSPs) 70 were observed with heat exposure in both the lung of mice and alveolar type II epithelial cells (AT2). Furthermore, LRRK2 inhibition aggravated heat exposure-initiated Tc dysregulation, injury in the lung and AT2 cells, and enhanced HSP70 expression. In conclusion, LRRK2 is involved in heat-induced acute lung injury and AT2 cell dysfunction.

Decarbonization without borders: Evidence from China.

Addressing global climate change requires countries to achieve economic decarbonization. However, there is currently no appropriate indicator to measure a country's economic decarbonization. In this study, we define a "decarbonization value-added (DEVA)" indicator of environmental cost internalization, construct a DEVA accounting framework that takes into account trade and investment activities, and provide a Chinese story of "decarbonization without borders". The results show that pure domestic production activities involving production linkages between pure domestic-owned enterprises (DOEs) are the main source of DEVA in China, and therefore production linkages between DOEs should be strengthened. Although trade-related DEVA is higher than that of related to foreign direct investment (FDI) DEVA, the impact of FDI-related production activities on China's economic decarbonization is increasing. This impact is mainly reflected in high-tech manufacturing and trade and transportation industries. Further, we divided four FDI-related production modes. It is found that the upstream production mode of DOEs (i.e. "DOEs-DOEs" type, "DOEs-foreign-invested enterprises" type) leads to the main position of DEVA in China's FDI-related DEVA, and the overall trend is increasing. These findings help us better understand the impact of trade and investment activities on a country's economic and environmental sustainability, and thus provide an important reference for a country to formulate sustainable development policies centered on economic decarbonization.

Sex difference in effects of intermittent heat exposure on hepatic lipid and glucose metabolisms.

Global climate warming has drawn worldwide attention. However, the health impact of heat exposure is still controversial. This study aimed to explore the exact effects and sex differential vulnerability under intermittent heat exposure (IHE) patterns and tried to elucidate the potential mechanisms by which IHE modulated hepatic lipid and glucose homeostasis. Both female and male C57BL/6 N mice were randomly allocated to control group (22 ± 1 °C) or intermittent heat group (37 ± 1 °C for 6 h) for 9 consecutive days followed by 4-day recovery at 22 ± 1 °C in a whole-body exposure chamber. Male mice, but not female, being influenced by IHE with decreased body weight, improved insulin sensitivity and glucose tolerance. Next, the levels of hepatic triglyceride (TG) were decreased and free fatty acid (FFA) increased in male mice exposed to intermittent heat, accompanied with upregulated expression of anti-oxidative enzymes in the liver. In addition, IHE led to enhanced lipid catabolism in male mice by inducing fatty acid uptake, lipid lipolysis, mitochondrial/peroxisomal fatty acid oxidation and lipid export. And glycolysis and glucose utilization were induced by IHE in male mice as well. Mechanically, heat shock protein 70 (HSP70)/insulin receptor substrate 1 (IRS1)/AMPKα pathways were activated in response to IHE. These findings provide new evidence that IHE sex-dependently enhanced the metabolism of lipid and glucose in male mice through HSP70/IRS1/AMPKα signaling.

Preparation and characterization of high-strength and water resistant lignocelluloses based composites bonded by branched polyethylenimine (PEI).

High-strength and water resistant lignocelluloses based composites (LC) were fabricated using branched polyethylenimine (PEI) as the main bonding agent combined with glutaraldehyde cross-linking reaction and grinding pre-treatment. Physical and mechanical properties of different composites prepared were measured and investigated. It is evident that PEI was efficient in endowing LC with high strength and excellent water resistance. The obtained physical and mechanical properties of LC were complied with the requirement of the Chinese national standard for medium-density fiberboard (MDF). Most notably, the glutaraldehyde cross-linking and grinding pre-treatment could further improve these properties. When 5% PEI and 2.5% glutaraldehyde were incorporated, together with 2-hour grinding treatment, the LC prepared exhibited the optimum modulus of rupture (MOR) 58.1 MPa, modulus of elasticity (MOE) 5077 MPa, internal bonding strength (IB) 2.14 MPa, and thickness swell (TS) 30.2%. The excellent properties obtained could be attributed to the cross-linking effect and Schiff's base addition reaction among lignocelluloses, PEI and glutaraldehyde, which were confirmed by the Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) analysis. The high-strength LC prepared in this study is expected to be used as load-bearing material in structural application.