Multi-node wearable optical sensor based on microfiber Bragg gratings.

Flexibly wearable sensors are widely applied in health monitoring and personalized therapy. Multiple-node sensing is essential for mastering the health condition holistically. In this work, we report a multi-node wearable optical sensor (MNWOS) based on the cascade of microfiber Bragg gratings (µFBG), which features the reflective operation mode and ultra-compact size, facilitating the functional integration in a flexible substrate pad. The MNWOS can realize multipoint monitoring on physical variables, such as temperature and pressure, in both static and dynamic modes. Furthermore, the eccentric package configuration endows the MNWOS with the discernibility of bending direction in addition to the bending angle sensing. The multi-parameter sensing is realized by solving the sensing matrix that represents different sensitivity regarding the bending and temperature between FBGs. The MNWOS offers great prospect for the development of human-machine interfaces and medical and health detection.

Acute Effects of Exposure to Fine Particulate Matter and Its Constituents on Sex Hormone Among Postmenopausal Women - Beijing, Tianjin, and Hebei PLADs, China, 2018-2019.

What is already known on this topic?: Exposure to fine particulate matter (PM2.5) was linked to endocrine hormone disruption in the reproductive system. Nonetheless, it was unclear which specific components of PM2.5 were primarily responsible for these associations. What is added by this report?: The study presented the initial epidemiological evidence that brief exposure to PM2.5 can elevate estradiol levels in postmenopausal women. Various particle components had unique effects, with water-soluble ions and specific inorganic elements like Ag, As, Cd, Hg, Ni, Sb, Se, Sn, and Tl potentially playing significant roles in increasing estradiol levels. What are the implications for public health practice?: The study established that the prevalence of air pollution, along with its specific components, has been recognized as a novel risk factor affecting the balance of sex hormones.

The multi-year contribution of Indo-China peninsula fire emissions to aerosol radiation forcing in southern China during 2013-2019.

Fire emissions in Southeast Asia transported to southern China every spring (March-May), influencing not only the air quality but also the weather and climate. However, the multi-year variations and magnitude of this impact on aerosol radiation forcing in southern China remain unclear. Here, we quantified the multi-year contributions of fire emissions in Indo-China Peninsula (ICP) region to aerosol radiation forcing in the various southern Chinese provinces during the fire season (March-May) of 2013-2019 combining the 3-dimension chemical transport model and the Column Radiation Model (CRM) simulations. The models' evaluations showed they reasonably capture the temporal and spatial distribution of surface aerosol concentrations and column aerosol optical properties over the study regions. The fire emissions over the ICP region were found to increase the aerosol optical depth (AOD) value by 0.1 (15 %) and reduce the single scattering albedo (SSA) in three southern regions of China (Yunnan-YN, Guangxi-GX, and Guangdong-GD from west to east), owing to increases in the proportions of black carbon (BC, 0.4 % ± 0.1 %) and organic carbon (OC, 3.0 % ± 0.9 %) within the aerosol compositions. The transported smoke aerosols cooled surface but heated the atmosphere in the southern China regions, with the largest mean reduction of -5 Wm-2 (-3 %) in surface shortwave radiation forcing and the maximum daily contributions of about -15 Wm-2 (-15 %) to the atmosphere radiation forcing in the GX region, followed by the GD and YN regions. The impacts of ICP fire emissions on aerosol optical and radiative parameters declined during 2013-2019, with the highest rate of 0.393 ± 0.478 Wm-2 yr-1 in the GX for the shortwave radiation forcing in the atmosphere. Besides, their yearly changes in the contribution were consistent with the annual fire emissions in the ICP region. Such strong radiative perturbations of ICP fire emissions were expected to influence regional meteorology in southern China and should be considered in the climate simulations.

Wildfire-related PM2.5 and cardiovascular mortality: A difference-in-differences analysis in Brazil.

Brazil has experienced unprecedented wildfires recently. We aimed to investigate the association of wildfire-related fine particulate matter (PM2.5) with cause-specific cardiovascular mortality, and to estimate the attributable mortality burden. Exposure to wildfire-related PM2.5 was defined as exposure to annual mean wildfire-related PM2.5 concentrations in the 1-year prior to death. The variant difference-in-differences method was employed to explore the wildfire-related PM2.5-cardiovascular mortality association. We found that, in Brazil, compared with the population in the first quartile (Q1: ≤1.82 µg/m3) of wildfire-related PM2.5 exposure, those in the fourth quartile (Q4: 4.22-17.12 µg/m3) of wildfire-related PM2.5 exposure had a 2.2% (RR: 1.022, 95% CI: 1.013-1.032) higher risk for total cardiovascular mortality, 3.1% (RR: 1.031, 95% CI: 1.014-1.048) for ischaemic heart disease mortality, and 2.0% (RR: 1.020, 95% CI: 1.002-1.038) for stroke mortality. From 2010 to 2018, an estimation of 35,847 (95% CI: 22,424-49,177) cardiovascular deaths, representing 17.77 (95% CI: 11.12-24.38) per 100,000 population, were attributable to wildfire-related PM2.5 exposure. Targeted health promotion strategies should be developed for local governments to protect the public from the risk of wildfire-related cardiovascular premature deaths.

The carbon budget of China: 1980-2021.

As one of the world's largest emitters of greenhouse gases, China has set itself the ambitious goal of achieving carbon peaking and carbon neutrality. Therefore, it is crucial to quantify the magnitude and trend of sources and sinks of atmospheric carbon dioxide (CO2), and to monitor China's progress toward these goals. Using state-of-the-art datasets and models, this study comprehensively estimated the anthropogenic CO2 emissions from energy, industrial processes and product use, and waste along with natural sources and sinks of CO2 for all of China during 1980-2021. To recognize the differences among various methods of estimating greenhouse emissions, the estimates are compared with China's National Greenhouse Gas Inventories (NGHGIs) for 1994, 2005, 2010, 2012, and 2014. Anthropogenic CO2 emissions in China have increased by 7.39 times from 1980 to 12.77 Gt CO2 a-1 in 2021. While benefiting from ecological projects (e.g., Three Norths Shelter Forest System Project), the land carbon sink in China has reached 1.65 Gt CO2 a-1 averaged through 2010-2021, which is almost 15.81 times that of the carbon sink in the 1980s. On average, China's terrestrial ecosystems offset 14.69% ± 2.49% of anthropogenic CO2 emissions through 2010-2021. Two provincial-level administrative regions of China, Xizang and Qinghai, have achieved carbon neutrality according to our estimates, but nearly half of the administrative regions of China have terrestrial carbon sink offsets of less than 10% of anthropogenic CO2 emissions. This study indicated a high level of consistency between NGHGIs and various datasets used for estimating fossil CO2 emissions, but found notable differences for land carbon sinks. Future estimates of the terrestrial carbon sinks of NGHGIs urgently need to be verified with process-based models which integrate the comprehensive carbon cycle processes.

Selective Electroreduction of 5-Hydroxymethylfurfural to Dimethylfuran in Neutral Electrolytes via Hydrogen Spillover and Adsorption Configuration Adjustment.

5-Hydroxymethylfurfural (HMF), one of the essential C6 biomass derivatives, has been deeply investigated in electrocatalytic reduction upgrading. Nevertheless, the high product selectivity and rational design strategy of electrocatalysts for electrocatalytic HMF reduction is still a challenge. Here, a high selective electro-reduction of HMF to dimethylfuran (DMF) on palladium (Pd) single atom loaded on titanium dioxide (Pd SA/TiO2 ) via hydrogen spillover and adsorption configuration adjustment in neutral electrolytes is achieved. Combining density functional theory calculations and in situ characterization, it is revealed that Pd single atom could weaken the interaction between Pd atoms and adsorbed hydrogen (*H) to promote the *H spillover for increasing *H coverage on the surface and maintain the tilted adsorption configuration to activate C═O bond; thus the selectivity of DMF on Pd SA/TiO2 increases to 90.33%. Besides, it is elaborated that low *H coverage on TiO2 favors the formation of bis(hydroxymethyl)hydro-furoin (BHH), and the flat adsorption configuration of HMF on Pd nanoparticles benefits to form 2,5-dihydroxymethylfuran (DHMF). This work provides a promising approach for modifying electrocatalysts to realize the selective electroreduction of HMF to value-added products.

Application of Acupotomy in a Knee Osteoarthritis Model in Rabbit.

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department, which seriously reduces the quality of life of people with KOA. Among several pathogenic factors, the biomechanical imbalance of the knee joint is one of the main causes of KOA. Acupotomology believes that restoring the mechanical balance of the knee joint is the key to treating KOA. Clinical studies have shown that acupotomy can effectively reduce pain and improve knee mobility by reducing adhesion, contracture of soft tissues, and stress concentration points in muscles and tendons around the knee joint. In this protocol, we used the modified Videman method to establish a KOA model by immobilizing the left hindlimb in a straight position. We have outlined the method of operation and the precautions related to acupotomy in detail and evaluated the efficacy of acupotomy in conjunction with the theory of "Modulating Muscles and Tendons to Treat Bone Disorders" through the detection of the mechanical properties of quadriceps femoris and tendon, as well as cartilage mechanics and morphology. The results show that acupotomy has a protective effect on cartilage by adjusting the mechanical properties of the soft tissues around the knee joint, improving the cartilage stress environment, and delaying cartilage degeneration.

Nano-injectable pH/NIR-responsive hydrogel for chemo-photothermal synergistic drug delivery.

Conventional cancer treatments are highly toxic and ineffective; therefore, it is essential to develop less toxic and minimally invasive treatment methods. A pH/Near Infra-red (NIR) dual-responsive, nano-injectable smart hydrogel was fabricated by incorporating CuS nanoparticles into the hydrogel networks formed by a random copolymer of N-isopropylacrylamide (NIPAM) and double-bond functionalized uracil. Microstructural characterizations of synthesized polymer and hydrogels were carried out using transmission electron microscope (TEM), scanning electron microscope (SEM), nuclear magnetic resonance (NMR) and fourier transform infrared spectroscopy (FT-IR). Multiple hydrogen bonding interactions between uracils function as physical cross-linking points to construct the network structure of the polymeric nanogel without the addition of additional cross-linking agents, ensuring the material's safety. The amino group on the structure of uracil gives the uracil-modified polymeric hydrogel excellent pH responsiveness. Notably, as a temperature-responsive material, poly (N-isopropylacrylamide) (PNIPAM) nanogel solution can achieve in situ gel formation (within 100 s at 37°C) above its lower critical solution temperature (LCST), granting injectability to polymeric solutions. Moreover, using a hierarchical construction strategy, the variable loading of DOX and CuS was achieved. First, a heterogeneous system was created by encapsulating doxorubicin (DOX) inside the nanogel via hydrophobic and π-π stacking interactions, followed by the introduction of CuS nanoparticles as photosensitizers outside of the nanogels. Due to the presence of CuS nanoparticles, the gel is able to convert NIR light into local heat to enhance the destruction of tumor cells while simultaneously achieving rapid in situ gel formation. The in situ-forming hydrogel showed promising tissue biocompatibility. The in vitro antitumor test demonstrated the capacity of the nanocomposite hydrogel for chemo-photothermal synergistic therapy. Therefore, this prepared platform has the potential to become a safe and effective, smart-responsive drug carrier for chemotherapy and PTT synergy, a minimally invasive material for tumor treatment.

Global population exposure to landscape fire air pollution from 2000 to 2019.

Wildfires are thought to be increasing in severity and frequency as a result of climate change1-5. Air pollution from landscape fires can negatively affect human health4-6, but human exposure to landscape fire-sourced (LFS) air pollution has not been well characterized at the global scale7-23. Here, we estimate global daily LFS outdoor fine particulate matter (PM2.5) and surface ozone concentrations at 0.25° × 0.25° resolution during the period 2000-2019 with the help of machine learning and chemical transport models. We found that overall population-weighted average LFS PM2.5 and ozone concentrations were 2.5 µg m-3 (6.1% of all-source PM2.5) and 3.2 µg m-3 (3.6% of all-source ozone), respectively, in 2010-2019, with a slight increase for PM2.5, but not for ozone, compared with 2000-2009. Central Africa, Southeast Asia, South America and Siberia experienced the highest LFS PM2.5 and ozone concentrations. The concentrations of LFS PM2.5 and ozone were about four times higher in low-income countries than in high-income countries. During the period 2010-2019, 2.18 billion people were exposed to at least 1 day of substantial LFS air pollution per year, with each person in the world having, on average, 9.9 days of exposure per year. These two metrics increased by 6.8% and 2.1%, respectively, compared with 2000-2009. Overall, we find that the global population is increasingly exposed to LFS air pollution, with socioeconomic disparities.

Enhancements on volatile organic compounds (VOCs) adsorption and desorption performance of ZSM-5 by fabricating hierarchical MCM-41.

ZSM-5 zeolite has been considered a promising adsorbent for capturing VOCs. However, its hydrophilicity and narrow micropore structure limit their practical application especially under humid atmospheres. In this study, the pure silica mesoporous molecular sieve MCM-41 was assembled on ZSM-5 zeolite with different SiO2/Al2O3 ratios (SARs) via a surfactant-mediated recrystallization method. Then, its adsorption-desorption behaviors were investigated using n-hexane, toluene, and ethyl acetate as VOC model molecules. The results showed that the hydrophobicity of ZSM-5/MCM-41 composites and their VOC diffusion behaviors were significantly improved. Furthermore, the SARs of the ZSM-5 precursors had a remarkable influence on the adsorption performance of ZSM-5/MCM-41 composites. ZSM-5/MCM-41(130) was the optimum option, and its dynamic adsorption capacity for ethyl acetate (111.30 mg·g-1) was higher than that of the corresponding ZSM-5 zeolites even under statured humidity. Meanwhile, the ratios of dynamic adsorption capacities at humid and dry atmospheres (qs,wet/qs,dry) of ZSM-5/MCM-41(130) for n-hexane, toluene, and ethyl acetate were 84.89%, 61.46%, and 73.81% respectively. The results will provide guidelines for the preparation of hydrophobic adsorbents.

Association between long-term exposure to wildfire-related PM2.5 and mortality: A longitudinal analysis of the UK Biobank.

Little is known about the associations between long-term exposure to wildfire-related fine particulate matter (PM2.5) and mortality. We aimed to explore theses associations using the data from the UK Biobank cohort. Long-term wildfire-related PM2.5 exposure was defined as the 3-year cumulative concentrations of wildfire-related PM2.5 within a 10-km buffer surrounding the residential address for each individual. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the time-varying Cox regression model. We included 492,394 participants aged between 38 and 73 years. We found that after adjusting for potential covariates, a 10 µg/m3 increase of wildfire-related PM2.5 exposure was associated with a 0.4% higher risk of all-cause mortality (HR = 1.004 [95% CI: 1.001, 1.006]) and nonaccidental mortality (HR = 1.004 [95% CI: 1.002, 1.006]), and a 0.5% higher risk of neoplasm mortality (HR = 1.005 [95% CI: 1.002, 1.008]). However, no significant associations were observed between wildfire-related PM2.5 exposure and mortality from cardiovascular, respiratory, and mental diseases. Additionally, no significant modification effects of a series of modifiers were observed. Targeted health protection strategies should be adopted in response to wildfire-related PM2.5 exposure, in order to reduce the risk of premature mortality.

Near-infrared microfiber Bragg grating for sensitive measurement of tension and bending.

Fiber-optic devices working in the visible and near-infrared windows are attracting attention due to the rapid development of biomedicine that involves optics. In this work, we have successfully realized the fabrication of near-infrared microfiber Bragg grating (NIR-µFBG), which was operated at the wavelength of 785 nm, by harnessing the fourth harmonic order of Bragg resonance. The NIR-µFBG provided the maximum sensitivity of axial tension and bending to 211 nm/N and 0.18 nm/deg, respectively. By conferring the considerably lower cross-sensitivity, such as response to temperature or ambient refractive index, the NIR-µFBG can be potentially implemented as the highly sensitive tensile force and curve sensor.

Wildfire-related PM2.5 and health economic loss of mortality in Brazil.

BACKGROUND: Wildfire imposes a high mortality burden on Brazil. However, there is a limited assessment of the health economic losses attributable to wildfire-related fine particulate matter (PM2.5). METHODS: We collected daily time-series data on all-cause, cardiovascular, and respiratory mortality from 510 immediate regions in Brazil during 2000-2016. The chemical transport model GEOS-Chem driven with Global Fire Emissions Database (GFED), in combination with ground monitored data and machine learning was used to estimate wildfire-related PM2.5 data at a resolution of 0.25°â€ˆ× 0.25°. A time-series design was applied in each immediate region to assess the association between economic losses due to mortality and wildfire-related PM2.5 and the estimates were pooled at the national level using a random-effect meta-analysis. We used a meta-regression model to explore the modification effect of GDP and its sectors (agriculture, industry, and service) on economic losses. RESULTS: During 2000-2016, a total of US$81.08 billion economic losses (US$5.07 billion per year) due to mortality were attributable to wildfire-related PM2.5 in Brazil, accounting for 0.68% of economic losses and equivalent to approximately 0.14% of Brazil's GDP. The attributable fraction (AF) of economic losses due to wildfire-related PM2.5 was positively associated with the proportion of GDP from agriculture, while negatively associated with the proportion of GDP from service. CONCLUSION: Substantial economic losses due to mortality were associated with wildfires, which could be influenced by the agriculture and services share of GDP per capita. Our estimates of the economic losses of mortality could be used to determine optimal levels of investment and resources to mitigate the adverse health impacts of wildfires.

Assessment of solar energy potential in China using an ensemble of photovoltaic power models.

Development of solar energy is one of the key solutions towards carbon neutrality in China. The output of solar energy is dependent on weather conditions and shows distinct spatiotemporal characteristics. Previous studies have explored the photovoltaic (PV) power potential in China but with single models and low-resolution radiation data. Here, we estimated the PV power potential in China for 2016-2019 using an ensemble of 11 PV models based on hourly solar radiation at the resolution of 5 km retrieved by the Himawari-8 geostationary satellite. On the national scale, the ensemble method revealed an annual average PV power potential of 242.79 kWh m-2 with the maximum in the west (especially the Tibetan Plateau) and the minimum in the southeast (especially the Sichuan Basin). The multi-model approach shows inter-model spreads of 6 %-7 % distributed uniformly in China, suggesting a robust spatial pattern predicted by these models. The seasonal variation in general shows the largest PV power generation in summer months except for Tibetan Plateau, where the peak value appears in spring because the high cloud coverage dampens the regional solar radiation in summer. On the national scale, the deseasonalized PV power potential shows a high correlation with cloud coverage (R2 = 0.71, p < 0.01) but a low correlation with aerosol optical depth (R2 = 0.08, p < 0.05). Sensitivity experiments show that national PV power potential increases by 0.55 % per 1 W m-2 increase of radiation and 0.79 % per 1 m s-1 increase of wind speed, but decreases by 0.46 % per 1 °C increase of air temperature. These sensitivities provide a solid foundation for the future projection of PV power potential in China under climate change.

Soil respiration-driven CO2 pulses dominate Australia's flux variability.

The Australian continent contributes substantially to the year-to-year variability of the global terrestrial carbon dioxide (CO2) sink. However, the scarcity of in situ observations in remote areas prevents the deciphering of processes that force the CO2 flux variability. In this study, by examining atmospheric CO2 measurements from satellites in the period 2009-2018, we find recurrent end-of-dry-season CO2 pulses over the Australian continent. These pulses largely control the year-to-year variability of Australia's CO2 balance. They cause two to three times larger seasonal variations compared with previous top-down inversions and bottom-up estimates. The pulses occur shortly after the onset of rainfall and are driven by enhanced soil respiration preceding photosynthetic uptake in Australia's semiarid regions. The suggested continental-scale relevance of soil-rewetting processes has substantial implications for our understanding and modeling of global climate-carbon cycle feedbacks.

Global estimates of daily ambient fine particulate matter concentrations and unequal spatiotemporal distribution of population exposure: a machine learning modelling study.

BACKGROUND: Short-term exposure to ambient PM2·5 is a leading contributor to the global burden of diseases and mortality. However, few studies have provided the global spatiotemporal variations of daily PM2·5 concentrations over recent decades. METHODS: In this modelling study, we implemented deep ensemble machine learning (DEML) to estimate global daily ambient PM2·5 concentrations at 0·1° × 0·1° spatial resolution between Jan 1, 2000, and Dec 31, 2019. In the DEML framework, ground-based PM2·5 measurements from 5446 monitoring stations in 65 countries worldwide were combined with GEOS-Chem chemical transport model simulations of PM2·5 concentration, meteorological data, and geographical features. At the global and regional levels, we investigated annual population-weighted PM2·5 concentrations and annual population-weighted exposed days to PM2·5 concentrations higher than 15 µg/m3 (2021 WHO daily limit) to assess spatiotemporal exposure in 2000, 2010, and 2019. Land area and population exposures to PM2·5 above 5 µg/m3 (2021 WHO annual limit) were also assessed for the year 2019. PM2·5 concentrations for each calendar month were averaged across the 20-year period to investigate global seasonal patterns. FINDINGS: Our DEML model showed good performance in capturing the global variability in ground-measured daily PM2·5, with a cross-validation R2 of 0·91 and root mean square error of 7·86 µg/m3. Globally, across 175 countries, the mean annual population-weighted PM2·5 concentration for the period 2000-19 was estimated at 32·8 µg/m3 (SD 0·6). During the two decades, population-weighted PM2·5 concentration and annual population-weighted exposed days (PM2·5 >15 µg/m3) decreased in Europe and northern America, whereas exposures increased in southern Asia, Australia and New Zealand, and Latin America and the Caribbean. In 2019, only 0·18% of the global land area and 0·001% of the global population had an annual exposure to PM2·5 at concentrations lower than 5 µg/m3, with more than 70% of days having daily PM2·5 concentrations higher than 15 µg/m3. Distinct seasonal patterns were indicated in many regions of the world. INTERPRETATION: The high-resolution estimates of daily PM2·5 provide the first global view of the unequal spatiotemporal distribution of PM2·5 exposure for a recent 20-year period, which is of value for assessing short-term and long-term health effects of PM2·5, especially for areas where monitoring station data are not available. FUNDING: Australian Research Council, Australian Medical Research Future Fund, and the Australian National Health and Medical Research Council.

Projections of fire emissions and the consequent impacts on air quality under 1.5 °C and 2 °C global warming.

Fire is a major source of atmospheric aerosols and trace gases. Projection of future fire activities is challenging due to the joint impacts of climate, vegetation, and human activities. Here, we project global changes of fire-induced particulate matter smaller than 2.5 µm (PM2.5) and ozone (O3) under 1.5 °C/2 °C warming using a climate-chemistry-vegetation coupled model in combination with site-level and satellite-based observations. Compared to the present day, fire emissions of varied air pollutants increase by 10.0%-15.4% at the 1.5 °C warming period and 15.1%-22.5% at the 2 °C warming period, with the most significant enhancements in Amazon, southern Africa, and boreal Eurasia. The warmer climate promotes fuel dryness and the higher leaf area index increases fuel availability, leading to escalated fire flammability globally. However, moderate declines in fire emissions are predicted over the Sahel region, because the higher population density increases fire suppressions and consequently inhibits fire activities over central Africa. Following the changes in fire emissions, the population-weighted exposure to fire PM2.5 increases by 5.1% under 1.5 °C warming and 13.0% under 2 °C warming. Meanwhile, the exposure to fire O3 enhances by 10.2% and 16.0% in response to global warming of 1.5 °C and 2 °C, respectively. As a result, limiting global temperature increase to 1.5 °C can greatly reduce the risks of exposure to fire-induced air pollution compared to 2 °C.

Chronic pain recruits hypothalamic dynorphin/kappa opioid receptor signalling to promote wakefulness and vigilance.

Increased vigilance in settings of potential threats or in states of vulnerability related to pain is important for survival. Pain disrupts sleep and conversely, sleep disruption enhances pain, but the underlying mechanisms remain unknown. Chronic pain engages brain stress circuits and increases secretion of dynorphin, an endogenous ligand of the kappa opioid receptor (KOR). We therefore hypothesized that hypothalamic dynorphin/KOR signalling may be a previously unknown mechanism that is recruited in pathological conditions requiring increased vigilance. We investigated the role of KOR in wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep in freely moving naïve mice and in mice with neuropathic pain induced by partial sciatic nerve ligation using EEG/EMG recordings. Systemic continuous administration of U69,593, a KOR agonist, over 5 days through an osmotic minipump decreased the amount of NREM and REM sleep and increased sleep fragmentation in naïve mice throughout the light-dark sleep cycle. We used KORcre mice to selectively express a Gi-coupled designer receptor activated by designer drugs (Gi-DREADD) in KORcre neurons of the hypothalamic paraventricular nucleus, a key node of the hypothalamic-pituitary-adrenal stress response. Sustained activation of Gi-DREADD with clozapine-N-oxide delivered in drinking water over 4 days, disrupted sleep in these mice in a similar way as systemic U69,593. Mice with chronic neuropathic pain also showed disrupted NREM and total sleep that was normalized by systemic administration of two structurally different KOR antagonists, norbinaltorphimine and NMRA-140, currently in phase II clinical development, or by CRISPR/Cas9 editing of paraventricular nucleus KOR, consistent with endogenous KOR activation disrupting sleep in chronic pain. Unexpectedly, REM sleep was diminished by either systemic KOR antagonist or by CRISPR/Cas9 editing of paraventricular nucleus KOR in sham-operated mice. Our findings reveal previously unknown physiological and pathophysiological roles of dynorphin/KOR in eliciting arousal. Physiologically, dynorphin/KOR signalling affects transitions between sleep stages that promote REM sleep. Furthermore, while KOR antagonists do not promote somnolence in the absence of pain, they normalized disrupted sleep in chronic pain, revealing a pathophysiological role of KOR signalling that is selectively recruited to promote vigilance, increasing chances of survival. Notably, while this mechanism is likely beneficial in the short-term, disruption of the homeostatic need for sleep over longer periods may become maladaptive resulting in sustained pain chronicity. A novel approach for treatment of chronic pain may thus result from normalization of chronic pain-related sleep disruption by KOR antagonism.

The association between short-term ambient sulfur dioxide exposure and hospitalization costs of ischemic stroke: a hospital-based study in Chongqing, China.

Evidence of the short-term effects of ambient sulfur dioxide (SO2) exposure on the economic burden of ischemic stroke is limited. This study aimed to explore the association between short-term ambient SO2 exposure and hospitalization costs for ischemic stroke in Chongqing, the most populous city in China. The hospital-based study included 7271 ischemic stroke inpatients. Multiple linear regression models were used to estimate the association between SO2 concentration and hospitalization costs. Propensity score matching was used to compare the patients' characteristics when exposed to SO2 concentrations above and below 20 µg/m3. It is found that short-term SO2 exposure was positively correlated with the hospitalization costs of ischemic stroke. The association was more evident in males, people younger than 65, and people hospitalized in the cool seasons. Besides, among the components of hospitalization costs, medicine costs were most significantly associated with SO2. More interesting, the lower concentration of SO2, the higher costs associated with 1 µg/m3 SO2 change. Above all, SO2 was positively associated with hospitalization costs of ischemic stroke, even at its low levels. The measures to reduce the level of SO2 can help reduce the burden of ischemic stroke.