Pan AMPK Activation Protects Tubules in Rat Ischemic Acute Kidney Injury.

Acute Kidney Injury (AKI) is characterized by an abrupt decline in kidney function and has been associated with excess risks of death, kidney disease progression, and cardiovascular events. The kidney has a high energetic demand with mitochondrial health being essential to renal function and damaged mitochondria has been reported across AKI subtypes. 5' adenosine monophosphate-activated protein kinase (AMPK) activation preserves cellular energetics through improvement of mitochondrial function and biogenesis when ATP levels are low such as under ischemia-induced AKI. We developed a selective potent small molecule pan AMPK activator, compound 1, and tested its ability to increase AMPK activity and preserve kidney function during ischemia/reperfusion injury in rats. A single administration of 1 caused sustained activation of AMPK for at least 24 hours, protected against acute tubular necrosis, and reduced clinical markers of tubular injury such as NephroCheck and Fractional Excretion of Sodium (FENa). Reduction in plasma creatinine and increased Glomerular Filtration Rate (GFR) indicated preservation of kidney function. Surprisingly, we observed a strong diuretic effect of AMPK activation associated with natriuresis both with and without AKI. Our findings demonstrate that activation of AMPK leads to protection of tubular function under hypoxic/ischemic conditions which holds promise as a potential novel therapeutic approach for AKI. Significance Statement No approved pharmacological therapies currently exist for acute kidney injury. We developed Compound 1 which dose-dependently activated AMPK in the kidney and protected kidney function and tubules after ischemic renal injury in the rat. This was accompanied by natriuresis in injured as well as uninjured rats.

Multi-Threshold Recurrence Rate Plot: A Novel Methodology for EEG Analysis in Alzheimer's Disease and Frontotemporal Dementia.

This study introduces Multi-Threshold Recurrence Rate Plots (MTRRP), a novel methodology for analyzing dynamic patterns in complex systems, such as those influenced by neurodegenerative diseases in brain activity. MTRRP characterizes how recurrence rates evolve with increasing recurrence thresholds. A key innovation of our approach, Recurrence Complexity, captures structural complexity by integrating local randomness and global structural features through the product of Recurrence Rate Gradient and Recurrence Hurst, both derived from MTRRP. We applied this technique to resting-state EEG data from patients diagnosed with Alzheimer's Disease (AD), Frontotemporal Dementia (FTD), and age-matched healthy controls. The results revealed significantly higher recurrence complexity in the occipital areas of AD and FTD patients, particularly pronounced in the Alpha and Beta frequency bands. Furthermore, EEG features derived from MTRRP were evaluated using a Support Vector Machine with leave-one-out cross-validation, achieving a classification accuracy of 87.7%. These findings not only underscore the utility of MTRRP in detecting distinct neurophysiological patterns associated with neurodegenerative diseases but also highlight its broader applicability in time series analysis, providing a substantial tool for advancing medical diagnostics and research.

Do we empathize humanoid robots and humans in the same way? Behavioral and multimodal brain imaging investigations.

Humanoid robots have been designed to look more and more like humans to meet social demands. How do people empathize humanoid robots who look the same as but are essentially different from humans? We addressed this issue by examining subjective feelings, electrophysiological activities, and functional magnetic resonance imaging signals during perception of pain and neutral expressions of faces that were recognized as patients or humanoid robots. We found that healthy adults reported deceased feelings of understanding and sharing of humanoid robots' compared to patients' pain. Moreover, humanoid robot (vs. patient) identities reduced long-latency electrophysiological responses and blood oxygenation level-dependent signals in the left temporoparietal junction in response to pain (vs. neutral) expressions. Furthermore, we showed evidence that humanoid robot identities inhibited a causal input from the right ventral lateral prefrontal cortex to the left temporoparietal junction, contrasting the opposite effect produced by patient identities. These results suggest a neural model of modulations of empathy by humanoid robot identity through interactions between the cognitive and affective empathy networks, which provides a neurocognitive basis for understanding human-robot interactions.

Mechanism of acupuncture in attenuating cerebral ischaemia-reperfusion injury based on nuclear receptor coactivator 4 mediated ferritinophagy.

OBJECTIVE: To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury (CIRI) and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4 (NCOA4) mediated ferritinophagy. METHODS: Sprague-Dawley male rats were divided into four groups: the sham group, model group, acupuncture group, and sham acupuncture group. After 2 h of middle cerebral artery occlusion (MCAO), reperfusion was performed for 24 h to induce CIRI. The rats were treated with acupuncture at the Neiguan (PC6) and Shuigou (GV26) acupoints. Their neurological function was evaluated by taking their Bederson scores at 2 h after ischaemia and 24 h after reperfusion. Triphenyltetrazolium chloride staining was applied to assess the cerebral infarct volume at 24 h after reperfusion. The malondialdehyde (MDA) and ferrous iron (Fe2+) levels were observed after 24 h of reperfusion using an assay kit. Western blotting was performed to detect the expression of NCOA4 and ferritin heavy chain 1 (FTH1) at 24 h after reperfusion. Moreover, the colocalization of ferritin with neurons, NCOA4 with microtubule-associated protein 1 light chain 3 (LC3), and NCOA4 with ferritin was visualized using immunofluorescence staining. RESULTS: Acupuncture significantly improved neurological function and decreased cerebral infarct volume in the acupuncture group. Following CIRI, the expression of NCOA4, LC3 and FTH1 was increased, which enhanced ferritinophagy and induced an inappropriate accumulation of Fe2+ and MDA in the ischaemic brain. However, acupuncture dramatically downregulated the expression of NCOA4, LC3 and FTH1, inhibited the overactivation of ferritinophagy, and decreased the levels of MDA and Fe2+. CONCLUSIONS: Acupuncture can inhibit NCOA4-mediated ferritinophagy and protect neurons against CIRI in a rat model.

Achievements and challenges in improving air quality in China: Analysis of the long-term trends from 2014 to 2022.

Due to the implementation of air pollution control measures in China, air quality has significantly improved, although there are still additional issues to be addressed. This study used the long-term trends of air pollutants to discuss the achievements and challenges in further improving air quality in China. The Kolmogorov-Zurbenko (KZ) filter and multiple-linear regression (MLR) were used to quantify the meteorology-related and emission-related trends of air pollutants from 2014 to 2022 in China. The KZ filter analysis showed that PM2.5 decreased by 7.36 ± 2.92% yr-1, while daily maximum 8-h ozone (MDA8 O3) showed an increasing trend with 3.71 ± 2.89% yr-1 in China. The decrease in PM2.5 and increase in MDA8 O3 were primarily attributed to changes in emission, with the relative contribution of 85.8% and 86.0%, respectively. Meteorology variations, including increased ambient temperature, boundary layer height, and reduced relative humidity, also contributed to the reduction of PM2.5 and the enhancement of MDA8 O3. The emission-related trends of PM2.5 and MDA8 O3 exhibited continuous decrease and increase, respectively, from 2014 to 2022, while the variation rates slowed during 2018-2020 compared to that during 2014-2017, highlighting the challenges in further improving air quality, particularly in simultaneously reducing PM2.5 and O3. This study recommends reducing NH3 emissions from the agriculture sector in rural areas and transport emissions in urban areas to further decrease PM2.5 levels. Addressing O3 pollution requires the reduction of O3 precursor gases based on site-specific atmospheric chemistry considerations.

Influence of pollution control measures on the reduction of black carbon in an urban site of megacity, Tianjin, China based on ground-monitored and MERRA-2 reanalysis data.

The concentration of particulate matter (PM) has been reduced significantly with the implementation of air pollution control plans in Tianjin. However, as an important component of PM that can lead to global warming and adverse health effects, the influence of pollution control measures (PCM) on black carbon (BC) has been less studied. In this study, ten years of BC concentration satellite-based reanalysis data were collected from MERRA-2 (Modern-Era Retrospective Analysis for Research and Applications, Version 2), and their reliability was verified using ground-monitored BC data. Using the proposed Kolmogorov-Zurbenko and artificial neural network (KZ-ANN) model, the influences of meteorology and emission measures were separated. The results indicated that the overall meteorological conditions were not conducive to BC diffusion, especially in autumn and winter with low temperature, surface solar radiation, boundary layer height, and high atmospheric pressure, all of which increased the BC concentration. This study also found that although a significant reduction in BC emissions was observed in Tianjin (the total emissions of BC in 2020 dropped by 52 % compared with the level in 2013), the change in emission-influenced BC was relatively low (the concentration of emission-influenced BC in 2022 dropped by only 2.39 % compared to that in 2013). The reduction of emission-influenced BC concentration during the air pollution prevention control and action plan (APPC) was higher than the level during of the three-year action plan for winning the blue sky defense war (abbreviated as the Blue Sky Defense War). In addition, the lockdown measures during the Corona Virus Disease 2019 (COVID-19) did not have beneficial effect on the reduction of emission-influenced BC concentration. This phenomenon can be explained by the long-range transport of BC from surrounding areas, which was also proven by the results of the backward trajectory analysis. Therefore, efforts on emissions reduction in Tianjin were diminished. It is necessary to cooperate with the governments in surrounding areas to implement joint BC control measures, especially in autumn and winter.

Health Service Utilization and Its Associations with Depression and Sexual Risk Behaviors Among Transgender Women in Shanghai, China.

Purpose: Given the limited research on health care utilization among transgender women in China, we described the use of primary health care and gender-affirming health care, and the associations between utilization of gender-affirming health care and depression and sexual risk behaviors. Methods: We conducted a cross-sectional survey in 2017 among a purposive sample of transgender women in Shanghai, China (N=199). We examined correlates of health care utilization and its association with depression and sexual risk behaviors with Chi-square (χ2), Fisher's exact tests, and analysis of variance. Results: The majority of the sample (78.5%) only had physician appointments when having an illness, while about one-fifth of the sample had physician appointments for yearly checkups. Nineteen out of 199 participants (9.5%) received gender-affirming surgery, among which only five used hormone therapy prescribed by a doctor (26.3%). Receiving some form of gender-affirming surgery was associated with higher depression scores [Welch's F(2, 12.22)=4.16, p=0.04], engagement in sex work (p=0.001), having 7 or more male sexual partners in the last 30 days (p=0.003), lifetime unprotected sex with a man (p=0.050), and unprotected sex with a main partner (p=0.043). Compared with transgender women who received both breast augmentation and vulvo-vaginoplasty (mean=5.86), those who received breast augmentation only (mean=12.33) scored higher on depression (p=0.04). Conclusions: Access to gender-affirming health care is low among transgender women in this study. The utilization of gender-affirming surgery is associated with depression and sexual risk behaviors. Findings suggest China should establish national guidelines on transgender-related health care and set up more clinics to provide consultation and services for the transgender population in China.

[Chemical Constituents and Sources of PM2.5 Around the Wuhan Military Games Period].

Hourly monitoring datasets of PM2.5 mass concentration and associated chemical compositions were used to investigate the variations in their mass concentrations before, during, and after the 7th Military World Games held in Wuhan. Furthermore, the source analysis was conducted through PMF combined with the backward trajectory and concentration weighted trajectory cluster analysis. The study revealed the variations in PM2.5 compositions and sources around the Wuhan Military Games period and their response to local and surrounding regional control measures. This can provide a reference for regional precise prevention and control of PM2.5. Under the influence of emission reduction measures, PM2.5 mass concentration during the control period [(31.3±12.0) µg·m-3] decreased by 14.7% compared with that before the control period, whereas the secondary components were obviously formed, in which sulfate, nitrate, and ammonium(SNA) increased by 25.6% in total. After the control period, owing to the decrease in humidity and the influence of the northwest air mass, the mass concentration of SNA decreased by 36.9%, whereas the mass concentration of mineral elements increased by 4.7 times. The source apportionment results indicated that there was no significant difference between the vehicle emissions before and after the control(P<0.05). Compared with that in the non-control period, the contributions of industrial emission and coal burning decreased by 68.1% and 43.7%, respectively, whereas the contribution of secondary inorganic aerosol increased by 89.5%. With the lack of large-scale control of vehicle emissions, the mass concentrations of NO3- and NOx increased by 6.13 µg·m-3 and 3.56 µg·m-3, respectively. The vehicle emissions peaked at 21:00 [(10.9±3.67) µg·m-3], reflecting the emissions of cargo vehicles, which were only allowed to pass at night during the control period. With the banning of ship navigation, the ship emission in the middle and lower reaches of the Yangtze River significantly decreased(48.8%). There were also high values of fugitive dust and industrial emissions near the Anhui section of the Yangtze River waterway, which reflected the dense distribution of industrial activities and road transportation along the Yangtze River. After the control period, the fugitive dust increased by 6.6 times, and the source areas were mainly distributed in Xiangyang and Jingmen.

Enhancing Mental Health and Medication Adherence Among Men Who Have Sex With Men Recently Diagnosed With HIV With a Dialectical Behavior Therapy-Informed Intervention Incorporating mHealth, Online Skills Training, and Phone Coaching: Development Study Using Human-Centered Design Approach.

BACKGROUND: Mental health problems are common among men who have sex with men (MSM) living with HIV and may negatively affect medication adherence. Psychosocial interventions designed to address these urgent needs are scarce in China. Incorporating behavioral health theories into intervention development strengthens the effectiveness of these interventions. The absence of a robust theoretical basis for interventions may also present challenges to identify active intervention ingredients. OBJECTIVE: This study aims to systematically describe the development of a mobile health-based intervention for MSM recently diagnosed with HIV in China, including the theoretical basis for the content and the considerations for its technological delivery. METHODS: We used intervention mapping (IM) to guide overall intervention development, a behavioral intervention technology model for technological delivery design, and a human-centered design and cultural adaptation model for intervention tailoring throughout all steps of IM. RESULTS: The dialectical behavior therapy (DBT)-informed intervention, Turning to Sunshine, comprised 3 components: app-based individual skills learning, group-based skills training, and on-demand phone coaching. The theoretical basis for the intervention content is based on the DBT model of emotions, which fits our conceptualization of the intervention user's mental health needs. The intervention aims to help MSM recently diagnosed with HIV (1) survive moments of high emotional intensity and strong action urges, (2) change emotional expression to regulate emotions, and (3) reduce emotional vulnerability, as well as (4) augment community resources for mental health services. Technological delivery considerations included rationale of the medium, complexity, and esthetics of information delivery; data logs; data visualization; notifications; and passive data collection. CONCLUSIONS: This study laid out the steps for the development of a DBT-informed mobile health intervention that integrated app-based individual learning, group-based skills training, and phone coaching. This intervention, Turning to Sunshine, aims to improve mental health outcomes for MSM newly diagnosed with HIV in China. The IM framework informed by human-centered design principles and cultural adaptation considerations offered a systematic approach to develop the current intervention and tailor it to the target intervention users. The behavioral intervention technology model facilitated the translation of behavioral intervention strategies into technological delivery components. The systematic development and reporting of the current intervention can serve as a guide for similar intervention studies. The content of the current intervention could be adapted for a broader population with similar emotional struggles to improve their mental health outcomes.

Differences in compositions and effects of VOCs from vehicle emission detected using various methods.

Vehicle exhaust and oil fuel evaporation emit volatile organic compounds (VOCs). The differences in VOC compositions and their effects determined using different methods have not been addressed sufficiently. In this study, VOC samples are obtained from single gasoline and diesel vehicle exhausts using a portable emission measurement system, from a tunnel in Yichang City, and from gasoline and diesel evaporation at gas stations. A total of 107 VOCs are analysed. The calculated VOC source profiles (based on VOC source profiles of single-vehicle type and vehicle fleet composition in the tunnel) and the tested source profiles (from a tunnel test) are compared. The results show that gasoline burning can reduce alkenes from a mass fraction of 53.1% (for evaporation) to 3.6% (for burning), as well as increase the mass fraction of alkenes from 1.3% (for diesel evaporation) to 34.0% (for diesel burning). The calculated VOC source profiles differed from the tested VOC source profiles, with a coefficient of divergence of 0.6. Ethane, ethylene, n-undecane, and n-dodecane are used to distinguish VOCs in gasoline and diesel exhausts. Cis-2-butene, 2-methylpentane, m/p-xylene, o-xylene, and n-decane can be used to separate gasoline from diesel. The xylene/ethylbenzene ratios accurately reveal the photochemical age. Gasoline burning increases health risks associated with VOCs compared with gasoline evaporation. Furthermore, it modifies the main contributor to ozone formation potential. This study is expected to facilitate refined VOC source apportionment and studies pertaining to speciated emission inventories.

Sedimentary records of persistent organic pollutants (OCPs and PCBs) in Ngoring Lake, the central Tibetan Plateau, China: Impacts of westerly atmospheric transport and cryospheric melting.

Lake sediments in remote alpine regions are used to infer information on persistent organic pollutants (POPs) delivery via long-range atmospheric transport (LRAT) with limited influences from local sources. When studying the deposition history of POPs on the Tibetan Plateau, regions influenced by westerly air mass flow have received insufficient attention compared with regions governed by the monsoon. Herein, we collected and dated two sediment cores from Ngoring Lake to reconstruct the depositional time trends of 24 organochlorine pesticides (OCPs) and 40 polychlorinated biphenyls (PCBs) and assess the response to emission reductions and climate change. DDTs, HCHs, hexachlorobenzene (HCB), and PCBs were all detected in the sediment core at low concentrations of 110-600, 4.3-400, 8.1-60, and 3.3-71 pg/g, respectively. The composition of PCBs, DDTs, and HCHs was dominated by congeners with 3 and 4 chlorines (avg. 70 %), p,p'-DDT (avg. 90 %), and ß-HCH (avg. 70 %), respectively, indicating the influence of LRAT and the contribution of technical DDT and technical HCH from potential source regions. Temporal trends of PCB concentrations normalized by total organic carbon echoed the peak of global emissions of PCBs around 1970. The rising trend of concentrations of ß-HCH and DDTs after the 1960s in sediments was mainly explained by the input of contaminants with melting ice and snow from a cryosphere shrinking under global warming. This study verifies that westerly air mass flow brings fewer contaminants to the lacustrine environment on the Tibetan Plateau than the monsoon and demonstrates the impacts of climate change on the secondary emission of POPs from the cryosphere to the sediments.

[Impacts of Emission and Meteorological Conditions on Air Pollutants at Various Sites Around the COVID-19 Lockdown in Wuhan].

The random forest algorithm was used to separate the mass concentrations of six air pollutants (SO2, NO2, CO, PM10, PM2.5, and O3) contributed by emissions and meteorological conditions. Their variations for five types of sites including Wuhan's central urban, suburb, industrial, the third ring road traffic, and urban background sites were investigated. The results showed that the values of PM2.5/CO, PM10/CO, and NO2/CO during the lockdown period decreased by 10.8-21.7, 9.34-24.7, and 14.4-22.1 times compared with the period before the lockdown, indicating that the contributions of emissions to PM2.5, PM10, and NO2 were reduced. O3/CO increased by 50.1-61.5 times, implying that the secondary formation increased obviously. The contributions of emissions to various types of pollutants all increased after the lockdown. During the lockdown period, affected by the operation of some uninterrupted industrial processes, PM2.5 concentrations in industrial areas dropped the least (20.5%). Compared with the lockdown period, residential activities, transportation, and industrial production were basically restored after the lockdown, resulting in the alleviation of the reduction in PM2.5 emission-related concentrations. The increase in emission-related O3 concentrations could be associated with the decreased NO and PM2.5 concentrations during the lockdown period. The elevated O3 partially offset the improved air quality brought by the reduced NO2and PM2.5 concentrations. After the lockdown, ρ(O3) related with meteorology at the suburban and urban background sites increased by 16.2 µg·m-3 and 16.1 µg·m-3, respectively, which could be attributed to the increased ambient temperature and decreased relative humidity. The decrease in PM2.5 and increase in O3 concentrations caused by reduced traffic and industrial emissions at the third ring road traffic and central urban regions can provide reference for the current coordinated and precise control of PM2.5 and O3 in subregions.

Heterogeneous changes of chemical compositions, sources and health risks of PM2.5 with the "Clean Heating" policy at urban/suburban/industrial sites.

China has enacted the "Clean Heating" (CH) policy in north China. The domain-specific impacts on PM2.5 constituents and sources in small cities are still lacking, which obstruct the further policy optimization. Here, we performed an intensive observation covering the heating period (HP) and pre-heating period (PHP) in winter of 2017 at urban (UR), industrial (IS), and suburban (SUR) sites in one of the "2 + 26" cities. The mean PM2.5 concentrations at UR and IS decreased by 15.2 % and 4.6 %, while increased by 9.8 % at SUR in the HP compared with the PHP, indicating the heterogeneous responses. The lowest contribution percentages of coal combustion (14.6 %) and industrial emissions (17.1 %) to PM2.5 at UR in the HP implied the CH policy played more effective role. The most increase in NO3-/SO42- ratio by 26.8 % and the highest NO3- concentration at UR in the HP were linked mainly with the thermal-NOx emitted from natural gas (NG) burning in view of NOx emission reductions from other sources. The highest concentrations of OC, SO42-, K+, and Cl-, and contribution percentages of biomass burning (20.0 %) and coal combustion (24.8 %) to PM2.5 at SUR in the HP evidenced the enhanced usage of biomass/coal. Coal banning in the HP at IS and UR led to the obvious decreases in OC, SO42-, As, and Sb. Secondary nitrate became the largest PM2.5 source at IS and UR in the HP. Coal banning, emission control on large-size enterprises and ignored control on small-size enterprises efficiently modified the concentrations and health risks of heavy metals. The lowest carcinogenic risks moved from SUR in the PHP to UR in the HP. The policies on de-NOx of NG-burning related enterprises, reduction of biomass/coal usage in suburban area, and strict regulation of small-size enterprises were urgently need to further improve the air quality.

Determinants of Willingness to Use PrEP Among Gay and Bisexual Men in China Before Implementation: A Structural Equation Modeling Assessment.

With the recent endorsement of PrEP by the Chinese government, research is urgently needed to better understand factors impacting PrEP uptake among gay, bisexual, and other men who have sex with men (GBMSM) in China. This study examined willingness to use PrEP for HIV prevention among GBMSM in China through structural equation modeling. We examined the relationship among PrEP-related attitudes, subjective norms, PrEP-related knowledge and beliefs about medicines and willingness to use PrEP. The analysis showed a good fit between the data and both the measurement model (RMSEA = 0.060) and structural model (RMSEA = 0.054). Knowledge, attitudes, and subjective norms were significantly related to intention to use PrEP, whereas the effect of general beliefs about medicines was insignificant. These effect mechanisms point to the importance of designing interventions to support PrEP uptake that target knowledge, enhance positive attitudes about PrEP within social networks, and build positive social norms around PrEP among sexually active GBMSM.

Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury.@*METHODS@#Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side.@*RESULTS@#Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group.@*CONCLUSION@#Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.

Clinicopathological characteristics of gastric SMARCA4-deficient undifferentiated/rhabdoid carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of gastric SMARCA4-deficient undifferentiated carcinoma, and to discuss the daily diagnostics of this entity and analyze its prognosis. Methods: The cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed at the Department of Pathology, Peking University Cancer Hospital, China from January 2010 to August 2022 were collected. The histological sections were reviewed, the immunohistochemical results and clinicopathological features were analyzed, and relevant literature was reviewed. Results: Pure foci of undifferentiated carcinoma were seen in 7 cases, and 1 case was accompanied by a moderately differentiated tubular adenocarcinoma component. Undifferentiated carcinoma foci showed similar sheet-like or solid diffuse growth pattern, medium-sized tumor cells characterized by 1-2 nucleoli, and abundant cytoplasm and rhabdoid appearance. The average patient age was 65±8 years. Six patients were male and 2 were female. Immunohistochemical staining showed that undifferentiated carcinoma of all 8 tumors were negative for SMARCA4 (BRG1). Among 7 patients who underwent SMARCA2 (BRM) and SMARCB1 (INI1) staining, 4 cases showed loss of BRM expression, 2 cases showed weakly positive staining, and 1 case was diffusely positive, but all 7 cases were diffusely strong positive for INI1. The neuroendocrine marker, synaptophysin, was weakly positive in 5 cases, while CgA and CD56 were negative in 8 cases. Ki-67 index was more than 70%. Two cases were mismatch repair deficient and showed the loss of MLH1/PMS2 expression, while 1 case showed only MSH2 loss. PD-L1 staining showed that combined positive score (CPS)≥1 in 4 cases (CPS ranging from 1 to 55) and CPS<1 in the other 3 cases. Four patients had clinical stage Ⅳ disease. Two of them died within 3 months after diagnosis. Conclusions: Gastric SMARCA4-deficient undifferentiated carcinoma/rhabdoid carcinoma is a rare group of highly malignant tumors with a poor prognosis. Loss of the core subunit of SWI/SNF complex may be associated with the development of dedifferentiated histological pattern and aggressive tumor progression, which may be more frequently accompanied with mismatch repair deficiency.

Effects of psychological intervention on empathy fatigue in nurses: A meta-analysis.

Objective: The purpose of this meta-analysis is to systematically assess the effects of psychological intervention on empathy fatigue among nursing staff. Method: Five electronic databases are searched separately from their establishment to April 8th, 2022. The research team independently performs paper selection, quality assessment, data extraction and analysis for all included studies. PRISMA guidelines are used to report this meta-analysis. Results: A total of seven randomized controlled trials (RCTs) covering 513 nursing staff are included. The meta-analysis results show that the empathy fatigue score (SMD = -0.22, 95% CI: -0.42~-0.02, P = 0.03) and burnout (SMD = -0.37, 95% CI: -0.56~-0.19, P < 0.001) are lower than the control group. The empathy satisfaction score of the psychological intervention group is higher than that of the control group (SMD = 0.45, 95% CI: 0.27-0.63, P < 0.001). The differences are statistically significant (P < 0.05). Subgroup analysis finds significant heterogeneity in the impact of different departments on psychological intervention at ≥6 weeks (I 2 = 71%, P = 0.01) and <6 weeks (I 2 = 0%, P = 0.75) (P = 0.05). Different departments also show significant heterogeneity in the effects of psychological intervention: ICU (I 2 = 73%, P = 0.02), pediatric (I 2 = 53%, P = 0.14) and other departments (I 2 = 0%, P = 0.63). The differences are statistically significant (P = 0.0007). Besides, the results show that both mindfulness intervention (SMD = 0.50, 95% CI: 0.24-0.77, P = 0.0002) and other interventions (SMD = 0.41, 95% CI: 0.16-0.65, P = 0.001) are statistically significant difference in the level of empathy satisfaction between the psychological intervention group and the control group. Conclusion: Psychological intervention has a coordinated improvement effect on empathy fatigue, empathy satisfaction and burnout, and can also improve the quality of life of nursing staff.

Global brown carbon emissions from combustion sources.

Light-absorbing organic carbon (OC), sometimes known as Brown Carbon (BrC), has been recognized as an important fraction of carbonaceous aerosols substantially affecting radiative forcing. This study firstly developed a bottom-up estimate of global primary BrC, and discussed its spatiotemporal distribution and source contributions from 1960 to 2010. The global total primary BrC emission from both natural and anthropogenic sources in 2010 was 7.26 (5.98-8.93 as an interquartile range) Tg, with 43.5% from anthropogenic sources. High primary BrC emissions were in regions such as Africa, South America, South and East Asia with natural sources (wild fires and deforestation) contributing over 70% in the former two regions, while in East Asia, anthropogenic sources, especially residential solid fuel combustion, accounted for over 80% of the regional total BrC emissions. Globally, the historical trend was mainly driven by anthropogenic sources, which increased from 1960 to 1990 and then started to decline. Residential emissions significantly impacted on emissions and temporal trends that varied by region. In South and Southeast Asia, the emissions increased obviously due to population growth and a slow transition from solid fuels to clean modern energies in the residential sector. It is estimated that in primary OC, the global average was about 20% BrC, but this ratio varied from 13% to 47%, depending on sector and region. In areas with high residential solid fuel combustion emissions, the ratio was generally twice the value in other areas. Uncertainties in the work are associated with the concept of BrC and measurement technologies, pointing to the need for more studies on BrC analysis and quantification in both emissions and the air.

Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions.

Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared with current anticoagulants. The discovery of potent FXIa inhibitors with good oral bioavailability has been challenging. Herein, we describe our discovery effort, utilizing nonclassical interactions to improve potency, cellular permeability, and oral bioavailability by enhancing the binding while reducing polar atoms. Beginning with literature-inspired pyridine N-oxide-based FXIa inhibitor 1, the imidazole linker was first replaced with a pyrazole moiety to establish a polar C-H···water hydrogen-bonding interaction. Then, structure-based drug design was employed to modify lead molecule 2d in the P1' and P2' regions, with substituents interacting with key residues through various nonclassical interactions. As a result, a potent FXIa inhibitor 3f (Ki = 0.17 nM) was discovered. This compound demonstrated oral bioavailability in preclinical species (rat 36.4%, dog 80.5%, and monkey 43.0%) and displayed a dose-dependent antithrombotic effect in a rabbit arteriovenous shunt model of thrombosis.

[Real-time Composition and Sources of VOCs in Summer in Wuhan].

The hourly concentrations of 102 volatile organic compounds (VOCs) in Wuhan from June to July in 2019 were obtained using an online monitoring instrument. The ρ(VOCs) varied from 24.9 to 254 µg·m-3, with a mean value of (67.7±32.2) µg·m-3. According to the air quality standard of ozone, the observation period was divided into clean and polluted episodes of O3. The differences in meteorological parameters, VOC concentrations, compositions, sources, and ozone formation potential (OFP) between clean and polluted episodes were analyzed and compared. The average mass concentrations of NOx, CO, and VOCs in polluted periods exceeded those of clean periods by 34.9%, 25.0%, and 27.8%, respectively. The mass concentrations of alkanes, alkenes, aromatic hydrocarbons, and oxygenated volatile organic compounds in polluted periods were higher than those in clean periods by 40.7%, 39.5%, 26.9%, and 21.5%, respectively. The average OFP in polluted periods[(102±69.6) µg·m-3] exceeded that of clean periods by 33.5%. The average contribution rates of LPG combustion, industrial sources, vehicle emissions, natural sources, and solvent usage to VOCs were 3.4%, 2.5%, 0.2%, 1.3%, and 1.4% lower than those of the clean periods, respectively, whereas the gasoline evaporation increased by 8.8% in polluted periods. The contributions of vehicle emissions and gasoline evaporation exhibited higher values in the morning and evening, with lower values in the afternoon, which may have been related to peak vehicles emissions. The contribution of LPG combustion peaked along with the cooking time. The concentration weighted trajectory showed that the main sources of VOCs in polluted periods were from local emissions and surrounding regions in the northeastern direction of Wuhan. In polluted periods, gasoline evaporation and LPG combustion should be emphasized for preventing O3 pollution in the summer in Wuhan.