Extreme temperature events (ETEs), including heat wave and cold spell, have been linked to myocardial infarction (MI) morbidity; however, their effects on MI mortality are less clear. Although ...ambient fine particulate matter (PM
) is suggested to act synergistically with extreme temperatures on cardiovascular mortality, it remains unknown if and how ETEs and PM
interact to trigger MI deaths.
A time-stratified case-crossover study of 202 678 MI deaths in Jiangsu province, China, from 2015 to 2020, was conducted to investigate the association of exposure to ETEs and PM
with MI mortality and evaluate their interactive effects. On the basis of ambient apparent temperature, multiple temperature thresholds and durations were used to build 12 ETE definitions. Daily ETEs and PM
exposures were assessed by extracting values from validated grid datasets at each subject's geocoded residential address. Conditional logistic regression models were applied to perform exposure-response analyses and estimate relative excess odds due to interaction, proportion attributable to interaction, and synergy index.
Under different ETE definitions, the odds ratio of MI mortality associated with heat wave and cold spell ranged from 1.18 (95% CI, 1.14-1.21) to 1.74 (1.66-1.83), and 1.04 (1.02-1.06) to 1.12 (1.07-1.18), respectively. Lag 01-day exposure to PM
was significantly associated with an increased odds of MI mortality, which attenuated at higher exposures. We observed a significant synergistic interaction of heat wave and PM
on MI mortality (relative excess odds due to interaction >0, proportion attributable to interaction >0, and synergy index >1), which was higher, in general, for heat wave with greater intensities and longer durations. We estimated that up to 2.8% of the MI deaths were attributable to exposure to ETEs and PM
at levels exceeding the interim target 3 value (37.5 μg/m
) of World Health Organization air quality guidelines. Women and older adults were more vulnerable to ETEs and PM
. The interactive effects of ETEs or PM
on MI mortality did not vary across sex, age, or socioeconomic status.
This study provides consistent evidence that exposure to both ETEs and PM
is significantly associated with an increased odds of MI mortality, especially for women and older adults, and that heat wave interacts synergistically with PM
to trigger MI deaths but cold spell does not. Our findings suggest that mitigating both ETE and PM
exposures may bring health cobenefits in preventing premature deaths from MI.
To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress (CRS) in rats and the underlying mechanisms.
Forty male Wistar rats were ...divided into 4 groups according to their baseline sucrose preference: control group, model group, and Rg1-treated groups (5 and 10 mg/kg). Except for control group, the groups were exposed to CRS (6 h/day) for 28 days. All drugs were intraperitoneally administered once daily to CRS rats after restraint stress for 14 days. The behavioral tests were carried out via the open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and the Morris water maze (MWM) 4 weeks following CRS induction. The levels of serum corticosterone (CORT) and the activities of the antioxidant defense biomarkers (SOD, MDA and GSH-x) in the prefrontal cortex (PFC) were analyzed using commercial ELISA kits. The levels of the neurotransmitter (5-HT, 5-HIAA, Ach, NE, GABA and Glu) in the PFC were measured by ultra-performance liquid chromatography tandem mass spectrometry. The protein expression of BDNF, Trkb, Bax and Bcl-2 in the PFC was detected by western blotting.
Owing to increased sucrose consumption in the SPT, decreased immobility time in the FST, and the improved cognitive performance in MWM, chronic treatment with Ginsenoside Rg1 was found to significantly attenuate depression- like behaviors (anhedonia, behavioral despair and poor spatial memory) in rats. Moreover, CRS exposure caused evident alterations in the levels of the neurotransmitters (5-HT, 5-HIAA, Ach, GABA and Glu) and the activities of the antioxidant defense biomarkers (SOD, MDA and GSH-x) in the PFC and the levels of corticosterone in serum. However, Ginsenoside Rg1 treatment could restore these levels to normal values. Additionally, Ginsenoside Rg1 treatment significantly reverted the decreased expression of BDNF, Trkb and Bcl-2 and the increased expression of Bax in the PFC of CRS rats.
Ginsenoside Rg1 could attenuate the CRS-induced depression-like behaviors, in part, by regulating neurotransmitter levels and HPA function, antagonizing oxidative stress and apoptosis, and restoring BDNF-TrkB signaling in PFC. Altogether, our results provide a novel basis regarding the potential therapeutic effects of Rg1 on depression.
To determine efficacy of intraoperative microvascular Doppler ultrasound in assisting subinguinal microsurgical varicocelectomy for pain relief in the treatment of painful varicoceles, compared to ...the microsurgery without Doppler ultrasound.
Total 153 patients underwent microsurgical varicocelectomy were randomly allocated to two groups: Groups 1 and 2 included 82 and 71 patients monitored with and without using intraoperative microvascular Doppler ultrasound, respectively. The assessments were compared between two groups, including intraoperative parameters (vessel numbers and operative time) and postoperative outcomes (pain resolution, complications and recurrence).
The average numbers of internal spermatic veins ligated (13.87±6.43 vs 11.72±5.66) and arteries preserved (1.96±0.87 vs 1.73±0.86) were significantly greater in Group 1 with Doppler ultrasound. Precisely, the smaller size of the internal spermatic veins was ligated and the more encircled arteries were also preserved in Group 1. In two groups with and without using Doppler ultrasound, 56 (68.3%) and 36 (50.7%) patients experienced a complete resolution of pain, 21 (25.6%) and 29 (40.9%) patients experienced partial resolution, whereas 5 (6.1%) and 6 (8.5%) patients experienced no change in the chronic pain, respectively. Thus, patients in Group 1 had a better outcome in chronic pain resolution (P = 0.033). The operative time, complications and recurrence rate were not different between the two groups.
Subinguinal microsurgical varicocelectomy is an effective method to treat painful varicoceles. With the assistance of Doppler Ultrasound monitoring, greater numbers of vessels were identified and a better outcome of pain resolution was achieved.
Hypochlorous acid(HOCl) plays a vital role in many physiological and pathological processes as one of reactive oxygen species(ROS). Developing highly sensitive and selective methods for HOCl ...detection is of significant interest. In this work, we developed a benzothiazole based probe 1 for ratiometric fluorescence detection of hypochlorite in living cells. The probe can detect HOCl with high selectivity, fast response(within 30 s) as well as low detection limit(0.18 mmol/L). Fluorescence co-localization studies demonstrated that probe 1 was a mitochondria-targeted fluorescent probe. Furthermore, confocal fluorescence images of He La cell indicated that probe 1 could be used for monitoring intracellular HOCl in living cells. Finally, test strips experiment suggests that the probe 1 can detect the hypochlorous acid in tap water accompanied by remarkable color change.
To investigate the association of NFKB1 -94 ins/del ATTG, NFKBIA -826C>T and NFKBIA -881A>G polymorphisms with risk of lung cancer in a Chinese population.
Genotyping of the polymorphisms were ...performed on 1,436 subjects (718 cases and 718 controls) by using PCR-RFLP technique, followed by DNA sequencing.
We found a significant risk reduction associated with heterozygous ins/del (OR=0.705, 95% CI=0.566-0.878, P=0.002) and variant del/del (OR=0.342, 95% CI=0.221-0.528, P<0.001) genotypes of the NFKB1 polymorphism. In contrast, the heterozygous and variantgenotypes of theNFKBIA polymorphisms showed association with increased lung cancer risk (NFKBIA -826 CT,OR=1.256, 95%CI=1.004-1.572, P=0.046; TT,OR=1.773, 95% CI=1.131-2.778, P=0.013; NFKBIA -881 AG,OR=1.277, 95% CI=1.023-1.599, P=0.031; GG,OR=1.801, 95% CI=1.169-2.775, P=0.008). Several genotypic combinations of the three polymorphisms also showed significant association with lung cancer risk. The risk association of NFKB1 polymorphism remained significant when analyses were done according to gender and smoking status (P<0.05). The significance of NFKBIA risk association was not observed when gender-specific analyses were made (P>0.05), while only NFKBIA -881 GG genotype showed significant risk association among smokers when analyzed according to smoking status (P=0.032).
Polymorphisms in NFKB1 and NFKBIAgenes were associated with risk of lung cancer.
Determining the priority control source and pollutant is the key for the eco-health protection and risk management around gold smelting area. To this end, a case study was conducted to explore the ...pollution characteristics, source apportionment, ecological risk and human health risk of toxic metals (TMs) in agricultural soils surrounding a gold smelting enterprise. Three effective receptor models, including positive matrix factorization model (PMF), ecological risk assessment (ERA), and probabilistic risk assessment (PRA) have been combined to apportion eco-human risks for different targets. More than 95.0% of samples had a Nemerow pollution index (NPI) > 2 (NPImean=4.27), indicating moderately or highly soil TMs contamination. Four pollution sources including gold smelting activity, mining source, agricultural activity and atmosphere deposition were identified as the major sources, with the contribution rate of 17.52%, 44.16%, 13.91%, and 24.41%, respectively. For ecological risk, atmosphere deposition accounting for 30.8% was the greatest contributor, which was mainly loaded on Hg of 51.35%. The probabilistic health risk assessment revealed that Carcinogenic risks and Non-carcinogenic risks of all population were unacceptable, and children suffered from a greater health risk than adults. Gold smelting activity (69.2%) and mining source (42.0%) were the largest contributors to Carcinogenic risks and Non-carcinogenic risks, respectively, corresponding to As and Cr as the target pollutants. The priority pollution sources and target pollutants were different for the eco-health protection. This work put forward a new perspective for soil risk control and management, which is very beneficial for appropriate soil remediation under limited resources and costs.
Display omitted
•Identified atmosphere deposition as a priority control for ecological risk.•Gold smelting activity and mining activity are priority pollution source for health risk.•Hg, As and Cr are target pollutants for eco-health control.•Priority control source and pollutant for eco-health protection are different.
•Subjective social support, but not objective social support, was associated with suicide risk.•Negative (but not positive) coping style was associated with suicide risk.•MDD patients with suicide ...risk had high level of perceived stressfulness.•Perceived stressfulness can mediate the effects of subjective social support and negative coping style on suicide risk.
Risk factors for suicide have been widely investigated in patients with major depressive disorder (MDD); However, far less research has been conducted on protective factors for suicide.
The diagnosis of MDD and suicide risk were evaluated by the Mini‐International Neuropsychiatric Interview (MINI). Social support and coping behaviors were assessed by the Social Support Rate Scale (SSRS) and Simplified Coping Style Questionnaire (SCSQ), respectively. Life stressors were captured by the Life Events Scale (LES). Severity of depression was assessed by 17-item Hamilton Depression Rating Scale (HAMD-17). Logistic regression analysis and path analyses were used to test the association of protective factors, risk factors, life stress and suicide risk.
Patients with suicide risk showed a significantly lower level of subjective social support (adjusted P < 0.012), a higher level of perceived stressfulness (P < 0.001) and negative coping style (P = 0.008) compared with patients without suicide risk. Path analysis showed that perceived stressfulness can mediate the protective effect of subjective social support and deleterious effect of negative coping style on suicide risk.
Cross-sectional design, and retrospective recall of stressful life events.
This study suggests that subjective social support and negative coping style may be regarded as a protective factor and a risk factor for suicide risk in MDD patients, respectively, and perceived stressfulness mediates their roles in suicide. Further suicide prevention and intervention strategies should focus on increasing individual subjective social support and improving coping strategies to enhance their resilience.
Conventional cloud detection methods are easily affected by mixed pixels, complex surface structures, and atmospheric factors, resulting in poor cloud detection results. To minimize these problems, a ...new Universal Dynamic Threshold Cloud Detection Algorithm (UDTCDA) supported by a priori surface reflectance database is proposed in this paper. A monthly surface reflectance database is constructed using long‐time‐sequenced MODerate resolution Imaging Spectroradiometer surface reflectance product (MOD09A1) to provide the surface reflectance of the underlying surfaces. The relationships between the apparent reflectance changes and the surface reflectance are simulated under different observation and atmospheric conditions with the 6S (Second Simulation of the Satellite Signal in the Solar Spectrum) model, and the dynamic threshold cloud detection models are developed. Two typical remote sensing data with important application significance and different sensor parameters, MODIS and Landsat 8, are selected for cloud detection experiments. The results were validated against the visual interpretation of clouds and Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observation cloud measurements. The results showed that the UDTCDA can obtain a high precision in cloud detection, correctly identifying cloudy pixels and clear‐sky pixels at rates greater than 80% with error rate and missing rate of less than 20%. The UDTCDA cloud product overall shows less estimation uncertainty than the current MODIS cloud mask products. Moreover, the UDTCDA can effectively reduce the effects of atmospheric factors and mixed pixels and can be applied to different satellite sensors to realize long‐term, large‐scale cloud detection operations.
Key Points
UDTCDA with prior surface reflectance database support is proposed
UDTCDA detects clouds more effectively than current MODIS cloud mask products
UDTCDA can be applied to different satellite data and achieve large‐scale and long‐term cloud detection
•AXL and Gas6 are highly expressed in cell lines and patient samples including TNBC.•AXL-CAR-T cells exhibit specific cytotoxicity to AXL-positive tumor cells.•AXL-CAR-T cells displayed a significant ...anti-tumor effect and in vivo persistence.
Identifying targets for chimeric antigen receptor-modulated T lymphocyte (CAR-T) therapy against solid tumors is an urgent problem to solve. In this study, we showed for the first time that the receptor tyrosine kinase, AXL, is overexpressed in various tumor cell lines and patient tumor tissues including triple negative breast cancer (TNBC) cell lines and patient samples, making AXL a potent novel target for cancer therapy, specifically for TNBC treatment. We also engineered T cells with a CAR consisting of a novel single-chain variable fragment against AXL and revealed its antigen-specific cytotoxicity and ability to release cytokines in a TNBC cell line and other AXL-positive tumors in vitro. Furthermore, AXL-CAR-T cells displayed a significant anti-tumor effect and in vivo persistence in a TNBC xenograft model. Taken together, our findings indicate that AXL-CAR-T cells can represent a promising therapeutic strategy against TNBC.
Abstract
Context
In 2015, we reported an increased prevalence of thyroid disease in a county of low habitual selenium (Se) intake in comparison to a neighboring county with higher intake in a ...cross-sectional survey in Shaanxi Province, China.
Objective
To explore longitudinal effects of low Se status, a prospective cohort study was conducted in the same area from 2013 to 2019, and thyroid peroxidase autoantibodies (TPO-Abs) and disease incidence were compared.
Methods
A total 1254 individuals from 1500 reinvited participants were successfully enrolled. Venous blood, fingernails, and urine samples were collected and analyzed to evaluate thyroid status, TPO-Abs, serum Se, and urinary iodine. Diagnosis of Hashimoto thyroiditis (HT) was based on elevated thyrotropin, presence of TPO-Abs, and ultrasound characteristics. Se deficiency was categorized using a serum concentration of 80 µg/L as a threshold, and tested by logistic regression for a relationship to TPO-Abs and HT.
Results
Se deficiency was observed in 46.2% of participants from the adequate-Se county (Ziyang) and in 89.7% from the low-Se county (Ningshan). Se concentrations in fingernails differed strongly by residency (Ziyang vs Ningshan; 678.7 vs 364.3 μg/kg; Z = –9.552; P < .001). Newly diagnosed HT in Ziyang was less frequent than in Ningshan (0.09% vs 0.31%; χ 2 = 4.350; P = .037). The conversion rate to seropositive TPO-Abs was 10.2% in Ningshan vs 5.6% in Ziyang. Excluding iodine as confounding factor, low-Se was confirmed as a risk factor for HT (relative risk 95% CI; 3.65 1.03-12.90; P < .05).
Conclusion
The data indicate an increased incidence of TPO-Ab seroconversion with low Se supply and support the hypothesis that Se deficiency contributes to HT as a modifiable risk factor.