Racial and ethnic influences on carotid atherosclerosis: Epidemiology and risk factors.

Carotid atherosclerosis-related stenosis, marked by atherosclerotic plaque formation in the carotid artery, significantly increases ischemic stroke risk. Its prevalence varies across ethnic groups, reflecting racial disparities. Epidemiological studies have highlighted different susceptibilities to carotid stenosis among racial groups. Native Americans and Whites show greater vulnerability, indicating genetic and environmental influences. The impact of carotid stenosis is more severe in Hispanic and Black populations, with a higher incidence of related brain injuries, underscoring the need for targeted interventions. Comparative imaging studies between Chinese and White individuals reveal unique patterns of carotid stenosis, enhancing understanding of its pathophysiology and management across ethnicities. This review also categorizes risk factors, distinguishing those with racial disparity (such as genetic loci, sleep apnea, and emotional factors, socioeconomic status) from those without. In summary, racial disparities affect carotid stenosis, leading to varying susceptibilities and outcomes among ethnic groups. Recognizing these differences is essential for developing effective prevention, diagnosis, and management strategies. Addressing these disparities is critical to reducing ischemic stroke's burden across populations. Continued research and targeted interventions are crucial to improve outcomes for individuals at risk of carotid stenosis and its complications.

Developing a deep learning model for predicting ovarian cancer in Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US) Category 4 lesions: A multicenter study.

PURPOSE: To develop a deep learning (DL) model for differentiating between benign and malignant ovarian tumors of Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US) Category 4 lesions, and validate its diagnostic performance. METHODS: A retrospective analysis of 1619 US images obtained from three centers from December 2014 to March 2023. DeepLabV3 and YOLOv8 were jointly used to segment, classify, and detect ovarian tumors. Precision and recall and area under the receiver operating characteristic curve (AUC) were employed to assess the model performance. RESULTS: A total of 519 patients (including 269 benign and 250 malignant masses) were enrolled in the study. The number of women included in the training, validation, and test cohorts was 426, 46, and 47, respectively. The detection models exhibited an average precision of 98.68% (95% CI: 0.95-0.99) for benign masses and 96.23% (95% CI: 0.92-0.98) for malignant masses. Moreover, in the training set, the AUC was 0.96 (95% CI: 0.94-0.97), whereas in the validation set, the AUC was 0.93(95% CI: 0.89-0.94) and 0.95 (95% CI: 0.91-0.96) in the test set. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive values for the training set were 0.943,0.957,0.951,0.966, and 0.936, respectively, whereas those for the validation set were 0.905,0.935, 0.935,0.919, and 0.931, respectively. In addition, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the test set were 0.925, 0.955, 0.941, 0.956, and 0.927, respectively. CONCLUSION: The constructed DL model exhibited high diagnostic performance in distinguishing benign and malignant ovarian tumors in O-RADS US category 4 lesions.

Transcriptome analysis of the degradation process of organic nitrogen by two heterotrophic nitrifying and aerobic denitrifying bacteria.

The heterotrophic nitrification aerobic denitrification bacteria (HNDS) can perform nitrification and denitrification at the same time. Two HNDS strains, Achromobacter sp. HNDS-1 and Enterobacter sp. HNDS-6 which exhibited an amazing ability to solution nitrogen (N) removal have been successfully isolated from paddy soil in our lab. When peptone or ammonium sulfate as sole N source, no significant difference in gene expression related to nitrification and denitrification of the strains was found according to the transcriptome analysis. The expression of phosphomethylpyrimidine synthase (thiC), ABC transporter substrate-binding protein, branched-chain amino acid ABC transporter substrate-binding protein, and RNA polymerase (rpoE) in HNDS-1 were significantly upregulated when used peptone as N source, while the expression of exopolysaccharide production protein (yjbE), RNA polymerase (rpoC), glutamate synthase (gltD) and ABC-type branched-chain amino acid transport systems in HNDS-6 were significantly upregulated. This indicated that these two strains are capable of using organic N and converting it into NH4+-N, then utilizing NH4+-N to synthesize amino acids and proteins for their own growth, and strain HNDS-6 can also remove NH4+-N through nitrification and denitrification.

A retrospective cohort study of implantable venous access port-related and peripherally inserted central catheter-related complications in patients with hematological malignancies in China.

Objective: We explored the differences in deep venous catheterization-associated complications between patients with hematological malignancies after peripherally inserted central catheter placement and such patients after implantable venous access port catheterization. Introduction: peripherally inserted central catheters and implantable venous access ports are the most popular devices used for chemotherapy. However, no study has revealed differences between peripherally inserted central catheters and implantable venous access ports in Chinese patients with hematological malignancies. Methods: The clinical data of 322 patients with hematological malignancies who were treated from January 1, 2020 to December 30, 2021 were included in a retrospective cohort study. Postoperative color Doppler ultrasonography and follow-up results were used to compare the incidence rates of deep venous catheterization -associated complications after peripherally inserted central catheters and implantable venous access ports catheterization. Results: The relative risk of catheter-related complications considering the type of device was 8.3 (95% CI = 3.0-22.8). In addition, chi-square segmentation analysis revealed a significant difference in the complication rate between the internal jugular vein and the basilic vein (χ2 = 22.002, p < 0.0001) and between the subclavian vein and the basilic vein (χ2 = 28.940, p < 0.0001). Conclusion: Implantable venous access ports are safer than peripherally inserted central catheters for Chinese patients with hematological malignancies. The implantation of implantable venous access ports could be firstly considered for systematic anti-cancer treatment.

Brood success of sex-role-reversed pheasant-tailed jacanas: the effects of social polyandry, seasonality, and male mating order.

Multiple mating by avian females may increase hatching and overall brood success; however, reproductive effort and parental investment are costly, and females may be gradually depleted, with lowered outputs over time. Thus, males in social polyandry systems may differ greatly in their reproductive gains. In the present study, we investigated the reproductive outputs of social polyandrous and sex-role-reversed pheasant-tailed jacanas, Hydrophasianus chirurgus, to assess the effects of polyandry, seasonality, and male mating order on breeding success. Female jacanas produced multiple clutches, either by leaving two or more clutches with an individual male (22%), or by mating with two or more males (78%). The polyandrous females laid both the first and second clutches earlier and showed a breeding period more than twice as long as that of monandrous females. Both polyandry and seasonality affected the fate of a clutch, where clutches from polyandrous females and the early season had higher hatching and brood success rates, but the number of polyandrous females declined over the season. Polyandrous females not only laid more clutches and eggs, and gained more hatchlings and fledglings, but also achieved higher per-clutch outputs and hatching rates than monandrous females. In polyandry groups, males gained higher total hatchlings and fledglings, although not total clutches or eggs, than males in monandry or bi-andry groups. Moreover, males in polyandry groups achieved higher hatchlings and fledglings per clutch and higher hatching and brood success rates. In polyandry groups, the first-mating males obtained more clutches, eggs, and hatchlings; however, they did not have higher success rates, nor total fledglings and per-clutch outputs, than males who mated later. Overall, the results indicate a selective advantage of polyandry for the jacanas studied, particularly in the early breeding season. This advantage, however, differs both between the sexes and intra-sexually, suggesting strong connections with certain ecological/environmental conditions in addition to the jacanas' own quality.

The effect of the re-segmentation method on improving the performance of rectal cancer image segmentation models.

BACKGROUND: Rapid and accurate segmentation of tumor regions from rectal cancer images can better understand the patientâs lesions and surrounding tissues, providing more effective auxiliary diagnostic information. However, cutting rectal tumors with deep learning still cannot be compared with manual segmentation, and a major obstacle to cutting rectal tumors with deep learning is the lack of high-quality data sets. OBJECTIVE: We propose to use our Re-segmentation Method to manually correct the model segmentation area and put it into training and training ideas. The data set has been made publicly available. Methods: A total of 354 rectal cancer CT images and 308 rectal region images labeled by experts from Jiangxi Cancer Hospital were included in the data set. Six network architectures are used to train the data set, and the region predicted by the model is manually revised and then put into training to improve the ability of model segmentation and then perform performance measurement. RESULTS: In this study, we use the Resegmentation Method for various popular network architectures. CONCLUSION: By comparing the evaluation indicators before and after using the Re-segmentation Method, we prove that our proposed Re-segmentation Method can further improve the performance of the rectal cancer image segmentation model.

Hydrochloric Acid-Induced Acute Lung Injury Models: Dynamic Change and Quantitative Analysis of Modified Lung Ultrasound Scoring System and High-Resolution Computed Tomography.

OBJECTIVE: Acute lung injury (ALI) has become a research hotspot due to its significant public health impact. To explore the value of the use of modified lung ultrasound (MLUS) scoring system for evaluating ALI using a rabbit model of ALI induced by hydrochloric acid (HCl) and investigate its correlation with high-resolution computed tomography (HRCT) and histopathological scores. METHODS: Twenty New Zealand laboratory rabbits were randomly assigned to control group (N = 5) and 3 experimental groups (N = 5 each). The control group received instillation of physiological saline, while the 3 experimental groups received 2 mL/kg of different doses of HCl instillation (mild group: pH 1.5, moderate group: pH 1.2, and severe group: pH 1.0) through the trachea under ultrasound guidance. Pulmonary ultrasound (using Mindray Reason9 linear array probes with frequency of 6-15 mHz) and HRCT examinations were performed before modeling (0H) and at 1H, 2H, 4H, 8H, 12H after modeling. The experimental rabbits were sacrificed at 12H for examination of gross lung morphology and hematoxylin-eosin-stained histopathological sections. The correlation of MLUS scores with HRCT/histopathological scores was assessed. RESULTS: All rabbits in the experimental groups showed oxygenation index PaO2/FiO2<300. Successful establishment of ALI model was proven by autopsy (successful modeling rate: 100%). The pathological damage increased with increase in HCl dosage. MLUS scores showed a positive correlation with HRCT scores/pathological severity. There was a strong positive correlation between MLUS scores and histopathological scores (r = 0.963, p < 0.05) as well as between HRCT scores and histopathological scores (r = 0.932, p < 0.05). CONCLUSION: Transtracheal injection of different dosages of HCl under ultrasound guidance induced different degrees of ALI. The MLUS scoring system can be used for semiquantitative evaluation of ALI, and is suitable as a screening tool.

Asprosin contributes to pathogenesis of obesity by adipocyte mitophagy induction to inhibit white adipose browning in mice.

BACKGROUND: Asprosin (ASP) is a newly discovered adipokine secreted by white adipose tissue (WAT), which can regulate the homeostasis of glucose and lipid metabolism. However, it is not clear whether it can regulate the browning of WAT and mitophagy during the browning process. Accordingly, this study aims to investigate the effects and possible mechanisms of ASP on the browning of WAT and mitophagy in vivo and in vitro. METHODS: In in vivo experiments, some mouse models were used including adipose tissue ASP-specific deficiency (ASP-/-), high fat diet (HFD)-induced obesity and white adipose browning; in in vitro experiments, some cell models were also established and used, including ASP-deficient 3T3-L1 preadipocyte (ASP-/-) and CL-316243 (CL, 1 µM)-induced browning. Based on these models, the browning of WAT and mitophagy were evaluated by morphology, functionality and molecular markers. RESULTS: Our in vivo data show that adipose tissue-specific deletion of ASP contributes to weight loss in mice; supplementation of ASP inhibits the expressions of browning-related proteins including UCP1, PRDM16 and PGC1ɑ during the cold exposure-induced browning, and promotes the expressions of mitophagy-related proteins including PINK1 and Parkin under the conditions of whether normal diet (ND) or HFD. Similarly, our in vitro data also show that the deletion of ASP in 3T3-L1 cells significantly increases the expressions of the browning-related proteins and decreases the expressions of the mitophagy-related proteins. CONCLUSIONS: These data demonstrate that ASP deletion can facilitate the browning and inhibit mitophagy in WAT. The findings will lay an experimental foundation for the development of new drugs targeting ASP and the clinical treatment of metabolic diseases related to obesity.

Slow-Light-Enhanced Polarization Division Multiplexing Infrared Absorption Spectroscopy for On-Chip Wideband Multigas Detection in a 1D Photonic Crystal Waveguide.

Slow-light photonic crystal waveguide (PCW) gas sensors based on infrared absorption spectroscopy play a pivotal role in enhancing the on-chip interaction between light and gas molecules, thereby significantly boosting sensor sensitivity. However, two-dimensional (2D) PCWs are limited by their narrow mode bandwidth and susceptibility to polarization, which restricts their ability for multigas measurement. Due to quasi-TE and quasi-TM mode guiding characteristics in one-dimensional (1D) PCW, a novel slow-light-enhanced polarization division multiplexing infrared absorption spectroscopy was proposed for on-chip wideband multigas detection. The optimized 1D PCW gas sensor experimentally shows an impressive slow-light mode bandwidth exceeding 100 nm (TM, 1500-1550 nm; TE, 1610-1660 nm) with a group index ranging from 4 to 25 for the two polarizations. The achieved bandwidth in the 1D PCW is 2-3 times that of the reported quasi-TE polarized 2D PCWs. By targeting the absorption lines of different gas species, multigas detection can be realized by modulating the lasers and demodulating the absorption signals at different frequencies. As an example, we performed dual-gas measurements with the 1D PCW sensor operating in TE mode at 1.65 µm for methane (CH4) detection and in TM mode at 1.53 µm for acetylene (C2H2) detection. The 1 mm long sensor achieved a remarkable limit of detection (LoD) of 0.055% for CH4 with an averaging time of 17.6 s, while for C2H2, the LoD was 0.18%. This polarization multiplexing sensor shows great potential for on-chip gas measurement because of the slow-light enhancement in the light-gas interaction effect as well as the large slow-light bandwidth for multigas detection.

Mid-infrared auto-correction on-chip waveguide gas sensor based on 2f/1f wavelength modulation spectroscopy.

Compared to the most commonly used on-chip direct absorption spectroscopy (DAS) gas detection technique, the second harmonic (2f) based on-chip wavelength modulation spectroscopy (WMS) proposed by our group has the faculty to suppress noise and improve performance, but the accuracy of 2f WMS is easily affected by optical power variation. A mid-infrared auto-correction on-chip gas sensor based on 2f/1f WMS was proposed for decreasing the influence of the variation of optical power. The limit of detection of methane (CH4) obtained by a chalcogenide waveguide with a length of 10 mm is 0.031%. Compared with the 2f WMS, the maximum relative concentration error of the auto-correction on-chip gas sensor was decreased by ∼5.6 times. The measurement error is ≤2% in a temperature variation range of 30°C. This auto-correction sensor without a complicated manual calibration is helpful to the high accuracy measurement for on-chip integrated gas sensing.

A Synthetic Steroid 5α-Androst-3ß, 5, 6ß-triol Alleviates Radiation-Induced Brain Injury in Mice via Inhibiting GBP5/NF-κB/NLRP3 Signal Axis.

Radiotherapy for head and neck tumors can lead to a severe complication known as radiation-induced brain injury (RIBI). However, the underlying mechanism of RIBI development remains unclear, and limited prevention and treatment options are available. Neuroactive steroids have shown potential in treating neurological disorders. 5α-Androst-3ß, 5, 6ß-triol (TRIOL), a synthetic neuroprotective steroid, holds promise as a treatment candidate for RIBI patients. However, the neuroprotective effects and underlying mechanism of TRIOL on RIBI treatment are yet to be elucidated. In the present study, our findings demonstrate TRIOL's potential as a neuroprotective agent against RIBI. In gamma knife irradiation mouse model, TRIOL treatment significantly reduced brain necrosis volume, microglial activation, and neuronal loss. RNA-sequencing, immunofluorescence, real-time quantitative polymerase chain reaction, siRNA transfection, and western blotting techniques revealed that TRIOL effectively decreased microglial activation, proinflammatory cytokine release, neuron loss, and guanylate-binding protein 5 (GBP5) expression, along with its downstream signaling pathways NF-κB and NLRP3 activation in vitro. In summary, TRIOL effectively alleviate RIBI by inhibiting the GBP5/NF-κB/NLRP3 signal axis, reducing microglia activation and pro-inflammation cytokines release, rescuing neuron loss. This study highlights the potential of TRIOL as a novel and promising therapy drug for RIBI treatment.

Ultra-Wideband Mid-Infrared Chalcogenide Suspended Nanorib Waveguide Gas Sensors with Exceptionally High External Confinement Factor beyond Free-Space.

On-chip waveguide sensors are potential candidates for deep-space exploration because of their high integration and low power consumption. Since the fundamental absorption of most gas molecules exists in the mid-infrared (e.g., 3-12 µm), it is of great significance to fabricate wideband mid-infrared sensors with high external confinement factor (ECF). To overcome the limited transparency window and strong waveguide dispersion, a chalcogenide suspended nanorib waveguide sensor was proposed for ultra-wideband mid-infrared gas sensing, and three waveguide sensors (WG1-WG3) with optimized dimensions exhibit a wide waveband of 3.2-5.6 µm, 5.4-8.2 µm, and 8.1-11.5 µm with exceptionally high ECFs of 107-116%, 107-116%, and 116-128%, respectively. The waveguide sensors were fabricated by a two-step lift-off method without dry etching to reduce the process complexity. Experimental ECFs of 112%, 110%, and 110% were obtained at 3.291 µm, 4.319 µm, and 7.625 µm, respectively, through methane (CH4) and carbon dioxide (CO2) measurements. A limit of detection of 5.9 ppm was achieved for an averaging time of 64.2 s through the Allan deviation analysis of CH4 at 3.291 µm, leading to a comparable noise equivalent absorption sensitivity of 2.3 × 10-5 cm-1 Hz-1/2 as compared to the hollow-core fiber and on-chip gas sensors.

Directly targeting ASC by lonidamine alleviates inflammasome-driven diseases.

BACKGROUND: Dysregulated activation of the inflammasome is involved in various human diseases including acute cerebral ischemia, multiple sclerosis and sepsis. Though many inflammasome inhibitors targeting NOD-like receptor protein 3 (NLRP3) have been designed and developed, none of the inhibitors are clinically available. Growing evidence suggests that targeting apoptosis-associated speck-like protein containing a CARD (ASC), the oligomerization of which is the key event for the assembly of inflammasome, may be another promising therapeutic strategy. Lonidamine (LND), a small-molecule inhibitor of glycolysis used as an antineoplastic drug, has been evidenced to have anti-inflammation effects. However, its anti-inflammatory mechanism is still largely unknown. METHODS: Middle cerebral artery occlusion (MCAO), experimental autoimmune encephalomyelitis (EAE) and LPS-induced sepsis mice models were constructed to investigate the therapeutic and anti-inflammasome effects of LND. The inhibition of inflammasome activation and ASC oligomerization by LND was evaluated using western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) in murine bone marrow-derived macrophages (BMDMs). Direct binding of LND with ASC was assessed using molecular mock docking, surface plasmon resonance (SPR), and drug affinity responsive target stability (DARTS). RESULTS: Here, we find that LND strongly attenuates the inflammatory injury in experimental models of inflammasome-associated diseases including autoimmune disease-multiple sclerosis (MS), ischemic stroke and sepsis. Moreover, LND blocks diverse types of inflammasome activation independent of its known targets including hexokinase 2 (HK2). We further reveal that LND directly binds to the inflammasome ligand ASC and inhibits its oligomerization. CONCLUSIONS: Taken together, our results identify LND as a broad-spectrum inflammasome inhibitor by directly targeting ASC, providing a novel candidate drug for the treatment of inflammasome-driven diseases in clinic.

High Flux Nanofiltration Membranes with Double-Walled Carbon Nanotube (DWCNT) as the Interlayer.

Nanofiltration (NF) membranes with a high permeability and rejection are of great interest in desalination, separation and purification. However, how to improve the permeation and separation performance still poses a great challenge in the preparation of NF membranes. Herein, the novel composite NF membrane was prepared through the interfacial polymerization of M-phenylenediamine (MPD) and trimesoyl chloride (TMC) on a double-walled carbon nanotube (DWCNT) interlayer supported by PES substrate. The DWCNT interlayer had a great impact on the polyamide layer formation. With the increase of the DWCNT dosage, the XPS results revealed an increase in the number of carboxyl groups, which decreased the crosslinking degree of the polyamide layer. Additionally, the AFM results showed that the surface roughness and specific surface area increased gradually. The water flux of the prepared membrane increased from 25.4 L/(m2·h) and 26.6 L/(m2·h) to 109 L/(m2·h) and 104.3 L/(m2·h) with 2000 ppm Na2SO4 and NaCl solution, respectively, under 0.5 MPa. Meanwhile, the rejection of Na2SO4 and NaCl decreased from 99.88% and 99.38% to 96.48% and 60.47%. The proposed method provides a novel insight into the rational design of the multifunctional interlayer, which shows great potential in the preparation of high-performance membranes.

Inhibition of the cGAS-STING Pathway Attenuates Lung Ischemia/Reperfusion Injury via Regulating Endoplasmic Reticulum Stress in Alveolar Epithelial Type II Cells of Rats.

Purpose: Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Cyclic GMP-AMP synthase (cGAS) is a cytosol dsDNA sensor, coupling with downstream stimulator of interferon genes (STING) located in the ER, which involves innate immune responses. The aim of our present study was to investigate the effects of cGAS on lung I/R injury via regulating ERS. Methods: We used Sprague-Dawley rats to make the lung I/R model by performing left hilum occlusion-reperfusion surgery. cGAS-specific inhibitor RU.521, STING agonist SR-717, and 4-phenylbutyric acid (4-PBA), the ERS inhibitor, were intraperitoneally administered in rats. Double immunofluorescent staining was applied to detect the colocalization of cGAS or BiP, an ERS protein, with alveolar epithelial type II cells (AECIIs) marker. We used transmission electron microscopy to examine the ultrastructure of ER and mitochondria. Apoptosis and oxidative stress in the lungs were assessed, respectively. The profiles of pulmonary edema and lung tissue injury were evaluated. And the pulmonary ventilation function was measured using a spirometer system. Results: In lung I/R rats, the cGAS-STING pathway was upregulated, which implied they were activated. After cGAS-STING pathway was inhibited or activated in lung I/R rats, the ERS was alleviated after cGAS was inhibited, while when STING was activated after lung I/R, ERS was aggravated in the AECIIs, these results suggested that cGAS-STING pathway might trigger ERS responses. Furthermore, activation of cGAS-STING pathway induced increased apoptosis, inflammation, and oxidative stress via regulating ERS and therefore resulted in pulmonary edema and pathological injury in the lungs of I/R rats. Inhibition of cGAS-STING pathway attenuated ERS, therefore attenuated lung injury and promoted pulmonary ventilation function in I/R rats. Conclusion: Inhibition of the cGAS-STING pathway attenuates lung ischemia/reperfusion injury via alleviating endoplasmic reticulum stress in alveolar epithelial type II cells of rats.

Preparation of Porous Silicate Cement Membranes via a One-Step Water-Based Hot-Dry Casting Method.

A commercial interest in the improvement in the separation performance and permeability of porous materials is driving efforts to deeply explore new preparation methods. In this study, the porous silicate cement membranes (PSCMs) were successfully prepared through an adjustable combination of hot-dry casting and a cement hydration process. The obtained membrane channel was unidirectional, and the surface layer was dense. The physical characteristics of the PSCMs including their pore morphology, porosity, and compressive strength, were diversified by adjusting the solid content and hot-dry temperature. The results indicated that with the solid content increasing from 40 wt. % to 60 wt. %, the porosity decreased by 8.07%, while the compressive strength improved by 12.46%. As the hot-dry temperature increased from 40 °C to 100 °C, the porosity improved by 23.04% and the BET specific surface area and total pore volume enlarged significantly, while the compressive strength decreased by 27.03%. The pore size distribution of the PSCMs exhibited a layered structure of macropores and mesopores, and the pore size increased with the hot-dry temperature. Overall, the PSCMs, which had typical structures and adjustable physical characteristics, exhibited excellent permeability and separation performance.

Inhibition of cGAS in Paraventricular Nucleus Attenuates Hypertensive Heart Injury Via Regulating Microglial Autophagy.

Neuroinflammation in the cardiovascular center plays a critical role in the progression of hypertensive heart disease. And microglial autophagy is involved in the regulation of neuroinflammation. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, senses mitochondrial DNA (mtDNA) and regulates autophagy. The detailed mechanisms of central cGAS affects neuroinflammatory response in hypertensive heart disease via regulating autophagy remain unknown. Angiotensin II (Ang II, 1.5 mg·kg-1·12 h-1, 2 weeks) was intraperitoneally injected to induce hypertension in mice. The cGAS-STING pathway was activated in the paraventricular nucleus (PVN) of Ang II-induced hypertensive mice. The contractile dysfunction of heart was alleviated in Ang II-induced hypertensive cGAS-/- mice. To observe the central effects of cGAS on regulating hypertensive heart disease, the RU.521 (a cGAS inhibitor) was intracisternally infused in hypertensive mice. Intracisternal infusion of the RU.521-alleviated myocardial interstitial fibrosis, cardiomyocyte hypertrophy, and the contractile dysfunction in Ang II-induced hypertensive mice. Intracisternal infusion of RU.521 attenuated the microglial activation, neuroinflammation, sympathetic/parasympathetic activity ratio, and lowered blood pressure. The autophagic flux in the PVN cells was blocked, while intracisternal infusion of RU.521 alleviated this effect in the Ang II-induced hypertensive mice. In vitro, it was found that cGAS-STING activation-induced autophagic flux blockage, while when the impaired autophagic flux was facilitated by rapamycin, an autophagy inducer, the microglial M1 polarization was decreased correspondingly. In conclusion, cGAS induces the inflammatory phenotype of microglia via impairing autophagic flux, thereby participating in neuroinflammation, which leads to sympathetic overactivation in hypertension and further caused hypertensive myocardial injury.

TRIOL Inhibits Rapid Intracellular Acidification and Cerebral Ischemic Injury: The Role of Glutamate in Neuronal Metabolic Reprogramming.

As one of the key injury incidents, tissue acidosis in the brain occurs very quickly within several minutes upon the onset of ischemic stroke. Glutamate, an excitatory amino acid inducing neuronal excitotoxicity, has been reported to trigger the decrease in neuronal intracellular pH (pHi) via modulating proton-related membrane transporters. However, there remains a lack of clarity on the possible role of glutamate in neuronal acidosis via regulating metabolism. Here, we show that 200 µM glutamate treatment quickly promotes glycolysis and inhibits mitochondrial oxidative phosphorylation of primary cultured neurons within 15 min, leading to significant cytosolic lactate accumulation, which contributes to the rapid intracellular acidification and neuronal injury. The reprogramming of neuronal metabolism by glutamate is dependent on adenosine monophosphate-activated protein kinase (AMPK) signaling since the inhibition of AMPK activation by its selective inhibitor compound C significantly reverses these deleterious events in vitro. Moreover, 5α-androst-3ß,5α,6ß-TRIOL (TRIOL), a neuroprotectant we previously reported, can also remarkably reverse intracellular acidification and alleviate neuronal injury through the inhibition of AMPK signaling. Furthermore, TRIOL remarkably reduced the infarct volume and attenuated neurologic impairment in acute ischemic stroke models of middle cerebral artery occlusion in vivo. In summary, we reveal a novel role of glutamate in rapid intracellular acidification injury resulting from glutamate-induced lactate accumulation through AMPK-mediated neuronal reprogramming. Moreover, inhibition of the quick drop in neuronal pHi by TRIOL significantly reduces the cerebral damages, suggesting that it is a promising drug candidate for ischemic stroke.

Hydrogen sulfide reduces cell death through regulating autophagy during submergence in Arabidopsis.

KEY MESSAGE: Hydrogen sulfide positively regulates autophagy and the expression of hypoxia response-related genes under submergence to enhance the submergence tolerance of Arabidopsis. Flooding seriously endangers agricultural production, and it is quite necessary to explore the mechanism of plant response to submergence for improving crop yield. Both hydrogen sulfide (H2S) and autophagy are involved in the plant response to submergence. However, the mechanisms by which H2S and autophagy interact and influence submergence tolerance have not been thoroughly elucidated. Here, we reported that exogenous H2S pretreatment increased the level of endogenous H2S and alleviated plant cell death under submergence. And transgenic lines decreased in the level of endogenous H2S, L-cysteine desulfurase 1 (des1) mutant and 35S::GFP-O-acetyl-L-serine(thiol)lyase A1 (OASA1)/des1-#56/#61, were sensitive to submergence, along with the lower transcript levels of hypoxia response genes, LOB DOMAIN 41 (LBD41) and HYPOXIA RESPONSIVE UNKNOWN PROTEIN 43 (HUP43). Submergence induced the formation of autophagosomes, and the autophagy-related (ATG) mutants (atg4a/4b, atg5, atg7) displayed sensitive phenotypes to submergence. Simultaneously, H2S pretreatment repressed the autophagosome producing under normal conditions, but enhanced this process under submergence by regulating the expression of ATG genes. Moreover, the mutation of DES1 aggravated the sensitivity of des1/atg5 to submergence by reducing the formation of autophagosomes under submergence. Taken together, our results demonstrated that H2S alleviated cell death through regulating autophagy and the expression of hypoxia response genes during submergence in Arabidopsis.

Observation of five types of leaders contained in a negative triggered lightning.

A negative triggered lightning involving five types of leaders was recorded by high-speed camera using frame rate of 20,000 fps and fast antennas at different distances. Five types of leaders contained one upward positive stepped leader, one upward positive dart leader, ten downward negative dart leader, one bidirectional leader and three downward negative dart-stepped leaders were propagated successively in the same channel. The upward positive dart leader occurred after initial continuous current pulse with average 2-D speed of 1.40 × 106 m/s and started second continuous current process. The bidirectional leader was transformed from decaying unidirectional leader and showed the unique electric field changes. Faster return strokes are found to be induced by downward leaders propagating evenly and deposit more positive charge in the following residual channel. The positive charge can inhibit the potential initiation of an upward positive leader and boost the propagation of the next downward negative leader.