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Cholangiojejunostomy (CJ) is a popular operation; however, no specific anastomotic device is available. A novel magnamosis device for CJ was developed in 2017; here, we evaluated the feasibility and safety of the device.Between January 2017 and December 2019, 23 patients who underwent CJ using a novel magnamosis device were enrolled. For the CJ: the parent magnet was placed in the proximal duct, and the purse-string suture was tightened over the rod of the parent magnet. The magnamosis device was introduced into the jejunum, and the mandrel penetrated the jejunum at the anastomotic site, before insertion into the rod of the parent magnet. After rotating the knob, the distance between two magnets was shortened enough to achieve coupling.Sixteen patients (69.6%) underwent open CJ, while 7 (30.4%) underwent laparoscopic CJ; 21 patients (91.3%) underwent choledochojejunostomy, and 2 (8.7%) underwent right or left hepatic duct jejunostomy. The mean time for completion of CJ was 9.2±2.5 min; it was significantly shorter for open CJ than for the laparoscopic way (8±1.2 min vs. 11.8±2.5 min, P0.05). Only one patient (4.3%) suffered bile leakage after operation and was cured by conservative treatment. The magnets were discharged with a postoperative duration of 66.7±47.2 days, with a 100% expulsion rate. After a median follow-up of 15 months, only one patient (4.3%) developed inflammatory anastomotic stricture.The novel magnamosis device is a simple, safe, and effective modality for CJ.

Glioblastoma is the most common and aggressive type of malignant brain tumor with poor survival and limited therapeutic options. Theranostic anticancer agents with dual functions of diagnosis and therapy are highly attractive. Self-immolation reaction is a promising approach for theranostic prodrugs triggered by the tumor microenvironment. Overexpression of hydrogen sulfide (H

The propagation properties of electromagnetic waves radiated by vertical electric dipole on different surfaces such as land or sea water are discussed. The problem is studied by the method of moments and the modified mirror image method,which can improve the calculation efficiency. The influence of impedance surface and other factors are analyzed. The simulation results show that the characteristic parameters of seawater media have some influence on the radiation performance of electromagnetic waves, and the effects of different factors on the radiation performance are proposed. It has certain significance to the design and engineering practice of VLF communication antenna.

Background It remains uncertainwhetherlow-level electrical stimulation (LL-ES) of the ventricular ganglionated plexi (GP) improves heart function. This study investigatedthe anti-arrhythmic and anti-heart failure effects of LL-ES of the aortic root ventricular ganglionated plexi (ARVGP). Methods Thirty dogs were divided randomly into control, drug, and LL-ES groups after performing rapid right ventricular pacing to establish a heart failure (HF) model. The inducing rate of arrhythmia; levels of bioactive factors influencing HF, including angiotensin II type I receptor (AT-1R), transforming growth factor-beta (TGF-β), matrix metalloproteinase (MMP), and phosphorylated extracellular signal-regulated kinase (p-ERK1/2); left ventricular stroke volume (LVSV), and left ventricular ejection fraction (LVEF)were measured after treatment with placebo, drugs, and LL-ES. Results The inducing rate of atrial arrhythmia decreased from 60% in the control group to 50% in the drug group and 10% in the LL-ES group (P = 0.033 vs. drug group) after 1 week of treatment. The ventricular effective refractory period was prolonged from 139±8 ms in the drug group to 166±13 ms in the LL-ES group (P = 0.001). Compared to the drug group, the expressions of AT-1R, TGF-β, and MMP proteins were down-regulated in the LL-ES group, whereas that of p-ERK1/2 was significantly increased (all P = 0.001). Moreover, in the LL-ES group, LVSVincreased markedly from 13.16±0.22 to 16.86±0.27mL, relative to that in the drug group (P = 0.001), and LVEF increased significantly from 38.48% ±0.53% to 48.94% ±0.57% during the same time frame (P = 0.001). Conclusion Short-term LL-ES of ARVGP had both anti-arrhythmic and anti-inflammatory effectsand contributed to the treatment of tachycardia-induced HF and its associated arrhythmia. This article is protected by copyright. All rights reserved.

Compared to other vertebrates, the regenerative capacity of appendages in mammals is very limited. Deer antlers are an exception and can fully regenerate annually in postnatal mammals. This process is initiated by the antler stem cells (AnSCs). AnSCs can be divided into three types: (1) Antlerogenic periosteum cells (for initial pedicle and first antler formation); (2) Pedicle periosteum cells (for annual antler regeneration); and (3) Reserve mesenchyme cells (RMCs) (for rapid antler growth). Previous studies have demonstrated that AnSCs express both classic mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs), and are able to differentiate into multiple cell types in vitro. Thus, AnSCs were defined as MSCs, but with partial ESC attributes. Near-perfect generative wound healing can naturally occur in deer, and wound healing can be achieved by the direct injection of AnSCs or topical application of conditioned medium of AnSCs in rats. In addition, in rabbits, the use of both implants with AnSCs and cell-free preparations derived from AnSCs can stimulate osteogenesis and repair defects of bone. A more comprehensive understanding of AnSCs will lay the foundation for developing an effective clinical therapy for wound healing and bone repair.

Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, O,O-chelated complexes [Os(η6-p-cymene)(Curc)Cl] (OsCUR-1, Curc = curcumin) and [Os(η6-biphenyl)(Curc)Cl] (OsCUR-2), and N,N-chelated complexes [Os(η6-biphenyl)(dpq)I]PF6 (OsDPQ-2, dpq = pyrazino[2,3-f][1,10]phenanthroline) and [Os(η6-biphenyl)(bpy)I]PF6 (OsBPY-2, bpy = 2,2'-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC50: 2.6-5.8 μM, photocytotoxicity index PI = 23-34), especially toward cisplatin-resistant cancer cells, but were nontoxic to normal cells. They localized mainly in mitochondria in the dark but translocated to the nucleus upon photoirradiation, generating DNA and mitochondrial damage, which might contribute toward overcoming cisplatin resistance. Mitochondrial damage, apoptosis, ROS generation, DNA damage, angiogenesis inhibition, and colony formation were observed when A549 lung cancer cells were treated with OsCUR-2. The photochemistry of these Os-arene complexes was investigated by a combination of NMR, HPLC-MS, high energy resolution fluorescence detected (HERFD), X-ray adsorption near edge structure (XANES) spectroscopy, total fluorescence yield (TFY) XANES spectra, and theoretical computation. Selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) occurred under blue light or UVA excitation. This new approach to the design of novel Os-arene complexes as phototherapeutic agents suggests that the novel curcumin complex OsCUR-2, in particular, is a potential candidate for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT).

The authors [13] introduced a general inertial Krasnosel’skiǐ–Mann algorithm: $$ \left\{ \begin{aligned}&y_n=x_n+\alpha _n(x_n-x_{n-1}),\\&z_n=x_n+\beta _n(x_n-x_{n-1}),\\&x_{n+1}=(1-\lambda _n)y_n+\lambda _nT(z_n) \end{aligned} \right. $$ for each \(n\ge 1\) and showed its convergence with the control conditions \(\alpha _n,\beta _n\in [0,1).\) In this paper, we present the convergence analysis of the general inertial Krasnosel’skiǐ–Mann algorithm with the control conditions \(\alpha _n\in [0,1]\), \(\beta _n\in (-\infty ,0]\) and \(\alpha _n\in [-1,0]\), \(\beta _n\in [0,+\infty )\), respectively. Also, we provide the convergence rate for the general inertial Krasnosel’skiǐ–Mann algorithm under mild conditions on the inertial parameters and some conditions on the relaxation parameters, respectively. Finally, we show that a numerical experiment provided compares the choice of inertial parameters.

Highlights • Soluble trunked RBD protein linked TT peptide was prepared to high homogeneity and purity by prokaryotic expression, chromatography purification and the rational renaturation. • The candidate subunit vaccine molecule could stimulate strong humoral and cellular immune response in mice. • By the approach of prokaryotic expression system, it would be possible to prevent and eliminate COVID-19 on a global scale., Without approved vaccines and specific treatments, COVID-19 is spreading around the world with above 26 million cases and approximately 864 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 – Gly548 of spike protein of SARS-CoV-2 linked with Gln830 – Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5) were expressed and renatured. The antigenicity and immunogenicity of S1-4 were evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency was measured preliminarily by microneutralization assay (MN50). The soluble S1-4 and S1-5 protein was prepared to high homogeneity and purity. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity supplemented with Th1-type immunity. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralizing antibody titer 256. Recombinant SARS-CoV-2 RBD with a built in T helper epitope could stimulate both strong humoral immunity supplemented with cellular immunity in mice, demonstrating that it could be a promising subunit vaccine candidate.

Accumulating evidence suggests the role of developmental exposure of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism remains unclear. Using a rat model, we investigated the neonatal exposure of BPA on lipid metabolism in adult and the underlying mechanisms. From postnatal day1(PND1) to PND10, male rats were exposed to BPA via daily subcutaneous injection with 10 µg/100 µL BPA (1.24-0.5 mg/kg body weight/day, a dose below the US-EPA LOAEL). After fasting for 8 h, adult rats aged 80 days showed elevated levels of serum free fatty acid (FFA), glycerol and glucose, and increased levels of FFA and glycerol in visceral adipose tissue. The expression levels of key enzymes of lipolysis, adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl), were increased in visceral adipose tissue from BPA-exposed rats after fasting. On the other hand, transcription levels of lipogenic genes remained unchanged. Differentiation of visceral adipocyte in rats takes place neonatally. In our study, neonatal BPA exposure induced DNA hypomethylation of Atgl in visceral adipose tissue. In 3T3-L1 cell, administration of 10

Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anti-cancer therapies. To exploit the synthetic lethality concept in the design of chemical anti-cancer agents, we developed a bio-orthogonally catalyzed lethality (BCL) strategy to generate targeting anti-tumor metallodrugs both in vitro and in vivo. Metallodrug Ru-rhein was generated from two non-toxic species Ru-N3 and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction without the need of an external copper catalyst. The non-toxic species Ru-arene complex Ru-N3 and rhein-alkyne were designed to perform this strategy, and the mitochondrial targeting product Ru-rhein was generated in high yield (>83%) and showed high anti-tumor efficacy in vitro. This BCL strategy achieved a remarkable tumor suppression effect on the tumor-bearing mice models. It is interesting that the combination of metal-arene complexes with rhein via CuAAC reaction could transform two non-toxic species into a targeting anti-cancer metallodrug both in vitro and in vivo, while the product Ru-rhein was non-toxic towards normal cells. This is the first example that exclusive endogenous copper was used to generate metal-based anti-cancer drugs for cancer treatment. The anti-cancer mechanism of Ru-rhein was studied and autophagy was induced by increased reactive oxygen species and mitochondrial damage. The generality of this BCL strategy was also studied and it could be extended to other metal complexes such as Os-arene and Ir-arene complexes. Compared with the traditional methods for cancer treatment, this work presented a new approach to generating targeting metallodrugs in vivo via the BCL strategy from non-toxic species in metal-based chemotherapy., This work established a 'bioorthogonally catalyzed lethality' strategy to generate tumor-targeting metallodrugs both in vitro and in vivo.

Without approved vaccines and specific treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the world with above 20 million COVID-19 cases and approximately 700 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 – Gly548 of Spike protein of SARS-CoV-2 linked with Gln830 – Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5), and prokaryotic expression, chromatography purification and the rational renaturation of the protein were performed. The antigenicity and immunogenicity of S1-4 protein was evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency of it was measured by virus neutralization test in Vero E6 cells with SARS-CoV-2. S1-4 protein was prepared to high homogeneity and purity by prokaryotic expression and chromatography purification. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity compared with S1-5 protein. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralization antibody GMT 256. The candidate subunit vaccine molecule could stimulate strong humoral and Th1 and Th2-type cellular immune response in mice, giving us solid evidence that S1-4 protein could be a promising subunit vaccine candidate.

A rational design is reported of Fe-doped cobalt telluride nanoparticles encapsulated in nitrogen-doped carbon nanotube frameworks (Fe-Co

To investigate the gene diagnosis and phenotypes analysis for a couple with β-thalassemia suspected from of blood routine test and hemoglobin electrophoresis, as well as the prenatal gene diagnosis of the fetus.The gene mutation of β-globin in the samples of peripheral blood of pregnant woman and her husband, as well as amniotic fluid of pregnant woman were analyzied and identified by using PCR-RDB and Sanger sequencing.The detection showed that the heterozygote mutation of IVS-Ⅱ-654 (CT), which is common mutation of β-globin gene, existed in pregnant woman, while her husband carried a rare mutation CD29 (c.90 CT) of β-globin gene. The prenatal diagnosis indicated that the fetus inherited with mutation from the parents, fetus genotype was βThe CD29(CT) mutation of β-globin gene has been identified in Chinese population first. Although this mutation type is symonymous mutation, but its carrier displays phenotype of β-thalaessmia. Therefore, the attention to this mutation should be paid considering the genetic risk. It contributes to genetic counseling and prenatal gene diagnosis.一种罕见的同义突变导致的β-地中海贫血的基因诊断和表型分析.对血常规和血红蛋白电泳筛查结果提示疑为β-地中海贫血携带者的孕妇及其丈夫进行β-地中海贫血基因诊断，鉴定其表型并对胎儿进行产前基因诊断.采用聚合酶链式反应-反向点杂交（PCR-RDB）方法及DNA测序方法分析并鉴定孕妇及其丈夫的外周血和孕妇的羊水样本的β-珠蛋白基因突变.检测到孕妇本人为常见的β-珠蛋白基因IVS-Ⅱ-654 (CT)位点杂合突变，其丈夫携带一种罕见β-珠蛋白基因CD29 (c.90 CT)位点杂合突变，产前基因诊断出胎儿基因型为β本研究在中国人群中确切基因鉴定出β-珠蛋白基因CD29 (c.90 CT)突变，此突变类型虽为同义突变但其携带者表现为β

Myeloperoxidase (MPO)-mediated oxidative stress has been suggested to play an important role in the pathological dysfunction of epileptic brains. However, there is currently no robust brain-imaging tool to detect real-time endogenous hypochlorite (HClO) generation by MPO or a fluorescent probe for rapid high-throughput screening of antiepileptic agents that control the MPO-mediated chlorination stress. Herein, we report an efficient two-photon fluorescence probe (named HCP) for the real-time detection of endogenous HClO signals generated by MPO in the brain of kainic acid (KA)-induced epileptic mice, where HClO-dependent chlorination of quinolone fluorophore gives the enhanced fluorescence response. With this probe, we visualized directly the endogenous HClO fluxes generated by the overexpression of MPO activity in vivo and ex vivo in mouse brains with epileptic behaviors. Notably, by using HCP, we have also constructed a high-throughput screening approach to rapidly screen the potential antiepileptic agents to control MPO-mediated oxidative stress. Moreover, from this screen, we identified that the flavonoid compound apigenin can relieve the MPO-mediated oxidative stress and inhibit the ferroptosis of neuronal cells. Overall, this work provides a versatile fluorescence tool for elucidating the role of HClO generation by MPO in the pathology of epileptic seizures and for rapidly discovering additional antiepileptic agents to prevent and treat epilepsy.

Triboelectric nanogenerators (TENGs) are widely applied to self-powered devices and force sensors. TENGs consist of the electrode-layer frequently made of high-cost conductors (Ag, Au, ITO) and the tribo-layer of rigid negative-triboelectricity fluoropolymers (PTFE, FEP). The surface morpholoy is studied for enhancing performance. Here, a high-performance Al/PDMS-TENG is proposed with a complex morphology of overlapped deep two-height microneedles (OL-DTH-MN) fabricated by the integrated process of low-cost CO2 laser ablation and PDMS casting for self-powered devices and high-sensitivity force/pressure sensors. The high open-circuit voltage and short-circuit current of the OL-DTH-MN-TENG are 167 V and 129.3 µA. Also, the sensitivity of the force/pressure sensor of the OL-DTH-MN-TENG is very high, 1.03 V N-1 and about 3.11 V kPa-1 , at an area of 30 cm2 that is much higher than the sensitivity of about 0.18-0.414 V N-1 and 0.013-0.29 V kPa-1 of conventional TENG sensors. Meanwhile, the high-performance OL-DTH-MN-TENG not only exhibits the energy storage capability of charging a 0.1 µF capacitor to 2.75 V at 1.19 s, to maximum 3.22 V, but also activates various self-powered devices including lighting colorful 226 LEDs connected in series, the "2020-ME-NCKU" advertising board, a calculator and a temperature sensor. Numerical simulation is also performed to support the experiments.

Background: a2A adrenoceptor receptor (a2A-AR) plays an important role in inflammatory response in Kupffer cells in sepsis. Blockage of a2A-AR inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor a (TNF-a) production and protects the target organ functions in sepsis animal models; however, its expression and function in microglia have remained obscure. This study aimed to determine whether a2A-AR was expressed in microglia and whether its activation would exacerbate microglial inflammation and sepsis-related neurological dysfunction. Methods: Western blotting and immunofluorescence were used to detect a2A-AR expression in BV-2 microglia. Enzyme-linked immunosorbent assay (ELISA) was used to assess the TNF-a production in the supernatant after LPS induced BV-2 cells were pretreated with a2A-AR agonist BHT933, and/or a2A-AR antagonist BRL44408, and also in the supernatants derived from BV-2 cells treated with BHT933 and/or PKC inhibitor. Signaling pathways including JNK，P38，ERK，IκBa, CREB and PCK were detected by western blotting. a2A-AR gene knock-out (KO) and wild type (WT) mice were prepared by intraperitoneal injection of LPS. Lectin /TNF-a labeled microglia and synaptophysin/NeuN expression in the hippocampus were localized by immunofluorescence. Morris water maze test, Rotating-stick test, Elevated plus maze test and Open-field test were conducted over 4 weeks.Results: a2A-AR was constitutively expressed in BV-2 microglia, which was enhanced by LPS. Pretreatment with BHT933 promoted LPS-induced IκB and JNK phosphorylation, and TNF-a secretion in BV-2 microglia which were abrogated by BRL44408. Activation of a2A-AR by BHT933 also increased PKC phosphorylation in LPS-treated BV-2 microglia. PKC inhibitor significantly reversed the promoting effects of BHT933 on IκB and JNK phosphorylation as well as TNF-a secretion in LPS-treated BV-2 microglia. Furthermore, LPS treatment significantly increased hippocampal microglia activation and TNF-a expression, decreased hippocampal synaptophysin expression, and impaired cognitive and motor functions in WT mice, all of which were markedly reversed by a2A-AR gene knockout. Conclusion: a2A-AR activation promotes LPS-induced IκB and JNK phosphorylation as well as TNF-a production in microglia through the PKC signaling pathway. Knockout of a2A-AR gene significantly improves LPS-induced cognitive and motor impairments in mice, indicating that a2A-AR is a potential therapeutic target for sepsis-associated encephalopathy.

Spontaneous intramural hematoma of the alimentary canal has rarely been reported. We present two cases in which anticoagulation therapy brings spontaneous intramural hematoma of the alimentary canal. In one case, the lesion was located in the ileum, and the other was located in the ascending colon and distal ileum. Both patients were cured through conservative treatment. We suggest that increased attention should be paid if a patient has acute abdominal pain with a history of oral anticoagulant therapy, and the diagnosis of spontaneous intermural hematoma should be considered.

Theranostic anticancer agents with dual functions of diagnosis and therapy are in highly demand for breast cancer. Herein, a triphenylphosphonium (TPP)-decorated aggregation-induced emission (AIE)-based Pt(IV) prodrug ACPt was developed, which exhibited superior anticancer performance with novel anticancer mechanism of dual modulation of apoptosis and autophagy inhibition. The experimental data showed that ACPt induced increased reactive oxygen species (ROS), and decreased mitochondrial membrane potential (MMP). The morphology and function of mitochondria were also severely damaged and ACPt showed strong inhibition to both mitochondrial and glycolytic bioenergetics. Moreover, DNA damage and cell cycle arrest in the S-phase were also observed after the ACPt treatment, eventually leading to the apoptosis and autophagy inhibition of cancer cells. Furthermore, ACPt also indicated excellent anti-proliferation activity in 3D multicellular tumor spheroids (MCTSs), suggesting the potential to inhibit solid tumors in vivo. Our observation demonstrated that ACPt could serve as a promising anticancer theranostic agent toward breast cancers for prodrug activation monitoring and image-guided chemotherapy.

In this paper, two diiron complexes have been prepared by CO exchange and structurally characterized. Treatment of complex [Fe2(CO)6{μ-SCH2CH(CH2O2CCH3)S}] (1) with diphenyl-2-pyridylphosphine in t...

Background:A series of novel 2,6-dichloro-4-(trifluoromethyl)phenyl)-3-(difluoromethyl)- 1H-pyrazole-4-carboxamide derivatives were designed and synthesized.Methods:All the title compounds were confirmed by 1H NMR and MS.Results and Conclusion:The primarily nematicidal activity results indicated that some of them exhibited moderate control efficacy against the tomato root-knot nematode disease caused by Meloidogyne incognita.

A highly sensitive and sandwiched electrochemiluminescence (ECL) aptasensor was proposed for detection of insulin by using fullerene nano-materials/bovine serum albumin@luminol (nano-C60/BSA@luminol) nanohybrid as signal probe. Herein, Ferrocenecarboxylic acid@aptamer II (Fc@aptamer II) and nano-C60/BSA@luminol nanocomposites were synthesized for the first time and applied to carry out dual-amplification strategy in the luminol-hydrogen peroxide (luminol-H2O2) system. Notably, nano-C60/BSA with large specific surface area and advantageous biocompatibility can enable high loading of luminol and further enhance ECL intensity. Furthermore, the obtained nano-C60/BSA@luminol nanohybrid was used as ECL signal probe owing to the presence of massive luminol and played an important role of acting as capture probe to recognize aptamer I. Besides, it is very crucial that Fc showed superior catalytic effect for H2O2, which generated more excited state luminol as well as strong ECL signal. Additionally, the as-prepared ECL aptasensor provided a wide linear range from 0.0001 to 1000 ng/mL and a low detection limit of 0.04 pg/mL (S/N = 3) and correlation coefficient (R2) was 0.993 for insulin. In conclusion, the as-proposed ECL aptasensor would open a new vista for sensitive detection of insulin and suggested favorable application prospect in bioanalysis.

The vibration performance of a simulation for a hidden-frame supported glass curtain wall (HFSGCW) was tested using a Laser Doppler Vibrometer (LDV) in this paper. The effect of silicon structural sealant on the first order inherent frequency of HFSGCW and the spectral characteristics per LDV on different points were studied. Meanwhile, the test results of LDV were verified using traditional sensors (DASP modal analysis system) in order to evaluate the feasibility of LDV used for safety state evaluation of HFSGCW. Results show that the first order inherent frequency obtained by LDV matches well with DASP modal analysis results. The first order inherent frequency decreases with an increase of sealant failure，and the first order frequency amplitude scale of structural sealant upper point increases significantly after the structural silicon sealant is destroyed. The safety state of HFSGCW is divided into three levels. Meanwhile, a safety state rapid evaluation model and key detection technologies of HFSGCW based on LDV is proposed.

Background: Hypoxemia is a typical symptom of acute respiratory distress syndrome (ARDS). Ventilations are always needed for correcting hypoxemia. To avoid pulmonary morbidity, low tidal volume ventilation is often applied. The ventilation strategy will certainly result in hypercapnia. Our previous study found that hypercapnia could induce IL-1β overproduction in hypoxia-activated microglia. However, the underlying mechanism has remained unclear. This study aimed to explore whether hypercapnia would promote microglial pyroptosis via inhibiting mitophagy in adult rats with hypoxemia. Methods: Cerebral oxygen extraction ratio (CERO2), partial pressure of brain tissue oxygen (PbtO2), and reactive oxygen species (ROS) production in brain tissue in a rat model of hypercapnia/hypoxemia were evaluated. Along with this, the oxygen consumption rate (OCR) and ROS production of BV-2 microglial cells were evaluated after 15% CO2/0.2% O2 treatment. Mitophagy was observed using transmission electron microscopy (TEM). The protein expression level of LC3-II/I, p62, caspase-1, gasdermin D-N domains (GSDMD-N), IL-1β and IL-18 in microglial cells were detected before and after application of a ROS scavenger in vivo and in vitro. Results: PbtO2 level was elevated by hypercapnia in the hypoxemic rats in the first 1.5 h, but it was significantly decreased 2 h after ventilation. This was further evident by the increased levels of CERO2 at 3 h after ventilation. Besides, a high concentration of CO2 treatment could increase the levels of OCR in hypoxic BV-2 microglial cells in vitro. Expression levels of LC3-II were reduced, while those of p62 were increased by hypercapnia in the hypoxic hippocampus and BV-2 microglia. Autophagosomes could be seen in hypoxia treated microglial cells under TEM, while those were rarely observed in hypercapnia + hypoxia treated microglia. Hypercapnia markedly increased the production of ROS and the expression of caspase-1, GSDMD-N, IL-1β, and IL-18 in hypoxia-activated microglia both in vivo and in vitro. Pharmacological scavenging ROS inhibited microglial pyroptosis and expression of IL-1β and IL-18.Conclusion: Hypercapnia-induced mitophagy inhibition may promote pyroptosis and enhance IL-1β and IL-18 release in hypoxia-activated microglia.