IKK1 aggravates ischemia-reperfusion kidney injury by promoting the differentiation of effector T cells.

Ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI), and experimental work has revealed detailed insight into the inflammatory response in the kidney. T cells and NFκB pathway play an important role in IRI. Therefore, we examined the regulatory role and mechanisms of IkappaB kinase 1 (IKK1) in CD4+T lymphocytes in an experimental model of IRI. IRI was induced in CD4cre and CD4IKK1Δ mice. Compared to control mice, conditional deficiency of IKK1 in CD4+T lymphocyte significantly decreased serum creatinine, blood urea nitrogen (BUN) level, and renal tubular injury score. Mechanistically, lack in IKK1 in CD4+T lymphocytes reduced the ability of CD4 lymphocytes to differentiate into Th1/Th17 cells. Similar to IKK1 gene ablation, pharmacological inhibition of IKK also protected mice from IRI. Together, lymphocyte IKK1 plays a pivotal role in IRI by promoting T cells differentiation into Th1/Th17 and targeting lymphocyte IKK1 may be a novel therapeutic strategy for IRI.

YOLOv5s-Fog: An Improved Model Based on YOLOv5s for Object Detection in Foggy Weather Scenarios.

In foggy weather scenarios, the scattering and absorption of light by water droplets and particulate matter cause object features in images to become blurred or lost, presenting a significant challenge for target detection in autonomous driving vehicles. To address this issue, this study proposes a foggy weather detection method based on the YOLOv5s framework, named YOLOv5s-Fog. The model enhances the feature extraction and expression capabilities of YOLOv5s by introducing a novel target detection layer called SwinFocus. Additionally, the decoupled head is incorporated into the model, and the conventional non-maximum suppression method is replaced with Soft-NMS. The experimental results demonstrate that these improvements effectively enhance the detection performance for blurry objects and small targets in foggy weather conditions. Compared to the baseline model, YOLOv5s, YOLOv5s-Fog achieves a 5.4% increase in mAP on the RTTS dataset, reaching 73.4%. This method provides technical support for rapid and accurate target detection in adverse weather conditions, such as foggy weather, for autonomous driving vehicles.

Role of carnitine in adaptation of Chromohalobacter salexigens DSM 3043 and its mutants to osmotic and temperature stress in defined medium.

L-Carnitine is widespread in nature, but little information is available on its metabolism and physiological functions in moderate halophiles. In this study, we found that Chromohalobacter salexigens DSM 3043 could utilize carnitine not only as a nutrient, but also as an osmolyte. When grown at 37 °C under salt-stress conditions, the strain utilized carnitine as an osmoprotectant by enzymatically converting it into GB. When grown at low and high temperature, both carnitine and its metabolic intermediate GB were simultaneously accumulated intracellularly, serving as cryoprotectants and thermoprotectants. The genes (csal_3172, csal_3173, and csal_3174) which were predicted to participate in L-carnitine degradation to GB were deleted to construct the corresponding mutants. The effects of salinity and temperature on the growth rates and cytoplasmic solute pools of the C. salexigens wild-type and mutant strains were investigated. 13C-NMR analysis revealed that GB was still detected in the Δcsal_3172Δcsal_3173Δcsal_3174 mutant grown in a defined medium with added DL-carnitine, but not with L-carnitine, indicating that an unidentified D-carnitine degradation pathway exists in C. salexigens. Taken together, the data presented in this study expand our knowledge on carnitine metabolism and its physiological functions in C. salexigens exposed to single or multiple environmental abiotic stress.

circ-Katnal1 Enhances Inflammatory Pyroptosis in Sepsis-Induced Liver Injury through the miR-31-5p/GSDMD Axis.

Background: Sepsis is a systemic inflammatory response that can elicit organ dysfunction as well as circulatory diseases in serious cases. When inflammatory responses are especially dysregulated, severe complications can arise, including sepsis-induced liver injury. Various microRNAs along with circular (circ) RNAs are involved in inflammatory responses; nevertheless, their functions in regulating sepsis-induced liver injury remain unknown. The cecal ligation and puncture (CLP) procedure can induce liver injury as well as polymicrobial sepsis. Methods: In this study, CLP was used to induce liver injury as well as polymicrobial sepsis. Then, liver function, inflammatory cytokine expression, and hepatic histopathology were evaluated. High-throughput sequencing was employed to investigate the abnormal hepatic circRNA expression after CLP. Raw264.7 cells were utilized to simulation an in vitro sepsis inflammation model with LPS induce. The relative mRNA as well as protein levels of TNF-α, IL-1ß, and IL-6 was explored by quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays. We explored functional connections among circRNAs, miR-31-5p, and gasdermin D (GSDMD) using dual-luciferase reporter assays. Western blot was employed to test GSDMD, caspase-1, and NLRP3 expression in mice and cell models. Results: Our results showed that CLP-induced sepsis promoted liver injury via increasing inflammatory pyroptosis. The abnormal expression of circ-Katnal1 played an important role in CLP-induced sepsis. Downregulating circ-Katnal1 suppressed LPS-induced inflammatory pyroptosis in Raw264.7 cells. Bioinformatics and luciferase reporter results confirmed that miR-31-5p and GSDMD were downstream targets of circ-Katnal1. Inhibiting miR-31-5p or upregulating GSDMD reversed the protective effects of silencing circ-Katnal1. Conclusion: Taken together, circ-Katnal1 enhanced inflammatory pyroptosis in sepsis-induced liver injury through the miR-31-5p/GSDMD axis.

Role of N,N-Dimethylglycine and Its Catabolism to Sarcosine in Chromohalobacter salexigens DSM 3043.

Chromohalobacter salexigens DSM 3043 can grow on N,N-dimethylglycine (DMG) as the sole C, N, and energy source and utilize sarcosine as the sole N source under aerobic conditions. However, little is known about the genes and enzymes involved in the conversion of DMG to sarcosine in this strain. In the present study, gene disruption and complementation assays indicated that the csal_0990, csal_0991, csal_0992, and csal_0993 genes are responsible for DMG degradation to sarcosine. The csal_0990 gene heterologously expressed in Escherichia coli was proven to encode an unusual DMG dehydrogenase (DMGDH). The enzyme, existing as a monomer of 79 kDa with a noncovalently bound flavin adenine dinucleotide, utilized both DMG and sarcosine as substrates and exhibited dual coenzyme specificity, preferring NAD+ to NADP+ The optimum pH and temperature of enzyme activity were determined to be 7.0 and 60°C, respectively. Kinetic parameters of the enzyme toward its substrates were determined accordingly. Under high-salinity conditions, the presence of DMG inhibited growth of the wild type and induced the production and accumulation of trehalose and glucosylglycerate intracellularly. Moreover, exogenous addition of DMG significantly improved the growth rates of the four DMG- mutants (Δcsal_0990, Δcsal_0991, Δcsal_0992, and Δcsal_0993) incubated at 37°C in S-M63 synthetic medium with sarcosine as the sole N source. 13C nuclear magnetic resonance (13C-NMR) experiments revealed that not only ectoine, glutamate, and N-acetyl-2,4-diaminobutyrate but also glycine betaine (GB), DMG, sarcosine, trehalose, and glucosylglycerate are accumulated intracellularly in the four mutants.IMPORTANCE Although N,N-dimethylglycine (DMG) dehydrogenase (DMGDH) activity was detected in cell extracts of microorganisms, the genes encoding microbial DMGDHs have not been determined until now. In addition, to our knowledge, the physiological role of DMG in moderate halophiles has never been investigated. In this study, we identified the genes involved in DMG degradation to sarcosine, characterized an unusual DMGDH, and investigated the role of DMG in Chromohalobacter salexigens DSM 3043 and its mutants. Our results suggested that the conversion of DMG to sarcosine is accompanied by intramolecular delivery of electrons in DMGDH and intermolecular electron transfer between DMGDH and other electron acceptors. Moreover, an unidentified methyltransferase catalyzing the production of glycine betaine (GB) from DMG but sharing no homology with the reported sarcosine DMG methyltransferases was predicted to be present in the cells. The results of this study expand our understanding of the physiological role of DMG and its catabolism to sarcosine in C. salexigens.

Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-κB pathway.

Paraquat (PQ) is one of the most extensively used herbicides, possessing high toxicity for humans and animals. The lung is the main target organ by the poisoning of PQ resulting in acute lung injury. Nonetheless, molecular mechanisms underlying PQ-induced lung injury remain unclear. Here, we ask if angiopoietin-like protein 2 (Angptl2), a pro-inflammatory protein, contributes to inflammation that accelerates acute lung injury. The results indicated that abundant Angptl2 expression was observed in lung tissues of PQ-treated mice. Histological analysis revealed that PQ-induced histological changes were alleviated by Angptl2 knockout (Angptl2-/-). Angptl2-/- in PQ-treated mice attenuated acute lung injury progression by reducing the number of total cells, total leukocytes, neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and reducing inflammatory response through the inactivation of nuclear factor kappa B (NF-κB) pathway. Angptl2-/- reduced oxidative stress in PQ-treated mice, as evidenced by the enhanced superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) levels in serum or lung tissue samples, which was accompanied with increased expressions of nuclear respiratory factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1). PQ-induced fibrosis was also improved in Angptl2-/- mice by decreasing pulmonary transforming growth factor (TGF)-ß1 expressions. In vitro, we found that Angptl2 knockdown-suppressed inflammation, oxidative stress and fibrosis was restored by increasing NF-κB activation in PQ-incubated A549 cells; however, the results above were significantly reversed by inactivating NF-κB using its inhibitor, Bay 11-7085 or LY2409881. Therefore, Angptl2 could provide therapeutic effects on PQ-induced acute lung injury through inhibiting inflammation, oxidative stress and fibrosis by regulating NF-κB pathway.

MicroRNA-126 (MiR-126): key roles in related diseases.

In eukaryotes such as humans, some non-coding single-stranded RNAs (ncRNAs) help to regulate the pre- and post-transcriptional expression of certain genes, which in turn control many important physiological processes, such as cell proliferation, distinctions, invasion, angiogenesis, and embryonic development. microRNA-126 is an important member of these miRNAs that can be directly or indirectly involved in the control of angiogenesis. Recently, numerous studies have expounded that microRNA-126 can inhibit or promote angiogenesis as well as attenuate inflammatory responses through complex molecular mechanisms. As such, it serves as a biomarker or potential therapeutic target for the prediction, diagnosis, and treatment of relevant diseases. In this review, we present the advancements in research regarding microRNA-126's role in the diagnosis and treatment of related diseases, aiming to provide innovative therapeutic options for the diagnosis and treatment of clinically relevant diseases.

Machine learning prediction models and nomogram to predict the risk of in-hospital death for severe DKA: A clinical study based on MIMIC-IV, eICU databases, and a college hospital ICU.

AIM: To establish a prediction model and assess the risk factors for severe diabetic ketoacidosis (DKA) in adult patients during the ICU. INTRODUCTION: With DKA hospitalization rates consistently increasing, in-hospital mortality has become a growing concern. METHODS: DKA patients aged >18 years old in the US-based critical care database (Medical Information Mart for Intensive Care (MIMIC-IV)) were considered. Independent risk factors for in-hospital mortality were screened using extreme gradient boosting (XGBoost) and the Bayesian information criterion (BIC) optimal subset regression. One predictive model was developed using machine learning extreme gradient boosting (XGBoost), and the other one was a nomogram based on logistic regression to estimate risks of in-hospital mortality with severe DKA. Established models were assessed by using internal validation and external validation. The MIMIC-IV was split into training and testing samples in a 7:3 ratio. The eICU Collaborative Research Database and admissions data from the department of critical care medicine of the first affiliated hospital of Harbin medical university were used for independent validation. The discriminatory ability of the model was determined by illustrating a receiver operating curve (ROC) and calculating the C-index. Meanwhile, the calibration plot and Hosmer-Lemeshow goodness-of-fit test (HL test) was conducted to evaluate the performance of our new build model. Decision curve analysis (DCA) was performed to assess the clinical net benefit. Net Reclassification Improvement (NRI) was used to compare the predictive power of the two models. RESULTS: A multivariable model that included acute physiology score III (APS III), the highest levels of blood plasma osmolality (osmolarity_max), minimum osmolarity (osmolarity_min)/osmolarity _max, vasopressor, and the highest levels of blood lactate was represented as the nomogram. The C- index of the nomogram model was 0.915 (95% CI: 0.966-0.864) in the training dataset and 0.971 (95% CI: 0.992-0.950) in the internal validation. The nomogram's sensitivity was well according to all data's HL test (P > 0.05). DCA showed that our model was clinically valuable. The XGB (extreme gradient boosting) model achieved an AUC (area under the curve) of 0.950 (95% CI, 0.920-0.980); however, the nomogram model made was more effective than XGB based on NRI. CONCLUSION: The predictive XGB and nomogram models for predicting in-hospital patient deaths with DKA were effective. The forecast models can help clinical physicians promptly identify patients at high risk of DKA, prevent in-hospital deaths, and promptly intervene.

CircPTP4A2 Promotes Microglia Polarization in Cerebral Ischemic Stroke via miR-20b-5p/YTHDF1/TIMP2 Axis.

Activated microglia play dual roles in ischemic stroke (IS) according to its polarization states. Herein, we investigated the function of circPTP4A2 in regulating microglia polarization in IS. IS models were established by MACO/R and OGD/R treatment. TTC staining was employed to detect cerebral infarct size. Cell vitality was measured using CCK-8 assay. CD16 and CD206 levels were examined using flow cytometry. The interactions between circPTP4A2, miR-20b-5p, and YTHDF1 were analyzed by dual-luciferase reporter gene, RIP, or RNA pull-down assays. circPTP4A2 was upregulated in IS patients. circPTP4A2 knockdown alleviated MCAO/R-induced cerebral injury in mice. circPTP4A2 knockdown promoted microglia M2 polarization after OGD/R. circPTP4A2 promoted YTHDF1 expression by sponging miR-20b-5p. The promoting effect of circPTP4A2 knockdown on microglia M2 polarization was abrogated by miR-20b-5p inhibition. YTHDF1 activated the NF-κB pathway by increasing TIMP2 mRNA stability and expression. circPTP4A2 downregulation promoted microglia M2 polarization to inhibit IS development by regulating the miR-20b-5p/YTHDF1/TIMP2/NF-κB axis.

Flexible integrated sensor with asymmetric structure for simultaneously 3D tactile and thermal sensing.

The human body detects tactile stimuli through a combination of pressure force and temperature signals via various cutaneous receptors. The development of a multifunctional artificial tactile perception system has potential benefits for future robotic technologies, human-machine interfaces, artificial intelligence, and health monitoring devices. However, constructing systems beyond simple pressure sensing capabilities remains challenging. Here, we propose an artificial flexible and ultra-thin (50 µ m) skin system to simultaneously capture 3D tactile and thermal signals, which mimics the human tactile recognition process using customized sensor pairs and compact peripheral signal-converting circuits. The 3D tactile sensors have a flower-like asymmetric structure with 5-ports and 4 capacitive elements in pairs. Differential and average signals would reveal the curl and amplitude values of the fore field with a resolution of 0.18/mm. The resistive thermal sensors are fabricated with serpentine lines and possess stable heat-sensing performance (165 mV/°C) under shape deformation conditions. Real-time monitoring of the skin stimuli is displayed on the user interface and stored on mobile clients. This work offers broad capabilities relevant to practical applications ranging from assistant prosthetics to artificial electronic skins.

Wireless, Smart Hemostasis Device with All-Soft Sensing System for Quantitative and Real-Time Pressure Evaluation.

The properly applied pressure between the skin and hemostasis devices is an essential parameter for preventing bleeding and postoperative complications after a transradial procedure. However, this parameter is usually controlled based on the subjective judgment of doctors, which might cause insufficient hemostatic effect or thrombosis. Here this study develops a compact and wireless sensing system for continuously monitoring the pressure applied on the radial artery and wrist skin in clinical practice. A liquid metal (LM)-based all-soft pressure sensor is fabricated to enable conformal attachment between the device and skin even under large deformation conditions. The linear sensitivity of 0.007 kPa-1 among the wide pressure range of 0-100 kPa is achieved and the real-time detection data can be wirelessly transmitted to mobile clients as a reference pressure value. With these devices, detailed pressure data can be collected, analyzed, and stored for medical assistance as well as to improve surgery quality.

Glycopolymer brushes for the affinity adsorption of RCA120: effects of thickness, grafting density, and epitope density.

The interactions between glycopolymer brushes and lectin are very important for the development of affinity membrane chromatography in protein separation. Here, we report the combination of surface-initiated atom transfer radical polymerization (SI-ATRP) and surface plasmon resonance (SPR) to investigate the relationship between the structure of glycopolymer brushes and the affinity adsorption of lectin. The glycopolymer brushes were fabricated from self-assembly of 11-mercapto-1-undecanol (MUD)/1-undecanethiol (UDT) mixture, immobilization of ATRP initiators, and then SI-ATRP of 2-lactobionamidoethyl methacrylate (LAMA). Brush thickness and grafting density were adjusted by controlling polymerization time and thiol ratio in MUD/UDT mixture, respectively. Sugar epitope density was also controlled through copolymerization of 2-hydroxylethyl methacrylate (HEMA) with LAMA. Ricinus communis agglutinin (RCA(120)), one kind of lectin that can bind galactose specifically, was chosen to study the effects of brush architectures on lectin adsorption. SPR results indicate not only the thickness but also the grafting density and the epitope density of glycopolymer brushes can achieve the best performance of sugar cluster effect in affinity adsorption of lectin. In addition, the mass transport effect is crucial in the adsorption process. We propose that it is important to keep the balance between the sugar cluster effect and the mass transport effect in the preparation of high-performance affinity membrane chromatography.

Poly(2-hydroxyethyl methacrylate) brush surface for specific and oriented adsorption of glycosidases.

We present a detailed picture to screen general ligands from simple chemicals for fabricating affinity surface to glycosidase enzymes. The surface was constructed by grafting poly(2-hydroxyethyl methacrylate) (PHEMA) brush on SPR gold chip via surface-initiated atom-transfer radical polymerization, after which poly(methoxyethyl methacrylate) (PMEMA) and poly(oligo(ethylene glycol) methacrylate) (POEGMA) brushes were also prepared for comparison. SPR measurements were adopted to monitor the early-stage adsorption of two glycosidases and three other typical proteins. PHEMA resists the adsorption of lysozyme, bovine serum albumin, and fibrinogen, while it is capable of specifically adsorbing ß-glucosidase (GLU) and ß-galactosidase (GAL). These are quite different from the nonspecific adsorption of PMEMA and the anti-nonspecific adsorption of POEGMA to the studied proteins, because PHEMA is the acceptor substrate of the glycosidases. About 69.6 and 93.7 ng/cm(2) of GAL and GLU are adsorbed on the PHEMA brush surface, of which more than 49.6 ng/cm(2) is remained after washing with PBS. The specific adsorption process is appropriately described by Freundlich isothermal model rather than Langmuir one, and is also indicated to be spontaneous, endothermic, and entropy driven through thermodynamic studies. Taking into account all stated results above, we propose that molecular recognition takes place between the hydroxyl groups of PHEMA and the active sites of glycosidases, which subsequently enables the oriented adsorption of glycosidases on the brush surface. The adsorbed enzyme can be effectively eluted with 1.0 M aqueous solution of ethanol. Our findings open the door to the further development in the design of novel acceptor substrate-ligand affinity chromatography for enzyme purification.

Heme oxygenase-1 modulates thrombomodulin and activated protein C levels to attenuate lung injury in cecal ligation and puncture-induced acute lung injury mice.

Acute lung injury (ALI) is often associated with sepsis and is the most common cause of acute respiratory failure. The authors evaluated the role of the heme oxygenase (HO)/carbon monoxide (CO) system on lung injury in a cecal ligation and puncture (CLP)-induced mouse model of ALI. The authors established CLP-induced ALI in C57BL/6 mice. They pretreated CLP-induced mice with HO-1 inducer (hemin) or HO-1 inhibitor (Zn protoporphyrin [Znpp]) and determined various lung injury parameters including partial pressure of arterial oxygen, thrombosis, edema, and plasma malondialdehyde (MDA), and myeloperoxidase (MPO) level. Enzyme-linked immunosorbent assay (ELISA) was performed to measure plasma thrombomodulin (TM) and activated protein C (APC) levels. TM and HO-1 expression in lung tissue was evaluated by immunofluorescence staining and Western blotting. Survival rate was also monitored. CLP-induced ALI was associated with decreased partial pressure of arterial oxygen, and increased thrombosis, edema, and plasma MDA, and MPO level. Plasma TM was significantly up-regulated, whereas cell surface TM in lung tissue was significantly decreased in the CLP group compared to the sham animals. Pretreatment with hemin caused up-regulation of HO-1 expression and improved partial pressure of arterial oxygen. Hemin pretreatment also caused a significant decrease in plasma TM along with increased cell surface TM expression in lung tissue, suggesting attenuation of lung injury. Survival data showed that no difference for survival between CLP animals pretreated with hemin or Znpp. Taken together, HO-1 exerts its protective effects on CLP-induced ALI via regulating cell surface TM and APC expression and modulating blood coagulation.

Imbalance between tissue inhibitor of metalloproteinase 1 and matrix metalloproteinase 9 after cardiopulmonary resuscitation.

AIMS: This study aimed to determine whether (a) there was an imbalance between matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) after cardiopulmonary resuscitation (CPR) in a canine model of prolonged ventricular fibrillation (VF); (b) with the duration of VF, the degree of the imbalance would be greater; and (c) there was a relationship between the level of MMP-9 or TIMP-1 and the cardiac function. METHODS AND RESULTS: Ventricular fibrillation was electrically induced in 24 dogs. The animals were randomly divided into 3 groups (sham control, n = 8; 8-minute VF, n = 8; 12-minute VF, n = 8). Echocardiographic measurement and hemodynamic variables were recorded before VF and after return of spontaneous circulation. Tissue inhibitor of metalloproteinase 1 (TIMP-1) and MMP-9 were analyzed by Western blot and immunohistochemistry. Compared with sham controls, dogs under VF and CPR showed significantly decreased level of TIMP-1 (P < .001), and with the duration of VF, the level of TIMP-1 declined (P < .01). The level of MMP-9 did not achieve statistical significance in the 3 groups (P > .05); however, they were higher in VF and longer duration VF groups. The ratios of TIMP-1/MMP-9 were lower in VF groups (P < .05). There was a negative correlation between TIMP-1 and left atrium dimension and left ventricular diastolic dimensions (r = -0.83 and r = -0.96, respectively; P < .01) and a positive correlation between TIMP-1 and left ventricular ejection fraction (r = 0.85; P < .01). CONCLUSIONS: There was an imbalance between TIMP-1 and MMP-9 after CPR. It may partly contribute to the postresuscitation cardiac dysfunction.

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19.

In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

Clinical characteristics and severity of beta and delta variants of SARS-CoV-2 and the effect of vaccine on delta variants.

Background: The Delta variant of concern (VOC) is rapidly becoming the dominant strain globally. We report the clinical characteristics and severity of hospitalized patients infected with Delta and Beta VOCs during the local outbreak in Harbin, Heilongjiang Province, China, and the effect of vaccines on the Delta variant. Methods: We collected a total of 735 COVID-19 patients from the First Affiliated Hospital of Harbin Medical University, including 96 cases infected with the Delta VOC and 639 cases infected with the Beta VOC. Demographic, clinical characteristic and laboratory findings were collected and compared. Results: Differences in viral shedding, IgG and IgM levels, and the neutrophil-to-lymphocyte ratio were noted between the Delta and Beta VOCs (p < 0.05). Survival analysis of the two groups revealed longer viral shedding of the Delta VOC (p < 0.05). For the Delta VOC, the longer the vaccination period, the lower the IgG and IgM levels. IgM levels were higher in the convalescent plasma group, whereas lymphocyte counts were lower. Conclusions: Delta VOC virus shedding was longer compared with Beta VOC shedding. Vaccination with inactivated vaccines can reduce the severe illness rate of the Delta VOC. IgG and IgM levels are reduced as the time period between the first and second vaccine doses increases.

Melatonin Exerts Cardioprotective Effects by Inhibiting NLRP3 Inflammasome-Induced Pyroptosis in Mice following Myocardial Infarction.

Myocardial infarction- (MI-) induced myocardial damage is mainly attributed to the loss of cardiomyocytes. Pyroptosis is a newly recognized form of programmed cell necrosis that is associated with the progression of MI. Melatonin has been shown to exert cardioprotective effects against cardiac damage in multiple cardiovascular diseases. However, the effect of melatonin on pyroptosis-induced cardiac injury in MI has not been elucidated. Herein, we found that melatonin administration ameliorated cardiac dysfunction and reduced cardiomyocyte death both in mice following coronary artery ligation and in H9C2 cells exposed to hypoxia. The results also showed that pyroptosis was induced both in vivo and in vitro, as evidenced by increased NLRP3, cleaved caspase-1, GSDMD-N, and mature IL-1ß and IL-18 levels, and these changes were decreased by melatonin treatment. Furthermore, we observed that TLR4 and NF-κB levels were increased by MI or hypoxia, and these increases were reversed by melatonin. The antipyroptotic action of melatonin was abrogated by treatment with an agonist of the TLR4/NF-κB signaling pathway. Our results indicate that melatonin can exert cardioprotective effects by inhibiting NLRP3 inflammasome-induced pyroptosis through modulation of the TLR4/NF-κB signaling pathway and provide strong evidence for the utility of melatonin in the treatment of MI.

Knockdown CD44 promote the inflammatory response through the autophagy pathway in mouse models of pulmonary contusion.

BACKGROUND: The effects of CD44, via the anti-inflammatory functions of autophagy, on lung injuries following pulmonary contusion (PC) and cell apoptosis were investigated. METHODS: Acute lung injury (ALI) mouse models were established by inducing lung injury via PC. This injury was verified using hematoxylin and eosin (H&E) staining, following which bronchoalveolar lavage fluid (BALF) was collected from these mice for analysis and further experimentation. CD44, LC3 I/II ratio, Beclin-1, and p62 expression levels in A549 cells were determined using immunohistochemistry, and western blot assays. CCK-8, flow cytometry, and acridine orange/ethidium bromide (AO/EB) fluorescence staining were used to quantify cell growth induced by BALF. LC3 II and LC3 I expression was determined through immunofluorescence. CD44-knockdown mice were used to demonstrate lung function after PC. RESULTS: The successful establishment of the ALI mouse models, created via PC was confirmed by an enhanced inflammatory response in the lung tissue, markers of cell autophagy. The ALI mice were found to have elevated CD44 expression. The viability of A549 cells exposed to BALF was downregulated, while the knockdown of CD44 promoted this effect. AO/EB and flow cytometry also indicated that the knockdown of CD44 promoted the cell apoptosis induced by BALF. Western blot analysis showed that knockdown of CD44 can inhibit LC3 I/II, p62, and Beclin-1 expression induced by BALF exposure. Additionally, knockdown of CD44 in mice was found to promote PC-induced lung injury through the attenuation of autophagy. CONCLUSIONS: Knockdown CD44 was shown to inhibit cell growth and induced cell apoptosis via autophagy signaling pathways, promote mice with ALI induced by PC in vivo and in vitro.

COVID-19 patient with an incubation period of 27 d: A case report.

BACKGROUND: As a highly contagious disease, coronavirus disease 2019 (COVID-19) is wreaking havoc around the world due to continuous spread among close contacts mainly via droplets, aerosols, contaminated hands or surfaces. Therefore, centralized isolation of close contacts and suspected patients is an important measure to prevent the transmission of COVID-19. At present, the quarantine duration in most countries is 14 d due to the fact that the incubation period of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is usually identified as 1-14 d with median estimate of 4-7.5 d. Since COVID-19 patients in the incubation period are also contagious, cases with an incubation period of more than 14 d need to be evaluated. CASE SUMMARY: A 70-year-old male patient was admitted to the Department of Respiratory Medicine of The First Affiliated Hospital of Harbin Medical University on April 5 due to a cough with sputum and shortness of breath. On April 10, the patient was transferred to the Fever Clinic for further treatment due to close contact to one confirmed COVID-19 patient in the same room. During the period from April 10 to May 6, nucleic acid and antibodies to SARS-CoV-2 were tested 7 and 4 times, respectively, all of which were negative. On May 7, the patient developed fever with a maximum temperature of 39℃, and his respiratory difficulties had deteriorated. The results of nucleic acid and antibody detection of SARS-CoV-2 were positive. On May 8, the nucleic acid and antibody detection of SARS-CoV-2 by Heilongjiang Provincial Center for Disease Control were also positive, and the patient was diagnosed with COVID-19 and reported to the Chinese Center for Disease Control and Prevention. CONCLUSION: This case highlights the importance of the SARS-CoV-2 incubation period. Further epidemiological investigations and clinical observations are urgently needed to identify the optimal incubation period of SARS-CoV-2 and formulate rational and evidence-based quarantine policies for COVID-19 accordingly.