Pathological Characteristics and Classification of Unstable Coronary Atherosclerotic Plaques.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.

Survey on the Construction Status of Forensic Virtual Autopsy Laboratory and the Applicability of Laboratory Accreditation.

OBJECTIVES: To survey the development status and actual needs of virtual autopsy technology in China and to clarify the applicability of forensic virtual autopsy laboratory accreditation. METHODS: The questionnaire was set up included three aspects：(1) the current status of virtual autopsy technology development; (2) the accreditation elements such as personnel, equipment, entrustment and acceptance, methods, environmental facilities; (3) the needs and suggestions of practicing institutions. A total of 130 forensic pathology institutions were surveyed by online participation through the Questionnaire Star platform. RESULTS: Among the 130 institutions, 43.08% were familiar with the characteristics of virtual autopsy technology, 35.38% conducted or received training in virtual autopsy, and 70.77% have establishment needs (including maintenance). Relevant elements were suitable for laboratory accreditation. CONCLUSIONS: Virtual autopsy identification has gained social recognition. There is a demand for accreditation of forensic virtual autopsy laboratory. After the preliminary assessment, considering the characteristics and current situation of this technology, China National Accreditation Service for Conformity Assessment (CNAS) can first carry out the accreditation pilot of virtual autopsy project at large comprehensive forensic institutions with higher identification capability, and then CNAS can popularize the accreditation in a wide range when the conditions are suitable.

All-Water Etching-Free Electron Beam Lithography for On-Chip Nanomaterials.

Electron beam lithography uses an accelerated electron beam to fabricate patterning on an electron-beam-sensitive resist but requires complex dry etching or lift-off processes to transfer the pattern to the substrate or film on the substrate. In this study, etching-free electron beam lithography is developed to directly write a pattern of various materials in all-water processes, achieving the desired semiconductor nanopatterns on a silicon wafer. Introduced sugars are copolymerized with metal ions-coordinated polyethylenimine under the action of electron beams. The all-water process and thermal treatment result in nanomaterials with satisfactory electronic properties, indicating that diverse on-chip semiconductors (e.g., metal oxides, sulfides, and nitrides) can be directly printed on-chip by an aqueous solution system. As a demonstration, zinc oxide patterns can be achieved with a line width of 18 nm and a mobility of 3.94 cm2 V-1 s-1. This etching-free electron beam lithography strategy provides an efficient alternative for micro/nanofabrication and chip manufacturing.

Reconstruction and Quantitative Evaluation of Blunt Injury Cases by Finite Element Method.

OBJECTIVES: To reconstruct the cases of acceleration craniocerebral injury caused by blunt in forensic cases by finite element method (FEM), and to study the biomechanical mechanism and quantitative evaluation method of blunt craniocerebral injury. METHODS: Based on the established and validated finite element head model of Chinese people, the finite element model of common injury tool was established with reference to practical cases in the forensic identification, and the blunt craniocerebral injury cases were reconstructed by simulation software. The cases were evaluated quantitatively by analyzing the biomechanical parameters such as intracranial pressure, von Mises stress and the maximum principal strain of brain tissue. RESULTS: In case 1, when the left temporal parietal was hit with a round wooden stick for the first time, the maximum intracranial pressure was 359 kPa; the maximum von Mises stress of brain tissue was 3.03 kPa at the left temporal parietal; the maximum principal strain of brain tissue was 0.016 at the left temporal parietal. When the right temporal was hit with a square wooden stick for the second time, the maximum intracranial pressure was 890 kPa; the maximum von Mises stress of brain tissue was 14.79 kPa at the bottom of right temporal lobe; the maximum principal strain of brain tissue was 0.103 at the bottom of the right temporal lobe. The linear fractures occurred at the right temporal parietal skull and the right middle cranial fossa. In case 2, when the forehead and left temporal parietal were hit with a round wooden stick, the maximum intracranial pressure was 370 kPa and 1 241 kPa respectively, the maximum von Mises stress of brain tissue was 3.66 kPa and 26.73 kPa respectively at the frontal lobe and left temporal parietal lobe, and the maximum principal strain of brain tissue was 0.021 and 0.116 respectively at the frontal lobe and left temporal parietal lobe. The linear fracture occurred at the left posterior skull of the coronary suture. The damage evaluation indicators of the simulation results of the two cases exceeded their damage threshold, and the predicted craniocerebral injury sites and fractures were basically consistent with the results of the autopsy. CONCLUSIONS: The FEM can quantitatively evaluate the degree of blunt craniocerebral injury. The FEM combined with traditional method will become a powerful tool in forensic craniocerebral injury identification and will also become an effective means to realize the visualization of forensic evidence in court.

Fast and accurate measurement of the polarization-dependent detection efficiency of superconducting nanowire single photon detectors.

Superconducting nanowire single photon detectors (SNSPDs) have been extensively investigated due to their superior characteristics, including high system detection efficiency, low dark count rate and short recovery time. The polarization sensitivity introduced by the meandering-type superconductor nanowires is an intrinsic property of SNSPD, which is normally measured by sweeping hundreds of points on the Poincaré sphere to overcome the unknown birefringent problem of the SNSPD's delivery fiber. In this paper, we propose an alternative method to characterize the optical absorptance of SNSPDs, without sweeping hundreds of points on the Poincaré sphere. It is shown theoretically that measurements on the system detection efficiencies (SDEs) subject to cases of four specific photon polarization states are sufficient to reveal the two eigen-absorptances of the SNSPD. We validate the proposed method by comparing the measured detection spectra with the spectra attained from sweeping points on the Poincaré sphere and the simulated absorption spectra.

Dysregulated lipolysis and lipophagy in lipid droplets of macrophages from high fat diet-fed obese mice.

Obesity is associated with lipid droplet (LD) accumulation, dysregulated lipolysis and chronic inflammation. Previously, the caspase recruitment domain-containing protein 9 (CARD9) has been identified as a potential contributor to obesity-associated abnormalities including cardiac dysfunction. In the current study, we explored a positive feedback signalling cycle of dysregulated lipolysis, CARD9-associated inflammation, impaired lipophagy and excessive LD accumulation in sustaining the chronic inflammation associated with obesity. C57BL/6 WT and CARD9-/- mice were fed with normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5 months. Staining of LDs from peritoneal macrophages (PMs) revealed a significant increase in the number of cells with LD and the number of LD per cell in the HFD-fed WT but not CARD9-/- obese mice. Rather, CARD9 KO significantly increased the mean LD size. WT obese mice showed down regulation of lipolytic proteins with increased diacylglycerol (DAG) content, and CARD9 KO normalized DAG with restored lipolytic protein expression. The build-up of DAG in the WT obese mice is further associated with activation of PKCδ, NF-κB and p38 MAPK inflammatory signalling in a CARDD9-dependent manner. Inhibition of adipose triglyceride lipase (ATGL) by Atglistatin (Atg) resulted in similar effects as in CARD9-/- mice. Interestingly, CARD9 KO and Atg treatment enhanced lipophagy. In conclusion, HFD feeding likely initiated a positive feedback signalling loop from dysregulated lipolysis, CARD9-dependent inflammation, impaired lipophagy, to excessive LD accumulation and sustained inflammation. CARD9 KO and Atg treatment protected against the chronic inflammation by interrupting this feedforward cycle.

[Evaluation of brain injury caused by stick type blunt instruments based on convolutional neural network and finite element method].

The finite element method is a new method to study the mechanism of brain injury caused by blunt instruments. But it is not easy to be applied because of its technology barrier of time-consuming and strong professionalism. In this study, a rapid and quantitative evaluation method was investigated to analyze the craniocerebral injury induced by blunt sticks based on convolutional neural network and finite element method. The velocity curve of stick struck and the maximum principal strain of brain tissue (cerebrum, corpus callosum, cerebellum and brainstem) from the finite element simulation were used as the input and output parameters of the convolutional neural network The convolutional neural network was trained and optimized by using the 10-fold cross-validation method. The Mean Absolute Error (MAE), Mean Square Error (MSE), and Goodness of Fit ( R 2) of the finally selected convolutional neural network model for the prediction of the maximum principal strain of the cerebrum were 0.084, 0.014, and 0.92, respectively. The predicted results of the maximum principal strain of the corpus callosum were 0.062, 0.007, 0.90, respectively. The predicted results of the maximum principal strain of the cerebellum and brainstem were 0.075, 0.011, and 0.94, respectively. These results show that the research and development of the deep convolutional neural network can quickly and accurately assess the local brain injury caused by the sticks blow, and have important application value for understanding the quantitative evaluation and the brain injury caused by the sticks struck. At the same time, this technology improves the computational efficiency and can provide a basis reference for transforming the current acceleration-based brain injury research into a focus on local brain injury research.

E-cigarette exposure with or without heating the e-liquid induces differential remodeling in the lungs and right heart of mice.

Various cardiopulmonary pathologies associated with electronic cigarette (EC) vaping have been reported. This study investigated the differential adverse effects of heating-associated by-products versus the intact components of EC aerosol to the lungs and heart of mice. We further dissected the roles of caspase recruitment domain-containing protein 9 (CARD9)-associated innate immune response and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in EC exposure-induced cardiopulmonary injury. C57BL/6 wild type (WT), CARD9-/-, and NLRP3-/- mice were exposed to EC aerosol 3 h/day, 5 days/week for 6 month with or without heating the e-liquid with exposure to ambient air as the control. In WT mice, EC exposure with heating (EwH) significantly increased right ventricle (RV) free wall thickness at systole and diastole. However, EC exposure without heating (EwoH) caused a significant decrease in the wall thickness at systole. RV fractional shortening was also markedly reduced following EwH in WT and NLRP3-/- mice. Further, EwH activated NF-κB and p38 MAPK inflammatory signaling in the lungs, but not in the RV, in a CARD9- and NLRP3-dependent manner. Levels of circulatory inflammatory mediators were also elevated following EwH, indicating systemic inflammation. Moreover, EwoH activated TGF-ß1/SMAD2/3/α-SMA fibrosis signaling in the lungs but not the RV of WT mice. In conclusion, EC aerosol exposure following EwH or EwoH induced differential cardiopulmonary remodeling and CARD9 innate immune response and NLRP3 inflammasome contributed to the adverse effects.

Strike Velocity Prediction of Stick Blunt Instruments Based on Backpropagation Neural Network.

OBJECTIVES: To analyze and predict the striking velocity range of stick blunt instruments in different populations, and to provide basic data for the biomechanical analysis of blunt force injuries in forensic identification. METHODS: Based on the Photron FASTCAM SA3 high-speed camera, Photron FASTCAM Viewer 4.0 and SPSS 26.0 software, the tester's maximum striking velocity of stick blunt instruments and related factors were calculated and analyzed, and inputed to the backpropagation (BP) neural network for training. The trained and verified BP neural network was used as the prediction model. RESULTS: A total of 180 cases were tested and 470 pieces of data were measured. The maximum striking velocity range was 11.30-35.99 m/s. Among them, there were 122 female data, the maximum striking velocity range was 11.63-29.14 m/s; there were 348 male data, the maximum striking velocity range was 20.11-35.99 m/s. The maximum striking velocity of stick blunt instruments increased with the increase of weight and height, but there was no obvious increase trend in the male group; the maximum striking velocity decreased with age, but there was no obvious downward trend in the female group. The maximum striking velocity of stick blunt instruments has no significant correlation with the material and strike posture. The root mean square error (RMSE), the mean absolute error (MAE) and the coefficient of determination (R2) of the prediction results by using BP neural network were 2.16, 1.63 and 0.92, respectively. CONCLUSIONS: The prediction model of BP neural network can meet the demand of predicting the maximum striking velocity of different populations.

Endoplasmic Reticulum Stress Is Associated with the Mesencephalic Dopaminergic Neuron Injury in Stressed Rats.

An increasing number of people are in a state of stress due to social and psychological pressures, which may result in mental disorders. Previous studies indicated that mesencephalic dopaminergic neurons are associated with not only reward-related behaviors but also with stress-induced mental disorders. To explore the effect of stress on dopaminergic neuron and potential mechanism, we established stressed rat models of different time durations and observed pathological changes in dopaminergic neurons of the ventral tegmental area (VTA) through HE and thionine staining. Immunohistochemistry coupled with microscopy-based multicolor tissue cytometry (MMTC) was employed to investigate the number changes of dopaminergic neurons. Double immunofluorescence labelling was used to investigate expression changes of endoplasmic reticulum stress (ERS) protein GRP78 and CHOP in dopaminergic neurons. Our results showed that prolonged stress led to pathological alteration in dopaminergic neurons of VTA, such as missing of Nissl bodies and pyknosis in dopaminergic neurons. Immunohistochemistry with MMTC indicated that chronic stress exposure resulted in a significant decrease in dopaminergic neurons. Double immunofluorescence labelling showed that the endoplasmic reticulum stress protein took part in the injury of dopaminergic neurons. Taken together, these results indicated the involvement of ERS in mesencephalic dopaminergic neuron injury induced by stress exposure.

Application Value of CTA in the Computer-Aided Diagnosis of Subarachnoid Hemorrhage of Different Origins.

Subarachnoid hemorrhage (SAH) is difficult to detect because of its circulation through subarachnoid space, which leads to a high rate of missed diagnosis. Based on the above background, the purpose of this study is to study the application value of brain CT angiography (CTA) in computer-aided diagnosis of subarachnoid hemorrhage with a wide range of brain digital subtraction angiography as a gold standard. This paper collected images and related medical records of 111 patients with spontaneous subarachnoid hemorrhage receiving brain CTA and DSA examinations from February 2015 to November 2019 in the neurology department of our hospital. In contrast to the number, position, length, width, and neck width of the causative aneurysm detected by DSA, we evaluated the diagnostic results of CTA and evaluated whether there was statistical difference between the two detectives of intracranial aneurysms. The results showed that the area under ROC curve of subtraction CTA and conventional CTA was 1.000 and 0.818, respectively, which indicated that the former had better display effect on internal carotid aneurysm (AUC > 0.9), while the latter had medium value (0.7 < AUC ≤ 0.9), and the difference was statistically significant (z = 2.390, p=0.017).

A potential role of caspase recruitment domain family member 9 (Card9) in transverse aortic constriction-induced cardiac dysfunction, fibrosis, and hypertrophy.

Macrophage- and monocyte-derived cytokines are elevated in the myocardium of pressure-overloaded hearts, where they play critical roles in pathological remodeling. Caspase recruitment domain family member 9 (CARD9) regulates macrophage cytokine secretion, but its role in a transverse aortic constriction (TAC) model of pressure overload has not been evaluated. To investigate whether CARD9 may serve as a valuable therapeutic target, wild-type (WT) and CARD9-knockout mice were subjected to 3 months of TAC, and then cardiac function, hypertrophy, and fibrosis were analyzed. The expression of protein markers of myocardial autophagy and nuclear factor kappa B signaling was also investigated. At 1 month after TAC, cardiomyocyte contractile dynamics were measured in a separate cohort to further assess contractility and diastolic function. In WT but not CARD9-/- mice, TAC resulted in severe cardiomyocyte contractile dysfunction at 1 month and functional decrements in fractional shortening at 3 months in vivo. Furthermore, CARD9-/- mice did not develop cardiac fibrosis or hypertrophy. CARD9-/- mice also had decreased protein expression of inhibitor of κB kinase-α/ß, decreased phosphorylation of p65, and increased expression of protein markers of autophagy. These findings suggest that CARD9 plays a role in pathological remodeling and cardiac dysfunction in mouse hearts subjected to TAC and should be investigated further.

Fabrication of superconducting niobium nitride nanowire with high aspect ratio for X-ray photon detection.

The niobium nitride (NbN) nanowires fabricated with the high-quality ultra-thin NbN film with a thickness of 3 nm-6 nm were widely used for single photon detectors. These nanowires had a low aspect ratio, less than 1:20. However, increasing the thickness and the aspect ratio of highly-uniformed NbN nanowires without reducing the superconductivity is crucial for the device in detecting high-energy photons. In this paper, a high-quality superconducting nanowire with aspect ratio of 1:1 was fabricated with optimized process, which produced a superconducting critical current of 550 µA and a hysteresis of 36 µA at 2.2 K. With the optimization of the electron beam lithography process of AR-P6200.13 and the adjustion of the chamber pressure, the discharge power, as well as the auxiliary gas in the process of reactive ion etching (RIE), the meandered NbN nanowire structure with the minimum width of 80 nm, the duty cycle of 1:1 and the depth of 100 nm were finally obtained on the silicon nitride substrate. Simultaneously, the sidewall of nanowire was vertical and smooth, and the corresponding depth-width ratio was more than 1:1. The fabricated NbN nanowire will be applied to the detection of soft X-ray photon emitted from pulsars with a sub-10 ps time resolution.

A Long-Term Pilot Study on Sex and Spinal Cord Injury Shows Sexual Dimorphism in Functional Recovery and Cardio-Metabolic Responses.

More than a quarter of a million individuals in the US live with spinal cord injury (SCI). SCI disrupts neural circuitry to vital organs in the body. Despite severe incidences of long-term peripheral complications from SCI, the cardio-metabolic consequences and divergences in sex-related responses are not well described. We examined the effects of SCI on functional recovery, cardiac structure and function, body composition, and glucose metabolism on adult female and male Sprague Dawley (SD) rats. SCI was induced at T10 via contusion. Measured outcomes include behavioral assessment, body weight, dual-energy X-ray absorptiometry (DEXA) for body composition, echocardiography for cardiac structure and function, intraperitoneal glucose tolerance test (IPGTT) for glucose metabolism, insulin tolerance test (ITT), and histology of cardiac structure at the endpoint. There was a decrease in body fat percentage in both sexes, with SCI females disproportionately affected in percent body fat change. Left ventricular internal diameter during systole (LVIDs) was decreased in SCI females more than in SCI males. No significant differences in glucose metabolism were observed up to 20 weeks post-injury (PI). These data show significant cardio-metabolic differences as a consequence of SCI and, furthermore, that sex is an underlying factor in these differences.

Pathological changes induced by phosphine poisoning: a study on 8 children.

Aluminum phosphide (ALP) has been extensively used as an economical and effective insecticide, rodenticide, and fumigant. The active ingredient of ALP is phosphine (PH3), the use of which can lead to accidental inhalation and mass poisoning with high mortality. Exposure to PH3 will give rise to global damage in the human body. This study reviewed 4 fatal accidents including 8 children with PH3 poisoning and aimed to determine the pathological changes that resulted from exposure to PH3 and, secondly, aimed to determine whether oxidative stress was involved in PH3-induced neurotoxicity using histopathological and immunohistochemistry (IHC) methods. After focusing on the pathological changes on the major organs, we found severe damage induced by PH3 in many systems, especially the neurological system, including neuronal, axonal, and vascular injuries as well as oxidative damage with increased expression of 4-hydroxy-2-trans-nonenal (4HNE), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and 3-nitrotyrosine (3-NT) in the brain, which indicated that oxidative stress was a crucial mechanism for neuronal death in PH3 toxicity. Moreover, we observed severe myocardial and hepatocellular fatty degeneration in the tissues of the heart and liver. We considered that these characteristic changes are a suggestive sign of PH3 poisoning and partly explained the toxic mechanism of PH3 (inhibition of mitochondrial oxidative phosphorylation). We hope that this research could improve the understanding of the toxicity of PH3 in both forensic and clinical practice.

iTRAQ-based proteomic analysis discovers potential biomarkers of diffuse axonal injury in rats.

Diffuse axonal injury (DAI) is one of the most common and severe pathological consequences of traumatic brain injury (TBI). The molecular mechanism of DAI is highly complicated and still elusive, yet a clear understanding is crucial for the diagnosis, treatment, and prognosis of DAI. In our study, we used rats to establish a DAI model and applied isobaric tags for relative and absolute quantitation (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins (DEPs) in the corpus callosum. As a result, a total of 514 proteins showed differential expression between the injury groups and the control. Among these DEPs, 14 common DEPs were present at all seven time points postinjury (1, 3, 6, 12, 24, 48, and 72 h). Next, bioinformatic analysis was performed to elucidate the pathogenesis of DAI, which was found to possibly involve calcium ion-regulatory proteins (e.g., calsenilin and ryanodine receptor 2), cytoskeleton organization (e.g., peripherin, NFL, NFM, and NFH), apoptotic processes (e.g., calsenilin and protein kinase C delta type), and inflammatory response proteins (e.g., complement C3 and C-reactive protein). Moreover, peripherin and calsenilin were successfully confirmed by western blotting to be significantly upregulated during DAI, and immunohistochemical (IHC) analysis revealed that their expression increased and could be observed in axons after injury, thus indicating their potential as DAI biomarkers. Our experiments not only provide insight into the molecular mechanisms of axonal injury in rats during DAI but also give clinicians and pathologists important reference data for the diagnosis of DAI. Our findings may expand the list of DAI biomarkers and improve the postmortem diagnostic rate of DAI.

The Water Diffusion of Brain Following Hypoglycemia in Rats - A Study with Diffusion Weighted Imaging and Neuropathologic Analysis.

We established hypoglycemic rat models and divided them into three groups (the sham group, the acute hypoglycemia group and the recovery group). The brain water diffusion was examined using DWI. Thereafter, neuropathologic examinations were performed in order to evaluate the distribution of brain damage. The expression of AQP4 and Caspase3 was also examined using Western blot. We aimed to determine the specific brain regions which were vulnerable to hypoglycemia in relation to the water diffusion and neuropathology. The DWI scanning showed abnormal water diffusion in the cortex, hippocampus and hypothalamus during each stage of hypoglycemia. In the acute hypoglycemia group, the apparent diffusion coefficient (ADC) of the dentate gyrus (DG) and the hypothalamus was increased, while the ADC of the somatosensory cortex (SSc), subcortex and striatum (Str) was decreased. After glucose reperfusion and a 7-day recovery period, most of the hypoglycemia-induced changes in ADC returned to normal, except in the hypothalamus, posterior SSc and DG, which demonstrated increased ADC levels. The lowest AQP4 expression was observed in the cortex of the acute hypoglycemia group. Furthermore, there was increased Caspase3 expression in the hippocampus of the recovery group. The expression of Caspase3 in the hypothalamus was most prominent in the acute hypoglycemia group. Our work revealed that hypoglycemia significantly influenced the water diffusion of the brain. The decrease of AQP4 was associated with the formation of cytotoxic edema in acute hypoglycemia. Hypoglycemia primarily tends to damage the cerebral cortex, hippocampus and hypothalamus and may result in permanent injury to the brain.

Caspase recruitment domain-containing protein 9 (CARD9) knockout reduces regional ischemia/reperfusion injury through an attenuated inflammatory response.

Ischemic heart disease remains a leading cause of morbidity and mortality in the United States. Interventional reperfusion induces further damage to the ischemic myocardium through neutrophil infiltration and acute inflammation. As caspase recruitment domain-containing protein 9 (CARD9) plays a critical role in innate immune response and inflammation, we hypothesized that CARD9 knockout would provide protection against ischemia and reperfusion (I/R) injury through attenuation of acute inflammatory responses. C57BL/6 wild-type (WT) and CARD9-/- mice were subjected to 45 min left anterior descending (LAD) coronary artery occlusion followed by 24-h reperfusion. Area at risk (AAR) and infarct size were measured by Evans blue and triphenyltetrazolium chloride (TTC) staining. Frozen heart sections were stained with anti-mouse GR-1 antibody to detect infiltrated neutrophils. Concentrations of cytokines/chemokines TNF-α, IL-6, CXCL-1 and MCP-1 were determined in heart tissue homogenate and serum by ELISA assay. Western immunoblotting analyses were performed to measure the phosphorylation of p38 MAPK. Our results indicate that following I/R, infarct size was significantly smaller in CARD9-/- mice compared to WT. The number of infiltrated neutrophils was significantly lower in CARD9-/- mice compared to WT. Levels of TNF-α, IL-6, CXCL-1 and MCP-1 were significantly reduced in heart tissue and serum from CARD9-/- mice compared to WT. CARD9-/- mice also exhibited significantly lower levels of phosphorylated p38 MAPK. Taken together, our results suggest that CARD9 knockout protects the heart from ischemia/reperfusion (I/R) injury, possibly through reduction of neutrophil infiltration and attenuation of CARD9-associated acute inflammatory signaling.

The essential function of CARD9 in diet-induced inflammation and metabolic disorders in mice.

Inflammation and metabolic disorder are common pathophysiological conditions, which play a vital role in the development of obesity and type 2 diabetes. The purpose of this study was to explore the effects of caspase recruitment domain (CARD) 9 in the high fat diet (HFD)-treated mice and attempt to find a molecular therapeutic target for obesity development and treatment. Sixteen male CARD9-/- and corresponding male WT mice were fed with normal diet or high fat diet, respectively, for 12 weeks. Glucose tolerance, insulin resistance, oxygen consumption and heat production of the mice were detected. The CARD9/MAPK pathway-related gene and protein were determined in insulin-responsive organs using Western blotting and quantitative PCR. The results showed that HFD-induced insulin resistance and impairment of glucose tolerance were more severe in WT mice than that in the CARD9-/- mice. CARD9 absence significantly modified O2 consumption, CO2 production and heat production. CARD9-/- mice displayed the lower expression of p38 MAPK, JNK and ERK when compared to the WT mice in both HFD- and ND-treated groups. HFD induced the increase of p38 MAPK, JNK and ERK in WT mice but not in the CARD9-/- mice. The results indicated that CARD9 absence could be a vital protective factor in diet-induced obesity via the CARD9/MAPK pathway, which may provide new insights into the development of gene knockout to improving diet-induced obesity and metabolism disorder.