When-to-Loop: Enhanced Loop Closure for LiDAR SLAM in Urban Environments Based on SCAN CONTEXT.

Global Navigation Satellite Systems (GNSSs) frequently encounter challenges in providing reliable navigation and positioning within urban canyons due to signal obstruction. Micro-Electro-Mechanical System (MEMS) Inertial Measurement Units (IMUs) offers an alternative for autonomous navigation, but they are susceptible to accumulating errors. To mitigate these influences, a LiDAR-based Simultaneous Localization and Mapping (SLAM) system is often employed. However, these systems face challenges in drift and error accumulation over time. This paper presents a novel approach to loop closure detection within LiDAR-based SLAM, focusing on the identification of previously visited locations to correct time-accumulated errors. Specifically, the proposed method leverages the vehicular drivable area and IMU trajectory to identify significant environmental changes in keyframe selection. This approach differs from conventional methods that only rely on distance or time intervals. Furthermore, the proposed method extends the SCAN CONTEXT algorithm. This technique incorporates the overall distribution of point clouds within a region rather than solely relying on maximum height to establish more robust loop closure constraints. Finally, the effectiveness of the proposed method is validated through experiments conducted on the KITTI dataset with an enhanced accuracy of 6%, and the local scenarios exhibit a remarkable improvement in accuracy of 17%, demonstrating improved robustness in loop closure detection for LiDAR-based SLAM.

Association between serum iron status and the risk of five bone and joint-related diseases: a Mendelian randomization analysis.

Background: According to reports, iron status has been associated with the risk of bone and joint-related diseases. However, the exact role of iron status in the development of these conditions remains uncertain. Method: We obtained genetic data on iron status, specifically serum iron, ferritin, transferrin saturation (TSAT), and transferrin, as well as data on five common bone and joint-related diseases (osteoarthritis, osteoporosis, rheumatoid arthritis [RA], ankylosing spondylitis [AS], and gout) from independent genome-wide association studies involving individuals of European ancestry. Our primary approach for causal estimation utilized the inverse variance weighted (IVW) method. To ensure the reliability of our findings, we applied complementary sensitivity analysis and conducted reverse causal analysis. Result: Using the IVW method, we revealed a positive causal relationship between ferritin levels and the risk of osteoarthritis (OR [95% CI], 1.0114 [1.0021-1.0207]). Besides, we identified a protective causal relationship between serum iron levels and TSAT levels in the risk of RA (OR [95% CI] values of serum iron and TSAT were 0.9987 [0.9973-0.9999] and 0.9977 [0.9966-0.9987], respectively). Furthermore, we found a positive causal relationship between serum iron levels and the risk of AS (OR [95% CI], 1.0015 [1.0005-1.0026]). Regarding gout, both serum iron and TSAT showed a positive causal relationship (OR [95% CI] values of 1.3357 [1.0915-1.6345] and 1.2316 [1.0666-1.4221] for serum iron and TSAT, respectively), while transferrin exhibited a protective causal relationship (OR [95% CI], 0.8563 [0.7802-0.9399]). Additionally, our reverse causal analysis revealed a negative correlation between RA and ferritin and TSAT levels (OR [95% CI] values of serum iron and TSAT were 0.0407 [0.0034-0.4814] and 0.0049 [0.0002-0.1454], respectively), along with a positive correlation with transferrin (OR [95% CI], 853.7592 [20.7108-35194.4325]). To ensure the validity of our findings, we replicated the results through sensitivity analysis during the validation process. Conclusion: Our study demonstrated a significant correlation between iron status and bone and joint-related diseases.

Bioactive Materials That Promote the Homing of Endogenous Mesenchymal Stem Cells to Improve Wound Healing.

Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.

Tangzhiping Decoction Improves Glucose and Lipid Metabolism and Exerts Protective Effects Against White Adipose Tissue Dysfunction in Prediabetic Mice.

Background: Prediabetes, characterized by a series of metabolic abnormalities, increases the risk of diabetes and cardiovascular diseases. Tangzhiping (TZP), a clinically validated traditional Chinese medicine formula, is used to treat impaired glucose tolerance. However, the underlying mechanism of TZP in intervening prediabetes is not fully elucidated. Purpose: The current study aimed to evaluate the protective effect of TZP against prediabetes mice and explore its potential mechanism. Methods: After establishing a prediabetic animal model through 12 weeks of high-fat diet (HFD) feeding, mice were subjected to TZP for 8 weeks. Various parameters related to body weight, glucose and lipid metabolism, and insulin sensitivity were measured. Histopathological examinations observed adipose cell size and liver lipid deposition. The Sable Promethion system assessed energy metabolism activity. Transcriptomic analysis of Epididymal white adipose tissue (EWAT) identified enriched pathways and genes. The key genes in the enriched pathways were identified through RT-PCR. Results: Our data revealed that the administration of TZP reduced body weight and fat mass in a prediabetes mouse model. TZP normalized the glucose and insulin levels, improved insulin resistance, and decreased plasma TC and FFA. The alleviation of adipose tissue hypertrophy and lipid deposition by TZP was demonstrated through pathological examination. Indirect calorimetry measurements indicated a potential increase in VO2 and EE levels with TZP. The results of EWAT transcription showed that TZP reversed pathways and genes related to inflammation and catabolic metabolism. RT-PCR demonstrated that the mRNA expression of inflammation and lipolysis, including Tlr2, Ccr5, Ccl9, Itgb2, Lipe, Pnpla2, Cdo1, Ces1d, Echs1, and Acad11, were changed by TZP treatment. Conclusion: TZP effectively alleviates obesity, impaired glucose and lipid metabolism, and insulin resistance. The effect of TZP might be associated with the regulation of gene expression in dysfunctional adipose tissue.

AMPK activation eliminates senescent cells in diabetic wound by inducing NCOA4 mediated ferritinophagy.

BACKGROUND: Diabetic wounds are one of the long-term complications of diabetes, with a disordered microenvironment, diabetic wounds can easily develop into chronic non-healing wounds, which can impose a significant burden on healthcare. In diabetic condition, senescent cells accumulate in the wound area and suppress the wound healing process. AMPK, as a molecule related to metabolism, has a close relationship with aging and diabetes. The purpose of this study was to investigate the effects of AMPK activation on wound healing and explore the underlying mechanisms. METHODS: AMPK activator A769662 was topically applied in wound models of diabetic mice. Alterations in the wound site were observed and analyzed by immunohistochemistry. The markers related to autophagy and ferritinophagy were analyzed by western blotting and immunofluorescence staining. The role of AMPK activation and ferritinophagy were also analyzed by western blotting. RESULTS: Our results show that AMPK activation improved diabetic wound healing and reduced the accumulation of senescent cells. Intriguingly, we found that AMPK activation-induced ferroptosis is autophagy-dependent. We detected that the level of ferritin had deceased and NCOA4 was markedly increased after AMPK activation treatment. We further investigated that NCOA4-mediated ferritinophagy was involved in ferroptosis triggered by AMPK activation. Most importantly, AMPK activation can reverse the ferroptosis-insensitive of senescent fibroblast cells in diabetic mice wound area and promote wound healing. CONCLUSIONS: These results suggest that activating AMPK can promote diabetic wound healing by reversing the ferroptosis-insensitive of senescent fibroblast cells. AMPK may serve as a regulatory factor in senescent cells in the diabetic wound area, therefore AMPK activation can become a promising therapeutic method for diabetic non-healing wounds.

Liver metabolomics reveals potential mechanism of Jieduan-Niwan formula against acute-on-chronic liver failure (ACLF) by improving mitochondrial damage and TCA cycle.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a refractory disease with high mortality, which is characterized by a pathophysiological process of inflammation-related dysfunction of energy metabolism. Jieduan-Niwan formula (JDNWF) is a eutherapeutic Chinese medicine formula for ACLF. However, the intrinsic mechanism of its anti-ACLF effect still need to be studied systematically. PURPOSE: This study aimed to investigate the mechanism of JDNWF against ACLF based on altered substance metabolic profile in ACLF the expression levels of related molecules. MATERIALS AND METHODS: The chemical characteristics of JDNWF were characterized using ultra performance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry. Wistar rats subjected to a long-term CCL4 stimulation followed by a combination of an acute attack with LPS/D-GalN were used to establish the ACLF model. Liver metabolites were analyzed by LC-MS/MS and multivariate analysis. Liver function, coagulation function, histopathology, mitochondrial metabolic enzyme activity and mitochondrial damage markers were evaluated. The protein expression of mitochondrial quality control (MQC) was investigated by western blot. RESULTS: Liver function, coagulation function, inflammation, oxidative stress and mitochondrial enzyme activity were significantly improved by JDNWF. 108 metabolites are considered as biomarkers of JDNWF in treating ACLF, which were closely related to TCA cycle. It was further suggested that JDNWF alleviated mitochondrial damage and MQC may be potential mechanism of JDNWF improving mitochondrial function. CONCLUSIONS: Metabolomics revealed that TCA cycle was impaired in ACLF rats, and JDNWF had a regulatory effect on it. The potential mechanism may be improving the mitochondrial function through MQC pathway, thus restoring energy metabolism.

Enzyme-responsive nanospheres target senescent cells for diabetic wound healing by employing chemodynamic therapy.

Evidence indicates that prolonged low-level inflammation and elevated-glucose-induced oxidative stress in diabetic wounds can accelerate senescence. The accumulation of senescent cells, in turn, inhibits cellular proliferation and migration, aggravating the inflammatory response and oxidative stress, ultimately impeding wound healing. In this study, we exploited the heightened lysosomal ß-galactosidase activity detected in senescent cells to develop an innovative drug delivery system by encapsulating Fe3O4 with galactose-modified poly (lactic-co-glycolic acid) (PLGA) (F@GP). We found that F@GP can selectively release Fe3O4 into senescent cells, inducing ferroptosis via the Fenton reaction in the presence of elevated intracellular H2O2 levels. This showed that F@GP administration can serve as a chemodynamic therapy to eliminate senescent cells and promote cell proliferation. Furthermore, the F@GP drug delivery system gradually released iron ions into the diabetic wound tissues, enhancing the attenuation of cellular senescence, stimulating cell proliferation, promoting re-epithelialization, and accelerating the healing of diabetic wounds in mice. Our groundbreaking approach unveiled the specific targeting of senescence by F@GP, demonstrating its profound effect on promoting the healing of diabetic wounds. This discovery underscores the therapeutic potential of F@GP in effectively addressing challenging cases of wound repair. STATEMENT OF SIGNIFICANCE: The development of galactose-modified PLGA nanoparticles loaded with Fe3O4 (F@GP) represents a significant therapeutic approach for the treatment of diabetic wounds. These nanoparticles exhibit remarkable potential in selectively targeting senescent cells, which accumulate in diabetic wound tissue, through an enzyme-responsive mechanism. By employing chemodynamic therapy, F@GP nanoparticles effectively eliminate senescent cells by releasing iron ions that mediate the Fenton reaction. This targeted approach holds great promise for promoting diabetic wound healing by selectively eliminating senescent cells, which play a crucial role in impairing the wound healing process. The innovative utilization of F@GP nanoparticles as a therapeutic intervention offers a novel and potentially transformative strategy for addressing the challenges associated with diabetic wound healing.

Erratum: Multifunctional sponge scaffold loaded with concentrated growth factors for promoting wound healing.

[This corrects the article DOI: 10.1016/j.isci.2022.105835.].

Circ_TNFRSF21 promotes cSCC metastasis and M2 macrophage polarization via miR-214-3p/CHI3L1.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a highly invasive disease with the potential to metastasize and cause fatality. Therefore, it is crucial to understand the mechanism behind cSCC in order to devise effective strategies to combat this disease. OBJECTIVE: We investigated the function of circ_TNFRSF21/miR-214-3p/CHI3L1 axis in cSCC. METHODS: The features of circ_TNFRSF21 was characterized using Sanger sequencing, and RNase R/actinomycin D treatment. Genes and M1/M2 markers levels were assessed by qRT-PCR and IHC. The proliferation, migration, and invasion of cells were evaluated by CCK-8, colony formation, EdU incorporation, and transwell assays. Tumor growth and metastasis in vivo were evaluated by nude mouse xenograft model. Interactions of circ_TNFRSF21/miR-214-3p and miR-214-3p/CHI3L1 were validated by RNA immunoprecipitation and dual luciferase assay. RESULTS: Circ_TNFRSF21 and CHI3L1 expression were elevated in both human cSCC tissues and cells, whereas miR-214-3p was reduced. Circ_TNFRSF21 silencing or miR-214-3p overexpression suppressed cSCC cell proliferation, migration, invasion, and M2 macrophage polarization. Circ_TNFRSF21 functioned as a sponge for miR-214-3p while miR-214-3p directly targeted CHI3L1. Knockdown of miR-214-3p reversed the effects of circ_TNFRSF21 knockdown on cSCC development, while CHI3L1 upregulation reversed the effects of miR-214-3p overexpression. Furthermore, knockdown of circ_TNFRSF21 inhibited cSCC tumor growth and metastasis in vivo. CONCLUSION: Circ_TNFRSF21 plays a significant role in cSCC progression by enhancing cell proliferation, migration, invasion, and M2 macrophage polarization through inhibiting miR-214-3p and subsequent disinhibition of CHI3L1. These findings deepen our understanding of the molecular mechanism of cSCC and propose the circ_TNFRSF21/miR-214-3p/CHI3L1 axis as promising diagnosis markers or therapeutic targets for cSCC.

Nanofiber Scaffolds as Drug Delivery Systems Promoting Wound Healing.

Nanofiber scaffolds have emerged as a revolutionary drug delivery platform for promoting wound healing, due to their unique properties, including high surface area, interconnected porosity, excellent breathability, and moisture absorption, as well as their spatial structure which mimics the extracellular matrix. However, the use of nanofibers to achieve controlled drug loading and release still presents many challenges, with ongoing research still exploring how to load drugs onto nanofiber scaffolds without loss of activity and how to control their release in a specific spatiotemporal manner. This comprehensive study systematically reviews the applications and recent advances related to drug-laden nanofiber scaffolds for skin-wound management. First, we introduce commonly used methods for nanofiber preparation, including electrostatic spinning, sol-gel, molecular self-assembly, thermally induced phase separation, and 3D-printing techniques. Next, we summarize the polymers used in the preparation of nanofibers and drug delivery methods utilizing nanofiber scaffolds. We then review the application of drug-loaded nanofiber scaffolds for wound healing, considering the different stages of wound healing in which the drug acts. Finally, we briefly describe stimulus-responsive drug delivery schemes for nanofiber scaffolds, as well as other exciting drug delivery systems.

Astragaloside IV Attenuates High-Glucose-Induced Impairment in Diabetic Nephropathy by Increasing Klotho Expression via the NF-κB/NLRP3 Axis.

Objective: Deficiencies in klotho are implicated in various kidney dysfunctions including diabetic nephropathy (DN) related to inflammatory responses. Klotho is closely related to inflammatory responses and is a potential target for ameliorating kidney failure. Pyroptosis, an inflammatory form of programmed cell death, is reported to take part in DN pathogenesis recently. This study is aimed at exploring whether and how klotho inhibited podocyte pyroptosis and whether astragaloside IV (AS-IV) protect podocyte through the regulation of klotho. Materials and Methods: SD rat model of DN and conditionally immortalized mouse podocytes exposed to high glucose were treated with AS-IV. Biochemical assays and morphological examination, cell viability assay, cell transfection, phalloidin staining, ELISA, LDH release assay, SOD and MDA detection, MMP assay, ROS level detection, flow cytometry analysis, TUNEL staining assay, PI/Hoechst 33342 staining, immunofluorescence assay, and western blot were performed to elucidate podocyte pyroptosis and to observe the renal morphology. Results: The treatment of AS-IV can improve renal function and protect podocytes exposed to high glucose. Klotho was decreased, and AS-IV increased klotho levels in serum and kidney tissue of DN rats as well as podocytes exposed to high glucose. AS-IV can inhibit DN glomeruli pyroptosis in vivo. In vitro, overexpressed klotho and treatment with AS-IV inhibited pyroptosis of podocytes cultured in high glucose. Klotho knockdown promoted podocyte pyroptosis, and treatment with AS-IV reversed this effect. Furthermore, the overexpression of klotho and AS-IV reduces oxidative stress levels and inhibited NF-κB activation and NLRP3-mediated podocytes' pyroptosis which was abolished by klotho knockdown. In addition, both the ROS inhibitor NAC and the NF-κB pathway inhibitor PDTC can inhibit NLRP3 inflammasome activation. NLRP3 inhibitor MCC950 can inhibit pyroptosis of podocytes exposed to high glucose. Conclusion: Altogether, our results demonstrate that the protective effect of AS-IV in upregulating klotho expression in diabetes-induced podocyte injury is associated with the inhibition of NLRP3-mediated pyroptosis via the NF-κB signaling pathway.

Defective NCOA4-dependent ferroptosis in senescent fibroblasts retards diabetic wound healing.

Cellular senescence describes a state of permanent proliferative arrest in cells. Studies have demonstrated that diabetes promotes the pathological accumulation of senescent cells, which in turn impairs cell movement and proliferation. Historically, senescence has been perceived to be a detrimental consequence of chronic wound healing. However, the underlying mechanism that causes senescent cells to remain in diabetic wounds is yet to be elucidated. Ferroptosis and ferritinophagy observed in diabetes are due to iron metabolism disorders, which are directly associated with the initiation and progression of diabetes. Herein, we reveal that senescent fibroblasts in diabetic wounds are resistant to ferroptosis and that impaired ferritinophagy may be a contributing cause. Further, the expression of NCOA4, a key factor that influences ferritinophagy, is decreased in both diabetic wound tissue and high glucose-induced senescent fibroblasts. Moreover, NCOA4 overexpression could render senescent fibroblasts more vulnerable to ferroptosis. A faster wound healing process was also linked to the induction of ferroptosis. Thus, resistance to ferroptosis impedes the removal of senescent fibroblasts; promoting ferritinophagy could reverse this process, which may have significant implications for the management of diabetic wounds.

Multifunctional sponge scaffold loaded with concentrated growth factors for promoting wound healing.

Although both are applied in regenerative medicine, acellular dermal matrix (ADM) and concentrated growth factor (CGF) have their respective shortcoming: The functioning of CGF is often hindered by sudden release effects, among other problems, and ADM can only be used in outer dressing for wound healing. In this study, a compound network with physical-chemical double cross-linking was constructed using chemical cross-linking and the intertwining of ADM and chitosan chains under freezing conditions; equipped with good biocompatibility and cell/tissue affinity, the heparin-modified composite scaffold was able to significantly promote cell adhesion and proliferation to achieve adequate fixation and slow down the release of CGF; polydopamine nanoparticles having excellent near-infrared light photothermal conversion ability could significantly promote the survival of rat autologous skin grafts. In a word, this multifunctional composite scaffold is a promising new type of implant biomaterial capable of delivering CGF to promote the healing of full-thickness skin defects.

Tongxinluo attenuates atherosclerosis by inhibiting ROS/NLRP3/caspase-1-mediated endothelial cell pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL) is one of the most common traditional Chinese medicines and plays a vital role in treating atherosclerosis (AS). Endothelial cell (EC) pyroptosis plays a crucial role in the development of AS. Previous research revealed the inhibitory function of TXL in EC apoptosis and autophagy. However, whether TXL can inhibit the pyroptosis of ECs has not been determined. AIM OF THE STUDY: To explore the influence of TXL on EC pyroptosis and determine its underlying mechanism of action in AS. MATERIALS AND METHODS: The TXL components were determined by ultra-performance liquid chromatography coupled with a photodiode array detector. We used ApoE-/- mice to establish a disease model of AS. After treatment with TXL, we recorded pathological changes in the mice and performed immunofluorescence staining of mice aortas. We also measured protein and gene levels to explore the influence of TXL on pyroptosis in vivo. The model was established by stimulating mouse aortic endothelial cells (MAECs) with oxidized low-density lipoprotein (ox-LDL) and analyzing the effect of TXL on pyroptosis by Western blotting (WB), real-time PCR (RT-PCR), and flow cytometry (FCM). We also investigated the impact of TXL on reactive oxygen species (ROS) by FCM and WB. RESULTS: Ten major components of TXL were detected. The vivo results showed that TXL inhibited the development of AS and decreased EC pyroptosis, the activation of caspase-1, and the release of inflammatory cytokines. The vitro experiments showed that TXL significantly reduced the extent of injury to MAECs by oxidized LDL (ox-LDL). TXL reversed the high expression of gasdermin D and other proteins induced by ox-LDL and had a significant synergistic effect with the caspase-1 inhibitor VX-765. We also confirmed that TXL decreased the accumulation of ROS and the expression levels of its essential regulatory proteins Cox2 and iNOS. When ROS accumulation was reduced, EC pyroptotic damage was reduced accordingly. CONCLUSION: Our results indicated that TXL inhibited EC pyroptosis in AS. Reducing the accumulation of ROS may be the essential mechanism of AS inhibition by TXL.

Application of postmortem MRI for identification of medulla oblongata contusion as a cause of death: a case report.

Whiplash injury is common in traffic accidents, and severe whiplash is characterized by cervical spinal cord injuries with cervical dislocation or fracture, that can be diagnosed by postmortem computed tomography (PMCT), postmortem magnetic resonance (PMMR), or conventional autopsy. However, for cervical spinal cord injury without fracture and dislocation, PMMR can be more informative because it provides higher resolution of soft tissues. We report the case of a 29-year-old male who died immediately following a traffic accident, in which the vehicle hit an obstacle at a high speed, causing deformation of the bumper and severe damage of the vehicle body. PMCT indicated no significant injuries or diseases related to death, but PMMR showed patchy abnormal signals in the medulla oblongata, and the lower edge of the cerebellar tonsil was herniated out of the foramen magnum. The subsequent pathological and histological results confirmed that death was caused by medulla oblongata contusion combined with cerebellar tonsillar herniation. Our description of this case of a rare but fatal whiplash injury in which there was no fracture or dislocation provides a better understanding of the potentially fatal consequences of cervical spinal cord whiplash injury without fracture or dislocation and of the underlying lethal mechanisms. Compared with PMCT, PMMR provides important diagnostic information in forensic practice for the identification of soft tissue injuries, and is therefore an important imaging modality for diagnosis of whiplash injury when there is no fracture or dislocation.

Overexpression of the Long Noncoding RNA HIF2PUT Inhibits Non-Small Cell Lung Cancer Cell Proliferation and Invasion Through HIF-2a Pathway.

Objective: The role and molecular mechanism of long-chain noncoding RNAs (lncRNAs) in lung cancer remain to be elucidated. The aim of this study was to investigate the association between a long coding RNA hypoxia-inducible factor-2α (HIF-2α) promoter upstream transcript (HIF2PUT) and clinical characteristics of non-small cell lung cancer (NSCLC) and its regulatory role in NSCLC. Materials and Methods: The correlation between HIF2PUT expression and pathological features of NSCLC was analyzed in NSCLC patient samples. Real-time polymerase chain reaction and Western blot were used to detect genes' mRNA and protein expression, respectively. Cell proliferation assay, invasion, and transwell assay were performed to determine the effects of HIF2PUT on NSCLC cells. Results: lncRNA HIF2PUT was downregulated in NSCLC tissues and cell lines. The authors found that HIF2PUT was mainly expressed in cytoplasm and overexpression of HIF2PUT attenuates cell proliferation and invasion in NSCLC cells. Moreover, low expression of HIF2PUT was significantly related to TNM stage (p = 0.045) and histological type (p = 0.025). Furthermore, HIF2PUT was found to play a role in cell proliferation and invasion in NSCLC through regulating HIF-2a. Conclusion: Based on this study, the inhibitory role of HIF2PUT on NSCLC proliferation, invasion could be blocked by HIF-2a silencing. In summary, this study suggests that HIF2PUT and HIF-2a may play an important role in the regulation of NSCLC progression, which provides new insights for clinical treatment.

Application of Targeted Coronary Angiography in the Diagnosis of Sudden Cardiac Death.

OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS: Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.

Successful surgical treatment of polybacterial gas gangrene confirmed by metagenomic next-generation sequencing detection: A case report.

BACKGROUND: We report on a case of Vibrio vulnificus (V. vulnificus) detected by metagenomics next-generation sequencing (mNGS) in a 53-year-old male patient with polymicrobial gas gangrene and successful treatment by surgery. This report raises awareness among dermatologists that when a patient is clinically suspected of a special type of pathogenic infection, the mNGS method should be preferred to identify the patient's pathogen infection as soon as possible and then take effective treatment in time to save patients' lives. CASE SUMMARY: A 53-year-old male who worked in the aquatic market complained of redness and swelling of the lower limbs, blisters and ulcers with fever for 3 d. We used mNGS to test the pathogens in ulcer secretions. The results were returned in 24 h and indicated: V. vulnificus, Fusobacterium necrophorum, Staphylococcus haemolyticus, Staphylococcus aureus, Streptococcus dysgalactiae and Klebsiella aerogenes. This patient was diagnosed with V. vulnificus infection. The emergency operation was performed immediately under combined lumbar and epidural anesthesia: Left leg expansion and exploration (August 10, 2021). After surgery, we continued to use piperacillin sodium tazobactam sodium 4.5 g every 8 h and levofloxacin 0.5 g for anti-infection treatment. The patient underwent further surgery under lumbar anesthesia on August 17, 2021 and August 31, 2021: Left leg deactivation and skin grafting, negative pressure closed drainage and right thigh skin removal. After treatment, the transplanted flap survived. CONCLUSION: We could confirm the diagnosis of Vibrio vulnificus infection within 24 h through mNGS detection and then immediately performed emergency surgery.

Functional and binding studies of gallic acid showing platelet aggregation inhibitory effect as a thrombin inhibitor.

Objective: This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. Methods: A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result. Results: Gallic acid was confirmed as a direct thrombin inhibitor with IC50 of 9.07 µmol/L and showed a significant inhibitory effect on thrombin induced platelet aggregation. SPR-based binding studies demonstrated that gallic acid interacted with thrombin with a KD value of 8.29 µmol/L. Molecular dynamics and binding free energy analysis revealed that thrombin-gallic acid system attained equilibrium rapidly with very low fluctuations, the calculated binding free energies was -14.61 kcal/mol. Ala230, Glu232, Ser235, Gly258 and Gly260 were the main amino acid residues responsible for thrombin inhibition by gallic acid, providing a mechanistic basis for further optimization. Conclusion: This study proved that gallic acid is a direct thrombin inhibitor with platelet aggregation inhibitory effect, which could provide a basis for the follow-up research and development for novel thrombin inhibitors.

Polydopamine modified acellular dermal matrix sponge scaffold loaded with a-FGF: Promoting wound healing of autologous skin grafts.

Despite increasing potentials as a skin regeneration template (DRT) to guide tissue healing, acellular dermal matrix (ADM) is still challenged by issues (like dense architecture, low cellular adhesion and poor vascularization), contributing to necrosis and shedding of upper transplanted skins. Modified with polydopamine (PDA), a novel and porous DRT capable of drug delivery was designed using porcine-derived ADM (PADMS) gels, termed PDA-PADMS. However, it was unclear whether it could efficiently deliver human acidic fibroblast growth factor (a-FGF) and regenerate skin defects. Herein, after being fabricated and optimized with PADMS gels in different ratios (1:6, 1:7, 1:8), PDA-PADMS loading a-FGF (PDA-PADMS-FGF) was evaluated by the morphology, physical& chemical properties, drug release and in-vitro biological evaluations, followed by full-thickness skin defects implanted with PDA-PADMS-FGF covered by transplanted skins. Apart from containing abundant collagen and elastin, porous PADMS (with a loose and uniform structure) was demonstrated to possess controlled release of a-FGF and biocompatibility attributed to PDA coating. Consistent with augmented cellular migration and proliferation in vitro, PDA-PADMS-FGF also accelerated wound healing and reduced scarring, improving collagen arrangement and neovascularization. In conclusion, PDA-PADMS-FGF has a good potential and application prospect as a matrix material for wound repair.