DH5α Outer Membrane-Coated Biomimetic Nanocapsules Deliver Drugs to Brain Metastases but not Normal Brain Cells via Targeting GRP94.

Receptor-mediated vesicular transport has been extensively developed to penetrate the blood-brain barrier (BBB) and has emerged as a class of powerful brain-targeting delivery technologies. However, commonly used BBB receptors such as transferrin receptor and low-density lipoprotein receptor-related protein 1, are also expressed in normal brain parenchymal cells and can cause drug distribution in normal brain tissues and subsequent neuroinflammation and cognitive impairment. Here, the endoplasmic reticulum residing protein GRP94 is found upregulated and relocated to the cell membrane of both BBB endothelial cells and brain metastatic breast cancer cells (BMBCCs) by preclinical and clinical investigations. Inspired by that Escherichia coli penetrates the BBB via the binding of its outer membrane proteins with GRP94, avirulent DH5α outer membrane protein-coated nanocapsules (Omp@NCs) are developed to cross the BBB, avert normal brain cells, and target BMBCCs via recognizing GRP94. Embelin (EMB)-loaded Omp@EMB specifically reduce neuroserpin in BMBCCs, which inhibits vascular cooption growth and induces apoptosis of BMBCCs by restoring plasmin. Omp@EMB plus anti-angiogenic therapy prolongs the survival of mice with brain metastases. This platform holds the translational potential to maximize therapeutic effects on GRP94-positive brain diseases.

Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic-pituitary-adrenal axis.

Elucidating the molecular mechanism underlying the hyperactivity of the hypothalamic-pituitary-adrenal axis during chronic stress is critical for understanding depression and treating depression. The secretion of corticotropin-releasing hormone (CRH) from neurons in the paraventricular nucleus (PVN) of the hypothalamus is controlled by salt-inducible kinases (SIKs) and CREB-regulated transcription co-activators (CRTCs). We hypothesised that the SIK-CRTC system in the PVN might contribute to the pathogenesis of depression. Thus, the present study employed chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioural tests, virus-mediated gene transfer, enzyme-linked immunosorbent assay, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription polymerase chain reaction, and immunofluorescence to investigate this connection. Our results revealed that both CSDS and CUMS induced significant changes in SIK1-CRTC1 signalling in PVN neurons. Both genetic knockdown of SIK1 and genetic overexpression of CRTC1 in the PVN simulated chronic stress, producing a depression-like phenotype in naive mice, and the CRTC1-CREB-CRH pathway mediates the pro-depressant actions induced by SIK1 knockdown in the PVN. In contrast, both genetic overexpression of SIK1 and genetic knockdown of CRTC1 in the PVN protected against CSDS and CUMS, leading to antidepressant-like effects in mice. Moreover, stereotactic infusion of TAT-SIK1 into the PVN also produced beneficial effects against chronic stress. Furthermore, the SIK1-CRTC1 system in the PVN played a role in the antidepressant actions of fluoxetine, paroxetine, venlafaxine, and duloxetine. Collectively, SIK1 and CRTC1 in PVN neurons are closely involved in depression neurobiology, and they could be viable targets for novel antidepressants.

Clusterin suppresses spermatogenic cell apoptosis to alleviate diabetes-induced testicular damage by inhibiting autophagy via the PI3K/AKT/mTOR axis.

BACKGROUND INFORMATION: Diabetes-induced testicular dysfunction is characterised by abnormal apoptosis of spermatogenic cells, but the underlying mechanism is poorly understood. This study aimed to investigate the roles of clusterin (CLU) in testicular damage associated with diabetes pathogenesis, as well as the molecular mechanism. A rat diabetes model was established using streptozocin, and the mouse spermatogenic cell line GC-1 spg was treated with high glucose as a cellular model. CLU was overexpressed in GC-1 spg cells, followed by detection of serum testosterone, cell proliferation, cell apoptosis and autophagy. RESULTS: CLU expression was significantly reduced and LC3 expression was elevated in testis tissues in the rat diabetes model and high glucose-treated GC-1 spg cells. High glucose led to suppressed viability, enhanced apoptosis, reduced Bcl-2 expression, elevated Bax expression and cleavage of Caspase-3/-9 in GC-1 spg cells, and these effects were abrogated by CLU overexpression. Additionally, CLU overexpression repressed LC3 and Beclin-1 expression, reduced the LC3II/LC3I ratio and promoted p62 expression in GC-1 spg cells in the presence of high glucose, and these effects were all mitigated by rapamycin treatment. Inhibition of PI3K/AKT/mTOR signalling with LY294002 activated autophagy in CLU-overexpressing GC-1 spg cells under high glucose conditions. CLU overexpression repressed autophagy and alleviated testicular damage in diabetic rats, which was also abrogated by LY294002 treatment. CONCLUSIONS: CLU expression is suppressed during diabetes-induced testicular damage, whereas CLU overexpression alleviates diabetes-induced testicular damage by activating PI3K/AKT/mTOR signalling to inhibit autophagy and further repress spermatogenic cell apoptosis.

A novel structurally identified epitope delivered by macrophage membrane-coated PLGA nanoparticles elicits protection against Pseudomonas aeruginosa.

The increasing prevalence of antibiotic resistance by Pseudomonas aeruginosa (PA) raises an urgent need for an effective vaccine. The outer membrane proteins of PA, especially those that are upregulated during infection, are ideal vaccine targets. However, the strong hydrophobicity of these proteins hinders their application for this purpose. In this study, we selected eight outer membrane proteins from PA with the most significantly upregulated expression. Their extracellular loops were analyzed and screened by using sera from patients who had recovered from PA infection. As a result, a novel immunogenic epitope (Ep167-193) from PilY1 (PA4554) was found. Moreover, we constructed a macrophage membrane-coated PLGA (poly lactic-co-glycolic acid) nanoparticle vaccine carrying PilY1 Ep167-193 (PNPs@M-Ep167-193) that elicits a Th2 immune response and confers adequate protection in mice. Our data furnished the promising vaccine candidate PNPs@M-Ep167-193 while providing additional evidence for structure-based epitope identification and vaccine design.

A community-level study on COVID-19 transmission and policy interventions in Wuhan, China.

The specific factors and response strategies that affect COVID-19 transmission in local communities remain under-explored in the current literature due to a lack of data. Based on primary COVID-19 data collected at the community level in Wuhan, China, our study contributes a community-level investigation on COVID-19 transmission and response strategies by addressing two research questions: 1) What community factors are associated with viral transmission? and 2) What are the key mechanisms behind policy interventions towards controlling viral transmission within local communities? We conducted two sets of analyses to address these two questions-quantitative analyses of the relationship between community factors and viral transmission and qualitative analyses of policy interventions on community transmission. Our findings show that the viral spread in local communities is irrelevant to the built environment of a community and its socioeconomic position but is related to its demographic composition. Specifically, groups under the age of 18 play an important role in viral transmission. Moreover, a series of community shutdown management initiatives (e.g., group buying, delivering supplies, and self-reporting of health conditions) play an important role in curbing viral transmission at the local level that can be applied to other geographic contexts.

Bioselective Synthesis of a Porous Carbon Collector for High-Performance Sodium-Metal Anodes.

Biomass-derived carbon materials prepared via pyrolysis from natural wood structures show potential for a storage application. Natural wood is composed of multiple carbon sources, including lignin, hemicellulose, and cellulose, which influence the formation and microstructure of pyrolysis carbon. However, the mechanism is not fully understood. In this work, vast lignin is selectively consumed via biodegradation with fungi from basswood. The results demonstrate that the as-prepared carbon material has a short-range ordered graphitic structure after thermal treatment. The improved graphitization degree of carbon suggests that cellulose is beneficial to graphite formation during pyrolysis. The elevated graphitization degree helps to improve the charge transfer and the thermodynamic stability of the electrode reaction. As a proof of concept, the obtained carbon current collector as a sodium-metal anode can undergo cycling at an areal capacity of 10 mAh cm-2 for over 4500 h and yield an excellent Coulombic efficiency of >99.5%.

A study of multinucleated giant cells in esophageal cancer.

OBJECTIVES: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multinucleated giant cell (MGC) in esophageal cancer. MATERIALS AND METHODS: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers. RESULTS: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063). CONCLUSIONS: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker.

A study of the possible role of Fab-glycosylated IgG in tumor immunity.

Previously we reported that administration of IgG could inhibit tumor progression in mouse models. At the same time, we also found that some IgGs have glycosylation modifications on their Fab fragments, which may have different biological functions than non-glycosylated IgG. In this study, we employed mouse tumor models to explore the roles of two different forms of IgG, i.e. Fab-glycosylated and Fab-non-glycosylated IgG, in tumor progression. The two types of IgGs were separated with ConA absorption which could react with glycan on the Fab arm but could not access glycan on the Fc fragment. In addition, we performed cytokine array, ELISA, western blotting, immunocytochemistry and other techniques to investigate the possible mechanisms of the actions of Fab-glycosylated IgG in the models. We found that Fab-glycosylated IgG, unlike Fab-non-glycosylated IgG, did not inhibit tumor growth and metastasis in the model. On the contrary, Fab-glycosylated IgG may bind to antigen-bound IgG molecules and macrophages through the glycosidic chain on the Fab fragment to affect antigen-antibody binding and macrophage polarization, which are likely to help tumor cells to evade the immune surveillance. A new mechanism of immune evasion with Fab-glycosylated IgG playing a significant role was proposed.

Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF.

As a widely-known neuropsychiatric disorder, the exact pathogenesis of depression remains elusive. MiRNA-206 (miR-206) is conventionally known as one of the myomiRs and has two forms: miR-206-3p and miR-206-5p. Recently, miR-206 has been demonstrated to regulate the biosynthesis of brain-derived neurotrophic factor (BDNF), a very popular target involved in depression and antidepressant responses. Here we assumed that miR-206 may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, quantitative real-time reverse transcription PCR, western blotting, immuofluorescence and virus-mediated gene transfer were used together. It was found that CSDS robustly increased the level of miR-206-3p but not miR-206-5p in the hippocampus. Both genetic overexpression of hippocampal miR-206-3p and intranasal administration of AgomiR-206-3p induced not only notable depressive-like behaviors but also significantly decreased hippocampal BDNF signaling cascade and neurogenesis in naïve C57BL/6J mice. In contrast, both genetic knockdown of hippocampal miR-206-3p and intranasal administration of AntagomiR-206-3p produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, it was found that the antidepressant-like effects induced by miR-206-3p inhibition require the hippocampal BDNF-TrkB system. Taken together, hippocampal miR-206-3p participates in the pathogenesis of depression by regulating BDNF biosynthesis and is a feasible antidepressant target.

Development of a chitosan-modified PLGA nanoparticle vaccine for protection against Escherichia coli K1 caused meningitis in mice.

BACKGROUND: Escherichia coli K1 (E. coli K1) caused neonatal meningitis remains a problem, which rises the urgent need for an effective vaccine. Previously, we rationally designed and produced the recombinant protein OmpAVac (Vo), which elicited protective immunity against E. coli K1 infection. However, Vo has limited stability, which hinders its future industrial application. METHOD: Chitosan-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared and used as carried for the recombinant Vo. And the safety, stability and immunogenicity of Vo delivered by chitosan-modified PLGA nanoparticles were tested in vitro and in a mouse model of bacteremia. RESULTS: We successfully generated chitosan-modified PLGA nanoparticles for the delivery of recombinant Vo (VoNP). In addition, we found that a freeze-drying procedure increases the stability of the VoNPs without changing the shape, size distribution and encapsulation of the Vo protein. Unlike aluminum adjuvant, the nanoparticles that delivered Vo were immunoprotective in mice even after storage for as long as 180 days. CONCLUSIONS: We identified an effective strategy to improve the stability of Vo to maintain its immunogenicity, which will contribute to the future development of vaccines against E. coli K1.

LncRNA MAFG-AS1 Promotes the Progression of Bladder Cancer by Targeting the miR-143-3p/COX-2 Axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) are potential biomarkers that are very important for the development of cancer. Studies show that lncRNAs are significantly correlated with the carcinogenesis and progression of bladder cancer (BLCA). In this research, we aimed at probing into the role of lncRNA MAFG-AS1 in the tumorigenesis of BLCA. METHODS: RT-qPCR was employed to detect MAFG-AS1 expression in BLCA tissues and cells. MAFG-AS1 siRNA and overexpression plasmid were transfected into 5637 and T24 BLCA cell lines to inhibit or upregulate MAFG-AS1 expression, respectively, and then the regulatory functions of MAFG-AS1 on BLCA cell proliferation, migration, and invasion were assessed using cell counting kit-8 (CCK-8) assay, EdU method, and Transwell experiments, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation were conducted to validate the targeting relationships between MAFG-AS1 and miR-143-3p, and miR-143-3p and COX-2. In addition, miR-143-3p was repressed in MAFG-AS1-silenced 5637 and T24 cell lines, and the function of MAFG-AS1/miR-143-3p axis in BLCA cells was further evaluated. The regulatory effects of MAFG-AS1 and miR-143-3p on the expression of COX-2 protein were detected by Western blot. RESULTS: MAFG-AS1 was remarkably upregulated in BLCA patient tissues and cell lines, and its high expression was closely related to histological grade, tumor size, and lymph node metastasis. Silencing of MAFG-AS1 inhibited BLCA cell proliferation, metastasis, and invasion, while overexpression of MAFG-AS1 in BLCA cells had opposite biological effects. MAFG-AS1 was proved to target miR-143-3p to repress its expression. Moreover, it was confirmed that MAFG-AS1 and miR-143-3p could modulate COX-2 expression. CONCLUSION: The MAFG-AS1/miR-143-3p/COX-2 axis contributes to BLCA progression.

Crystal structure of PA0833 periplasmic domain from Pseudomonas aeruginosa reveals an unexpected enlarged peptidoglycan binding pocket.

PA0833 of Pseudomonas aeruginosa is recently identified as an OmpA C-like protein that is able to interact with bacterial peptidoglycan (PGN). In this study, we reported the biochemical and structural characterization of the PGN-binding periplasmic-domain of PA0833 (PA0833-PD). Via mutagenesis, key residues responsible for engaging PGN were identified, which also enables us to localize the PGN-binding pocket in a 2.0 Šcrystal structure solved in this study. In contrast to its homologous proteins (as represented by AbOmpA-PD of Acinetobacter baumannii) that interact with PGN by directly engaging the DAP (diaminopimelate) moiety, PA0833-PD exhibits an enlarged PGN-binding pocket due to residue insertions and the formation of an extra α-helix in one lateral side of the pocket. Accordingly, single DAP molecule does not show detectable interactions with PA0833-PD in solution, highlighting that other PGN-components, in addition to DAP, are also required to restore the full binding capacity observed between PA0833 and PGN.

Targeted sequencing of circulating cell-free DNA in stage II-III resectable oesophageal squamous cell carcinoma patients.

BACKGROUND: The aim of this study was to investigate the potential of cell-free DNA (cfDNA) as a disease biomarker in oesophageal squamous cell carcinoma (ESCC) that can be used for treatment response evaluation and early detection of tumour recurrence. METHODS: Matched tumour tissue, pre- and post-surgery plasma and WBCs obtained from 17 ESCC patients were sequenced using a panel of 483 cancer-related genes. RESULTS: Somatic mutations were detected in 14 of 17 tumour tissues. Putative harmful mutations were observed in genes involved in well-known cancer-related pathways, including PI3K-Akt/mTOR signalling, Proteoglycans in cancer, FoxO signalling, Jak-STAT signalling, Chemokine signalling and Focal adhesion. Forty-six somatic mutations were found in pre-surgery cfDNA in 8 of 12 patients, with mutant allele frequencies (MAF) ranging from 0.24 to 4.91%. Three of the 8 patients with detectable circulating tumour DNA (ctDNA) had stage IIA disease, whereas the others had stage IIB-IIIB disease. Post-surgery cfDNA somatic mutations were detected in only 2 of 14 patients, with mutant allele frequencies of 0.28 and 0.36%. All other somatic mutations were undetectable in post-surgery cfDNA, even in samples collected within 3-4 h after surgery. CONCLUSION: Our study shows that somatic mutations can be detected in pre-surgery cfDNA in stage IIA to IIIB patients, and at a lower frequency in post-surgery cfDNA. This indicates that cfDNA could potentially be used to monitor disease load, even in low disease-stage patients.

Guiding Uniform Li Plating/Stripping through Lithium-Aluminum Alloying Medium for Long-Life Li Metal Batteries.

The uncontrolled growth of Li dendrites upon cycling might result in low coulombic efficiency and severe safety hazards. Herein, a lithiophilic binary lithium-aluminum alloy layer, which was generated through an in situ electrochemical process, was utilized to guide the uniform metallic Li nucleation and growth, free from the formation of dendrites. Moreover, the formed LiAl alloy layer can function as a Li reservoir to compensate the irreversible Li loss, enabling long-term stability. The protected Li electrode shows superior cycling over 1700 h in a Li|Li symmetric cell.

MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells.

The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/ß-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, ß-catenin, E-cadherin, N-cadherin, Snail, GSK-3ß, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/ß-catenin pathway to protect the ß-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/ß-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/ß-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.

Total hip arthroplasty following failure of tantalum rod implantation for osteonecrosis of the femoral head with 5- to 10-year follow-up.

BACKGROUND: Total hip arthroplasty (THA) with failure of tantalum rod implant for osteonecrosis of the femoral head (ONFH) will be the only choice for patients. However,it remains unknown whether tantalum rod implantation has an adverse effect on the survival time of implants following conversion to THA. The aim of this study was to retrospectively evaluate the clinical and radiographic outcomes of conversion to THA in patients who were previously treated with implantation of a tantalum rod. METHODS: This study included 31 patients (39 hips), who underwent conversion to THA due to failure of core decompression with an implanted tantalum rod. Among these 31 patients, 26 patients were male and five patients were female. The mean age of these patients was 49.3 years old (range: 36-64 years old). The control group included 33 patients (40 hips), who underwent total hip replacement without tantalum rod implantation. The hip Harris score, implant wear, osteolysis, radiolucencies and surgical complications were recorded during the follow-up. The distribution of tantalum debris in the proximal, middle and distal periprosthetic femoral regions, radiolucent lines and osteolysis were analyzed on post-operative radiographs. RESULTS: There were no significant differences in Harris score, liner wear and complications between the two groups (P > 0.05). Osteolysis and radiolucent lines more likely occurred in patients with tantalum debris distributed in three regions than in one or two regions (P < 0.05). CONCLUSIONS: The mid-term clinical outcome of patients who underwent THA with tantalum rod implantation was not different from those without a tantalum rod, suggesting that tantalum debris did not increase the liner wear rate. However, the distribution of periprosthetic tantalum debris in the proximal, middle and distal femoral regions may increase the risk of femoral osteolysis and radiolucent lines.

Hypoxia pathway genetic variants predict survival of non-small-cell lung cancer patients receiving platinum-based chemotherapy.

Hypoxia is a hallmark of solid tumors and has been implicated in the development of advanced disease and poor clinical outcome. In this multi-stage study, we aimed to assess whether genetic variations in hypoxia pathway genes might affect overall survival (OS) in patients with advanced-stage non-small cell lung cancer (NSCLC). We genotyped 598 potentially functional and tagging single nucleotide polymorphisms (SNPs) in 42 genes of the hypoxia pathway in 602 advanced stage NSCLC patients who received platinum-based chemotherapy or chemoradiation (discovery phase). Significant SNPs were validated in an additional 278 advanced stage patients (validation phase). Cox proportional hazard regression analysis was used to evaluate the association of each SNP with OS. Results showed in chemotherapy only group the median survival time (MST) of NSCLC patients with RPA1: rs2270412 AA+GA genotype versus GG genotype was 10.5 versus 12.7 month [P = 0.004, hazard ratio (HR) = 1.42, 95% CI: 1.16-1.74, combined set]. The MST of patients with EXO1: rs9350 GA+AA genotype versus GG genotypes was 13.2 months versus 11.5 months (P = 0.009, HR = 0.70, 95% CI: 0.56-0.87, combined set). Patients harboring two unfavorable genotypes had a 2.02-fold increased risk of death (P = 3.16E-6) and chemoradiation would improve survival for them (HR = 0.75, 95% CI: 0.51-1.10, P = 0.27, combined set). The MST for patients with 0, 1, and 2 unfavorable genotypes was 13.2, 12.7 and 8.9 months, respectively (P = 0.0002, combined set). In summary, two variants in RPA1 and EXO1 were associated with poor survival in NSCLC patients treated by platinum-based chemotherapy. Adding radiotherapy could improve survival in patients harboring these risk genotypes.

Vaccination with a recombinant OprL fragment induces a Th17 response and confers serotype-independent protection against Pseudomonas aeruginosa infection in mice.

Pseudomonas aeruginosa (PA) is the major causative agent of nosocomial infection. Despite of adequate use of antibiotics, it still represents a major challenge in controlling PA infection. The local pulmonary Th17 response plays an important protective role against PA infection. And the Th17-mediated protection is antibody independent, so we hypothesized that it would be an optimal strategy of a vaccine for PA control to induce an effective Th17 response. Herein we report the successful production of a recombinant fragment of the OprL (reOprL) of PA. Purified reOprL forms homogeneous monomers in solution and vaccination with reOprL elicited a remarkable Th17 response. In addition, reOprL vaccination conferred effective serotype-independent protection against PA infection, which relied on the Th17 response. Our data suggest that reOprL is a good candidate for the future development of Th17 immunity based PA vaccines.

Anterior wrist and medial malleolus as the novel sites of tissue selection: a retrospective study on electric shock death through the hand-to-foot circuit pathway.

Our previous work demonstrated that characteristic changes could occur in the anterior wrist and medial malleolus in electric deaths through the hand-to-foot electric circuit pathway in an electric shock rat model. However, whether the same phenomenon occurs in humans is unknown. The aim of the present retrospective study was to ascertain whether the anterior wrist and medial malleolus could also be selected as the promising and significant sites in electric death through the hand-to-foot circuit pathway. Nineteen human cases from the autopsy and one clinical survivor who sustained a severe electric shock through the hand-to-foot circuit pathway were analyzed. Additional ten autopsy patients who died from traffic accidents and sudden cardiac attacks were used as the control group. Histopathological changes in the soft tissues of the anterior wrist and medial malleolus in all autopsy patients, as well as the electric current pathway of the survivor, were observed. The results showed that the nuclear polarizations in the anterior wrist and medial malleolus soft tissues of the electric death were extremely noticeable as compared with the controls. The most severe electrical injury in the survivor occurred in the anterior wrist. These findings suggest that the soft tissues of the anterior wrist and/or the medial malleolus as the narrowest parts of the limbs could be used as the complementary sites for tissue selection and considered as necessary locations for examinations to assess the electric death in medicolegal identification.

Anterior wrist and medial malleolus: the optimal sites for tissue selection in electric death through hand-to-foot circuit pathway.

Specific morphological changes may be absent in some cases of electrocution shocked by the voltage of 220 V or lower. In this study, we attempted to demonstrate that the anterior wrist and medial malleolus were the optimal sites with promising and significant changes in electric death through the hand-to-foot circuit pathway. We established an electric shock rat model and observed histopathologic changes in the anterior wrist and medial malleolus. The results showed that the current intensities in the left anterior wrist and right medial malleolus were remarkably higher than those in the other sites, and the nuclei long/short (L/S) axis ratios of the arterial endotheliocyte and the skeletal muscle cell in these two areas were significantly higher than those in other parts of the body. These findings suggested that the anterior wrist and/or medial malleolus soft tissues as the narrowest parts of the limbs could be used as promising and useful sites for the assessment of electrical shock death, especially in forensic pathologic evaluation.