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Purpose: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset., Methods: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias., Results: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases., Conclusion: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the efficacy and safety of 3D-printed tissue compensations in breast cancer patients receiving breast reconstruction and postmastectomy radiotherapy (PMRT)., Methods and Materials: We enrolled patients with breast cancer receiving breast reconstruction and PMRT. The dose distribution of target and skin, conformability, and dose limit of organs at risk (OARs) were collected to evaluate the efficacy of the 3D-printed bolus. Radiation Therapy Oncology Group (RTOG) radiation injury classification was used to evaluated the skin toxicities., Results: A total of 30 patients diagnosed between October 2019 to July 2021 were included for analysis. Among all the patients, the 3D-printed bolus could ensure the dose coverage of planning target volume (PTV) [homogeneity index (HI) 0.12 (range: 0.08-0.18)], and the mean doses of D99%, D98%, D95%, D50%, D2% and Dmean were 4606.29cGy, 4797.04cGy, 4943.32cGy, 5216.07cGy, 5236.10cGy, 5440.28cGy and 5462.10cGy, respectively. The bolus demonstrated an excellent conformability, and the mean air gaps between the bolus and the chest wall in five quadrants were 0.04cm, 0.18cm, 0.04cm, 0.04cm and 0.07cm, respectively. In addition, the bolus had acceptable dosage limit of OARs [ipsilateral lung: Dmean 1198.68 cGy, V5 46.10%, V20 21.66%, V30 16.31%); heart: Dmean 395.40 cGy, V30 1.02%, V40 0.22%; spinal cord planning risk volume (PRV): Dmax 1634 cGy] and skin toxicity (grade 1, 76.0%; grade 2, 21.0%; grade 3, 3.3%)., Conclusion: The 3D-printed bolus offers advantages in terms of dose uniformity and controllable skin toxicities in patients receiving breast reconstruction and PMRT. Further research is needed to comprehensively evaluate the effectiveness of the 3Dprinted bolus in this patient subset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Xiang, Tan, Zeng, Yang, Wei, Yu, Dai, Xu and Liu.)

Background: Young breast cancer patients are more likely to develop aggressive tumor characteristics and a worse prognosis than older women, and different races and ethnicities have distinct epidemiologies and prognoses. However, few studies have evaluated the clinical biological features and relapse patterns in different age strata of young women in Asia., Objective: We aimed to explore survival differences and the hazard function in young Chinese patients with breast cancer (BC) by age., Methods: The patients were enrolled from West China Hospital, Sichuan University. The chi-squared test, a Kaplan-Meier analysis, a log-rank test, a Cox multivariate hazards regression model, and a hazard function were applied for data analysis. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as end points., Results: We included 1928 young BC patients diagnosed between 2008 and 2019. Patients aged 18 to 25, 26 to 30, 31 to 35, and 36 to 40 years accounted for 2.7% (n=53), 11.8% (n=228), 27.7% (n=535), and 57.7% (n=1112) of the patients, respectively. The diagnosis of young BC significantly increased from 2008 to 2019. Five-year LRFS, DMFS, BCSS, and OS for the entire population were 98.3%, 93.4%, 94.4%, and 94%, respectively. Patients aged 18 to 25 years had significantly poorer 5-year LRFS (P<.001), 5-year DMFS (P<.001), 5-year BCSS (P=.04), and 5-year OS (P=.04) than those aged 31 to 35, 26 to 30, and 36 to 40 years. The hazard curves for recurrence and metastasis for the whole cohort continuously increased over the years, while the BC mortality risk peaked at 2 to 3 years and then slowly decreased. When stratified by age, the annualized hazard function for recurrence, metastasis, and BC mortality in different age strata showed significantly different trends, especially for BC mortality., Conclusions: The annual diagnosis of young BC seemed to increase in Chinese patients, and the distinct age strata of young BC patients did not differ in survival outcome or failure pattern. Our results might provide strategies for personalized management of young BC., (©Jun Wang, Ting Luo, Zhong-zheng Xiang, Ming-min He, Yuan-yuan Zeng, Tian Yang, Xiao-yuan Wei, Siting Yu, Ze-lei Dai, Ning-yue Xu, Chen-feng Tan, Lei Liu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 18.07.2023.)

Cottonseed meal (CSM) is a good source of dietary proteins but is unsuitable for human consumption due to its gossypol content. To unlock its potential, we developed a protein extraction process with a gossypol removal treatment to generate CSM protein isolate (CSMPI) with ultra-low gossypol content. This process successfully reduced the free and total gossypol content to 4.8 ppm and 147.2 ppm, respectively, far below the US FDA limit. In addition, the functional characterisation of CSMPI revealed a better oil absorption capacity and water solubility than pea protein isolate. Proteome profiling showed that the treatment improved protein identification, while SDS-PAGE analysis indicated that the treatment did not induce protein degradation. Amino acid analysis revealed that post-treated CSMPI was rich in branched-chain amino acids (BCAAs). Mass spectrometry analysis of various protein fractions obtained from an in vitro digestibility assay helped to establish the digestibility profile of CSM proteins. Several potential allergens in CSMPI were also found using allergenic prediction software, but further evaluation based on their digestibility profiles and literature reviews suggests that the likelihood of CSMPI allergenicity remains low. Overall, our results help to navigate and direct the application of CSMPIs as alternative proteins toward nutritive human food application.

Objective: To explore the effect of electroacupuncture (EA) combined with Schwann cell (SC) transplantation (SCT) on remyelination of axons and neuregulin (Nrg1) in rats with compressed spinal cord injury(CSCI),so as to explore the mechanism of EA and SCT underlying improvement of CSCI., Methods: SD female rats were randomly divided into normal, mo-del, EA, SCT, and EA+ SCT groups ( n =40 per group). A self-developed model of spinal compressed injury was adopted in this study. Rats of the model group were administrated laminectomy without treatment. Rats in the EA group were administrated EA stimulation at "Dazhui"(GV14), "Mingmen"(GV7), bilateral "Zusanli" (ST36) and "Taixi" (KI3) on the second day post-surgery for 10 min. Rats in the SC group were administrated SCT at 1 week post-surgery, and in the EA+SC group were given EA stimulation combined with SCT. The injured spinal cord tissue was obtained 0, 2, 4 and 8 weeks after compressed spinal injury. The functional recovery was assessed by Basso-Beattie-Bresnahan (BBB) score. The survivals and migration of SC after transplantation, myelination were observed by immunofluorescence. The ultrastructure of myelin in injured site was observed by transmission electron microscope，and the expression levels of glial fibrillary acidic protein (GFAP), protein zero(P0), and Nrg1 and Nrg1-ntf (cleavage protein of Nrg1) proteins of the spinal cord were detected by Western blot., Results: Compared with the normal group, BBB scores in the model group was significantly decreased（ P <0.05）,nervous fibers were demyelinated, numbers of normal and newborn myelination were decreased( P <0.05)，expression of P0 was significantly increased ( P <0.05)，expression of GFAP was significantly increased( P <0.05)，and the expression levels of Nrg1 and Nrg1-ntf proteins were decreased( P <0.05). In comparison with the model group, the BBB scores in the EA, SCT and EA+SCT groups were significantly increased（ P <0.05, P <0.01）, demyelination was improved, numbers of normal and newborn myelinations were increased( P <0.05, P <0.01)，expressions of P0 were significantly increased ( P <0.05, P <0.01)，expressions of GFAP were significantly decreased( P <0.05)，and the expression levels of Nrg1 and Nrg1-ntf proteins were increased ( P <0.05, P <0.01).The differences were most significant in the EA+SCT group among the three groups., Conclusion: EA can improve the locomotor function in CSCI rats, which may be rela-ted to its functions in promoting the survival and migration of transplanted SC and remyelination, and increasing the expressions of Nrg1 and its cleavage protein after SC transplantation.

Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that hypoxic tumours synthesize hypoxia-sensitive proteins for packing into EVs to modulate their microenvironment for cancer progression. In the current report, we employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia sensitive proteins in tumour-derived EVs protein. The results revealed that hypoxia stimulated cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Together, these data indicate that lung-cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may, therefore, offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.

Studies have shown that the process of extracellular vesicles (EVs) secretion and lysosome status are linked. When the lysosome is under stress, the cells would secrete more EVs to maintain cellular homeostasis. However, the process that governs lysosomal activity and EVs secretion remains poorly defined and we postulated that certain proteins essential for EVs biogenesis are constantly synthesized and preferentially sorted to the EVs rather than the lysosome. A pulsed stable isotope labelling of amino acids in cell culture (pSILAC) based quantitative proteomics methodology was employed to study the preferential localization of the newly synthesized proteins into the EVs over lysosome in mHypoA 2/28 hypothalamic cell line. Through proteomic analysis, we found numerous newly synthesized lysosomal enzymes-such as the cathepsin proteins-that preferentially localize into the EVs over the lysosome. Chemical inhibition against cathepsin D promoted EVs secretion and a change in the EVs protein composition and therefore indicates its involvement in EVs biogenesis. In conclusion, we applied a heavy isotope pulse/trace proteomic approach to study EVs biogenesis in hypothalamic cells. The results demonstrated the regulation of EVs secretion by the cathepsin proteins that may serve as a potential therapeutic target for a range of neurological disorder associated with energy homeostasis.

This prospective one-year follow-up study was conducted from 835 visits in 178 rheumatoid arthritis (RA) patients. Tender-/swollen-joint count, Health Assessment Questionnaire Disability Index (HAQ-DI), Disease Activity Score 28-ESR (DAS28-ESR), DAS28-CRP, Simplified Disease Activity Index (SDAI) and DAS28-monocyte chemotactic protein-1 (DAS28-MCP-1) scores were obtained every 3 months. Radiographs of hands and feet were acquired at baseline and one year. We evaluated the correlation and accuracy of activity scores in predicting remission, HAQ-DI changes and radiographic changes. DAS28-MCP-1 correlated strongly with DAS28-ESR, DAS28-CRP and SDAI scores (0.830, 0.899 and 0.931, respectively, with all P < 0.001). Score changes of DAS28-MCP-1 were comparable to those of DAS28-ESR, DAS28-CRP and SDAI in predicting changes in HAQ-DI and bone erosion. DAS28-MCP-1 (<2.2) was better than DAS28-ESR (<2.6) in indicating modified American Rheumatism Association remission and 2011 American College of Rheumatology/European League Against Rheumatism remission (75.61% vs. 36.99% and 81.71% vs. 49.13%, respectively) with odds ratios of 5.28 and 4.62 (both P < 0.001), respectively. We compared DAS28-MCP-1 with SDAI (≦3.3) in indicating remission with odds ratios of 2.63 (P = 0.002) and 0.98, respectively (and DAS28-MCP-1 with DAS28-CRP < 2.5: 1.33 and 0.92). Therefore, DAS28-MCP-1 is useful as an alternative in assessing RA activity.

Objective: To observe the effect of electroacupuncture (EA) on the expression of apolipoprotein E (ApoE) and related proteins of inflammation and anti-oxidative stress in spinal cord in mice with spinal cord injury (SCI), so as to explore its mechanisms underlying function repair., Methods: Thirty-six female C57BL/6 mice were equally randomized into 3 groups: sham operation, model and EA. The SCI model was established by clamping the spinal cord for 25 s with a serrefine after laminectomy of the 1 st lumbar vertebra (L1). EA (1.5 Hz/7.5 Hz, 1.0 mA) was applied to bila-teral "Zusanli" (ST36) and "Sanyinjiao" (SP6) for 10 min, once a day for 7 days. The hindlimb locomotor function was assessed according to the state of the range of motion, coordination, claw gesture of the hind leg ankle-joint, trunk stabi-lity and the tail posture by using Basso Mouse Scale(BMS). The histopathological changes of the injured area of the spinal cord were determined by H.E. staining. The expression levels of ApoE, phosphorylated nuclear transcription factor-κB(p-NF-κB), interleukin 1 beta(IL-1β), phosphorylated extracellular regulatory protein kinase(p-ERK1/2), extracellular regulatory protein kinase(ERK1/2), nuclear factor erythroid 2-related factor 2(Nrf2) and heme oxidase-1(HO-1) in the spinal cord were detected by Western blot, and the glial fibrillary acidic protein (GFAP)-positive astrocytes were displayed by immunofluorescence staining., Results: After modeling, the BMS scores were significantly decreased in the model group compared with the sham operation group ( P <0.05). Following EA, the BMS scores were markedly increased in the EA group relevant to the model group ( P <0.05), suggesting an improvement of the hindlimb locomotor function. H.E. stain showed structural disorder with lots of cavities, severe inflammatory infiltration with large quantity of inflammatory cells, and apparent reduction of normal neurons in the injured spinal cord tissue of model group, which was milder in the EA group. The expression levels of ApoE, p-NF-κB, IL-1β, p-ERK1/2 (not ERK1/2), Nrf2 and HO-1 were significantly increased in the model group than those in the sham operation group ( P <0.05). Compared with the model group, the expression levels of ApoE, p-ERK1/2, Nrf2 and HO-1 were further notably up-regulated ( P <0.05), and those of p-NF-κB and IL-1β proteins obviously down-regulated in the EA group ( P <0.05). Immunoflorescence staining showed that the number of GFAP-positive cells was apparently increased in the model group compared with the sham operation group and observably decreased in the EA group relevant to the model group ( P <0.05)., Conclusion: EA can significantly improve locomotor function in SCI mice, which is associated with its effects in reducing inflammation, oxi-dative stress reactions and reactive astrocyte proliferation via up-regulating expression of ApoE, p-ERK1/2, and Nrf2/HO-1 (antioxidant pathway) and inhibiting IL-1β and NF-κB expression.

Vascular factors that reduce blood flow to the brain are involved in apparition and progression of dementia. We hypothesized that cerebral hypoperfusion (CH) might alter the molecular compositions of brain intercellular communication mechanisms while affecting the neurovascular unit in preclinical and clinical human dementias. To test that hypothesis, mice were subjected to bilateral common carotid stenosis (BCAS) and the molecular compositions of brain-derived and circulating extracellular vesicles (EVs) were assessed. Murine brain vesicle profiles were then analyzed in parallel with brain EVs from post-mortem subjects affected by preclinical Alzheimer's Disease (AD) and mixed dementias. Brain EVs were identified with molecular mediators of hypoxia responses, neuroprotection and neurotoxicity in BCAS mice, patterns also partially resembled by subjects with preclinical AD and mixed dementias. Together these findings indicate that brain EVs represent a promising source of therapeutic targets and circulating markers of neurovascular insult in idiopathic dementias. Furthermore, the results obtained generate novel and compelling hypotheses about the molecular involvement of the vascular component in the etiology of human dementias., (© 2019 International Society of Neuropathology.)

Background: Polycomb group (PcG) proteins play important roles in animal and plant development and stress response. Polycomb repressive complex 1 (PRC1) and PRC2 are the key epigenetic regulators of gene expression, and are involved in almost all developmental stages. PRC1 catalyzes H2A monoubiquitination resulting in transcriptional silencing or activation. The PRC1 components in the green lineage were identified and evolution and conservation was analyzed by bioinformatics techniques. RING Finger Protein 1 (RING1), B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Like Heterochromatin Protein 1 (LHP1) and Embryonic Flower 1 (EMF1) are the PRC1 core components and Vernalization 1 (VRN1), VP1/ABI3-Like 1/2/3 (VAL1/2/3), Alfin-like 1-7 (AL1-7), Inhibitor of growth 1/2 (ING1/2), and Early Bolting in Short Days (EBS) / Short Life (SHL) are the associated factors., Results: Each PRC1 subunit possesses special domain organizations, such as RING and the ring finger and WD40-associated ubiquitin-like (RAWUL) domains for RING1 and BMI1, chromatin organization modifier (CHROMO) and chromo shadow (ChSh) domains for LHP1, one or two B3 DNA binding domain(s) for VRN1, B3 and zf-CW domains for VAL1/2/3, Alfin and Plant HomeoDomain (PHD) domains for AL1-7, ING and PHD domains for ING1/2, Bromoadjacent homology (BAT) and PHD domains for EBS/SHL. Six new motifs are uncovered in EMF1. The PRC1 core components RING1 and BMI1, and the associated factors VAL1/2/3, AL1-7, ING1/2, and EBS/SHL exist from alga to higher plants, whereas LHP1 only occurs in higher plants. EMF1 and VRN1 are present only in eudicots. PRC1 components undergo duplication in the plant evolution. Most of plants carry the homologous core component LHP1, the associated factor EMF1, and several homologs in RING1, BMI1, VRN1, AL1-7, ING1/2/3, and EBS/SHL. Cabbage, cotton, poplar, orange and maize often exhibit more gene copies than other species. Domain organization analysis shows that duplicated gene functions may be of diverse., Conclusions: The PRC1 core components RING1 and BMI1, and the associated factors VAL1/2/3, AL1-7, ING1/2, and EBS/SHL originate from algae. The core component LHP1 is from moss and the associated factors EMF1 and VRN1 are from dicotyledon. PRC1 components are of functional redundancy and diversity in evolution.

Objective: To observe the effect of electroacupuncture (EA) combined with transplantation of Schwann cells (SCs) on limb locomotor, myelin sheath repair and expression of CD4 and CD8 in compressed spinal cord injury (CSCI) rats, so as to explore its mechanisms underlying improvement of CSCI., Methods: A total of 45 female SD rats were randomly divided into normal control, model, EA, Schwann cell (SC) transplantation, and EA＋SC transplantation groups ( n ＝9 rats in each group). The CSCI model was established by laminectomy at T12-L2 and clip compression. Rats of the SC transplantation group accepted injection of the cultured SC suspension (2×10 6 /6 µL) into the central, upper and lower sites of the injured spinal cord (5 mm in depth) 7-8 days after CSCI modeling. EA (2 Hz) was applied to bilateral "Zusanli" (ST36) and "Sanyinjiao" (SP6) for 10 min, once daily and 6 days a week for 3 weeks. The Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) was used to evaluate the function state of CSCI. Morphological changes of the regional injured tissue were observed under light microscope after H．E. staining. The myelin sheath repair state and survival of SCs were detected by Luxol fast blue (LFB) staining and immunofluorescence histochemistry, and the expression of CD4, CD8 and P0 of the injured spinal cord was detected by Western blot., Results: Compared with the normal control group, the BBB scores at the time-points of 0 d, and 1, 2, and 3 weeks were significantly decreased in the model group ( P <0.001), and those of the EA＋SC transplantation group at the 2 nd and 3 rd week were significantly higher than those of the model group ( P <0.05). No significant changes of BBB scores were found after EA and SC transplantation relevant to the model group ( P >0.05). LFB staining showed a disordered arrangement of the nerve fibers in the white matter, myelinociasis and obvious decrease of the medullated fibers in the model group, and these situations were relatively milder in both EA and SC transplantation groups and obviously milder in the EA＋SC transplantation group. H．E. staining displayed that the structure of the injured region of the spinal cord was incomplete, accompanied with a large number of defect cavities and neuronal karyopyknosis in the model group, while the structure was relatively clear, with an increase of the normal neurons and fewer neuronal karyopyknosis in the EA＋SC transplantation group. Compared with the normal control group, MBP in the model group was significantly decreased ( P <0.001)，and P0 was significantly increased ( P <0.001). Compared with the model group, the expressions of MBP and P0 were significantly increased in the EA, SC transplantation, and EA＋SC transplantation groups ( P <0.01, P <0.001), and was significantly higher in the EA＋SC transplantation group than in both EA and SC transplantation groups ( P <0.001). The average immunofluorescence intensity of Hoechst33342-labeled SCs was significantly higher in the EA＋SC transplantation group than in the SC transplantation group ( P <0.05). After CSCI, the expression levels of spinal CD4, CD8 and P0 proteins had no significant changes in comparison with the normal control group ( P >0.05), while after the intervention and in comparison with the model group, the expression levels of P0 protein were significantly increased in the EA, SC transplantation and EA＋SC transplantation groups ( P <0.05), and was significantly higher in the EA＋SC transplantation group than in both EA and SC transplantation groups ( P <0.05). The expression levels of CD4 and CD8 proteins were significantly lower in the EA＋SC transplantation group than in the SC transplantation group ( P <0.05)．., Conclusion: EA＋SCs transplantation can improve the locomotor function in CSCI rats, which may be related to its effects in increasing the survival of transplanted SCs to promote the remyelination and in reducing the immune rejecting reaction.

Developing tumors rapidly outgrow their oxygen supply and are subject to hypoxia, which stimulates hypersecretion of tumor-derived exosomes that promote angiogenesis, metastasis, and immunosuppression, but the molecular mediators of these pathological effects remain poorly defined. Using quantitative proteomics, we identified that exosomes produced by hypoxic tumor cells are highly enriched in immunomodulatory proteins and chemokines including CSF-1, CCL2, FTH, FTL, and TGFβ. Modeling exosome effects on tumor-infiltrating immune cells, we observed a potent ability of these hypoxia-induced vesicles to influence macrophage recruitment and promote M2-like polarization both in vitro and in vivo. In addition, hypoxic, but not normoxic, tumor exosomes enhanced oxidative phosphorylation in bone marrow-derived macrophages via transfer of let-7a miRNA, resulting in suppression of the insulin-Akt-mTOR signaling pathway. Together, these data demonstrate that hypoxia promotes tumor secretion of biomolecule-loaded exosomes that can modify the immunometabolic profile of infiltrating monocyte-macrophages to better evade host immunity and enhance tumor progression.

Objective: To observe the therapeutic effect of electroacupuncture (EA) of "Zusanli" (ST36) and " Ashi "-point on the healthy side (opposing needling) on muscular injury and expression of myogenin (myoG) and fast myosin skeletal heavy chain (Fast MyHC) proteins in the gastrocnemius muscle (GM) tissues in skeletal muscle contusion rats，so as to explore its mechanism underlying improvement of skeletal muscle injury., Methods: A total of 54 male SD rats were divided into normal control (n ＝ 6)，model ( n ＝24) and opposing needling (EA, n ＝24) groups. The latter two groups were further randomized into 3, 5, 7 and 14 d subgroups ( n ＝6 per subgroup). The skeletal muscle contusion model of the hind-limb was established by using a self-made striking device. EA (1 Hz/3 Hz，1－2 mA) was applied to ST36 and " Ashi "-point on the uninjured side of the hind-limb for 15 min every time, once a day for 3, 5, 7 and 14 days, respectively. The injured GM was harvested on the 3 rd, 5 th, 7 th and 14 th day after muscular contusion. The morphological changes of the injured GM and the mean cross-sectional areas (CSAs) of the neonatal muscle cells were observed by microscope after H．E. staining. The immunoactivity of desmin protein (myogenic marker protein of myoblast cell) of GM was detected by immunofluorescence stain on the 7 th day after injury, and the expression levels of myoG (on the 3 rd and 5 th day after injury) and fast MyHC protein of GM tissues (on the 7 th and 14 th day after injury) were detected by Western blot., Results: H．E. staining of GS tissue showed fewer neuronal myocytes with disordered arrangement at different sizes, and appearance of some collagenous fibers among the mesenchyme on day 7 and 14 after muscular contusion, which was relatively milder in the EA group. In the EA group, the CSA values of the neonatal muscle cells were significantly larger than those in the model group on the day 7 th ( P <0.05), 14 th ( P <0.001) after injury. On day 7 after muscular contusion, the desmin was found to express on the cellular membrane of GM in the normal control group, while in the model group, the desmin expressed mainly in the cellular plasma in the model group, and on the cellular membrane of neonatal myocytes in the EA group, respectively. The desmin positive myocytes showed disordered arrangement and different sizes after muscular contusion, whereas the situations of the EA group were close to those of the normal control group. Desmin expression was up-regulated in the EA group compared with the model group which was not significant difference ( P >0.05). On the 3 rd and 5 th day after muscular contusion, the expression level of myoG protein was significantly up-regulated in the model group compared with the normal control group ( P <0.001), and significantly up-regulated in the EA group than that in the model group ( P <0.001). On the 7 th and14 th day after contusion, the expression level of fast MyHC protein was significantly down-regulated in the model group relevant to the normal control group ( P <0.001), and markedly up-regulated in the EA group relevant to the model group ( P <0.01)．., Conclusion: EA of ST36 and " Ashi "-point on the contralateral limb can up-regulate the expression of myoG and fast MyHC proteins of GM in acute skeletal muscle contusion rats, which may contribute to its effect in promoting the repair of skeletal muscle injury.

Objective: To observe the effect of electroacupuncture (EA) on morphological changes of denervated gastrocnemius(GS) and the expression of fork-head protein(FOXO3A), muscle atrophy F-box(MAFbx)and myogenic differentiation antigen (Myod1) in sciatic nerve injury rats, so as to reveal its mechanism underlying improvement of myoatrophy., Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham operation, model and EA groups ( n ＝6 per group). The model of gastrocnemius atrophy was established by crushing the right sciatic nerve. Then, EA (2 Hz) was applied to the right "Zusanli" (ST36) and "Huantiao" (GB30) for 10 min, once a day for 14 successive days. The wet weight of the GS on both sides was weighted to calculate the wet weight ratio (the injured side /the healthy side), and the cross-sectional area (CSA) and diameter of GS fibers were measured after H．E. staining. The expressions of FOXO3A, MAFbx and Myod1 protein and mRNA in the GS tissue were tested using Western blot and fluorescence quantitative PCR, separately., Results: Following modeling, the GS wet weight ratio, CSA and fiber diameter were smaller in the model group than those in the sham group ( P <0.01), and were significantly higher in the EA group than in the model group ( P <0.01). H．E. staining showed that the GS fibers became smaller and the myocyte got round in the model group, while the GS fibers were bigger and the myocyte was relatively regular in morphology in the EA group. After modeling, the expression levels of FOXO3A, MAFbx and Myod1 mRNA and protein were evidently higher in the model group ( P <0.01); Moreover, after EA treatment, modeling-induced increasing of expression levels of FOXO3A and MAFbx mRNA and protein were revised ( P <0.01), while the increased expression level of Myod1 was further up-regulated relavant to that in the model group ( P <0.01)．., Conclusion: EA of ST36 and GB30 can suppress the up-regulated expression of FOXO3A and MAFbx mRNA and protein and further promote the expression of Myod1 mRNA and protein in the GS tissue in rats with denervated GS atrophy, which may contribute to its function in relieving the myoatrophy, promoting the skeletal muscle protein hydrolysis and differentiation of satellite cells.

Objective: To observe the effect of "Neiguan" (PC6)-electroacupuncture (EA) preconditioning on serum metabolites in myocardial ischemia-reperfusion injury (MIRI) rats, so as to reveal its mechanism underlying improvement of ischemic myocardium from metabonomics., Methods: A total of 48 male SD rats were randomly divided into control, model, EA "Neiguan"(PC6) and EA "Hegu"(LI4) groups ( n ＝12 rats/ group). Rats of the control group were just banded on animal boards for 30 min, once daily for 7 days. The MIRI model was established by occlusion of the left anterior descending branch of the left coronary artery for 40 min, followed by reperfusion for 1 h, and rats of the model group were also banded as those in the control group. Before modeling, EA (10 Hz/50 Hz, 1 mA) was applied to bilateral "Neiguan"(PC6) and "Hegu"(LI4) for 30 min, once daily for 7 successive days. After the treatment, serum samples were collected to be analyzed by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy. The orthogonal partial least squares discriminate analysis (PLS-DA) was employed to distinguish the serum differential metabolic profile of rats in different groups and identify potential biomarkers., Results: After modeling, the ECG of model group and electroacupuncture groups showed T wave towering, and there was no obvious ST segment between R wave and T wave. The T wave decreased more than 0.2 mV after reperfusion, and there was no obvious ST segment. Compared with the control group, MIRI induced significant changes of metabolites in the serum including increase of acetoacetate acid, lectic acid, creatine, glycerol and glucose, and decrease of alanine, glutamine, glycerophosphoryl choline and phosphorylcholine. In comparison with the model group, PC6-EA preconditioning induced significant changes, including an increase of glucose, and a decrease of leucine，isoleucine, valine，3-hydroxybutyric acid，lactate，acetate，acetone，acetoacetate acid，pyruvic acid，glutamine，creatine and glycerol. There is no significant difference in metabolic patterns between "Hegu" group and model group. Metabolic pathway enrichment analysis indicated that the protective effect of PC6-EA pretreatment was realized mainly by regulating pathways of glycolysis, gluconeogenesis, citric acid metabolism, pyruvate metabolism, ketone body metabolism, etc., Conclusion: PC6-EA pretreatment has a role in regulating gluconeogenesis, pyruvate metabolism, amino metabolism, ketone body metabolism and energy metabolism in rats with MIRI, which maybe contribute to its protective effect on ischemic myocardium, but the specific metabolic pathways and mechanisms need being studied further.

Context: Insulin resistance (IR) and obesity differ among ethnic groups in Singapore, with the Malays more obese yet less IR than Asian-Indians. However, the molecular basis underlying these differences is not clear., Objective: As the skeletal muscle (SM) is metabolically relevant to IR, we investigated molecular pathways in SM that are associated with ethnic differences in IR, obesity, and related traits., Design, Setting, and Main Outcome Measures: We integrated transcriptomic, genomic, and phenotypic analyses in 156 healthy subjects representing three major ethnicities in the Singapore Adult Metabolism Study., Patients: This study contains Chinese (n = 63), Malay (n = 51), and Asian-Indian (n = 42) men, aged 21 to 40 years, without systemic diseases., Results: We found remarkable diversity in the SM transcriptome among the three ethnicities, with >8000 differentially expressed genes (40% of all genes expressed in SM). Comparison with blood transcriptome from a separate Singaporean cohort showed that >95% of SM expression differences among ethnicities were unique to SM. We identified a network of 46 genes that were specifically downregulated in Malays, suggesting dysregulation of components of cellular respiration in SM of Malay individuals. We also report 28 differentially expressed gene clusters, four of which were also enriched for genes that were found in genome-wide association studies of metabolic traits and disease and correlated with variation in IR, obesity, and related traits., Conclusion: We identified extensive gene-expression changes in SM among the three Singaporean ethnicities and report specific genes and molecular pathways that might underpin and explain the differences in IR among these ethnic groups.

Objective: To observe the effect of "Neiguan" (PC6)-electroacupuncture (EA) or moxibustion (Moxi) pretreatment on myocardial apoptosis and expression of autophagy related proteins light chain (LC) 3-Ⅰ and LC3-Ⅱ in rats with myocardial ischemia/reperfusion injury (MIRI), so as to explore their mechanisms underlying improvement of MIRI., Methods: Forty SD rats (half male and half female) were randomly divided into sham operation, model, ischemic preconditioning (IP), EA and Moxi groups ( n ＝8 in each group). EA (10 Hz/50 Hz, 1 mA) or Moxi (ignited moxa stick) was respectively applied to bilateral "Neiguan" (PC6) for 20 min, once daily for 7 days. The MIRI model was established by occlusion of the anterior descending branch of the left coronary artery for 40 min, followed by reperfusion for 60 min. The ultrastructural changes and autophagy of myocardial cells were observed by electron microscopy (EM), and the myocardial cellular apoptosis [apoptotic index ＝ (number of apoptotic cells/total number of cardiomyocytes)×100%] was detected by the terminal deoxyribonucleotidyl transferase mediated dUTP nick end labelling (TUNEL) method. The expressions of LC3-Ⅰ and LC3-Ⅱ proteins (markers for autophagy) in myocardial tissue were detected by Western blot., Results: Following MI, EM observation revealed a vague structure of cardiomyocytes and muscular horizontal grain, dissolution of myofibers, mitochondrial swelling, some autophagic vacuoles and autophagic lysosomes at different degrees and surrounded by a double membrane in the model group, these situations were apparently milder in the EA and Moxi groups. The apoptosis index, myocardial LC3-Ⅰ and LC3-Ⅱ protein expression levels, and the ratio of LC3-Ⅱ/Ⅰ were significantly increased in the model group relevant to the sham operation group ( P <0.05). After the treatment, the apoptosis index, the expression level of myocardial LC3-Ⅱ protein and the ratio of LC3-Ⅱ/Ⅰ were considerably down-regulated in the IP, EA and Moxi groups in comparison with those in the model group ( P <0.05). The effect of EA was obviously superior to those of IP and Moxi in down-regulating the apoptosis index ( P <0.05), but obviously inferior to those of IP and Moxi in down-regulating the levels of LC3-Ⅱ and LC3-Ⅱ/Ⅰ ( P <0.05). No significant changes were found in the expression of LC3-Ⅰ after IP, EA and Moxi interventions in comparison with the model group ( P >0.05), and no significant differences were observed in the apoptosis index and levels of LC3-Ⅱ and LC3-Ⅱ/Ⅰ between the IP and Moxi groups ( P >0.05)．., Conclusion: Both EA and moxibustion pretreatments, similar to IP, have a positive role in reducing myocardiocyte apoptosis and regulating autophagy-related protein expression in MIRI rats, which maybe contribute to their protective effects on ischemic myocardium.

Objective: To explore the effect of electroacupuncture(EA) on amyotrophia and expression of paired box7(Pax7), myogenic differentiation antigen-1 (Myod1), myogenin (Myog), myosin heavy chain- Ⅱa (Myh2), myosin heavy chain-Ⅱx (Myh1) and myosin heavy chain-Ⅰ (Myh7) of denervated gastrocnemius in rats with chronic constriction injury (CCI) of the right sciatic nerve, so as to explore its mechanisms underlying postponing development of amyotrophia., Methods: Sixty-six SD adult male rats were randomly divided into sham operation (sham) group ( n ＝24), model group ( n ＝24) and EA group ( n ＝18). The denervated muscle (gastrocnemius) atrophy model was established by CCI of the right sciatic nerve. EA (2 Hz，1.0 mA) was applied to the right "Zusanli"(ST36) and "Huantiao"(GB30) for 10 min, once a day, six times a week and for 1, 2 and 4 weeks, respectively. After complete dissection of bilateral gastrocnemius muscles, their wet weight levels were measured and the ratio of wet weight (＝that of the operation side/that of the non-operation side) was calculated, and the cross-sectional area (CSA) and diameter of the gastronemius were detected after fixation in 4% paraformaldehyde, sectioning, and H．E. staining. The expression levels of Pax7, Myod1, Myog, Myh2, Myh1 and Myh7 mRNAs in the gastrocnemius tissue after 3 weeks of modeling were detected with quantitative real time-PCR (qPCR)., Results: After 1 week of modeling, the ratios of wet weight of gastrocnemius and the CSA and fiber diameter at the 2 nd , 3 rd and 5 th week were significantly smaller in the model group than in the sham group ( P <0.05). The expression levels of Myod1 and Myog mRNAs were significantly up-regulated ( P <0.01), and those of Myh2, Myh1 and Myh7 considerably down-regulated in the model group compared with the sham group ( P <0.05, P <0.01). No significant changes were found in the expression levels of Pax7 mRNA after modeling and EA intervention ( P >0.05)．Following EA intervention, the CSA and diameterof the gastronemius were obviously increased ( P <0.05), and the expression levels of Myod1, Myog and Myh7 further markedly or remarkably up-regulated in comparison with the model group ( P <0.05, P <0.01). No significant changes were found in the ratio of wet weight of gastrocnemius at the 3 time-points, and the expression levels of Myh2 mRNA and Myh1 mRNA in the EA group relevant to the model group after 3 weeks of modeling ( P >0.05)., Conclusion: EA treatment may delay gastrocnemius atrophy in CCI rats, which is possibly associated with its effects in up-regulating the expression of Myod1, Myog and Myh7 mRNAs to control the differentiation of the satellite cells and the muscle fiber type transformation.

Objective: To explore the effect of electroacupuncture (EA) on the expression of synovial AMP-activated protein kinase (AMPK) protein α， arginase-1 mRNA, nitric oxide synthase 2 (NOS 2) mRNA, NOD-like receptor protein 3 (NLRP 3) mRNA, and interleukin-1 β (IL-1 β) mRNA in acute gouty arthritis (AGA) rats, so as to explore its mechanisms underlying improvement of AGA via M 1/M 2 macrophage polarization., Methods: Male Wistar rats were randomly divided into normal control, model, medication (colchicine) and EA groups ( n ＝15 rats in each group). The AGA model was established by injection of sodium urate crystal (MSU) suspension (0.2 mL) into the articular cavity of the left knee. The rats of the normal control group received articular injection of normal saline (0.2 mL) of the left knee, and those of the medication group were treated by gavage of the colchicine (0.3 mg•kg －1 •d －1 ) once daily for 7 days. EA (2 Hz/10 Hz, 1.0 mA) was applied to "Zusanli"(ST 36) and "Sanyinjiao" (SP 6) of the left hind limb for 10 min, once daily for 7 days. The inflammatory conditions of the synovial membrane tissue of the left knee joint were observed by H．E. staining. The expression levels of phosphorylated AMPKα (p-AMPKα) protein, and arginase-1 (a maker of M 2 macrophages) mRNA, NOS 2 (a maker of M 1 macrophages) mRNA, NLRP 3 mRNA, and IL-1 β mRNA in the knee joint synovial tissue were detected by Western blot and quantitative real-time PCR, respectively., Results: Compared with the normal group, the inflammatory cell infiltration of the synovial tissue was more severe, the expression of p-AMPKα protein was significantly decreased ( P <0.01), and the expression levels of arginase-1, NOS 2, IL-1 β and NLRP 3 mRNAs were considerably increased in the model group ( P <0.01). The expression levels of p-AMPKα protein and arginase-1 mRNA were significantly up-regulated, and those of NOS 2, IL-1 β and NLRP 3 mRNAs obviously down-regulated in both EA and medication groups relevant to the model group ( P <0.01, P <0.05), suggesting an increase of M 2 macrophage and a decrease of M 1 macrophage activity after EA. No significant differences were found between the EA and medication groups in up-regulating p-AMPKα expression and in down-regulating NOS 2, IL-1 β and NLRP 3 mRNA expression ( P >0.05), except higher up-regulation of arginase-1 mRNA in the medication group ( P <0.05)．., Conclusion: EA intervention can up-regulate the expression of arginase-1 mRNA and p-AMPKα protein, and down-regulate the expression of NOS 2, IL-1 β and NLRP 3 mRNAs in synovial tissues in AGA rats, which may contribute to its anti-inflammatory effect by promoting conversion of macrophages from M 1 pro-inflammatory phenotype to M 2 anti-inflammatory phenotype.

Utilization of ubiquitous low-grade waste heat constitutes a possible avenue towards soft matter actuation and energy recovery opportunities. While most soft materials are not all that smart relying on power input of some kind for continuous response, we conceptualize a self-locked thermo-mechano feedback for autonomous motility and energy generation functions. Here, the low-grade heat usually dismissed as 'not useful' is used to fuel a soft thermo-mechano-electrical system to perform perpetual and untethered multimodal locomotions. The innately resilient locomotion synchronizes self-governed and auto-sustained temperature fluctuations and mechanical mobility without external stimulus change, enabling simultaneous harvesting of thermo-mechanical energy at the pyro/piezoelectric mechanistic intersection. The untethered soft material showcases deterministic motions (translational oscillation, directional rolling, and clockwise/anticlockwise rotation), rapid transitions and dynamic responses without needing power input, on the contrary extracting power from ambient. This work may open opportunities for thermo-mechano-electrical transduction, multigait soft energy robotics and waste heat harvesting technologies.

Objective: To determine whether intrapartum and newborn care practices improved in 11 large hospitals between 2008 and 2015., Design: Secondary data analysis of observational assessments conducted in 11 hospitals in 2008 and 2015., Setting: Eleven large government hospitals from five regions in the Philippines., Participants: One hundred and seven randomly sampled postpartum mother-baby pairs in 2008 and 106 randomly sampled postpartum mothers prior to discharge from hospitals after delivery., Interventions: A national initiative to improve quality of newborn care starting in 2009 through development of a standard package of intrapartum and newborn care services, practice-based training, formation of multidisciplinary hospital working groups, and regular assessments and meetings in hospitals to identify actions to improve practices, policies and environments. Quality improvement was supported by policy development, health financing packages, health facility standards, capacity building and health communication., Main Outcome Measures: Sixteen intrapartum and newborn care practices., Results: Between 2008 and 2015, initiation of drying within 5 s of birth, delayed cord clamping, dry cord care, uninterrupted skin-to-skin contact, timing and duration of the initial breastfeed, and bathing deferred until 6 h after birth all vastly improved (P<0.001). The proportion of newborns receiving hygienic cord handling and the hepatitis B birth dose decreased by 11-12%. Except for reduced induction of labor, inappropriate maternal care practices persisted., Conclusions: Newborn care practices have vastly improved through an approach focused on improving hospital policies, environments and health worker practices. Maternal care practices remain outdated largely due to the ineffective didactic training approaches adopted for maternal care.

One-dimensional (1D) metallic nanocrystals constitute an important class of plasmonic materials for localization of light into subwavelength dimensions. Coupled with their intrinsic conductive properties and extended optical paths for light absorption, metallic nanowires are prevalent in light-harnessing applications. However, the transverse surface plasmon resonance (SPR) mode of traditional multiply twinned nanowires often suffers from weaker electric field enhancement due to its low degree of morphological curvature in comparison to other complex anisotropic nanocrystals. Herein, simultaneous anisotropic stellation and excavation of multiply twinned nanowires are demonstrated through a site-selective galvanic reaction for a pronounced manipulation of light-matter interaction. The introduction of longitudinal extrusions and cavitation along the nanowires leads to a significant enhancement in plasmon field with reduced quenching of localized surface plasmon resonance (LSPR). The as-synthesized multimetallic nanostartubes serve as a panchromatic plasmonic framework for incorporation of photocatalytic materials for plasmon-assisted solar fuel production.

Objective: We have repeatedly demonstrated that electroacupuncture (EA) of "Neiguan"(PC 6) can improve myocardial ischemia in rats. The present study was designed to investigate the metabolomic profile of peripheral blood se-rum and myocardium involving EA-induced improvement of myocardial ischemia-reperfusion injury (MIRI) in rats by using nuclear magnetic resonance spectroscopy., Methods: Thirty male SD rats were equally randomized into blank control, model and EA groups. Rats of the control group were only banded for 20 min, once a day for 7 days. The MIRI model was established by occlusion of the anterior descending branch of the left coronary artery for 40 min, followed by reperfusion for 60 min, and rats of the model group were banded as those in the control group. EA (10 Hz/50 Hz, 1 mA) was applied to bilateral PC 6 for 20 min, once daily for 7 days. The blood samples and left ventricular myocardial tissues were collected for assaying the profiles of differential metabolites using 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy and multivariate statistical analysis such as the principal components analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) with SIMCA-P software 12.0., Results: A total of 19 differential metabolites (17 down-regulated, 2 up-regulated) in the serum and 14 differential metabolites (13 down-regulated and 1 up-regulated) in the ischemic left myocardium were identified after MIRI. Of the 19 serum differential metabolites, amino acids (leucine, isoleucine, valine,alanine, lysine, glycine, glutamine), 3-hydroxy butyric acid (3-HB), lactic acid, acetate, N-acetyl glycoprotein (NAc), acetone, acetoacetate, succinate, polyunsaturated fatty acids (PUFA), creatine, glycerophosphocholine (GPC) were down-regulated; while low density lipoprotein (LDL), LDL/very low density lipoprotein(LDL/VLDL)and glucose obviously up-regulated. Of the 14 myocardial differential metabolites, amino acids (alanine, lysine, glutamate, glutamine, aspartate, taurine, glycine, threonine), GPC, creatine, lactic acid, adenosine monophosphate (AMP), nicotinamide adenine dinucleotide (NAD＋) were significantly decreased, and glucose was up-regulated. Following EA treatment, most of the decreased serum differential metabolites except acetone, acetoacetate and PUFA, and the increased serum LDL, LDL/VLDL and glucose recovered, basically close to the control level; and the decreased myocardial creatine, GPC and NAD＋ were also apparently up-regulated and the increased myocardial glucose was down-regulated. But, myocardial threonine and AMP still presented a decreasing state. Although the pattern of myocardial differential metabolites of the EA group had a trend to be close to the control group, the significant difference still existed, while the metabolic pattern of serum metabolites in the EA group was close to that of the control group., Conclusion: EA stimulation of PC 6 can regulate serum or/and myocardial metabolites as amino acids, carbohydrates, lipids, etc. in MIRI rats, of which both serum and myocardial creatine, GPC and glucose may be jointly confer a favorable potential for EA-induced improvement of MIRI.

Surface plasmon-based photonics offers exciting opportunities to enable fine control of the site, span, and extent of mechanical harvesting. However, the interaction between plasmonic photothermic and piezoresponse still remains underexplored. Here, spatially localized and controllable piezoresponse of a hybrid self-polarized polymeric-metallic system that correlates to plasmonic light-to-heat modulation of the local strain is demonstrated. The piezoresponse is associated to the localized plasmons that serve as efficient nanoheaters leading to self-regulated strain via thermal expansion of the electroactive polymer. Moreover, the finite-difference time-domain simulation and linear thermal model also deduce the local strain to the surface plasmon heat absorption. The distinct plasmonic photothermic-piezoelectric phenomenon mediates not only localized external stimulus light response but also enhances dynamic piezoelectric energy harvesting. The present work highlights a promising surface plasmon coordinated piezoelectric response which underpins energy localization and transfer for diversified design of unique photothermic-piezotronic technology., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To observe the effect of electroacupuncture (EA) and moxibustion (Moxi) pretreatment on myocardial pathological and structural changes and expression of autophagy related protein LC 3 Ⅰ/Ⅱ and Beclin 1 in rats with myocardial ischemia-reperfusion injury (MI/RI), so as to explore their mechanisms underlying improving MI/RI., Methods: Forty SD rats were randomly divided into sham operation, model, ischemic preconditioning (IP), EA and Moxi groups ( n ＝8 in each group). EA (10 Hz/50 Hz，1 mA) or Moxi (ignited moxa stick) was respectively applied to bilateral "Neiguan"(PC 6) for 20 min, once daily for 7 days. The MI/RI model was established by occlusion of the anterior descending branch of the left coronary artery for 40 min, followed by reperfusion for 60 min. The left ventricular (LV) tissue samples were collected and analyzed for pathological (H.E. staining) and ultrastructural changes, for myocardial apoptosis (apoptotic index＝ number of apoptotic cells/total number of cardiomyocytes×100%) with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method, and for the expression of LC 3 and Beclin 1 in myocardial cells with Western blot., Results: Following MI/RI, H．E. staining revealed a disorder of arrangement of cardiomyocytes with vague border, inflammatory cell infiltration, intracellular swelling with bleeding, necrosis and dissolution of partial striated muscles of the left ventricle under light microscope, and dual staining of Uranyl acetate and leadnitrate showed atrophy, arrangement disorder, dissolution, necrosis, and interstitial edema of partial myocardial fibers, mitochondrial structural disorder, vacolation, and large body of autophagosomes with bilayers, etc. in ultrastructure, which was relatively lighter in both EA and Moxi groups. The apoptosis index, expression levels of myocardial LC 3 Ⅱ and Beclin 1 and the ratio of LC 3 Ⅱ/LC 3 Ⅰ were significantly higher in the model group than those in the sham operation group ( P <0.01), but the expression level of LC 3 Ⅰ was considerably down-regulated in the model group relevant to the sham operation group ( P <0.01). Following the intervention and MI preconditioning, the increased apoptosis index and expression levels of LC 3Ⅱ and Beclin 1 proteins and the ratio of LC 3Ⅱ/LC 3 Ⅰ were obviously down-regulated in the IP, EA and Moxi groups relevant to the model group ( P <0.01), and the decreased expression of LC 3 Ⅰ protein was up-regulated obviously in the 3 treatment groups ( P <0.05， P <0.01). The effects of EA were significantly superior to those of IP and Moxi groups in down-regulating apoptosis index and expression of LC 3 Ⅱ and Beclin 1 and the ratio of LC 3 Ⅱ/LC 3 Ⅰ and in up-regulating expression of LC 3 Ⅰ ( P <0.05, P <0.01)., Conclusion: Both EA and Moxi preconditioning of PC 6 have a protective effect on ischemic myocardium in MI/RI rats, which is probably related to their effects in regulating expression of myocardial autophagy proteins as LC 3 Ⅰ/Ⅱ and Beclin 1.

At present, there are various limitations to harvesting ambient waste heat which include the lack of economically viable material and innovative design features that can efficiently recover low grade heat for useful energy conversion. In this work, a thermal nanophotonic-pyroelectric (TNPh-pyro) scheme consisting of a metamaterial multilayer and pyroelectric material, which performs synergistic waste heat rejection and photothermal heat-to-electricity conversion, is presented. Unlike any other pyroelectric configuration, this conceptual design deviates from the conventional by deliberately employing back-reflecting NIR to enable waste heat reutilization/recuperation to enhance pyroelectric generation, avoiding excessive solar heat uptake and also retaining high visual transparency of the device. Passive solar reflective cooling up to 4.1 °C is demonstrated. Meanwhile, the photothermal pyroelectric performance capitalizing on the back-reflecting effect shows an open circuit voltage (V oc ) and short circuit current (I sc ) enhancement of 152 and 146%, respectively. In addition, the designed photoactive component (TiO 2 /Cu) within the metamaterial multilayer provides the TNPh-pyro system with an effective air pollutant photodegradation functionality. Finally, proof-of-concept for concurrent photothermal management and enhanced solar pyroelectric generation under a real outdoor environment is demonstrated.

Solar energy represents a robust and natural form of resource for environment remediation via photocatalytic pollutant degradation with minimum associated costs. However, due to the complexity of the photodegradation process, it has been a long-standing challenge to develop reliable photocatalytic systems with low recombination rates, excellent recyclability, and high utilization rates of solar energy, especially in the visible light range. In this work, a ternary hetero-nanostructured Ag-CuO-ZnO nanotube (NT) composite is fabricated via facile and low-temperature chemical and photochemical deposition methods. Under visible light irradiation, the as-synthesized ZnO NT based ternary composite exhibits a greater enhancement (∼300%) of photocatalytic activity than its counterpart, Ag-CuO-ZnO nanorods (NRs), in pollutant degradation. The enhanced photocatalytic capability is primarily attributed to the intensified visible light harvesting, efficient charge carrier separation and much larger surface area. Furthermore, our as-synthesised hybrid ternary Ag-CuO-ZnO NT composite demonstrates much higher photostability and retains ∼98% of degradation efficiency even after 20 usage cycles, which can be mainly ascribed to the more stable polar planes of ZnO NTs than those of ZnO NRs. These results afford a new route to construct ternary heterostructured composites with perdurable performance in sewage treatment and photocorrosion suppression.

Surface-enhanced Raman scattering (SERS) spectroscopy affords a rapid, highly sensitive, and nondestructive approach for label-free and fingerprint diagnosis of a wide range of chemicals. It is of great significance to develop large-area, uniform, and environmentally friendly SERS substrates for in situ identification of analytes on complex topological surfaces. In this work, we demonstrate a biodegradable flexible SERS film via irreversibly and longitudinally stretching metal deposited biocompatible poly(ε-caprolactone) film. This composite film after stretching shows surprising phenomena: three-dimensional and periodic wave-shaped microribbons array embedded with a high density of nanogaps functioning as hot-spots at an average gap size of 20 nm and nanogrooves array along the stretching direction. The stretched polymer surface plasmon resonance film gives rise to more than 10 times signal enhancement in comparison with that of the unstretched composite film. Furthermore, the SERS signals with high uniformity exhibit good temperature stability. The polymer SPR film with excellent flexibility and transparency can be conformally attached onto arbitrary nonplanar surfaces for in situ detection of various chemicals. Our results pave a new way for next-generation flexible SERS detection means, as well as enabling its huge potentials toward green wearable devices for point-of-care diagnostics.

Objective: To observe the effect of electroacupuncture (EA) and moxibustion (Moxi) pretreatment on expression of myocardial heat shock protein (HSP) in acute myocardial ischemia-reperfusion injury (MIRI) rabbits., Methods: A total of 72 New Zealand rabbits were randomly divided into 4 groups:sham operation, MIRI model, EA pretreatment and Moxi pretreatment ( n =18 rabbits in each group) which were further divided into 0, 24 and 48 h (time-point) subgroups ( n =6 in each). The MIRI model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 40 min and reperfusion for 60 min. EA and Moxi stimulation was respectively applied to bilateral "Neiguan"(PC 6) for 20 min, once daily for 5 days before ADB occlusion. The expressions of myocardial HSP 27, HSP 70 and HSP 90 were detected by immunohistochemistry. The pathological and ultrastructural changes of left ventricular ischemia tissue were observed under light and transmission electronic microscope (TEM), respectively., Results: Outcomes of H.E. staining and ultrastructure showed that MIRI-induced changes of disordered arrangement of cardiomyocytes, vague myocardial transverse striation, inflammatory infiltration, cardiac myofibre necrosis and fibrolysis (light microscope), and myofiber atrophy, vague and disorder in the arrangement of myofiber, myofilament necrosis, interstitial edema, mitochondrial swelling, microvessel expansion, etc. (TEM) were relatively milder in both EA and Moxi pretreatment groups (48 h). In comparison with the sham group, the expression levels of myocardial HSP 27, HSP 70 and HSP 90 had no significant changes after MIRI at the 3 time-points ( P >0.05). In the pretreatment groups, the expression levels of HSP 27 at 24 and 48 h in both EA and Moxi groups, HSP 70 at 48 h in both groups, HSP 70 at 0 and 24 h in the Moxi group were significantly up-regulated compared with the model group ( P <0.05, P <0.01). No significant changes were found in the expression of HSP 90 at the 3 time-points in the EA and Moxi pretreatment groups ( P >0.05). No significant differences were found between EA and Moxi in up-regulating expressions of myocardial HSP 27, HSP 70 and HSP 90 proteins at the 3 time-points ( P >0.05) except HSP 70 at 24 h (Moxi being stronger relative to EA, P <0.05)., Conclusions: EA and Moxi pretreatment has a protective effect on ischemic myocardium in MIRI rabbits, which Feb be associated with their actions in up-regulating myocardial HSP 27 and HSP 70 expression.

One-pot electroless galvanic cell deposition of a 3D hierarchical semiconductor-metal-semiconductor interlaced nanoarray is demonstrated. The fabricated 3D photoanode deviates from the typical planar geometry, and aims to optimize the effective surface area for light harvesting and long-range charge transfer-collection pathways., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

One of the most common knee injuries is ligament tear, which may initially manifest as an osseous injury in radiographs. Radiologists should therefore be able to recognize ligament tears of the knee as osseous abnormalities in images. This review focuses on the imaging features of knee ligament injuries and their related osseous injuries: anterior cruciate ligament (ACL) tear with Segond fracture; associated marrow contusion; ACL avulsion fracture; posterior cruciate ligament (PCL) tear with osseous avulsion of the ligament including arcuate sign; reverse Segond fracture; PCL avulsion fracture; medial collateral ligament tear with Pellegrini-Stieda disease; lateral collateral ligament tear with avulsion fracture of the fibular head; and patellar ligament injuries with Osgood-Schlatter and Sinding-Larsen-Johansson., (Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.)

We present a room temperature topotactic consolidation of cobalt and zinc constituents into monocrystalline CoZn hydroxide nanosheets, by a localized corrosion of zinc foils with cobalt precursors. By virtue of similar lattice orientation and structure coordination, the hybrid hydroxides amalgamate atomically without phase separation. Importantly, this in situ growth strategy, in combination with configurable percolated nanosheets, renders a high areal density of catalytic sites, immobilized structures, and conductive pathways between the nanosheets and underlying foils-all of which allow monocrystalline CoZn hydroxide nanosheet materials to function as effective electrodes for electrochemical oxygen evolution reactions. This convenient and eco-friendly topotactical transformation approach facilitates high-quality single crystal growth with improved multiphase purity and homogeneity, which can be extended to other transition metals for the fabrication of advanced functional nanocomposites., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Utilizing solar energy for environmental and energy remediations based on photocatalytic hydrogen (H2) generation and water cleaning poses great challenges due to inadequate visible-light power conversion, high recombination rate, and intermittent availability of solar energy. Here, we report an energy-harvesting technology that utilizes multiple energy sources for development of sustainable operation of dual photocatalytic reactions. The fabricated hybrid cell combines energy harvesting from light and vibration to run a power-free photocatalytic process that exploits novel metal-semiconductor branched heterostructure (BHS) of its visible light absorption, high charge-separation efficiency, and piezoelectric properties to overcome the aforementioned challenges. The desirable characteristics of conductive flexible piezoelectrode in conjunction with pronounced light scattering of hierarchical structure originate intrinsically from the elaborate design yet facile synthesis of BHS. This self-powered photocatalysis system could potentially be used as H2 generator and water treatment system to produce clean energy and water resources.

Disappearance of TAR-DNA-binding protein 43 kDa (TDP-43) from the nucleus contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS), but the nuclear function of TDP-43 is not yet fully understood. TDP-43 associates with nuclear bodies including Gemini of coiled bodies (GEMs). GEMs contribute to the biogenesis of uridine-rich small nuclear RNA (U snRNA), a component of splicing machinery. The number of GEMs and a subset of U snRNAs decrease in spinal muscular atrophy, a lower motor neuron disease, suggesting that alteration of U snRNAs may also underlie the molecular pathogenesis of ALS. Here, we investigated the number of GEMs and U11/12-type small nuclear ribonucleoproteins (snRNP) by immunohistochemistry and the level of U snRNAs using real-time quantitative RT-PCR in ALS tissues. GEMs decreased in both TDP-43-depleted HeLa cells and spinal motor neurons in ALS patients. Levels of several U snRNAs decreased in TDP-43-depleted SH-SY5Y and U87-MG cells. The level of U12 snRNA was decreased in tissues affected by ALS (spinal cord, motor cortex and thalamus) but not in tissues unaffected by ALS (cerebellum, kidney and muscle). Immunohistochemical analysis revealed the decrease in U11/12-type snRNP in spinal motor neurons of ALS patients. These findings suggest that loss of TDP-43 function decreases the number of GEMs, which is followed by a disturbance of pre-mRNA splicing by the U11/U12 spliceosome in tissues affected by ALS.

Primary lateral sclerosis (PLS) is clinically defined as a disorder selectively affecting the upper motor neuron (UMN) system. However, recently it has also been considered that PLS is heterogeneous in its clinical presentation. To elucidate the association of PLS, or disorders mimicking PLS, with 43-kDa TAR DNA-binding protein (TDP-43) abnormality, we examined two adult patients with motor neuron disease, which clinically was limited almost entirely to the UMN system, and was followed by progressive frontotemporal atrophy. In the present study, the distribution and severity, and biochemical profile of phosphorylated TDP-43 (pTDP-43) in the brains and spinal cords were examined immunohistochemically and biochemically. Pathologically, in both cases, frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) was evident, with the most severe degeneration in the motor cortex. An important feature in both cases was the presence of Bunina bodies and/or ubiquitin inclusions, albeit very rarely, in the well preserved lower motor neurons. The amygdala and neostriatum were also affected. pTDP-43 immunohistochemistry revealed the presence of many positively stained neuronal cytoplamic inclusions (NCIs) and dystrophic neurites/neuropil threads in the affected frontotemporal cortex and subcortical gray matter. By contrast, such pTDP-43 lesions, including NCIs, were observed in only a few lower motor neurons. pTDP-43 immunoblotting revealed that fragments of ∼25-kDa were present in the cortices, but not in the spinal cord in both cases. Genetically, neither of the patients had any mutation in the TDP-43 gene. In conclusion, we consider that although PLS may be a clinically significant disease entity, at autopsy, the majority of such clinical cases would present as upper-motor-predominant amyotrophic lateral sclerosis with FTLD-TDP., (© 2011 Japanese Society of Neuropathology.)

The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) is unclear. TAR DNA-binding proteins of 43 KDa (TDP-43) immunopositive cytoplasmic inclusions have been found in glia and neurons of ALS patients. The discovery of TDP-43 mutations in ALS patients indicates a direct role of TDP-43 in ALS. More than 30 mutations in the TDP-43 gene have been identified in patients with familial and sporadic ALS. ALS with a TDP-43 mutation is classified as ALS-10. The clinical features of ALS-10 are quite similar to those of sporadic ALS. Furthermore, the neuropathological findings for ALS-10, including TDP-43 immunopositive inclusions and Bunina bodies, are identical to those in sporadic ALS. Most of the mutations are located in the C-terminus of TDP-43, which may function as a binding domain of heterogeneous nuclear ribonucleoprotein. Frontotemporal lobar degeneration: FTLD and FTLD/MND (motor neuron disease) also have TDP-43 immunopositive inclusions. These disorders have been named as TDP-43 proteinopathy. However, patients with TDP-43 mutations rarely develop FTLD. Causative genes for familial FTLD and FTLD/MND are not linked to the TDP-43 gene. Thus, other factors may contribute to the TDP-43 pathology in these diseases. Further analysis is required to elucidate the molecular mechanism of ALS-10 and TDP-43 proteinopathy.

Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.

It has been reported that widespread multisystem degeneration can occur in patients with sporadic amyotrophic lateral sclerosis (SALS) who have survived for long periods with artificial respiratory support (ARS). We report a case of SALS of 8 years and 8 months duration in a 71-year-old woman, who received ARS for 7 years and 8 months. In this patient, the symptoms at the early stage were those of typical ALS, and a totally locked-in state with frontal lobe atrophy appeared a few years after the start of ARS. At autopsy, marked atrophy of the frontal lobe and brainstem tegmentum was evident. Microscopically, widespread multisystem degeneration with obvious neuronal loss was a feature. Bunina bodies and ubiquitinated inclusions were observed in the remaining lower motor neurons. Of interest was that Lewy body-like hyaline inclusions (LBHIs), which were later shown to be immunnoreactive (ir) for 43-kDa TAR DNA-binding protein (TDP-43) and ubiquitin, were also detected in neurons in various regions of the nervous system, including the lower and upper motor neuron nuclei. The distributions of neurons with TDP-43-ir and ubiquitin-ir cytoplasmic inclusions were also widespread in the nervous system, and in each region, the numbers of these neurons were apparently larger than those of neurons with LBHIs. Importantly, double-labeling immunofluorescence revealed that the widespread TDP-43-ir inclusions were often ubiqutinated. In conclusion, the entire pathological picture appeared to correspond well to the patient's long-standing, progressive disease, including the TDP-43 pathology with ubiquitination. These findings further strengthen the idea that TDP-43 abnormality is closely associated with the pathogenesis of SALS.

Findings of clinical, neuropathological and biochemical studies have supported the idea that frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) are part of a neurological disease spectrum. This concept is now further strengthened by the recent discovery of a 43-kDa transactivating responsive sequence DNA-binding protein (TDP-43) as a key component of the underlying neuropathology of FTLD-U, ALS with dementia (ALS-D) and ALS. Here we describe the clinicopathological features of selected autopsy cases belonging to this disease spectrum, and discuss the neuropathological similarities and differences between FTLD-U and ALS-D, with special reference to the morphology, distribution and density of ubiquitin/TDP-43-positive abnormal structures, along with a review of the literature.

Pathological transactivation-responsive DNA-binding protein 43 (TDP-43) has been identified as a component of ubiquitinated inclusions in frontotemporal lobar degeneration with motor neuron disease, as well as in sporadic and some forms of familial amyotrophic lateral sclerosis. To clarify whether pathological TDP-43 is present in other neurodegenerative diseases involving the motor neuron system, we immunohistochemically examined the brain and spinal cord affected by two CAG repeat (polyglutamine) diseases, Machado-Joseph disease (MJD) and spinal and bulbar muscular atrophy (SBMA), using polyclonal antibody against TDP-43. In all the MJD cases, TDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs), although few in number, were found only in the lower motor neurons in the brainstem and spinal cord. TDP-43-ir NCIs appeared as linear wisp-like, skein-like, or thick, somewhat rod-like bodies. These inclusions were also visualized with antibodies against phosphoserines 409 and 410 of TDP-43, and ubiquitin, but were not recognized by antibody against expanded polyglutamine stretches or ataxin-3. The ultrastructure of the TDP-43-ir NCIs was similar to that of the inclusions seen in sporadic ALS, consisting of bundles of parallel filaments. None of the SBMA cases showed abnormal TDP-43 immunoreactivity in any of the regions examined. Immunoblot analysis failed to recognize hyperphosphorylated TDP-43 at ~23 kDa in two MJD cases examined. However, the immunohistochemical findings strongly suggested that in MJD, in addition to the polyglutamine-dependent disease process, TDP-43-related pathogenesis is associated with degeneration and death of the lower motor neurons.

Recently, sporadic amyotrophic lateral sclerosis (SALS), a fatal neurological disease, has been shown to be a multisystem proteinopathy of TDP-43 in which both neurons and glial cells in the central nervous system are widely affected. In general, the natural history of SALS is short (<5 years). However, it is also known that a few patients may survive for 10 years or more, even without artificial respiratory support (ARS). In the present study using TDP-43 immunohistochemistry, we examined various regions of the nervous system in six patients with SALS of long duration (10-20 years) without ARS, in whom lower motor-predominant disease with Bunina bodies and ubiquitinated inclusions (UIs) in the affected lower motor neurons was confirmed. One case also showed UIs in the hippocampal dentate granule cells (UDG). In all cases, except one with UDG, the occurrence of TDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs) was confined to a few regions in the spinal cord and brainstem, including the anterior horns. In one case with UDG, TDP-43-ir NCIs were also detected in the substantia nigra, and some regions of the cerebrum, including the hippocampal dentate gyrus (granule cells). The number of neurons displaying NCIs in each region was very small (1-3 per region, except the dentate gyrus). On the other hand, the occurrence of TDP-43-ir glial cytoplasmic inclusions (GCIs) was more widespread in the central nervous system, including the cerebral white matter. Again, however, the number of glial cells displaying GCIs in each region was very small (1-3 per region). In conclusion, compared to the usual form of SALS, TDP-43 pathology shown in SALS of long duration was apparently mild in degree and limited in distribution, corresponding to the relatively benign clinical courses observed. It is now apparent that SALS of long duration is actually part of a TDP-43 proteinopathy spectrum.

To elucidate the maturation process of TDP-43-positive neuronal inclusions, we immunohistochemically and immunoelectron-microscopically examined multiple areas from the brain and spinal cord from ten patients with amyotrophic lateral sclerosis (ALS) and 25 control subjects. TDP-43 immunohistochemistry demonstrated three types of inclusions in ALS: skein-like, round, and dot-like inclusions. Skein-like inclusions were found in all cases of ALS. Dot-like inclusions were found in the anterior horn in seven cases of ALS, all of whom had round inclusions, but not in cases without round inclusions. In addition, careful examination revealed two types of diffuse punctate cytoplasmic staining: linear wisps and punctate granules. Linear wisps were present in all cases of ALS but in none of 25 controls. In contrast, punctate granules were detected in all cases of ALS as well as in five of 13 normal and in seven of 12 diseased controls. Immunoelectron-microscopy revealed that skein-like inclusions consisted of granule-associated parallel filaments. Round and dot-like inclusions were composed of granulo-filamentous structures. However, punctate granules corresponded to the mitochondria and were not immunostained with anti-ubiquitin, indicating that punctate granules represent cross-reaction. We assumed that linear wisps ("fine skein") aggregate as thicker and longer threads ("coarse skein"), whereas round inclusions arise from dot-like inclusions. These findings suggest that there are differences in the formation process between skein-like and round inclusions, despite the antigenic and ultrastructural similarities.

A nuclear protein, 43-kDa TAR DNA-binding protein (TDP-43), was recently identified as a component of the ubiquitinated inclusions (UIs) in frontotemporal lobar degeneration (FTLD-U) and sporadic amyotrophic lateral sclerosis (SALS). In the present study using immunohistochemistry, we examined various regions of the nervous system in a series of 35 SALS cases using a polyclonal antibody against TDP-43. Seven of the 35 cases had disease durations of more than 10 years with artificial respiratory support (ARS; duration: 69-156 months). In all cases, TDP-43-immunoreactive (ir) neuronal and glial cytoplasmic inclusions (NCIs and GCIs) were found together in many regions, including the histologically affected lower motor neuron nuclei. Cluster analysis of the distribution pattern of TDP-43-ir NCIs for cases without ARS (n = 28) identified two types (type 1, n = 16; type 2, n = 12). Type 2 was distinguished from type 1 by the presence of TDP-43-ir NCIs in the frontotemporal cortex, hippocampal formation, neostriatum and substantia nigra, and was significantly associated with dementia. Eleven of the 28 cases showed UIs in the hippocampal dentate granule cells, all of which had type-2 distribution pattern. Cases with ARS (n = 7) were also classified into the same types (type 1, n = 5; type 2, n = 2). Cases having type-1 distribution pattern (n = 21) showed no evident neuronal loss in most of the non-motor neuron nuclei where TDP-43-ir NCIs were present, whereas cases having type-2 distribution pattern (n = 14) often showed evident neuronal loss in the frontotemporal cortices, amygdaloid nuclei and substantia nigra. These findings indicate that SALS is a multisystem degenerative disease widely affecting both neurons and glial cells with a heterogeneous pattern of TDP-43-ir NCI distribution (SALS showing type-2 distribution pattern being closely linked to FTLD-U), and that long-term survival supported by a respirator has no apparent influence on the TDP-43 neuronal distribution pattern.

Study Design: Retrospective review and post-test-only control group design., Objective: To study the incidence and associated factors of ring apophysis fracture in adolescent lumbar disc herniation and to evaluate the long-term morbidity of untreated apophyseal fracture., Summary of Background Data: Ring apophysis fracture is a feature in adolescent disc herniation, but the incidence and prognosis are unknown. It is still controversial whether to remove the apophyseal fragment at time of discectomy., Methods: We studied 96 adolescents (mean age, 14.7 years) with clinical diagnosis of disc herniation proved by computerized tomography (CT). In CT scan ring, apophyseal fracture is classified by the size (large/small) and the location (central/lateral). We used modified Oswestry classification in the nonoperative patients for pain and functional evaluation. Patients with and without apophyseal fracture were compared to define the significance of the lesion., Results: Twenty-seven of the 96 CT studies (28%) demonstrated apophyseal fractures. All but 2 were at the level of the herniated disc. Large-central fragments were the most common in 16 patients (48%), large-lateral fragments in 2, small-central fragments in 6, and small-lateral fragment in 6. Rate of surgery was significantly higher in the disc herniation patients with apophyseal fractures. Sixty-four nonoperative patients were evaluated 6.6 years (range, 2.3-14.3) after the CT study and questionnaires were completed in 54 patients (84%). Patients with large apophyseal fragments had more chance of chronic back pain and limitation of daily activities than the patients with small fragments and patients without apophyseal fracture., Conclusion: Apophyseal fracture is not uncommon in adolescent lumbar disc herniation. The surgical decision must depend on clinical symptoms instead of radiologic findings, but disc herniation with apophyseal fracture may exhibit more severe symptoms. Patients with large apophyseal fragments must be informed of a greater chance of chronic back pain later on. Small apophyseal fragments had no clinical significance.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Accumulating evidence has shown that 43kDa TAR-DNA-binding protein (TDP-43) is the disease protein in ALS and frontotemporal lobar degeneration. We previously reported a familial ALS with Bumina bodies and TDP-43-positive skein-like inclusions in the lower motor neurons; these findings are indistinguishable from those of sporadic ALS. In three affected individuals in two generations of one family, we found a single base-pair change from A to G at position 1028 in TDP-43, which resulted in a Gln-to-Arg substitution at position 343. Our findings provide a new insight into the molecular pathogenesis of ALS.

Background: Multiplication of the alpha-synuclein gene (SNCA) (OMIM 163890) has been identified as a causative mutation in hereditary Parkinson disease or dementia with Lewy bodies., Objective: To determine the genetic, biochemical, and neuropathologic characteristics of patients with autopsy-confirmed autosomal dominant Lewy body disease, with particular reference to the dosage effects of SNCA., Design: Four-generation family study., Setting: Academic research. Patients We fractionated samples extracted from frozen brain tissues of 4 patients for biochemical characterization, followed by immunoblot analysis., Main Outcome Measures: We determined the dosages of SNCA and its surrounding genes by quantitative polymerase chain reaction analysis., Results: Quantitative polymerase chain reaction analysis revealed that 3 patients were heterozygous for SNCA duplication and 1 patient was homozygous for SNCA duplication. The homozygous patient showed earlier age at onset and earlier death, with more severe cognitive impairment than the heterozygous patients. Biochemical analysis revealed that phosphorylated alpha-synuclein accumulated in the sarkosyl-insoluble urea-extracted fraction of the brains of the patients., Conclusions: Pathologically confirmed Lewy body disease clinically characterized by progressive parkinsonism and cognitive dysfunction is caused by SNCA duplication. The homozygous patient demonstrated the most severe phenotype, suggesting that SNCA dosage has a considerable effect on disease phenotype even within a family. SNCA duplication results in the hyperaccumulation of phosphorylated alpha-synuclein in the brains of patients.

TDP-43 is a major component of ubiquitin-positive, tau-negative inclusions in amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration. We immunohistochemically examined the neostriatum from 14 cases of classic ALS (cALS), six cases of ALS with dementia (ALS-D), and 20 control subjects. TDP-43-positive, crescent or circular inclusions were found in neostriatal small neurons in 19 of 20 cases of ALS, but not in controls. Two types of inclusions were found in the large neurons: ubiquitin-positive, TDP-43-negative rod-like inclusions, and ubiquitin- and TDP-43-positive pleomorphic inclusions. The latter were specific to ALS; they were found in seven cases of cALS and in all of ALS-D. TDP-43-positive glial inclusions were also found in 12 cases of cALS and in all of ALS-D. These TDP-43-positive neuronal and glial inclusions were more numerous in ALS-D than cALS. In ALS-D, neuronal loss in the substantia nigra was found in all the cases, whereas mild gliosis without obvious neuronal loss was noted in the neostriaum in only two cases. These findings suggest that the neostriatum is also involved in the disease process of ALS with and without dementia.