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Yue Xu,1,&ast; Shuhong Zhang,1,&ast; Ping Wang,1,&ast; Yuanyuan Chen,1 Yazhan Mao,2 Xina Yuan,3 Yinyi Li,4 Mingming Li,1 Li Sheng,1 Xiaoqian Li,1 Na Gao1 1Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Respiratory, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 3College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 4Department of Outpatient, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Gao; Xiaoqian Li, Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China, Tel +86 18515165409, Email gaona301s@163.com; 41705763@qq.comObjective: This study aims to explore the correlates of frailty in hospitalized elderly hypertensive patients and its impact on clinical prognosis, and to construct a predictive model for the occurrence of frailty in this population.Methods: A cross-sectional and prospective observational cohort study was conducted, involving 312 elderly hypertensive patients diagnosed at the institution from January to June 2022. Frailty was diagnosed using the Fried Frailty Phenotype (FP), while the Charlson Comorbidities Index (CCI) assessed the presence of chronic conditions. Data analysis was performed using SPSS 22.0. Binary logistic regression analysis was conducted with frailty as the dependent variable to identify risk factors. Patients were followed for one year to monitor readmission rates and all-cause mortality.Results: Multivariate logistic regression identified CCI grade (P=0.030), gender (OR=21.618, 95% CI: 4.062– 115.061, P < 0.001), age (OR=1.147, 95% CI: 1.086– 1.211, P < 0.001), bedridden state (OR=11.620, 95% CI: 3.282– 41.140, P < 0.001), arrhythmia (OR=14.414, 95% CI: 4.558– 45.585, P < 0.001), heart failure (OR=5.439, 95% CI: 1.029– 28.740, P < 0.05), along with several biochemical markers, as independent predictors of frailty. A predictive model was developed, demonstrating a robust discriminative ability with an area under the receiver operating characteristic curve (AUC) of 0.915. Statistically significant differences in readmission rates and all-cause mortality were observed among the frail, pre-frail, and non-frail groups (P< 0.001), with the frail group exhibiting the highest incidence of these adverse outcomes. Notably, frailty emerged as a significant predictor of readmission (P< 0.05) but not of all-cause mortality in this cohort.Conclusion: This study establishes a robust frailty prediction model for elderly hypertensive patients, highlighting the influence of CCI grade, gender, age, and other clinical and biochemical factors on frailty. The model offers a valuable tool for healthcare providers to identify at-risk elderly individuals, facilitating targeted intervention strategies for cardiovascular disease management.Keywords: frailty, hypertension, older people, observational study, prediction model

Shunqin Fan, Xijun Wang, Ning Gao, Songli Wei Department of Anesthesiology, International Zhuang Medical Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of ChinaCorrespondence: Xijun Wang, Department of Anesthesiology, International Zhuang Medical Hospital affiliated to Guangxi University of Traditional Chinese Medicine, No. 8 Qiu Yue Road, Liang Qing District, Nanning, Guangxi, People’s Republic of China, Email gzmzk01@163.comBackground: Recurrent propofol anesthesia in the peak of neurodevelopment may lead to learning-memory decline. This study aimed to examine the efficacy of electroacupuncture pretreatment in ameliorating the aforementioned learning memory deficits and to explore its underlying mechanisms in a rat model of repeated propofol exposure.Methods: 10-day-old Sprague Dawley rats were randomly assigned to five groups: the control, fat emulsion, propofol, electroacupuncture pretreatment and electroacupuncture pretreatment combined with propofol groups. The electroacupuncture pretreatment involved three consecutive daily sessions, while propofol was received intraperitoneally once daily for five days. Following the modeling period, the rats’ learning-memory performance was assessed using the New Novel Arm Y-maze, New Object Recognition, and Morris Water Maze. The Nissl staining method was used to observe the development of hippocampal neurons, while Golgi staining was employed to observe hippocampal synaptic development.Results: The electroacupuncture pretreatment significantly attenuated the learning and memory impairment induced by recurring propofol exposure in rats. Additionally, it facilitated the development of hippocampal neurons and synaptic plasticity in the hippocampus. Immunofluorescence and Western Blot analyses were conducted to detect the expression of proteins related to apoptosis, learning memory, and synaptic plasticity. In the propofol group, the pro-apoptotic factors Caspase-3 and Bax was up-regulated, while the anti-apoptotic factor Bcl-2 was down-regulated, as compared to the blank group. Additionally, the phosphorylated cAMP-response element binding protein (pCREB), brain-derived neurotrophic factor (BDNF), synaptophysin, and growth associated protein-43 (GAP-43) was significantly decreased. In contrast, the electroacupuncture pretreatment combined with propofol group exhibited decreased the Caspase-3 and Bax and increased the Bcl-2, as compared to the propofol group, meanwhile, the pCREB, BDNF, Synaptophysin and GAP-43 was increased.Conclusion: Our findings indicate that electroacupuncture pretreatment can alleviate the learning and memory impairment induced by recurring propofol exposure in rats. This is achieved by enhancing hippocampal synaptic plasticity, activating the pCREB/BDNF pathway and inhibiting neuronal apoptosis.Keywords: electroacupuncture pretreatment, propofol, learning memory, synaptic plasticity

Yanmei Song,&ast; Huiyuan Chu,&ast; Fang Liu, Wenjie Guo, Na Gao, Che Chen, Shisan Bao Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Che Chen; Shisan Bao, Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, 35, Dingxi East Road, Chengguan, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 187 09312856 ; +81 180 176 84959, Email chen72123@163.com; profbao@hotmail.comPurpose: To investigate the role of IL-36 in the tumorigenesis of hepatocellular carcinoma (HCC). IL-36 composed of a natural antagonist (IL-36Ra) and three agonists (IL-36α, -β, -γ) that stimulate inflammation by binding to a common receptor consisting of IL-36R and IL-1RAcP. HCC is a common malignancy associated with high morbidity and mortality, often diagnosed at later stages. Although the exact role of IL-36α in HCC remains controversial, it is hypothesized that it may play a significant role in the development and progression of this cancer.Materials and Methods: In the current study, we measured both circulating and intrahepatic levels of IL-36α from HCC patients and healthy controls, using ELISA. The association between IL-36 and the differentiation of HCC was determined. Furthermore, the role IL-36 in both HCC and non-HCC cell lines was evaluated in vitro.Results: Circulating and intra-hepatic IL-36α was inversely correlated with differentiation of HCC, suggesting that IL-36α contribute to protection during the development of HCC. Based on bioinformatics, miR-27b-3p is closely related to downstream IL-36α. Thus, we determined miR-27b-3p expression in HCC tissues, showing upregulated miR-27b-3p was inversely correlated with IL-36α in HCC, perhaps via CXCL1 in HCC cells. It was confirmed that IL-36α inhibited HCC proliferation, viability and migration in vitro, consistent with reduced the expression of cytokines IL-1β, IL-18, implying that IL-36α inhibited the possible involvement of pyroptosis.Conclusion: Our data suggests that IL-36α may be a potential therapeutic target and a prediction biomarker for the management of HCC.Keywords: hepatocellular carcinoma, interleukin-36α, prognosis, biomarker

Xiaohang Zheng,1,2 Jianxin Qiu,1,2 Ning Gao,3 Ting Jiang,1,2 Ze Li,1,2 Weikang Zhang,1,2 Yuhang Gong,1,2 Zhenghua Hong,1,2 Huaxing Hong1,2 1Orthopedic Department, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 2Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 3Department of Cardiovascular Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Huaxing Hong; Zhenghua Hong, Taizhou Hospital Affiliated to Wenzhou Medical University, No. 150, Ximen Street, Taizhou City, Zhejiang Province, People’s Republic of China, Fax +86 0576-8512-0120, Email tzyyhhx@126.com; 0001hzh@163.comBackground: Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated inflammation and NLRP3-induced pyroptosis play essential roles in the development of OA. In this study, we examine whether paroxetine can inhibit pyroptosis and reduce osteoclast formation, thereby delaying the destruction of knee joints.Methods: We employed high-density cultures, along with quantitative polymerase chain reactions and Western blotting techniques, to investigate the effects of paroxetine on extracellular matrix synthesis and degradation. The expression levels of NF-κB and pyroptosis-related signaling pathway proteins were examined by Western blotting and immunofluorescence. Furthermore, the impact of paroxetine on RANKL-induced osteoclast formation was evaluated through TRAP staining and F-actin ring fluorescence detection. To investigate the role of paroxetine in vivo, we constructed a mouse model with destabilization of the medial meniscus (DMM) surgery. Safranin O-Fast Green staining, Hematoxylin-Eosin staining, and immunohistochemistry were conducted to observe the extent of knee joint cartilage deformation. In addition, TRAP staining was used to observe the formation of osteoclasts in the subchondral bone.Results: In the in vitro experiments with ATDC5, paroxetine treatment attenuated IL-1β-induced activation of the pyroptosis-related pathway and suppressed extracellular matrix catabolism by inhibiting the NF-kB signaling pathway. In addition, paroxetine treatment decreased the expression of RANKL-induced osteoclast marker genes and reduced osteoclast formation. In animal experiments conducted in vivo, mice treated with paroxetine exhibited thicker knee cartilage with a smoother surface compared to the DMM group. Additionally, the formation of osteoclasts in the subchondral bone was reduced in the paroxetine-treated mice. Further analysis revealed that paroxetine treatment played a role in preserving the balance of the extracellular matrix and delaying knee joint degeneration.Conclusion: Paroxetine can inhibit pyroptosis and reduce osteoclast formation via inhibiting the NF-κB signaling pathway, suggesting that it may have therapeutic effects in patients with OA.Keywords: paroxetine, pyroptosis, inflammation, osteoclasts, osteoarthritis

JianBo Wu,1,&ast; ZhuJun Tao,1,&ast; NingZhou Gao,1 Jie Shen,1 Zhi-Long Chen,1 HaiFeng Zhou,1 SongBai Zheng2 1Department of Pharmacy, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Geriatrics, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: HaiFeng Zhou, Department of Pharmacy, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 13918194105, Email zhouhaifeng23@126.comObjective: To evaluate the psychometric properties of the 14-item health literacy scale (HL-14) in patients living with type 2 diabetes mellitus (T2DM) in clinical setting.Methods: Cross-sectional study using item response theory and structural equation modeling (SEM) for testing the item difficulty and three dimensional-HL configurations was adopted in this study. Chinese patients living with T2DM admitted to endocrinology department of Huadong hospital were evaluated by the HL-14 including communication, functional and critical health literacy from August to December 2021.Results: The multidimensional random coefficients multinomial logistic model indicated the difficulty settings of the scale are appropriate for the study populations, and differential item functioning was not observed for sex in the study. SEM demonstrated that the three-dimensional configuration of the scale is good in the study population (x2/df=2.698, Comparative Fit Index = 0.965, Root Mean Square Error of Approximation = 0.076, standard residual mean root = 0.042).Conclusion: The HL-14 scale is a reliable and valid measurement, which can perform equitably across sex in evaluating the health literacy in Chinese patients living with T2DM. Moreover, the scale may help fill the gaps of multidimensional health literacy assessment and rapid screening of health literacy ability for clinical practice.Keywords: health literacy, type 2 diabetes, psychometric properties, multidimensional item response theory, structural equation model

Ning Gao,1,&ast; Meng Li,2,&ast; Weiming Wang,1 Lei Wang,3 Zhen Liu,4 Yufeng Guo1 1Department of Acupuncture and Moxibustion, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 2Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 3Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100020, People’s Republic of China; 4Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen Liu, Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No. 1 Xiyuan Playground, Haidian District, Beijing, People’s Republic of China, Email doctorliuzhen@126.com Yufeng Guo, Department of Acupuncture and Moxibustion, Guang’ an Men Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, People’s Republic of China, Email gamgyf@139.comBackground: In recent years, the incidence of herpes zoster has risen steeply, the exact pathogenesis of the acute pain and the transformation into postherpetic neuralgia are still obscure, and the absence of effective management remains a major therapeutic challenge. The purpose of this study was to perform a qualitative and quantitative bibliometric analysis of the 100 most cited papers on herpes zoster.Materials and methods: Related literature were retrieved from the Web of Science Core Collection. Excel and VOSviewer software were applied to quantitatively analyze, and construct the bibliometric network charts.Results: The Top 100 most-cited papers published between 2000 and 2018 showed a fluctuating downward trend. The most studies were published in the year of 2000 (n = 12). The article entitled “A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults” from Oxman MN, was the most-cited publication. The United States was the most contributing country, followed by the United Kingdom, and Italy. Finland occupied the highest citations per publication (CPP). The University of Colorado topped the list of institutions with the most publications with 18 articles and also had the most citations (average citations: 281.78 per article). Myron J Levin from the University of Colorado School of Medicine is the most published and most cited researcher overall, whereas Duke University’s John W Gnann tops the list in terms of average CPP.Conclusion: In terms of the quantity of T100 articles, researchers, and organizations, the US is the predominant country. The most T100 papers were published in the special journal Clinical Infectious Diseases. The most academic focus remain the remedies for postherpetic neuralgia and vaccine development for individualized groups.Keywords: herpes zoster, bibliometric study, top-cited, citation, VOSviewer

Among many efforts in the research of van der Waals (vdW) magnetic materials, increasing the Curie temperature above room temperature has been at the center of research in developing spintronics technology using vdW materials. Here an effective and reliable method of increasing the Curie temperature of ferromagnetic Fe3GeTe2 vdW materials by Ga implantation is reported. It is found that implanting Ga into Fe3GeTe2 by the amount of 10−3 Ga Å−3 could greatly enhance the Fe3GeTe2 Curie temperature by almost 100%. Spatially resolved microdiffraction and element-resolved X-ray absorption spectroscopy show little changes in the Fe3GeTe2 crystal structure and Fe valence state. In addition, the Ga implantation changes the Fe3GeTe2 magnetization from out-of-plane direction at low temperature to in-plane direction at high temperature. The result opens a new opportunity for tailoring the magnetic properties of vdW materials beyond room temperature.

Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in chiral magnet Co8Zn9Mn3 raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction.

An antiferromagnetic NiO spiral wall in Fe/NiO/Co0.5Ni0.5O/vicinal Ag(001) was created by rotating Fe magnetization and investigated using x-ray magnetic linear dichroism (XMLD). Different from the Mauri's 180° spiral wall, we find that the NiO spiral wall always switches its chirality at ∼90 rotation of the Fe magnetization, and unwinds the spiral wall back to a single domain with a further rotation of the Fe magnetization from 90° to 180°. The effect of this chirality switching on the magnetic anisotropy was studied using rotational magneto-optic Kerr effect (ROTMOKE) on Py/NiO/Co0.5Ni0.5O/vicinal Ag(001). We find that the original Mauri's model has to be corrected by an energy folding due to the chirality switching, which consequently converts the exchange bias from the Mauri's 180° spiral wall into a uniaxial anisotropy and a negative fourfold anisotropy.

The recent discovery of spin current transmission through antiferromagnetic insulating materials opens up vast opportunities for fundamental physics and spintronics applications. The question currently surrounding this topic is: whether and how could THz antiferromagnetic magnons mediate a GHz spin current? This mismatch of frequencies becomes particularly critical for the case of coherent ac spin current, raising the fundamental question of whether a GHz ac spin current can ever keep its coherence inside an antiferromagnetic insulator and so drive the spin precession of another ferromagnet layer coherently? Utilizing element- and time-resolved x-ray pump-probe measurements on Py/Ag/CoO/Ag/Fe75Co25/MgO(001) heterostructures, here we demonstrate that a coherent GHz ac spin current pumped by the Py ferromagnetic resonance can transmit coherently across an antiferromagnetic CoO insulating layer to drive a coherent spin precession of the Fe75Co25 layer. Further measurement results favor thermal magnons rather than evanescent spin waves as the mediator of the coherent ac spin current in CoO.

Wei Li,1,2,&ast; Nong Gao,2,&ast; Yi-Peng Pan,1 Xiu-Yun Ren2,3 1Department of Liver Transplantation, the Second Affiliated Hospital of Hainan Medical University, SanYa, People’s Republic of China; 2Department of Organ Transplantation, the Third Medical Center of General Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 3Department of Ultrasound Examination, Hainan Hospital of General Hospital of People’s Liberation Army, SanYa, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiu-Yun Ren, Department of Organ Transplantation, the Third Medical Center of General Hospital of People’s Liberation Army, Beijing, People’s Republic of China, Email rforestcloud@sina.comPurpose: This study aimed to investigate the application of color Doppler ultrasound (CDU) and contrast-enhanced ultrasound (CEU) in the early diagnosis of arterial steal syndrome (ASS) after orthotopic liver transplantation (OLT).Patients and Methods: A total of 1827 patients received OLT in our department between January 2007 and December 2021, and CDU and CEU were performed after surgery. Ultrasonographic data were collected and further analyzed. ASS was confirmed by digital subtraction angiography (DSA), and the use of splenic artery embolization was dependent on the DSA findings and clinical conditions. The ultrasonographic data were collected before and after embolization.Results: ASS was found in 23 patients (23/1827; 1.26%). CDU: the portal vein velocity was higher than normal in 17 patients (52.83± 21.74 cm/s); the hepatic artery flow signals disappeared in 7 patients; the hepatic artery velocity was 13.57± 5.85 cm/s in 16 patients. In 23 patients, the spleen artery velocity was 170.12± 32.04 cm/s. CEU: the hepatic artery was observed in 7 patients without hepatic artery flow signals on CDU; in 23 patients, the contrast agent reached the portal vein at the presence of contrast in the hepatic artery or earlier (difference: 2.21± 1.09 s). Splenic artery embolization was done in 17 of 23 patients with ASS. The hepatic artery flow velocity, hepatic artery resistance index, splenic artery velocity and time to the presence of contrast were significantly improved after embolization (P< 0.05).Conclusion: CDU and CEU are the preferred, effective tools in the diagnosis of ASS. Reduced peak hepatic artery velocity, increased spleen artery velocity and reduced time difference in the contrast reaching the portal vein and hepatic artery are indicative of ASS.Keywords: contrast-enhanced ultrasound, color Doppler ultrasound, liver transplantation, arterial steal syndrome

Na Gao,1,&ast; Linghui Xiao,1,&ast; Zheng Tao,2 Yanlin Zheng,1 Wanjie Wang,1 Hui Huang1 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Eye College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Huang, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Jinniu District, Chengdu, 610072, Sichuan Province, People’s Republic of China, Tel +86-18782917219, Fax +86-28-87732407, Email huanghui0021@163.comPurpose: To establish a high-glucose (HG) stressed cell model and study the expression of main components of the Dll4/Notch-VEGF signaling pathway under high-glucose stimulation.Methods: A model of HG-conditioned cells (human umbilical vein endothelial cells, HUVECs) was first established, and then the expression of Dll4, Notch1, Notch4 and VEGF in HG-stressed cells with or without Notch pathway blockage was analyzed by RT-PCR and Western blot. To observe cell migration, we also evaluated the Transwell assay.Results: HUVECs stimulated with 30mmol/L HG was selected as a cell model. RT-PCR and Western blot results showed that HG stimulation induced the expression of Dll4, Notch1 and VEGF and downregulated Notch4. The expressions were reversed after Notch pathway blockage; meanwhile, the blockage of Notch pathway inhibited cell migration under HG condition.Conclusion: The function of Notch4 in responses to HG stimulation deserves further researching. Combination therapy by blocking Dll4/Notch and VEGF pathways may provide us with a new way for anti-neovascularization.Keywords: Dll4, Notch1, Notch4, VEGF, endothelial cells

Can Hao &ast;, Bingjie Ma &ast;, Nan Gao, Tian Jin, Xiaoming Liu Pain Management Center, Shanghai Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 210092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoming Liu, Pain Management Center, Shanghai Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665# Kongjiang Road, Shanghai, 210092, People’s Republic of China, Tel +86-17721213706, Fax +86-21-25078707, Email brightlxm@gmail.comPurpose: Recent studies showed promotion of astrocyte autophagy in the spinal cord would provide analgesic effects. Silent information regulator T1 (SIRT1) and α subunit of peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α) are two master regulators of endogenous antioxidant defense and mitochondrial biogenesis. They play vital roles in both autophagy and neuropathic pain (NP). Our previous study showed that TSPO agonist Ro5-4864 elicited potent analgesic effects against NP, but the mechanisms remain unclear. This study aims to investigate the effects of TSPO agonist Ro5-4864 on autophagy and nuclear SIRT1/PGC-1α signaling in spinal dorsal horn.Methods: A rat model of L5 spinal nerve ligation (SNL) was adopted. Rats were randomly assigned to the Sham group, the SNL group, the Ro (TSPO agonist Ro5-4864) group and the Ro+3-MA group. The behavior assessments were conducted at baseline, on Day 1, 3, 7 and 14 after SNL. The autophagy-related proteins (ATG7, Beclin1, LC3, and P62) in spinal dorsal horn were assayed and the nuclear SIRT1/PGC-1α and downstream factors were analyzed.Results: Ro5-4864 alleviated the mechanical allodynia induced by SNL (P < 0.01 vs the SNL group), which could be totally abrogated by autophagy inhibitor 3-MA (P < 0.01 vs the Ro group). SNL induced elevated ATG7 (P < 0.01), Beclin1 (P < 0.01) and LC3-II/LC3-I (P < 0.01) contents and P62 accumulation (P < 0.01) on Day 7 and Day 14, which suggested an autophagy flux impairment. Ro5-4864 augmented ATG7 (P < 0.01), Beclin1 (P < 0.01) and LC3-II/LC3-I (P < 0.05) with decreased P62 (P < 0.01), which indicated a more fluent autophagic process. These effects were also totally abrogated by 3-MA (P < 0.01). Furthermore, Ro5-4864 activated the spinal nuclear SIRT1/PGC-1α signaling pathway.Conclusion: TSPO improved both autophagy impairment and mitochondrial biogenesis, which may provide a new strategy for the treatment of NP.Keywords: translocator protein, TSPO, neuropathic pain, autophagy, silent information regulator T1, SIRT1, α subunit of peroxisome proliferator-activated receptor-γ coactivator-1, PGC-1&#x03B1

Single crystalline Ag/Fe/Fe0.5Co0.5/MgO(001) films were grown by Molecular Beam Epitaxy and investigated by Magneto-Optic Kerr Effect (MOKE). We find that even though the 4-fold magnetic anisotropies of Ag/Fe/MgO(001) and Ag/Fe0.5Co0.5/MgO(001) films are different from the corresponding bulk values, their opposite signs allow a fine tuning of the 4-fold magnetic anisotropy in Ag/Fe/Fe0.5Co0.5/MgO(001) films by varying the Fe and Fe0.5Co0.5 film thicknesses. In particular, the critical point of zero anisotropy can be achieved in a wide range of film thicknesses. Using Rotational MOKE, we determined and constructed the anisotropy phase diagram in the Fe and Fe0.5Co0.5 thickness plane from which the zero anisotropy exhibits a linear relation between the Fe and Fe0.5Co0.5 thickness.

Using X-ray Magnetic Linear Dichroism (XMLD) measurement, we investigate the antiferromagnetic (AFM) NiO spin reorientation transition (SRT) in epitaxial NiO/CoO/MgO(0 0 1) system at room temperature and constructed a complete NiO spin phase diagram. Then utilizing Magneto-Optic Kerr Effect (MOKE) combined with a rotation magnetic field (ROTMOKE), we investigated the effect of NiO SRT on the magnetic anisotropy of a ferromagnetic (FM) Py overlayer in Py/NiO/CoO/MgO(0 0 1) system. We find that the Py coercivity and anisotropy only slightly enhanced for Py on top of out-of-plane NiO spins but greatly enhanced for Py on top of in-plane NiO spins. Both the uniaxial and fourfold anisotropies of the Py showed a clear dependence on the NiO spin orientation.

Using element-resolved x-ray magnetic circular dichroism and x-ray magnetic linear dichroism measurements, we studied Ni/CoO/vicinal MgO(001) and Ni/CoO/Fe/vicinal MgO(001) systems at 350 and 78 K. Above the CoO Néel temperature, the Ni magnetization is fully in plane and parallel to the atomic steps in both systems due to step-induced magnetic anisotropy. Below the CoO Néel temperature, the CoO spins in Ni/CoO/vicinal MgO(001) are fully in plane and parallel to the atomic steps and the Ni magnetization is fully in plane and perpendicular to the atomic steps due to the 90° Ni/CoO magnetic coupling. The CoO spins in Ni/CoO/Fe/vicinal MgO(001), however, develop an out-of-plane canted spin component in addition to the in-plane component parallel to the atomic steps. Consequently, the Ni magnetization is canted towards the out-of-plane direction by an appreciable angle. Photoemission electron microscopy imaging shows a 90° interfacial magnetic coupling at both the Ni/CoO and the CoO/Fe interfaces and an absence of a direct interlayer coupling, showing that the Ni spin canting is due to its coupling to the canted CoO spin components which is caused by the underlying ferromagnetic Fe layer in Ni/CoO/Fe/vicinal MgO(001).

Core 1- and 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O-glycans, was detected throughout the colon, whereas C3GnT, which controls core 3 O-glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1-derived O-glycans (IEC C1galt1-/-) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1- and 3-derived O-glycans (DKO) developed spontaneous colitis in both the distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1-/- mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than wild-type mucins. This study indicates that core 1- and 3-derived O-glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients.