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Meimei Hao, Yan Zhang, Shuangxing Hou, Yanling Chen, Ming Shi, Gang Zhao, Yanchun Deng Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China Abstract: Hyperhomocysteinemia (HHcy) has been recognized as an independent risk factor for atherosclerotic vascular disease. Here we report a patient who suffered from spinal cord demyelination combined with HHcy. The patient was admitted to our hospital with a diagnosis of acute myelitis. However, hormone therapy was ineffective. Further investigations revealed that he had HHcy and a homozygous mutation of the gene encoding methylenetetrahydrofolate reductase (MTHFR) c.677C>T, which is a key enzyme involved in homocysteine metabolism. In view of these findings, we treated the patient with B vitamins and his symptoms gradually improved. Spinal magnetic resonance imaging performed 3 months after onset showed near recovery of the lesion. To our knowledge, similar reports are rare. Keywords: demyelination, hyperhomocysteinemia, homocysteine, methylenetetrahydrofolate reductase, methylation

Study Design: Case report. Objective: To report a case of cervical myelopathy due to simultaneous anomalies at the level of atlas involving hypoplasia of the posterior arch of the atlas, partial ossification of the transverse atlantal ligament, and hypertrophy of the dens. Summary Of Background Data: Hypoplasia of the posterior arch of the atlas, ossification of the transverse atlantal ligament, and hypertrophy of the dens are all individually very rare clinical entities. We are not aware of previous reports describing the association of hypoplasia of the posterior arch of the atlas, partial ossification of the transverse atlantal ligament, and hypertrophy of the dens. Methods: The patient's medical history, physical examination, and radiographic evaluation are examined. Surgical treatment and clinical outcome are reported. In addition, available literature is also reviewed. Results: The patient's neurologic symptoms significantly improved after posterior decompressive surgery. Conclusion: We believe this is the first case of cervical myelopathy caused by simultaneous anomalies at the level of atlas involving hypoplasia of the posterior arch of the atlas, partial ossification of the transverse atlantal ligament, and hypertrophy of the dens. Surgical intervention improved the neurologic impairment. [ABSTRACT FROM AUTHOR]

Aims: Hydrogen sulfide (H 2 S) is a novel gas signaling molecule that has been researched in several physiological and pathological conditions, indicating that strategies targeting H 2 S may provide clinical benefits in diseases such as chronic cardiomyopathy. Here, we reveal the effect of H 2 S on chronic intermittent hypoxia (CIH)-related myocardial damage and its mechanistic relevance to phosphoinositol-3 kinase (PI3K)., Materials: Mice were subjected to a 4-week CIH process to induce myocardial damage, which was accompanied by daily administration of NaHS (a H 2 S donor) and LY294002 (an inhibitor of PI3K). Changes in heart function were evaluated via echocardiography. Histological examination was applied to assess heart tissue lesions. Myocardial apoptosis was detected by TUNEL staining and apoptosis-associated protein expression. Furthermore, the effects of NaHS on autophagy and the PI3K/AKT/mTOR pathway were investigated. Finally, the level of inflammation is also affected by related proteins., Key Findings: The CIH group presented increased myocardial dysfunction and heart tissue lesions. Echocardiography and histological analysis revealed that, compared with control mice, CIH-treated mice presented significantly more severe left ventricular remodeling and decreased myocardial contractile function. In addition, the apoptosis index and oxidative markers were significantly elevated in the CIH group compared with those in the control group. The autophagy marker Beclin-1 was decreased, while p62 was elevated by CIH treatment. H 2 S supplementation with NaHS significantly improved cardiac function and alleviated fibrosis, oxidative stress, and apoptosis but upregulated autophagy in CIH mice, and these effects were also observed in animals that underwent only PI3K blockade. Furthermore, PI3K/AKT pathway-mediated inhibition of the mammalian target of rapamycin (mTOR) pathway, the Nrf2/HO-1 pathway and proinflammatory NF-κB activity were shown to play a role in the therapeutic effect of NaHS after CIH stimulation., Competing Interests: Declarations. Ethical approval: This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Shanxi Medical University, Shanxi, China. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Improvements in the standard of living have led to increased attention to perianal disease. Although surgical treatments are effective, the outcomes of post-operative recovery (POR) are influenced by various factors, including individual differences among patients, the characteristics of the disease itself, and the psychological state of the patient. Understanding these factors can help healthcare providers develop more personalized and effective post-operative care plans for patients with perianal disease., Aim: To investigate the effect of illness perception (IP) and negative emotions on POR outcomes in patients with perianal disease., Methods: A total of 146 patients with perianal disease admitted to the First People's Hospital of Changde City from March to December 2023 were recruited. We employed a general information questionnaire, the Brief Illness Perception Questionnaire (B-IPQ), and the Hospital Anxiety and Depression Scale (HADS). We used the 15-item Quality of Recovery Score (QoR-15) to measure patients' recovery effects. Finally, we conducted Pearson's correlation analysis to examine the relationship between pre-operative IP and anxiety and depression levels with POR quality., Results: Fifty-three (36.3%) had poor knowledge of their disease. Thirty (20.5%) were suspected of having anxiety and 99 (67.8%) exhibited symptoms. Forty (27.4%) were suspected of having depression and 102 (69.9%) displayed symptoms. The B-IPQ, HADS-A, HADS-D, and QoR-15 scores were 46.82 ± 9.97, 12.99 ± 3.60, 12.58 ± 3.36, and 96.77 ± 9.85, respectively. There was a negative correlation between pre-operative IP, anxiety, and depression with POR quality. The influence of age and disease course on post-operative rehabilitation effect are both negative. The impact of B-IPQ, HADS-A, and HADS-D on POR was negative. Collectively, these variables accounted for 72.6% of the variance in POR., Conclusion: The quality of POR in patients with perianal disease is medium and is related to age, disease course, IP, anxiety, and depression., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Recently, ozone （O 3 ） pollution in Shangqiu has become increasingly prominent, especially in summer and autumn, crucially affecting the local environmental air quality. Based on the monitoring data of O 3 pollution days from the Environmental Monitoring Station in June and September 2022 （representing summer and autumn） in Shangqiu, an observation-based model （OBM） was used to study the causes and photochemical reaction characteristics of O 3 pollution in the city and precursor emission reduction strategies were studied. The observation results indicated that during summer in Shangqiu, the ρ （O 3 ） and O 3 daily maximum 8 h moving concentrations [ ρ （MDA8-O 3 ）] were 149.7 μg·m -3 and 195.4 μg·m -3 , whereas in autumn, ρ （O 3 ） and ρ （MDA8-O 3 ） were 119.8 μg·m -3 and 173.9 μg·m -3 , respectively； the O 3 concentration in summer was significantly higher than that in autumn. Ozone sensitivity research showed that the generation of O 3 in summer and autumn in Shangqiu was controlled by volatile organic compounds （VOCs）. Among them, oxygen-containing volatile organic compounds （OVOCs）, aromatic hydrocarbons, and alkenes contributed the most to the ozone generation potential （OFP） and ·OH reactivity （ L ·OH ）, and the control must have been strengthened. The OBM simulation results indicated that the maximum O 3 generation rates in summer and autumn were 23.0×10 -9 h -1 and 13.6×10 -9 h -1 , with maximum net generation rates of 17.4×10 -9 h -1 and 10.4×10 -9 h -1 and the maximum and maximum net generation rates of O 3 in summer were 1.68 times higher than those in autumn, indicating that the photochemical reactions in summer were significantly stronger than those in autumn. Compared with that in summer, the generation of O 3 in autumn was greatly influenced by regional inputs from other regions or cities, with a maximum input of 14.2×10 -9 h -1 . The prevention and control of O 3 pollution in the summer and autumn seasons in Shangqiu should mainly focus on controlling VOCs. The reduction ratio of VOCs/nitrogen oxides （NO x ） in autumn should be greater than that in summer and the reduction ratios of 3∶1 in summer and 4∶1 in autumn could be adopted for control.

The small G protein Arf1 has been identified as playing a selective role in supporting cancer stem cells (CSCs), making it an attractive target for cancer therapy. However, the current Arf1 inhibitors have limited translational potential due to their high toxicity and low specificity. In this study, two new potent small-molecule inhibitors of Arf1, identified as DU101 and DU102, for cancer therapy are introduced. Preclinical tumor models demonstrate that these inhibitors triggered a cascade of aging in CSCs and enhance anti-tumor immunity in mouse cancer and PDX models. Through single-cell sequencing, the remodeling of the tumor immune microenvironment induced by these new Arf1 inhibitors is analyzed and an increase in tumor-associated CD8+ CD4+ double-positive T (DPT) cells is identified. These DPT cells exhibit superior features of active CD8 single-positive T cells and a higher percentage of TCF1+PD-1+, characteristic of stem-like T cells. The frequency of tumor-infiltrating stem-like DPT cells correlates with better disease-free survival (DFS) in cancer patients, indicating that these inhibitors may offer a novel cancer immunotherapy strategy by converting the cold tumor immune microenvironment into a hot one, thus expanding the potential for immunotherapy in cancer patients., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) are attractive approaches for solving the global problem of water pollution, due to the generation of highly-active reactive oxygen species (ROS). Therefore, highly-efficient PMS activation is crucial for promoting the catalytic degradation of environmental pollutants. Here, bimetallic CoGeO 2 (OH) 2 nanosheets with abundant surface hydroxyl groups (CGH) were synthesized via a simple hydrothermal route for PMS activation and degradation of various organic contaminants for the first time. The abundant surface hydroxyl groups (≡Co-OH/≡Ge-OH) could promptly initiate PMS to generate highly-active species: singlet oxygen ( 1 O 2 ), sulfate radicals (SO 4 · - ) and hydroxyl radicals (HO • ), while the asymmetric electron distribution among Co-O-Ge bonds derived from the higher electronegativity of Ge than Co further enhances the quick electron transfer to promote the redox cycle of Co 2+ /Co 3+ and Ge 2+ /Ge 4+ , thereby achieving an outstanding catalytic capability. The optimal catalyst exhibits nearly 100 % catalytic degradation performance of dyes (Methylene blue, Rhodamine B, Methyl orange, Orange II, Methyl green) and antibiotics (Norfloxacin, Bisphenol A, Tetracycline) over a wide pH range of 3-11 and under different coexisting anion conditions (Cl - , HCO 3 - , NO 3 - , HA), suggesting the excellent adaptability for practical usage. This study could potentially lead to novel perspectives on the remediation of water areas such as groundwater and deep-water areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In Drosophila , long noncoding RNA Hsrω rapidly assembles membraneless organelle omega speckles under heat shock with unknown biological function. Here, we identified the distribution of omega speckles in multiple tissues of adult Drosophila melanogaster and found that they were selectively distributed in differentiated enterocytes but not in the intestinal stem cells of the midgut. We mimicked the high expression level of Hsrω via overexpression or intense heat shock and demonstrated that the assembly of omega speckles nucleates TBPH for the induction of ISC differentiation. Additionally, we found that heat shock stress promoted cell differentiation, which is conserved in mammalian cells through paraspeckles, resulting in large puncta of TDP-43 (a homolog of TBPH) with less mobility and the differentiation of human induced pluripotent stem cells. Overall, our findings confirm the role of Hsrω and omega speckles in the development of intestinal cells and provide new prospects for the establishment of stem cell differentiation strategies., Competing Interests: The authors declare no competing financial interests., (© 2024 The Author(s).)

The anti-tumor immune response relies on interactions among tumor cells and immune cells. However, the molecular mechanisms by which tumor cells regulate DCs as well as DCs regulate T cells remain enigmatic. Here, the authors identify a super signaling complex in DCs that mediates the Arf1-ablation-induced anti-tumor immunity. They find that the Arf1-ablated tumor cells release OxLDL, HMGB1, and genomic DNA, which together bound to a coreceptor complex of CD36/TLR2/TLR6 on DC surface. The complex then is internalized into the Rab7-marked endosome in DCs, and further joined by components of the NF-κB, NLRP3 inflammasome and cGAS-STING triple pathways to form a super signal complex for producing different cytokines, which together promote CD8+ T cell tumor infiltration, cross-priming and stemness. Blockage of the HMGB1-gDNA complex or reducing expression in each member of the coreceptors or the cGAS/STING pathway prevents production of the cytokines. Moreover, depletion of the type I IFNs and IL-1β cytokines abrogate tumor regression in mice bearing the Arf1-ablated tumor cells. These findings reveal a new molecular mechanism by which dying tumor cells releasing several factors to activate the triple pathways in DC for producing multiple cytokines to simultaneously promote DC activation, T cell infiltration, cross-priming and stemness., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Aims: The small GTPase protein ARF1 has been shown to be involved in the lipolysis pathway and to selectively kill stem cells in Drosophila melanogaster. However, the role of ARF1 in mammalian intestinal homeostasis remains elusive. This study aimed to explore the role of ARF1 in intestinal epithelial cells (IECs) and reveal the possible mechanism., Materials and Methods: IEC-specific ARF1 deletion mouse model was used to evaluate the role of ARF1 in intestine. Immunohistochemistry and immunofluorescence analyses were performed to detect specific cell type markers, and intestinal organoids were cultured to assess intestinal stem cell (ISC) proliferation and differentiation. Fluorescence in situ hybridization, 16S rRNA-seq analysis, and antibiotic treatments were conducted to elucidate the role of gut microbes in ARF1-mediated intestinal function and the underlying mechanism. Colitis was induced in control and ARF1-deficient mice by dextran sulfate sodium (DSS). RNA-seq was performed to elucidate the transcriptomic changes after ARF1 deletion., Key Findings: ARF1 was essential for ISC proliferation and differentiation. Loss of ARF1 increased susceptibility to DSS-induced colitis and gut microbial dysbiosis. Gut microbiota depletion by antibiotics could rescue the intestinal abnormalities to a certain extent. Furthermore, RNA-seq analysis revealed alterations in multiple metabolic pathways., Significance: This work is the first to elucidate the essential role of ARF1 in regulating gut homeostasis, and provides novel insights into the pathogenesis of intestinal diseases and potential therapeutic targets., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases (NDs). However, the mechanisms that link the central nervous system (CNS) and peripheral immune cells are still mostly unknown. We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate (ATP) releasing. Here, we demonstrate that IL-1β with elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activated γδ T cells in meninges. The activated γδ T cells then secreted IFN-γ that entered into parenchyma to activate the microglia-A1 astrocyte-C3-neuronal C3aR neurotoxic pathway. Remarkably, the neurodegenerative phenotypes of the neuronal Arf1 -ablated mice were strongly ameliorated by IFN- γ or C3 knockout. Finally, we show that the Arf1-reduction-induced neuroimmune- IFN- γ-gliosis pathway exists in human NDs, particularly in amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Full-endoscopic spinal surgery via transforaminal approach (TF-FESS) originated from the minimally invasive techniques of percutaneous interventional treatment of intervertebral disc diseases through posterolateral approach.Thanks to the continuous development and improvement of full-endoscopic equipment alongside surgical instruments and techniques, a developed technical system has been established in discectomy, spinal canal decompression, interbody fusion, etc. The combination of these basic techniques can treat relatively complex degenerative spinal diseases. The core techniques of TF-FESS include percutaneous puncture, foraminoplasty, spinal canal decompression, discectomy, annulus fibrosus suture, interbody fusion. This paper elaborates on the key points of the core techniques, indications, advantages, disadvantages, and prospects of the TF-FESS.

Objective: To observe the effect of renal artery denervation (RDN) on cardiac function in patients with acute myocardial infarction after percutaneous coronary intervention (AMI-PCI)., Methods: This is a single-centre, prospective randomized controlled study. A total of 108 AMI-PCI patients were randomly assigned to the RDN group or the control group at 1:1 ratio. All patients received standardized drug therapy after PCI, and patients in the RDN group underwent additional RDN at 4 weeks after the PCI. The follow-up period was 6 months after RDN. Echocardiography-derived parameters, cardiopulmonary exercise testing (CPET) data, Holter electrocardiogram, heart rate variability (HRV) at baseline and at the 6 months-follow up were analyzed., Results: Baseline indexes were similar between the two groups (all P > 0.05). After 6 months of follow-up, the echocardiography-derived left ventricular ejection fraction was significantly higher in the RDN group than those in the control group. Cardiopulmonary exercise test indicators VO 2 Max, metabolic equivalents were significantly higher in the RDN group than in the control group. HRV analysis showed that standard deviation of the normal-to-normal R-R intervals, levels of square root of the mean squared difference of successive RR intervals were significantly higher in the RDN group than those in the control group., Conclusions: RDN intervention after PCI in AMI patients is associated with improved cardiac function, improved exercise tolerance in AMI patients post PCI. The underlying mechanism of RDN induced beneficial effects may be related to the inhibition of sympathetic nerve activity and restoration of the sympathetic-vagal balance in these patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Objective: Obtaining sufficient decompression and solid fusion and avoiding approach-related injuries simultaneously are still challenging for the treatment of hard disc herniation in thoracolumbar junction. A combined full-endoscopic decompression and interbody fusion via a transforaminal approach was used to achieve this goal. The purpose of this study was to introduce the technical notes and clinical outcomes of this novel technique., Methods: Twenty segments of hard disc herniations in the thoracolumbar junction of 14 patients treated with full-endoscopic interbody fusion via the transforaminal approach between January 2018 and September 2021 were analyzed. The patients were an average age of 43.3 years. Full-endoscopic interbody fusion and discectomy via the transforaminal approach were performed under local anesthesia, followed by percutaneous pedicle screw system fixation under general anesthesia. Imaging, including magnetic resonance imaging (MRI), computed tomography (CT), and X-ray, was carried out. MRI was performed on the second day and 3 months postoperatively. CT was performed on the second day, 6 months, and 1 year (as needed) postoperatively. Back and radicular pain, neurological function, and thoracic spine function were scored using a visual analog scale, the Nurick scale, and modified Japanese Orthopaedic Association (mJOA) scale, and the Oswestry disability index at 1 week, 3 months, 6 months, and 1 year postoperatively., Results: All the operations were successfully completed, and no intraoperative conversion of the surgical methods occurred. Postoperative thoracolumbar junction MRI and CT examinations of all the patients revealed a sufficiently decompressed spinal cord or cauda equina, without any residual compression. At the 1-year follow-up, all the surgical segments were fused. Back and radicular pain was relieved in all the patients, and neurological function was restored. The average recovery rate of the mJOA was 72.5%, including seven excellent, five good, and two fair cases. Although dural tears occurred in two cases during the operation, no cerebrospinal fluid leakage or pseudomeningocele occurred during follow-up. No other surgical complications were noted., Conclusions: A combined full-endoscopic decompression and interbody fusion via a transforaminal approach can achieve complete spinal canal decompression and solid interbody fusion with fewer approach-related injuries. It is a safe and effective minimally invasive spine surgery for treating hard disc herniation in the thoracolumbar junction., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Introduction: Alzheimer's disease (AD) is characterized by increasing cognitive dysfunction, progressive cerebral amyloid beta (Aβ) deposition, and neurofibrillary tangle aggregation. However, the molecular mechanisms of AD pathologies have not been completely understood. As synaptic glycoprotein neuroplastin 65 (NP65) is related with synaptic plasticity and complex molecular events underlying learning and memory, we hypothesized that NP65 would be involved in cognitive dysfunction and Aβ plaque formation of AD. For this purpose, we examined the role of NP65 in the transgenic amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD., Methods: Neuroplastin 65-knockout (NP65 -/- ) mice crossed with APP/PS1 mice to get the NP65-deficient APP/PS1 mice. In the present study, a separate cohort of NP65-deficient APP/PS1 mice were used. First, the cognitive behaviors of NP65-deficient APP/PS1 mice were assessed. Then, Aβ plaque burden and Aβ levels in NP65-deficient APP/PS1 mice were measured by immunostaining and western blot as well as ELISA. Thirdly, immunostaining and western blot were used to evaluate the glial response and neuroinflammation. Finally, protein levels of 5-hydroxytryptamin (serotonin) receptor 3A and synaptic proteins and neurons were measured., Results: We found that loss of NP65 alleviated the cognitive deficits of APP/PS1 mice. In addition, Aβ plaque burden and Aβ levels were significantly reduced in NP65-deficient APP/PS1 mice compared with control animals. NP65-loss in APP/PS1 mice resulted in a decrease in glial activation and the levels of pro- and anti-inflammatory cytokines (IL-1β, TNF-α, and IL-4) as well as protective matrix YM-1 and Arg-1, but had no effect on microglial phenotype. Moreover, NP65 deficiency significantly reversed the increase in 5-hydroxytryptamine (serotonin) receptor 3A (Htr3A) expression levels in the hippocampus of APP/PS1 mice., Discussion: These findings identify a previously unrecognized role of NP65 in cognitive deficits and Aβ formation of APP/PS1 mice, and suggest that NP65 may serve as a potential therapeutic target for AD., 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 Wu, Cheng, Zheng, Liu, Hou, Liu, Huang and Yuan.)

In the present study, fourteen Exidia -like specimens were collected from China, France, and Australia. Based on morphological characteristics and phylogenetic analyses using the internal transcribed spacer regions (ITS) and the large subunit of nuclear ribosomal RNA gene (nLSU), four species in Exidia sensu lato , including Exidia saccharina and Tremellochaete atlantica , and two new species, Exidia subsaccharina and Tremellochaete australiensis , were identified. The four species are described and illustrated in detail. E. saccharina and T. atlantica , two known species from China are reported for the first time. E. subsaccharina and T. australiensis , two new species from France and Australia, respectively are also described. E. subsaccharina is characterized by its reddish brown to vinaceous brown basidiomata, slightly papillate hymenial surface, and narrowly allantoid basidiospores without oil drop measuring 12.5-17.5 × 4.2-5.5 μm. It differs from the similar species, E. saccharina , by distinctly larger basidiospores (12.5-17.5 × 4.2-5.5 vs. 10-14.2 × 3.2-4.5 μm). Tremellochaete australiensis is characterized by its white to grayish blue basidiomata, obviously and densely papillate hymenial surface, and allantoid basidiospores with oil drop measuring 13.8-16.2 × 4.8-6.5 μm. It also can be distinguished from the similar species, T. atlantica and T. japonica , by its distinctly larger basidiospores (13.5-17.8 × 4-5.2 vs. 10-11.8 × 4-4.8 μm in T. atlantica ; 9.4-11.8 × 3.5-4.2 μm in T. japonica )., 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 Tohtirjap, Hou, Rivoire, Gates, Wu and Dai.)

Objective: To evaluate and describe the clinical efficacy and safety of a modified unilateral biportal endoscopic lumbar discectomy., Methods: From February 2019 to February 2020, patients who met the inclusion criteria were treated using a modified unilateral biportal endoscopic lumbar discectomy. During the operation, the herniated disc was removed and the ligamentum flavum was preserved. Clinical efficacy was assessed via postoperative imaging and follow-up., Results: A total of 70 patients were followed up for more than 2 years, including 51 males and 19 females, aged 49.4 ± 16.0 years. All operations were completed and no complications were noted. Postoperative lumbar magnetic resonance imaging showed that the decompression of the nerve root was sufficient and the ligamentum flavum was preserved in all patients. Postoperative lumbar CT showed that the caudal lamina and inferior articular process of the cephalad vertebral were partially removed. Lower back and leg pain were significantly relieved after surgery, and the Oswestry Disability Index was significantly improved compared to presurgery measurements (P ＜ 0.01). After 2 years of follow-up, the sensory and muscle strength of nerve roots were significantly recovered (P ＜ 0.01). According to the MacNab score of the patients, 40 cases were defined as "excellent," 26 cases were "good," 2 cases were "fair," and 2 cases were "poor.", Conclusions: Modified unilateral biportal endoscopic lumbar discectomy can completely remove a lumbar herniated disc; relieve lower back and leg pain; improve lumbar function; reduce the risk of dural tearing, cerebrospinal fluid leakage, and epidural hematoma; and reduce the epidural adhesion and arachnoiditis caused by ligamentum flavum resection., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to compare the safety and clinical efficacy of full-endoscopic lumbar interbody fusion (FE-LIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)., Methods: A total of 70 patients with single-level lumbar degenerative diseases underwent FE-LIF or MIS-TLIF with a tubular retractor system from August 2018 to August 2020. Postoperatively, the efficacy and safety were compared using several clinical and radiological indices., Results: A total of 32 patients underwent FE-LIF and 38 received MIS-TLIF with a tubular retractor system, and all patients had no apparent complications. The FE-LIF group had higher radiation exposure, longer operation time, and less bleeding than the MIS-TLIF group (P < 0.05). Postoperative lumbar magnetic resonance imaging showed that the nerve decompression was sufficient. The pain in the lower back and legs was significantly relieved, and the Oswestry Disability Index (ODI) score was greatly improved after surgery (P < 0.01) in both the groups. The sensory and motor functions of nerve roots were remarkably recovered in both the groups at the 1-year follow-up (P < 0.05), and there was no significant difference in MacNab scores between the 2 groups. As per Mannion's fusion classification, the interbody fusion rate was significantly better in the FE-LIF group than in the MIS-TLIF group., Conclusions: FE-LIF, which is safe, effective, and minimally invasive, exhibits the same clinical efficacy as MIS-TLIF but with longer operation time and increased radiation exposure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective : The purpose of this study was to explore the effects of renal denervation (RDN) on cardiac function and malignant arrhythmia in patients with reduced left ventricular ejection fraction (HFrEF) and narrow QRS treated with an implantable cardioverter defibrillator (ICD). Methods: A total of 20 eligible HFrEF patients [left ventricular ejection fraction (LVEF) <40%] and narrow QRS complexes (QRS duration <120 ms) were randomized into either the ICD plus RDN group or the ICD only group during 17 April 2014 to 22 November 2016. Clinical data, including clinical characteristics, blood biochemistry, B-type natriuretic peptide, echocardiographic indexes, 6-min walk distance (6MWD), New York Heart Association (NYHA) classification, and count of ICD discharge events before and after the operation were analyzed. Patients were followed up for up to 3 years post ICD or ICD plus RDN. Results: Baseline clinical data were comparable between the two groups. Higher LVEF (%) (mixed model repeated measure, p = 0.0306) (39.50% ± 9.63% vs. 31.20% ± 4.52% at 1 year; 41.57% ± 9.62% vs. 31.40% ± 8.14% at 3 years), systolic blood pressure ( p = 0.0356), and longer 6MWD ( p < 0.0001) as well as reduction of NYHA classification ( p < 0.0001) were evidenced in the ICD plus RDN group compared to ICD only group during follow-up. Patients in the ICD plus RDN group experienced fewer ICD discharge events (2 vs. 40) and decreased diuretic use; rehospitalization rate (30% vs. 100%, p = 0.0031) and cardiogenic mortality rate (0% vs. 50%, p = 0.0325) were also significantly lower in the ICD plus RDN group than in the ICD only group during follow-up. Conclusion: ICD implantation plus RDN could significantly improve cardiac function and cardiac outcome as well as increase exercise capacity compared to ICD only for HFrEF patients with narrow QRS complexes., 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 © 2022 Yang, Xu, Gao, Shen, Li, Fa, Zhang, Wang, Hou, Hu, Jin and Liu.)

We previously showed that the Arf1-mediated lipolysis pathway sustains stem cells and cancer stem cells (CSCs); its ablation resulted in necrosis of stem cells and CSCs, which further triggers a systemic antitumor immune response. Here we show that knocking down Arf1 in intestinal stem cells (ISCs) causes metabolic stress, which promotes the expression and translocation of ISC-produced damage-associated molecular patterns (DAMPs; Pretaporter [Prtp] and calreticulin [Calr]). DAMPs regulate macroglobulin complement-related (Mcr) expression and secretion. The secreted Mcr influences the expression and localization of enterocyte (EC)-produced Draper (Drpr) and LRP1 receptors (pattern recognition receptors [PRRs]) to activate autophagy in ECs for ATP production. The secreted ATP possibly feeds back to kill ISCs by activating inflammasome-like pyroptosis. We identify an evolutionarily conserved pathway that sustains stem cells and CSCs, and its ablation results in an immunogenic cascade that promotes death of stem cells and CSCs as well as antitumor immunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the process of lignin extraction by the organic solvent method, the amount of alkali and the content of 1,4-butanediol are important conditions that affect lignin yield. The effects of alkali and alcohol contents on lignin recovery, removal rate, and structure were studied. In this reaction system, the removal rate of lignin increased with the increase of alkali content but decreased with the increase of alcohol content. Fourier transform infrared (FT-IR) analysis showed that the phenol hydroxyl group and the ether bond in lignin had different trends in different alkali and 1,4-butanediol environments, and four different infrared parameters in lignin had an obvious linear relationship. Gel permeation chromatography (GPC) results showed that high alkali content and high 1,4-butanediol content could lead to the fragmentation of lignin. In addition, lignin extracted from alkali-quantity factor series was selected to prepare activated carbon, CaCl 2 was selected as the activator, and its effects were studied. Results showed that in the process of extracting lignin, on the one hand, NaOH content affects the functional groups of activated carbon by affecting the aromatic structure of lignin; on the other hand, the NaOH content affects the graphitization degree and specific surface area of activated carbon by affecting the removal rate and the molecular weight of lignin., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Peroxidated lipids accumulate in the presence of reactive oxygen species and are linked to neurodegenerative diseases. Here we find that neuronal ablation of ARF1, a small GTPase important for lipid homeostasis, promoted accumulation of peroxidated lipids, lipid droplets and ATP in the mouse brain and led to neuroinflammation, demyelination and neurodegeneration, mainly in the spinal cord and hindbrain. Ablation of ARF1 in cultured primary neurons led to an increase in peroxidated lipids in co-cultured microglia, activation of the microglial NLRP3 inflammasome and release of inflammatory cytokines in an Apolipoprotein E-dependent manner. Deleting the Nlrp3 gene rescued the neurodegenerative phenotypes in the neuronal Arf1-ablated mice. We also observed a reduction in ARF1 in human brain tissue from patients with amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unrecognized role of peroxidated lipids released from damaged neurons in activation of a neurotoxic microglial NLRP3 pathway that may play a role in human neurodegeneration., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Elevated Wnt/β-catenin signaling has been commonly associated with tumorigenesis especially colorectal cancer (CRC). Here, an MST4-pβ-catenin Thr40 signaling axis essential for intestinal stem cell (ISC) homeostasis and CRC development is uncovered. In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates β-catenin at Thr40 to block its Ser33 phosphorylation by GSK3β. Thus, MST4 mediates an active process that prevents β-catenin from binding to and being degraded by β-TrCP, leading to accumulation and full activation of β-catenin. Depletion of MST4 causes loss of ISCs and inhibits CRC growth. Mice bearing either MST4 T178E mutation with constitutive kinase activity or β-catenin T40D mutation mimicking MST4-mediated phosphorylation show overly increased ISCs/CSCs and exacerbates CRC. Furthermore, the MST4-pβ-catenin Thr40 axis is upregulated and correlated with poor prognosis of human CRC. Collectively, this work establishes a previously undefined machinery for β-catenin activation, and further reveals its function in stem cell and tumor biology, opening new opportunities for targeted therapy of CRC., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

In order to reveal the correlation effect on the electronic properties in particular 5f electron occupation numbers of Pu/U ions in a (Pu,U) mixed oxide-PuUO4, a first principles calculation is performed by using density functional theory (DFT) plus a dynamical mean field theory (DMFT) scheme with the spin-orbit coupling (SOC) and on-site Coulomb repulsion for correlation effect due to localized Pu/U 5f orbitals. Results demonstrate that Pu/U 5f electron occupation numbers in the ground state of PuUO4 are mainly composed of 5f4/5f5 and 5f2/5f3 configurations, and exhibiting the intermediate occupation (IO) numbers with average 5f occupation numbers of about nf = 4.879 and 2.423 for Pu and U ions, respectively, irrespective of different Pu and U lattice sites in PuUO4. Pu 5f j = 5/2 and j = 7/2 components are in moderately and weakly correlated states, respectively, while U 5f j = 5/2 and j = 7/2 manifolds are both in weakly correlated states. jj and LS coupling schemes are feasible for Pu and U 5f electrons, respectively. In order to directly compare with the experimental angle-resolved photoemission spectrum (ARPES), we also estimate the momentum-resolved electronic spectrum function for this system.

Objective: To compare clinical effects of different postoperative rehabilitation modes on lumbar degenerative diseases, and explore influence of rehabilitation mode and other factors on postoperative effect., Methods: From June 2013 to July 2016, totally 900 patients were admitted from nine tertiary hospitals in Beijing to perform single segment bone grafting and internal fixation due to lumbar degenerative diseases were prospectively analyzed. There were 428 males and 472 females, the age of patient over 18 years old, with an average of (51.42±12.41) years old;according to patients' subjective wishes and actual residence conditions, all patients were divided into three groups, named as observation group 1 (performed integrated rehabilitation approach and orthopedic treatment model intervention), observation group 2 (performed integrated rehabilitation approach and orthopedic treatment, classified rehabilitation model intervention), and control group(performed routine rehabilitation model intervention). Visual analogue scale(VAS), Oswestry Disability Index(ODI) and Japanese Orthopaedic Association (JOA) were used to evaluate postoperative efficacy among three groups at 24 weeks. Possible factors affecting the postoperative efficacy including age, age grouping, gender, body mass index (BMI), BMI grouping, education level, visiting hospital, payment method of medical expenses, preoperative complications, preoperative JOA score, clinical diagnosis, surgery section, operative method, intraoperative bleeding volume, postoperative complications and rehabilitation mode were listed as independent variables, and postoperative ODI score at 24 weeks as dependent variables. Univariate analysis was used to analyze relationship between influencing factors and postoperative efficacy. Multiple linear regression was used to analyze relationship between influencing factors, rehabilitation mode and postoperative ODI score at 24 weeks, in further to find out the main reasons which affect postoperative efficacy, and to analyze impact of rehabilitation mode on postoperative efficacy., Results: All patients were followed up for 24 weeks after operation. All incisions healed at stage I with stable internal fixation. (1)Evaluation of postoperative efficacy:① There were no statistical differences in preoperative VAS and ODI among three groups( P >0.05), the degree of pain and dysfunction decreased among three groups after operation, and had differences in postoperative VAS and ODI among three groups ( P <0.05). There were no significant differences between observation group 1 and observation group 2( P >0.05); while compared with observation group 1 and control group, observation group 2 and control group, there were significant differences ( P <0.05). ②The function among three groups were improved in varying degrees after operation. There was difference in JOA score among three groups before operation and 24 weeks after operation ( P <0.05). There were no difference in JOA score among three groups between observation group 1 and observation group 2 ( P >0.05);while compared with observation group 1 and control group, observation group 2 and control group, there were significant differences ( P <0.05). (2)Influencing factors at 24 weeks after operation:①Univariate analysis showed gender, age, age grouping, education level, preoperative complications, clinical diagnosis, operative section, operative method, preoperative JOA score and rehabilitation mode had statistical significance with postoperative ODI score at 24 weeks ( P <0.05). BMI, BMI grouping, payment method of medical expenses, visiting hospital, intraoperative bleeding volume, postoperative complications had no statistical significance with postoperative ODI score at 24 weeks ( P <0.05).②Multivariate analysis results showed gender, rehabilitation mode, age, preoperative JOA score entered the equation eventually, stepwise multiple linear equation obtained had statistical significance ( F =12.294, P = 0.000). Among rehabilitation mode, standardized regression coefficient of the integrated rehabilitation approach and orthopedic treatment with classified rehabilitation model was absolute value of the largest (0.176), which had the greatest influence on postoperative curative effect. The degree of dysfunction in control group was higher than that in observation group 1 and observation group 2. Postoperative dysfunction was more severe in males than that of in females. Older age has higher degree of dysfunction after operation. Lower preoperative JOA score has higher degree of dysfunction after operation., Conclusion: Preoperative JOA score, gender, age could predict postoperative clinical effects of lumbar degenerative diseases in varying degrees treated with single level bone graft fusion and internal fixation. Different rehabilitation modes could improve clinical effects. Intergrated rehabilitation orthopedic treatment model and integrated rehabilitation approach and orthopedic treatment with classifiedrehabilitation model are superior to conventional rehabilitation model in improving patients' postoperative function and relieving pain, which is worthy of promoting in clinical.

Background: Conventional open laminectomy is considered to be the standard procedure for the treatment of thoracic ossified ligamentum flavum, but multi-segment thoracic laminectomy extensively removes the facet joints and ligamentous tissue, destroying the thoracic spine biomechanics and stability, may lead to delayed thoracic spine kyphosis deformities, which in turn can lead to potential neurological deterioration and local intractable pain., Objective: To introduce the technical notes and clinical outcome of ultrasonic osteotome assisted full-endoscopic en block resection of thoracic ossified ligamentum flavum., Study Design: A prospective cohort study., Setting: Hospital and outpatient surgery center., Methods: From January 2017 to March 2018, 15 patients with 1 - 2 segment thoracic ossified ligamentum flavum were treated with ultrasonic osteotome assisted full-endoscopic en block resection of thoracic ossified ligamentum flavum under local anesthesia. The magnetic resonance imaging and computed tomography of the thoracic spine was reexamined after the operation to evaluate the completeness of ossified ligamentum flavum resection and spinal cord decompression. The patients were followed up on the visual analog scale of back pain and radicular pain, Nurick score and mJOA score of neurological function, and Oswestry Disability Index at 1 week, 3 months, 6 months, one year, and 2 years after operation., Results: All operations of 17 segments thoracic ossified ligamentum flavum in 15 patients were successfully completed without intraoperative conversion to open surgery. There were no intraoperative spinal cord injuries, dura tears, postoperative cerebrospinal fluid leakage, postoperative infections, and postoperative spinal cord injury aggravated symptoms. Postoperative thoracic spine magnetic resonance imaging and computed tomography examinations of all patients showed that the spinal cord was fully decompressed without any residual pressure. Back pain and radicular pain were relieved significantly, and spinal cord function (Nurick, mJOA, and Oswestry Disability Index scores) was obviously restored. The mJOA recovery rate at the 2-year follow-up was 78.3% in average., Limitations: This is an observational cohort study with relative small sample and short-term follow-up., Conclusions: Ultrasonic assisted full-endoscopic en block resection of ossified ligamentum flavum is a safe and effective minimally invasive spine surgery for thoracic myelography caused by thoracic ossified ligamentum flavum.

Background: An annulus fissure or defect will inevitably be left on the posterior annulus fibrosus after almost all kinds of lumbar discectomy, which may lead to unsatisfying postoperative pain relief and recurrence of the disc herniation., Objective: The objective of this research is to introduce the technique of full-endoscopic annulus fibrosus suture following lumbar discectomy through the transforaminal or interlaminar approach, and to analyze the clinical outcome of full-endoscopic lumbar discectomy and annulus fibrosus suture., Study Design: This study used a prospective cohort design., Setting: The research was conducted in a hospital and outpatient surgery center., Methods: A total of 50 patients with noncontained lumbar disc herniation treated with full-endoscopic lumbar discectomy and annulus fibrosus suture were treated in our department between January 2018 and November 2018. Full-endoscopic single-stitch suture via the transforaminal approach (Group T) or double-stitch suture via the interlaminar approach (Group I) was selected according to the level of lesion. Lumbar magnetic resonance imaging (MRI) was reexamined on the second day and 3 months after operation to evaluate the completeness of the discectomy and the adequacy of nerve decompression. Patients were followed up on the second day, 3 months, 6 months, and one year after operation to evaluate the relief of low back pain and leg pain, using a visual analog scale (VAS, 100-point scale). At 3 months, 6 months, and one year after operation, the patients were followed up for recovery of lumbar spine function, using the Oswestry Disability Index (ODI). At the one-year follow-up, the MacNab score was used to evaluate the clinical outcome, and the recovery of nerve root function (sensation, muscle strength, and reflex) was recorded., Results: All operations were successfully completed, including 27 cases in Group T and 23 cases in Group I. There were no surgical complications and no recurrence of lumbar disc herniation. Lumbar MRI reexaminations of all patients showed that the herniated disc was completely removed and the nerves were fully decompressed. Postoperative low back pain and leg pain were significantly relieved, and the ODI score was significantly improved (P < .01) in both groups. At the one-year follow-up, the excellent and good rates as measured by the MacNab score were 92.6% in Group T and 91.3% in Group I with no significant difference between the 2 groups (P > .05). The impaired sensation and muscle strength in the low extremities of evolved nerve root of the 2 groups of patients recovered significantly at the one-year follow-up (P < .01), but the tendon reflex did not recover significantly (P > .05)., Limitations: This is an observational cohort study with relatively small sample sizes and short-term follow-up., Conclusions: Full-endoscopic lumbar discectomy and annulus fibrosus suture through either the transforaminal or interlaminar approach are safe and effective minimally invasive spinal surgery techniques that can reduce the recurrence rate of lumbar disc herniation after full-endoscopic lumbar discectomy.

Objective: To introduce the technical key points of lumbar annulus fibrosus suture under full-endoscope and analyze the clinical efficacy of full-endoscopic lumbar discectomy and annulus fibrosus suture., Methods: A total of 50 patients with non contained lumbar disc herniation treated with full-endoscopic lumbar discectomy and annulus fibrosus suture in our department between January 2018 and November 2018 were included. Full-endoscopic single-stitch suture through transforaminal approach or double-stitch suture through interlaminar approach was selected according to lesion level. The lumbar MRI and CT were reexamined on the second day and 3 months after surgery to evaluate the completeness of the discectomy and the adequacy of nerve decompression respectively. The patients were followed up on the second day, 3 months, 6 months, and 1 year after surgery for pain relief using visual analogue scale (VAS, 100 -point scale). The patients were followed up at 3 months, 6 months, and 1 year postoperatively for the recovery of lumbar spine function using Oswestry Disability Index(ODI). At the 1-year follow-up, the Macnab standard of lumbar spine function was evaluated, and the recovery of nerve root function (sensory, muscular and reflex) was recorded., Results: All operations were successfully completed, of which 27 patients were treated with transforaminal approach(including 8 cases of L 3, 4 and 19 cases of L 4, 5 ), and 23 patients(including 11 cases of L 4, 5 and 12 cases of L 5 S 1 ) with interlaminar approach. The average operation time was 43.2 minutes. There were no surgical complications and no recurrence of lumbar disc herniation. Postoperative lumbar MRI and CT examinations of all patients showed that the herniated disc was completely removed and the nerveswere fully decompressed. All patients had significant relief of low back pain and lower extremity radiation pain, and the ODI score improved significantly( P <0.01). At 1 year postoperative follow up, 17 patients got an excellent result, 29 good and 4 fair according to Macnab evaluation system. On the first year after surgery, the sense of damaged nerve roots and muscle strength were significantly restored ( P <0.01), but tendon reflexes were not significantly restored ( P >0.05)., Conclusion: Full-endoscopic lumbar discectomy and annulus fibrosus suture are safe and effective techniques for minimally invasive spinal surgery, which can reduce the recurrence rate of lumbar disc herniation after full endoscopic lumbar discectomy.

Objective: To study the technical notes and clinical efficacy of full-endoscopic thoracic intervertebral discectomy via transforaminal approach. Methods: We included 16 patients with thoracic disc herniation treated by full-endoscopic thoracic discectomy via transforaminal approach between January 2017 and September 2018 in ours department of orthopedics. The average age is 53.7 years. The compressionare classified by nature: 5 cases of soft thoracic disc herniation, 7 cases of calcified or ossified thoracic disc herniation, and 4 cases of osteophyte protrusion of the posterior edge of the adjacent vertebral body of the diseased disc. All patients had symptoms of thoracic myelopathy before operation, and 7 of them had radiculopathy. Via transforaminal approach under local anesthesia, enlarged foraminoplasty and full-endoscopic thoracic discectomy were used for treatment. Observe the changes of postoperative imaging, pain symptoms and recovery of spinal cord function at 1 week, 3 months, 6 months and 1 year after operation. Back pain and radicular pain were scored with VAS, neurological function was assessed with Nurick score and mJOA score, and thoracic spine function was assessed with Oswestry disability index (ODI). Results: All operations were successfully completed, and no intraoperative conversion of surgical methods occurred. Postoperative thoracic MRI and CT examinations of all patients showed that the spinal cord was fully decompressed without any residual compression. Back pain and radicular pain were all relieved obviously in all patients, and spinal cord function was obviously restored. Transient intercostal neuralgia occurred in 2 cases after operation, and no other surgical complications occurred. Conclusions: Full-endoscopic or fluoroscopic foraminoplasty and full-endoscopic thoracic discectomyvia transforaminal approach under local anesthesia is a safe and effective treatment for soft and hard thoracic disc herniation located on the ventral side of the spinal cord.

Cancer stem cells (CSCs) may be responsible for treatment resistance, tumor metastasis, and disease recurrence. Here we demonstrate that the Arf1-mediated lipid metabolism sustains cells enriched with CSCs and its ablation induces anti-tumor immune responses in mice. Notably, Arf1 ablation in cancer cells induces mitochondrial defects, endoplasmic-reticulum stress, and the release of damage-associated molecular patterns (DAMPs), which recruit and activate dendritic cells (DCs) at tumor sites. The activated immune system finally elicits antitumor immune surveillance by stimulating T-cell infiltration and activation. Furthermore, TCGA data analysis shows an inverse correlation between Arf1 expression and T-cell infiltration and activation along with patient survival in various human cancers. Our results reveal that Arf1-pathway knockdown not only kills CSCs but also elicits a tumor-specific immune response that converts dying CSCs into a therapeutic vaccine, leading to durable benefits.

Background: Exosomes are lipid-bilayer enclosed nano-sized vesicles that transfer functional cellular proteins, mRNA and miRNAs. Mesenchymal stem cells (MSCs) derived exosomes have been demonstrated to prevent memory deficits in the animal model of Alzheimer's disease (AD). However, the intravenously injected exosomes could be abundantly tracked in other organs except for the targeted regions in the brain. Here, we proposed the use of central nervous system-specific rabies viral glycoprotein (RVG) peptide to target intravenously-infused exosomes derived from MSCs (MSC-Exo) to the brain of transgenic APP/PS1 mice. MSC-Exo were conjugated with RVG through a DOPE-NHS linker., Results: RVG-tagged MSC-Exo exhibited improved targeting to the cortex and hippocampus after being administered intravenously. Compared with the group administered MSC-Exo, in the group administered RVG-conjugated MSC-Exo (MSC-RVG-Exo) plaque deposition and Aβ levels were sharply decreased and activation of astrocytes was obviously reduced. The brain targeted exosomes derived from MSCs was better than unmodified exosomes to improve cognitive function in APP/PS1 mice according to Morris water maze test. Additionally, although MSC-Exo injected intravenously reduced the expression of pro-inflammatory mediators TNF-α, IL-β, and IL-6, but the changes of anti-inflammatory factors IL-10 and IL-13 were not obvious. However, administration of MSC-RVG-Exo significantly reduced the levels of TNF-α, IL-β, and IL-6 while significantly raised the levels of IL-10, IL-4 and IL-13., Conclusions: Taken together, our results demonstrated a novel method for increasing delivery of exosomes for treatment of AD. By targeting exosomes to the cortex and hippocampus of AD mouse, there was a significant improvement in learning and memory capabilities with reduced plaque deposition and Aβ levels, and normalized levels of inflammatory cytokines., Competing Interests: This study was approved by the animal ethics committee of Shanghai University of TCM and the Animal Research Committee of Shanghai. All of the protocols were based on the “Guide for the Care and Use of Laboratory Animals” of the National Institutes of Health (USA) and efforts were made to minimize the number of animals used and any discomfort experienced.All participants have given consent for publication.The authors have no conflicts of interest to disclose.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Guanine nucleotide exchange factors (GEFs) are essential for small G proteins to activate their downstream signaling pathways, which are involved in morphogenesis, cell adhesion, and migration. Mutants of Gef26, a PDZ-GEF (PDZ domain-containing guanine nucleotide exchange factor) in Drosophila, exhibit strong defects in wings, eyes, and the reproductive and nervous systems. However, the precise roles of Gef26 in development remain unclear. In the present study, we analyzed the role of Gef26 in synaptic development and function. We identified significant decreases in bouton number and branch length at larval neuromuscular junctions (NMJs) in Gef26 mutants, and these defects were fully rescued by restoring Gef26 expression, indicating that Gef26 plays an important role in NMJ morphogenesis. In addition to the observed defects in NMJ morphology, electrophysiological analyses revealed functional defects at NMJs, and locomotor deficiency appeared in Gef26 mutant larvae. Furthermore, Gef26 regulated NMJ morphogenesis by regulating the level of synaptic Fasciclin II (FasII), a well-studied cell adhesion molecule that functions in NMJ development and remodeling. Finally, our data demonstrate that Gef26-specific small G protein Rap1 worked downstream of Gef26 to regulate the level of FasII at NMJs, possibly through a βPS integrin-mediated signaling pathway. Taken together, our findings define a novel role of Gef26 in regulating NMJ development and function., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Accumulative studies suggest that a fraction of cells within a tumor, known as cancer stem cells (CSCs) that initiate tumors, show resistance to most of the therapies, and causes tumor recurrence and metastasis. CSCs could be either transformed normal stem cells or reprogrammed differentiated cells. The eventual goal of CSC research is to identify pathways that selectively regulate CSCs and then target these pathways to eradicate CSCs. CSCs and normal stem cells share some common features, such as self-renewal, the production of differentiated progeny, and the expression of stem-cell markers, however, CSCs vary from normal stem cells in forming tumors. Specifically, CSCs are normally resistant to standard therapies. In addition, CSCs and non-CSCs can be mutually convertible in response to different signals or microenvironments. Even though CSCs are involved in human cancers, the biology of CSCs, is still not well understood, there are urgent needs to study CSCs in model organisms. In the last several years, discoveries in Drosophila have greatly contributed to our understanding of human cancer. Stem-cell tumors in Drosophila share various properties with human CSCs and maybe used to understand the biology of CSCs. In this chapter, we first briefly review CSCs in mammalian systems, then discuss stem-cell tumors in the Drosophila posterior midgut and Malpighian tubules (kidney) and their unique properties as revealed by studying oncogenic Ras protein (Ras V12 )-transformed stem-cell tumors in the Drosophila kidney and dominant-negative Notch (N DN )-transformed stem-cell tumors in the Drosophila intestine. At the end, we will discuss potential approaches to eliminate CSCs and achieve tumor regression. In future, by screening adult Drosophila neoplastic stem-cell tumor models, we hope to identify novel and efficacious compounds for the treatment of human cancers.

N-myc downstream-regulated gene 2 (NDRG2) has been implicated in the development of central nervous system and brain diseases such as brain tumors, ischemic stroke and neurodegenerative disorders. However, it remains unclear that the spatiotemporal distribution of NDRG2 in the human fetal brain. In this study, we examined the expression pattern of NDRG2 in different regions of human fetal brain at 16-28 gestational weeks (GWs) by using RT-PCR, western blot and immunohistochemistry. Firstly, RT-PCR revealed that mRNA of NDRG2 was detected in the human brain regions of fetuses at 16-28 GWs such as medulla oblongata (MdO), mesencephalon (MeE), cerebellum (Cbl), frontal lobe (Fr), ventricular (VZ)/subventricular zone (SVZ) and hippocampus (hip), and the expressions of NDRG2 mRNA in these human fetal brain regions were increased with gestational maturation. Furthermore, western blot and immunohistochemistry results revealed that at 28 GWs, the expression of NDRG2 protein was restricted to the MdO's olivary nucleus, MeE's aqueduct, cerebellar internal granular layers, cerebral cortex of the Fr, VZ/SVZ of lateral ventricle, and hippocampal dentate gyrus, and highest expression in the VZ/SVZ, and lowest in the MeE. Finally, double immunohistochemistry results showed that NDRG2 in the MdO, Cbl and VZ/SV at 28 GWS was mainly expressed in neurons (NeuN positive cells), and in some astrocytes (GFAP positive cells). Taken together, these results suggest that NDRG2 is mainly expressed in human fetal neurons of various brain regions during development, which may be involved in neuronal growth and maturation., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The present study describes a novel all-arthroscopic technique for medial and lateral meniscal allograft transplantation (MAT). Surgical instruments were specifically designed to assist in the all-arthroscopic approach for MAT. The bone plug attachment technique, either the arthroscopic-assisted or all-arthroscopic approach, attaches bone plugs to the anterior and posterior horns. In the present study, two sets of surgical implements were designed: One to produce bone plugs of predefined sizes in the anterior and posterior horns of the allograft meniscus (bone plug implements) and a second to create bone tunnels in the receptor tibial plateau to hold the bone plugs (bone tunnel implements). The present study demonstrated that an all-arthroscopic approach to MAT was feasible. Furthermore, the specifically designed surgical instruments allowed for consistent preparation of grafts and recipient tissues, contributing to a standardized approach to MAT. The present findings indicate that an all-arthroscopic approach to MAT may be achievable. They also provide the incentive for future clinical studies to directly compare the outcomes and to initiate the standardization of the procedure to optimize MAT and maximize patient outcomes and quality of life.

Nano-structures of [Zn(L)(atpt)] n (1) (L=1,2-bis(2-methylbenzimidazol-1-ylmethyl)benzene and H 2 atpt=2-aminoterephthalic acid) were obtained by hydrothermal and sonochemical approaches, characterized by scanning electron microscopy (SEM), IR, powder X-ray diffraction (PXRD), and elemental analysis. CP 1 features a 2D (4,4) network with the point symbol {4 4 .6 2 }, the 3D supramolecular architecture in CP 1 is controlled through π⋯π stacking interactions. The influence of various concentrations of initial reagents, power of ultrasound irradiation, and ultrasound time on the morphology and size of nano-structured CP 1 were studied in detail. In addition, the luminescence and photocatalytic properties of the nanoparticles of CP 1 for the degradation of methyl blue (MB) have also been investigated., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A new coordination polymer (CP), formulated as [Cd(L)(DCTP)] n (1) (L=1,1'-(1,4-butanediyl)bis(2-methylbenzimidazole), H 2 DCTP=2,5-dichloroterephthalic acid), was synthesized under hydrothermal conditions and the performance as luminescent probe was also investigated. Single-crystal X-ray diffraction reveals CP 1 is a 3D 3-fold interpenetrated dia network with large well-defined pores. It is found that CP 1 revealed highly sensitive luminescence sensing for Fe 3+ ions in acetonitrile solution with a high quenching efficiency of K SV =2541.238L·mol -1 and a low detection limit of 3.2μM (S/N=3). Moreover, the photocatalytic efficiency of 1 for degradation of methylene blue could reach 82.8% after 135min. Therefore, this coordination polymer could be viewed as multifunctional material for selectively sensing Fe 3+ ions and effectively degrading dyes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A nanoparticle of cobalt(II) coordination polymer (CP), [Co(L)(npht)] n (1) (H 2 npht=4-nitrophthalic acid, L=1,3-bis(5,6-dimethylbenzimidazol-1-ylmethyl)benzene) and its nanocomposite (Ag/CP 1) were obtained by the sonochemical approach and characterized by IR, elemental analysis, thermogravimetric analyses (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray powder diffraction (XRPD). CP 1 shows a 1D double chain containing two different helical chains, which is further extended into a two-dimensional supramolecular framework by C-H⋯O hydrogen bonding interactions. The photoluminescence properties and photocatalytic properties of the nanoparticles of CP 1 and Ag/CP 1 on the degradation of methylene blue (MB) were investigated, Ag/CP 1 exhibited excellent photocatalytic activity under UV and visible light, which can be attributed to the strong interactions between Ag nanorods and CP 1, which lead to electron-hole pair separation between Ag nanorods and CP 1. In addition, the photocatalytic mechanism is also carried out by introducing t-butyl alcohol (TBA) as a widely used ·OH scavenger. The influence of ultrasound irradiation time and power on the morphology and size of the nanostructure CP 1 were studied. The results indicated that a decrease in time and an increase in power led to a decrease of particle size., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Herein, a nickel coordination polymer (CP 1), {Ni(1,4-bib) 1.5 (TPA-Cl 2 )·H 2 O} n (1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene, H 2 TPA-Cl 2 = 2,5-dichloro-terephthalic acid), has been synthesized under solvothermal conditions. The structure of CP 1 is a 3D 3-fold interpenetrating framework with the sqc12 topology. The thermal stability and luminescence properties of CP 1 were investigated. Scanning electron microscopy (SEM) images of this material display that it possesses an irregular block 3D structure. Interestingly, CP 1 can serve as a multifunctional material via its luminescence sensing, electrochemical sensing, and photocatalytic properties. The experimental results indicate that CP 1 is an efficient luminescent sensor for the detection of Fe 3+ ions in an aqueous solution. In addition, CP 1 exhibits a sensitive and rapid electrochemical response to nitrite ions in water solution. The photocatalytic activities of CP 1 were evaluated in the degradation of different dye contaminants (MB, RhB, and MO), and the results demonstrate that its photocatalytic efficiency for the degradation of MB is highest (92.1% for MB, 85.7% for RhB, and 86.2% for MO). The effects of different dyes, different powers of UV light, and different amounts of catalyst CP 1 on the photocatalytic efficiency were also explored. Finally, the mechanism of the luminescence quenching effect toward Fe 3+ ions, electroreduction of nitrite ions, and photocatalytic degradation of different dyes have been investigated in detail.

Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.

The present study aimed to investigate protein expression levels of intra‑ and extracranial atherosclerosis in rabbits following administration of a high‑fat diet. Rabbits were randomly divided into control (group A; n=9) and high‑fat diet (group B; n=9) groups. At week 12, tissues were sectioned from the common carotid artery (CCA) and middle cerebral artery (MCA). Pathological analysis was performed. Differential protein expression levels were examined by 2‑D gel electrophoresis (2‑DE) and mass spectrometry (MS) analysis and validated by western blotting. Serum lipid levels, the intima‑media thickness (IMT) and degree of atherosclerosis of the CCA and MCA were increased at week 12 in the high‑fat diet group compared with rabbits that received a normal diet. 2‑DE and MS analysis of the protein extracted from CCA and MCA detected >439 different proteins; the expression of 25 proteins was altered, and 8 proteins [albumin A chain, tropomyosin α‑1 chain (TPM1), heat shock protein 70 (HSP70), α‑smooth muscle actin, β‑galactose binding agglutinin, TPM4 isoform 2, cell keratin 9, single octylic acid glyceride β‑2) demonstrated significant alterations in expression levels. Due to limited antibody sources, only three differentially expressed proteins (TPM1, HSP70 and α‑smooth muscle actin) were examined by western blotting. The results of our previous study demonstrated that hyperlipidemia affected the IMT of intracranial and extracranial cerebral arteries. In the present study, protein expression levels of TPM1 and α‑smooth muscle actin from extracranial cerebral arteries were significantly increased compared with intracranial cerebral arteries; however, protein expression levels of HSP70 from intracranial cerebral arteries was increased compared with extracranial cerebral arteries. The differences may be closely associated with cell proliferation and metastasis, and oxidoreduction, in intra‑ and extracranial cerebral atherosclerosis. HSP70 may have protective properties against atherosclerosis via underlying anti‑inflammatory mechanisms, furthermore, differential protein expression levels (TPM1, HSP70 and α‑smooth muscle actin) between intra‑ and extracranial cerebral arteries may facilitate the identification of novel biological markers for the diagnosis and treatment of cerebral arteriosclerosis.

Tumor-initiating cells (TICs) play important roles in tumor progression and metastasis. Identifying the factors regulating TICs may open new avenues in cancer therapy. Here, we show that TIC-enriched prostate cancer cell clones use more glucose and secrete more lactate than TIC-low clones. We determined that elevated levels of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) are critical for the metabolic switch and the maintenance of TICs in prostate cancer. Information from prostate cancer patient databases revealed that higher PCK2 levels correlated with more aggressive tumors and lower survival rates. PCK2 knockdown resulted in low TIC numbers, increased cytosolic acetyl-CoA and cellular protein acetylation. Our data suggest PCK2 promotes tumor initiation by lowering acetyl-CoA level through reducing the mitochondrial tricarboxylic acid (TCA) cycle. Thus, PCK2 is a potential therapeutic target for aggressive prostate tumors., Competing Interests: CONFLICTS OF INTEREST No conflicts of interest to declare.

Scrib is a membrane protein that is involved in the maintenance of apical-basal cell polarity of the epithelial tissues. However, Scrib has also been shown to be mislocalized to the cytoplasm in breast and prostate cancer. Here, for the first time, we report that Scrib not only translocates to the cytoplasm but also to the nucleus in hepatocellular carcinoma (HCC) cells, and in mouse and human liver tumor samples. We demonstrate that Scrib overexpression suppresses the growth of HCC cells in vitro, and Scrib deficiency enhances liver tumor growth in vivo. At the molecular level, we have identified the existence of a positive feed-back loop between Yap1 and c-Myc in HCC cells, which Scrib disrupts by simultaneously regulating the MAPK/ERK and Hippo signaling pathways. Overall, Scrib inhibits liver cancer cell proliferation by suppressing the expression of three oncogenes, Yap1, c-Myc and cyclin D1, thereby functioning as a tumor suppressor in liver cancer.

The hydrothermal reactions of 1,2,4,5-cyclohexanetetracarboxylic acid (H 4 L) with CoCl 2 ·2H 2 O and rigid or semi-rigid bis(imidazole) ligands were able to generate two Co(ii) coordination polymers (CPs), {[Co 5 (L) 2 (1,4-bimb)(μ 3 -OH) 2 (H 2 O) 8 ]·2H 2 O} n (1), {[Co(L) 0.5 (1,4-bib)]·H 2 O} n (2) (1,4-bimb = 1,4-bis(imidazol-1-ylmethyl)benzene, 1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene). CPs 1 and 2 were structurally characterized by elemental analysis, IR spectroscopy, X-ray powder diffraction and single crystal X-ray diffraction. CP 1 features a 3D 3,3,4,4,5-connected framework with an unprecedented {4 2 ·8·10 2 ·12}{4 3 ·6·8 6 } 2 {4 3 } 2 {4 6 } 2 {6 2 ·8} 2 topology, which represents the first example of CPs with such a topology. CP 2 possesses a three-fold interpenetration 3D framework with mog topology. The distinct structures of the two CPs may result from diverse coordination modes of the (L) 4- ligands and different structural characteristics of rigid or semi-rigid N-donor ligands. The thermal stabilities, photoluminescence properties and electrochemical behavior in the solid state for CPs 1 and 2 have been investigated. The photophysical studies indicated that CPs 1 and 2 are potential semiconductive materials. Moreover, both CPs 1 and 2 show high photocatalytic efficiency for the degradation of methylene blue (MB) under UV light irradiation and exhibit good stability and recyclability. A possible photocatalytic mechanism is speculated by introducing t-butyl alcohol (TBA) as a widely used ˙OH scavenger.

Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here, we use Drosophila imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades. Removal of Snr1 resulted in neoplastic tumorigenic overgrowth in imaginal epithelial tissues, whereas depletion of any other members of the SWI/SNF complex did not induce similar phenotypes. Unlike other components of the SWI/SNF complex that were detected only in the nucleus, Snr1 was observed in both the nucleus and the cytoplasm. Aberrant regulation of multiple signaling pathways, including Notch, JNK, and JAK/STAT, was responsible for tumor progression upon snr1 -depletion. Our results suggest that the cytoplasmic Snr1 may play a tumor suppressive role in Drosophila imaginal tissues, offering a foundation for understanding the pivotal role of SMARCB1/hSNF5 in suppressing MRT during early childhood. Cancer Res; 77(4); 862-73. ©2017 AACR ., (©2016 American Association for Cancer Research.)