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Electrochemical microscopy has been developed in the past decades for imaging biomolecules in single cells; however, electrochemical visualization of an intracellular protein in one cell is difficu...

Neuropathic pain (NP) is a chronic pain condition caused by lesion or disease of the somatosensory nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a neuroregulatory tool that uses pulsed magnetic fields to modulate the cerebral cortex. This review aimed to ascertain the therapeutic effect of rTMS on NP and potential factors regulating the therapeutic effect of rTMS. Database search included Web of Science, Embase, Pubmed, and Cochrane Library from inception to July 2021. Eligible studies included randomized controlled studies of the analgesic effects of rTMS in patients with NP. Thirty-eight studies were included. Random effect analysis showed effect sizes of -0.66 (95 % CI, -0.87 to -0.46), indicating that real rTMS was better than sham condition in reducing pain (P < 0.001). This comprehensive review indicated that stimulation frequency, intervention site, and location of lesion were important factors affecting the therapeutic effect. The findings of this study may guide clinical decisions and future research.

BACKGROUND: Vibration exercise has been investigated to enhance muscle activation, however, the effect of different amplitude vibratory exercises on cardiovascular stress is less understood. OBJECTIVE: Our study aims to explore the acute effect of shoulder vibratory exercises with different postures and amplitudes on the cardiovascular response in healthy adults. METHODS: Using a repeated measures randomized design, 36 subjects performed three different sessions with FLEXI-BAR exercise (FBE): (1) zero-amplitude, (2) small-amplitude, (3) large-amplitude. Each session included three different shoulder positions: 45-, 90- and 180-degree flexion. Heart rate variability (HRV), heart rate (HR) and rating of perceived exertion (RPE) were monitored continuously, while systolic blood pressure (SBP), diastolic blood pressure (DBP) and rate-pressure product (RPP) were measured before and after each exercise session. RESULTS: Compared with zero-amplitude, both small- and large-amplitude FBE protocols induced higher SBP. By contrast, DBP decreased with small- and large-amplitude. The RPP immediately after the exercise session were higher than at baseline. For high frequency, low frequency of HRV and HR there was a main effect of amplitude. CONCLUSION: Small- and large-amplitude FBE increased significantly SBP, RPE, HRV, HR and induced lower DBP, but the changes were modest, suggesting that FBE impose no extra threats to cardiovascular stress.

Background: Shin splint is one of the most common sports injuries after strenuous exercise. Kinesiology taping (KT) is a popular noninvasive remedy used in sports-related disorders, with the potential effects of relieving pain, facilitating proprioception, modulating muscle activation and correcting abnormal movement patterns. However, the exact efficacy of KT on shin splints is still unknown, and previous findings are inconsistent. Hence, this study aimed to conduct a systematic review to evaluate the current status of relevant evidence on its efficacy. Methods: The review was performed according to the PRISMA guidelines, and a systematic search of the literature was conducted in December 2020. Electronic databases, Embase, Scopus, Medline, Web of Science, PubMed and Biomed Central were searched for the identification of pertinent studies with pre-defined key terms on shin splints and KT. Results: Four studies with a total sample size of 141 participants were included and analyzed. Two studies had within-subject designs, whereas the other two were randomized clinical trials. Although the positive results of KT were reported by the studies, methodological quality varied from poor to moderate according to the Physiotherapy Evidence Database Scale or Non-Randomized Studies-of Interventions. Conclusion: In conclusion, this review revealed that the efficacy of KT on shin splints remains not clear. Evidence that supports its effectiveness in individuals with shin splints is currently limited. Further studies with good methodological quality and study design are warranted.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with high prevalence rate among the elderly population. A large number of clinical studies have suggested repetitive transcranial magnetic stimulation (rTMS) as a promising non-invasive treatment for patients with mild to moderate AD. However, the underlying cellular and molecular mechanisms remain largely uninvestigated. In the current study, we examined the effect of high frequency rTMS treatment on the cognitive functions and pathological changes in the brains of 4- to 5-month old 5xFAD mice, an early pathological stage with pronounced amyloidopathy and cognitive deficit. Our results showed that rTMS treatment effectively prevented the decline of long-term memories of the 5xFAD mice for novel objects and locations. Importantly, rTMS treatment significantly increased the drainage efficiency of brain clearance pathways, including the glymphatic system in brain parenchyma and the meningeal lymphatics, in the 5xFAD mouse model. Significant reduction of Aβ deposits, suppression of microglia and astrocyte activation, and prevention of decline of neuronal activity as indicated by the elevated c-FOS expression, were observed in the prefrontal cortex and hippocampus of the rTMS-treated 5xFAD mice. Collectively, these findings provide a novel mechanistic insight of rTMS in regulating brain drainage system and β-amyloid clearance in the 5xFAD mouse model, and suggest the potential use of the clearance rate of contrast tracer in cerebrospinal fluid as a prognostic biomarker for the effectiveness of rTMS treatment in AD patients. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01198-3.

BACKGROUND Tracheobronchial schwannomas are extremely rare tumors of neurogenic origin. Treatment includes surgery and interventional bronchoscopic therapy. Studies that have described interventional bronchoscopic therapy for tracheobronchial schwannoma have been reported in the published literature, but most of them are individual case reports, in which the long-term efficacy and recurrence are poorly understood. This study aimed to explore the feasibility, efficacy, and safety of interventional bronchoscopic therapy in adult patients with tracheobronchial schwannoma. METHODS Patients with pathologically diagnosed tracheobronchial schwannoma between January 2007 and December 2020 who underwent interventional bronchoscopic therapy in a single center in China were retrospectively reviewed. The clinical features, interventional bronchoscopic therapy procedures, complications, and follow-up results were analyzed. RESULTS A total of 7 patients (5 men and 2 women; median age, 56 years; age range, 26-63 years) were enrolled. Patients' symptoms were all significantly relieved after interventional bronchoscopic therapy, with mean American Thoracic Society Dyspnea Index score decreasing from 2.29±0.76 to 0.29±0.49 (t=6.481; P=0.001). No severe procedure-related complications were observed. Intraluminal tumors were found subsequently in three cases during a short-term follow-up (4 days to 1 month). One patient underwent surgery; thereafter got lost to follow-up, while the other 2 patients underwent a second endoscopic resection with good prognosis. Six patients received long-term follow-up (range, 2-12 years; median period, 6 years), with all patients being in stable conditions. CONCLUSIONS Interventional bronchoscopic therapy is an acceptable approach in the management of tracheobronchial schwannoma, and is a useful alternative to surgical resection, especially for those who are at a high risk of surgery or unwilling to undergo surgery. However, long-range bronchoscopic surveillance is necessary because of the possibility of tumor recurrence. Due to its benign nature, repeat endoscopic resection can still be considered after recurrence.

Yanqiao Zhao,1,2,* Ziping Zhang,2,3,* Suimin Guo,2 Beibei Feng,2,4 Xiaoyu Zhao,2,5 Xueqiang Wang,1,6 Yuling Wang2 1Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, People’s Republic of China; 2Department of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3School of Kinesiology, Shenyang Sport University, Shenyang, People’s Republic of China; 4Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People’s Republic of China; 5Department of Optometry, Fenyang College of Shanxi Medical University, Shanxi, People’s Republic of China; 6Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueqiang WangDepartment of Sport Rehabilitation, Shanghai University of Sport, 399 Changhai Road, Yangpu District, Shanghai, People’s Republic of ChinaEmail wangxueqiang@sus.edu.cnYuling WangDepartment of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-Sen University, No. 26, Erheng Road, Yuancun, Tianhe District, Guangzhou, People’s Republic of ChinaTel +86-20-38476737Email wangyul@mail.sysu.edu.cnBackground: Given the rapid growth of the global aging population, pain has become an unneglectable concern amongst the elderly. The quantity of scientific research outputs on pain in the elderly has increased over time, but only a small number of studies have used bibliometric methods to analyze scientific research in this field. This paper aimed to analyze scientific research on pain in the elderly published from 2000 to 2019 in a systematic manner using bibliometric methods.Methods: Articles on pain in the elderly published from 2000 to 2019 were retrieved from the Web of Science (WoS). Abstracts were coded on the basis of predetermined items (eg, type of article, topic, type of subjects, pain characteristics), and relevant information on the first author, citation scores, and article keywords were collected.Results: A total of 2105 articles were included in this study. Statistical analysis revealed that the publication of articles on pain in the elderly increased in frequency over time (P< 0.001). Most of the publications were original articles. Amongst the countries identified, the United States published the largest number of papers on this topic. Pain characteristics (50.21%), pain intervention (35.68%), and pain assessment (9.69%) were the main topics of research on geriatric pain. Back pain (12.30%) appeared to be the most popular pain type described in the included papers.Conclusion: This work provides researchers with an in-depth understanding of pain in the elderly by evaluating relevant publications in the past two decades. Researchers in this field are warranted to explore future directions on geriatric pain such as the transition from acute pain to chronic pain and the underlying mechanisms of pain in the elderly.Keywords: elderly, pain, bibliometric analysis

Neuroinflammation is the key factor associated with the progression of Parkinson’s disease (PD). Pramipexole (PPX) has anti-inflammatory and antioxidant properties. This study explored the effects of PPX on PD and its related mechanisms. A PD rat model was established using 6-hydroxydopamine (6-OHDA). Thirty rats were divided into the following three groups: control, PD, and PD + PPX. The rats in the PD and PD + PPX groups were first administered 6-OHDA and then respectively treated with saline and PPX. Afterward, rotational behavior tests were performed to evaluate the efficiency of PPX. The level of tyrosine hydroxylase (TH) was measured using immunohistochemical staining. Subsequently, real-time quantitative PCR (RT-qPCR) and western blot were used to determine the expression of α-synuclein (α-syn), nuclear receptor subfamily 4 group A member 2 (Nurr1), and nuclear factor kappa B (NF-κB). PPX improved the motor behavior of PD rats caused by 6-OHDA. The number of TH-positive neurons in the PD group was significantly lower than that in the control group (P

Cardiovascular diseases (CVDs) and diabetes are the leading causes of death worldwide, which underlines the urgent necessity to develop new pharmacotherapies. Cinnamon has been an eminent component of spice and traditional Chinese medicine for thousands of years. Numerous lines of findings have elucidated that cinnamon has beneficial effects against CVDs in various ways, including endothelium protection, regulation of immune response, lowering blood lipids, antioxidative properties, anti-inflammatory properties, suppression of vascular smooth muscle cell (VSMC) growth and mobilization, repression of platelet activity and thrombosis and inhibition of angiogenesis. Furthermore, emerging evidence has established that cinnamon improves diabetes, a crucial risk factor for CVDs, by enhancing insulin sensitivity and insulin secretion; regulating the enzyme activity involved in glucose; regulating glucose metabolism in the liver, adipose tissue and muscle; ameliorating oxidative stress and inflammation to protect islet cells; and improving diabetes complications. In this review, we summarized the mechanisms by which cinnamon regulates CVDs and diabetes in order to provide a theoretical basis for the further clinical application of cinnamon.

To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in north-western China, which has a high incidence of gastric cancer.Helicobacter pylori infection was analysed in 21 291 adults byThe infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR = 1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR = 1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR = 0.86, 95% CI: 0.83-0.90), individuals with high income (OR = 0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR = 0.93, 95% CI: 0.87-0.99) and individuals who consumed more fruit and vegetables (OR = 0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension and asthma were negatively correlated with H. pylori infection (P 0.05).The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetables, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extragastric diseases.Evaluer la prévalence de l'infection à Helicobacter pylori et les facteurs de risque et déterminer le sérotype des souches à Wuwei, situé dans le nord-ouest de la Chine, où l'incidence du cancer gastrique est élevée. MÉTHODES: L'infection à H. pylori a été analysée chez 21.291 adultes par un test respiratoire à l'urée auLa prévalence de l'infection à H. pylori est élevée à Wuwei. La principale souche répandue est du type I. L'âge, l'éducation, la profession, le revenu du ménage, la consommation de fruits et de légumes et l'habitude de manger rapidement sont des facteurs de risque indépendants d'infection à H. pylori, qui est également associée à des personnes ayant des antécédents de maladies extra-gastriques.

In the past two decades, polymer vesicles have aroused widespread interest and made significant developments. However, the applications of polymer vesicles in anti-infective therapy are still limited. Here, we construct a polymer vesicle (TPPBV) from a porphyrin alternating copolymer P(TPP

Background Whole body vibration (WBV) is currently increasing in popularity as a treatment modality for musculoskeletal disorders and improving health-related quality of life. Recent research has shown that WBV can reduce low back pain and improve the functional abilities for patients, however, optimal frequency and duration of vibration for therapeutic use is unclear. This review was conducted to summarize and determine the efficacy of whole body vibration therapy on individuals with non-specific low back pain (NLBP) and evaluated methodological quality of the included studies. Methods Online literature searches through the Web of Science, PubMed, Cochrane Library databases, PEDro, Ovid, EBSCO (Medline) and Scopus were conducted up to December 2019. Randomized controlled trials investigating the effect of WBV on pain intensity and/or functional ability in individuals with non-specific low back pain (NLBP) were included. Details of the sample characteristics, treatment of the comparison group, WBV parameters and outcome measures were recorded, and methodological quality appraised using the PEDro scale. Results 7 published RCTs (418 patients) were included in the systematic review. Due to heterogeneity in vibration parameters and prescriptions, and small number of studies, no meta-analysis was performed. Four out of the six included studies using pain as an outcome measure showed that WBV had a beneficial effect on pain compared with the control group, whereas only two trials were considered to be of high methodological quality. Among the six studies which measured functional ability, three studies with good quality reported significant between-group differences in favor of WBV. Conclusions There is limited evidence suggests that WBV is beneficial for NLBP when compared with other forms of interventions (stability training, classic physiotherapy, routine daily activity). Due to the small sample sizes and statistical heterogeneity, we still cannot draw conclusions that WBV is an effective intervention. Further high-quality studies are needed before clinical recommendations can be provided to support its use in a general population with NLBP and to explore the optimal treatment protocol. Trial registration PROSPERO registration number: CRD42017074775.

Circulating cancer-derived small extracellular vesicles (EVs) are nanoscale membranous vesicles shed from cancer cells that are released into surrounding body fluids. Small EVs contain biomolecules associated with cancer such as DNA and proteins for cell-to-cell communication. Therefore, small EVs have been regarded as important cancer biomarkers for liquid biopsy-based cancer diagnosis and drug treatment monitoring. However, because of the high heterogeneity and low level of small EVs in body fluids, there is a high demand for sensitive detection and characterization of such vesicles at a molecular level. In this study, we have developed a sensitive and effective approach to simultaneously profile multiple protein biomarkers expressed on cancer-derived small EVs using surface-enhanced Raman spectroscopy (SERS) nanotags in a single test, without complex isolation steps. Rapid and multiplexed phenotypic profiling of small EVs is achieved by mixing specific detection antibody-coated SERS nanotags, filtered conditioned EV-suspended medium (conditioned EVs), and capture antibody (CD63)-conjugated magnetic beads to form a sandwich immunoassay. As a proof-of-concept demonstration, we applied this approach to characterize pancreatic cancer-derived EVs by simultaneously detecting three specific EV surface receptors including Glypican-1, epithelial cell adhesion molecules (EpCAMs), and CD44 variant isoform 6 (CD44V6). The sensitivity of this method was measured down to 2.3 × 106 particles/mL, which is more sensitive and shows higher multiplexing capability than most other reported EV profiling techniques, such as western blot, enzyme-linked immunosorbent assay, and flow cytometry. Furthermore, phenotypic profiling of small EVs from colorectal cancer and bladder cancer cell lines (SW480 and C3) was conducted and compared to those derived from pancreatic cancer (Panc-1), highlighting the significant difference in EV phenotypes for various cancer cell types suspended in both phosphate-buffered saline and plasma. Thus, we believe that this technology enables a comprehensive evaluation of small secreted EV heterogeneity with high sensitivity, offering strong potential for accurate noninvasive cancer diagnosis and monitoring of drug treatment. In addition, this assay provides point-of-care use because of the easy sample preparation and portable nature of the Raman spectrometer.

Background Pelvic organ prolapse (POP) is a common health problem and has significant negative effects on a woman’s quality of life. The transvaginal mesh procedure is a durable reconstructive surgery, but the mesh kits are expensive for underdeveloped countries. Our previous case-series study showed that the use of self-cut mesh had a good success rate (91.8% at 1-year follow-up) and low complication rate. This trial is designed to compare a self-cut titanium-coated polypropylene mesh procedure with a mesh kit for the treatment of symptomatic stage III–IV anterior or apical prolapse in terms of efficacy, safety and cost-effectiveness. Methods The trial is a randomized controlled multicenter non-inferiority trial. The primary outcome measure is the composite success rate at 1-year follow-up. The secondary outcomes are anatomic outcomes of each vaginal segment (anterior, posterior and apical) using the POP-Q score, subjective improvement of quality of life according to questionnaires, intraoperative parameters, complications and costs. Analysis will be performed according to the intention-to-treat principle. Based on a comparable success rate of 90% and 10% as the margin (β = 0.2 and one-sided α = 0.025), about 312 patients in total from 11 centers will be recruited including 10% dropout. The aims of the research are to demonstrate whether the self-cut mesh procedure is non-inferior to the mesh-kit procedure and to investigate the performance of titanium-coated mesh for vaginal prolapse repair. Discussion This multicenter non-inferiority trial will evaluate whether the efficacy and safety of self-cut mesh is non-inferior to mesh kits in women with severe symptomatic stage III–IV anterior or apical prolapse. If we are able to show that the self-cut mesh procedure is non-inferior to the mesh-kit procedure in success rates, then the self-cut mesh procedure may be more cost-effective. Trial registration ClinicalTrials.gov, NCT03283124. Registered on 17 January 2018.

Atherosclerosis (AS) is the most common factor causing many cardiovascular and cerebrovascular diseases and has received considerable attention. The occurrence mechanism of AS is uncertain because it is a choronically pathological process that is influenced by multi-aspects, among which cytokines play the key roles in regulating the processes of the immune system. For example, two key cytokines, namely, IL-10 and MCP-1 (chemokine), which are involved in AS progression with varied levels, can be used for AS status monitoring and early diagnosis of AS-associated diseases. Hence, a new paper-based, surface-enhanced Raman spectroscopy (SERS) sensing platform was established for the detection of these two key cytokines. By combining a nanoporous networking membrane as the substrate and SERS nanotags as the probe for signal reading, together with a sandwich design, sensitive and specific identification and quantification of cytokine targets in human serum were achieved with excellent sensing characteristics. The lowest detectable concentration was determined to be 0.1 pg mL-1 for both IL-10 and MCP-1 in human serum. The assay also exhibits high specificity towards target cytokine detection, with low-nonspecific binding and acceptable cross-reactivity in the presence of other structurally similar targets. Finally, the practicability was validated by performing duplex detection in human serum, which further demonstrates the high specificity of the assay for the detection of target cytokines. Taken together, these promising results illustrate that this developed sensing assay is a candidate for clinical multi-target analysis in real environments.

Iron detection is one of the critical markers to diagnose multiple blood-related disorders that correspond to various biological dysfunctions. The currently available anemia detection approach can be used only for pre-treated blood samples that interfere with the actual iron level in blood. Real-time detection approaches with higher sensitivity and specificity are certainly needed to cope with the commercial level clinical analyses. Herein, we presented a novel strategy to determine the blood iron that can be easily practiced at commercial levels. The blend of well-known iron-cyanide chemistry with nanotechnology is advantageous with ultrahigh sensitivity in whole blood analysis without any pre-treatments. This approach is a combined detection system of the conventional assay (UV-visible spectroscopy) with surface-enhanced Raman scattering (SERS). Organic cyanide modified silver nanoparticles (cAgNPs) can selectively respond to Fe3+ ions and Hb protein with a detection limit of 10 fM and 0.46 μg mL-1, respectively, without being affected by matrix interfering species in the complex biological fluid. We confirmed the clinical potential of our new cAgNPs by assessing iron-status in multiple anemia patients and normal controls. Our SERS-based iron quantitation approach is highly affordable for bulk-samples, cheap, quick, flexible, and useful for real-time clinical assays. Such a method for metal-chelation has extendable features of therapeutics molecular tracking within more complex living systems at cellular levels.

Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be one of the important hospital-acquired pathogens. MRSA is also commonly associated with hospital-acquired infections and mortality. Quantitative and precise detection of MRSA is essential for rapid diagnosis and subsequent effective disease management strategies. We herein developed a highly specific method for rapid MRSA detection that combines surface-enhanced Raman spectroscopy (SERS) nanotags and polymerase chain reaction (PCR). SERS provided the sensitivity and spectral multiplexing capability while PCR provided the specificity required for the assay. The method was tested by the simultaneous detection of two MRSA specific genes (mecA and femA) amplified from genomic DNA isolated from clinical specimens. Magnetic isolation and rapid duplex detection were performed to obtain a detectable signal down to 104 input copies within 80 min. This demonstrated the potential of the SERS-PCR based approach for the accurate identification of MRSA at an early-diagnosis stage. This study also provides an alternative approach to the existing methods for detecting clinical targets without compromising sensitivity and selectivity, and with minimal handling steps. We thus believe that this approach will find a broad application in clinical applications.

Background: To investigate the expression of microRNA-29c (miR-29c) in glioma and its effects on cell proliferation and apoptosis. Methods: A retrospective analysis was performed on 76 glioma patients in People's Hospital of Weifang, Weifang, Shandong, China from May 2013 to June 2017 (experimental group) and 63 healthy subjects in the same period (control group). qRT-PCR was used to detect the miR-29c expression. Changes of serum miR-29c expression level and the correlation of miR-29c of glioma patients with the degree of tumor differentiation and pathological type were observed. Cells were grouped before transfection into blank group (no transfection), negative control group (transfected with miRNA NC) and experimental group (transfected with miR-29c mimics). CCK-8 assay was used to detect cell proliferation, flow cytometry to detect apoptosis. Results: Expression of miR-29c in serum was significantly lower in experimental group than that in control group (P

The accumulation of α-syn which induce endoplasmic reticulum stress (ERS) and mediate various signaling pathways involved in DA neuronal degeneration, and the apoptosis of dopamine (DA) neurons are pathological markers of Parkinson’s disease (PD). High-temperature requirement protein A2 (HtrA2) is synthesized in the endoplasmic reticulum, and the expression level of HtrA2 can be upregulated by drugs or by unfolded proteins. Ucf-101 is a specific inhibitor of HtrA2, and studies have shown that Ucf-101 reduced apoptosis in PC12 cells. Our study showed that PC12 cells treated with 60 μM 6-OHDA for 24 h had significantly decreased cell viability compared to that of controls. A low concentration (2.5 μM) of Ucf-101 decreased the apoptosis rate of the PD cell model, but a high concentration (≥10 μM) increased the apoptosis rate, compared to that of controls. 6-OHDA upregulated the expression of HtrA2, α-syn, CHOP, Grp78 and active caspase-3 and reduced the levels of TH and XIAP. Ucf-101 reduced the level of ERS and apoptosis both in vivo and in vitro. The ratio of p-GSK3β (Tyr216 to Ser9) increased in PD rats. However, Ucf-101 down-regulated the activation of GSK3β and activated the Wnt/β-catenin pathway that was caused by 6-OHDA. Ucf-101 activated the Wnt/β-catenin pathway and significantly attenuated 6-OHDA-induced neurotoxicity, which was related to the inhibition of ERS and the reduction of the apoptosis rate of PC12 cells and DA neurons in the midbrain of PD rats. Ucf-101 has certain neuroprotective effects.

The treatment of complete subglottic stenosis (SGS) remains a challenge due to anatomic and technological limitations. Placement of the Montgomery T-tube is an effective treatment option. For complete SGS patient combined with lower trachea collapse, the ventilation management during the T-tube insertion process is more complicated. Here, we report a case with complete SGS combined with severe lower trachea collapse, which was successfully managed with T-tube insertion under extracorporeal membrane oxygenation.

BODIPY derivatives have attracted much attention in the field of biological probes, but probes with a single imaging function are no longer innovative. In this paper, two multifunctional sulfonamide-BODIPY derivatives were designed and synthesized. Photophysical properties, cytotoxicity, in vitro and in vivo imaging, apoptosis, cell cycle, and molecular docking simulation were studied. The results showed that the compound had low cytotoxicity to normal cells, but had strong inhibitory effect on tumor cells. The IC50 value of compound 3 on HCT-116 cells was 58.61 ± 4.91 μmol/L, and 4 on HeLa cells was 52.29 ± 10.93 μmol/L. Cell imaging and mice experiments demonstrated that the probe had excellent biocompatibility and potential tumor targeting; and in vivo imaging of mice at different time periods showed that the fluorescence intensity of probes in subcutaneous lung tumor gradually increased with the extension of time. In addition, the flow cytometry analysis of 3 showed that the G1 phase of HCT-116 cells was inhibited and apoptosis of tumor cells was promoted. In molecular docking simulation, sulfonamide-BODIPY derivatives had high affinity scores with CDK2: −8.0 and −8.4 kcal·mol−1, and the multiple interactions with receptors provided conditions for the probes to recognize tumor cells.

Tembusu virus (TMUV)-associated disease is a growing cause of egg production decrease and encephalitis in domestic waterfowl, with expanding distribution. In previous studies, TMUV isolates were phylogenetically classified into two genetic lineages and different clusters with varied pathogenicity. However, little is known about the phenotypic and virulence characteristics of cluster 3 isolates within the duck TMUV lineage. In this study, the etiological agent causing egg drop in a laying chicken farm in southern China was investigated and a TMUV was isolated from pooled tissue samples. Genome sequencing and phylogenetic analysis grouped the isolate into TMUV cluster 3 with closest relation to the mosquito-origin TMUV YN12193. Cross-neutralization testing using convalescent sera revealed significant antigenic variation between the isolate and a representative strain of cluster 2.2. The experimental infection of SPF hens confirmed the ability of the isolate to replicate in multiple tissues and led to ovary damage. Additionally, high seroconversion rates (95.83%-100%) were detected in the three flocks following retrospective investigation. Our study demonstrates the occurrence of cluster 3 TMUV infection in laying chickens and that the virus exhibits significant antigenic variation compared with cluster 2 TMUV. This article is protected by copyright. All rights reserved.

Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adipose tissue macrophages (ATMs) would switch to pro-inflammatory M1 state during obesity, causing local and systemic inflammation. However, the regulatory mechanism of ATMs has not yet been well described within this process. Using a high-fat diet (HFD)–induced mouse obesity model, we found that the costimulatory molecule CD226 was highly expressed on ATMs and knockout (KO) of CD226 alleviated obesity caused by HFD. Loss of CD226 reduced the accumulation of ATMs and hindered macrophage M1 polarization, with lower serum proinflammatory cytokine levels. Furthermore, deficiency of CD226 on ATMs decreased the phosphorylation levels of VAV1, AKT, and FOXO1 and thereby upregulated PPAR-γ. Further administration of PPAR-γ inhibitor restored M1 phenotype in CD226KO ATMs. In summary, loss of CD226 alleviates the HFD-induced obesity and systemic inflammation through inhibition of the accumulation and M1 polarization of ATMs in which PPAR-γ-dependent signaling pathway is involved, suggesting that CD226 may be identified as a potential molecular target for the clinical treatment of obesity. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-03150-4.

With the development of computer technology and the popularity of the Internet, computer-assisted English teaching has increasingly become an important means of English learning. In the machine learning algorithm, the decision tree can make feasible and effective results for relatively large data sets in a relatively short time, and it is easy to understand and explain. Therefore, this paper attempts to propose a decision tree-based vocabulary difficulty judgment method in order to improve the accuracy and scientificity of English vocabulary difficulty judgment. Based on the above research contents, this paper designs and implements an English-assisted learning system which can meet the needs of different users for learning difficulty and has an exercise mechanism. The system is mainly composed of five core modules: retrieval module, fixed collocation module, keyword query module, new vocabulary module and single exercise module. Finally, the effect of English-assisted learning system is demonstrated and analyzed.

Hemorrhagic shock (HS) is common in clinical emergencies, leading to millions of deaths each year globally. CD226 is a costimulatory adhesion molecule expressed on both immune cells and endothelial cells (ECs) to regulate their metabolic activity and function. As endothelial dysfunction occurs after HS, the roles CD226 plays in vascular EC metabolism were investigated. CD226fl/fl Tekcre mice were adopted to achieve vascular EC-specific knockout of CD226, and subjected to HS modelling. Serum levels of crucial intermediate metabolites were evaluated through liquid chromatography-mass spectrometry analysis. Human umbilical vein ECs (HUVECs) were used to study the effects of CD226 under hypoxia in vitro. Seahorse analysis evaluated the cellular glycolysis and mitochondria bioenergetics. Results showed that CD226 deficiency in vascular ECs alleviated HS-induced intestinal damage and inflammatory response in mice. Animal studies indicated an improved energy metabolism when CD226 was knocked out in ECs after HS, as evidenced by enhanced glutamine-glutamate metabolism and decreased lactic acid levels. Glut-1 was upregulated in mouse vascular ECs after HS and HUVECs under hypoxia, combined with decreased CD226. Moreover, HUVECs with CD226 knockdown exhibited relieved mitochondrial damage and early apoptosis under hypoxia, whereas CD226 overexpression showed opposite effects. Seahorse analysis showed that downregulated CD226 significantly increased mitochondrial ATP production and glucose uptake in HUVECs under hypoxia. Additionally, Erk/PHD2 signaling-mediated HIF-1α/Glut-1 and HIF-2α/ASCT2 pathways were involved in CD226 regulation on HUVEC glutaminolysis after hypoxia. Hence, CD226 deficiency promotes bypass energy supply to vascular ECs under ischemic or hypoxic stress, to ameliorate the stress-mediated metabolic disturbance.

The molecular diagnosis of KRAS mutations has become crucial for clinical decision-making in colorectal cancer (CRC) treatments. Currently, the common methods for detecting mutations are based on quantitative PCR, DNA sequencing and droplet digital PCR (ddPCR), which require expensive specialized equipment and testing reagents. Herein, we propose a simple and specific strategy by integrating asymmetric PCR with surface-enhanced Raman spectroscopy (Asy-PCR/SERS) for the detection of KRAS G12V mutation, one of the most common driver mutations in CRC. To discriminate mutant targets from non-targets, Asy-PCR was applied to obtain single-stranded DNA (ssDNA) with unequal amounts of forward and reverse primers, subsequently, detection of the target mutant ssDNA amplicons was attempted by hybridization with Raman reporter-coded and allele-specific oligonucleotide-functionalized gold nanoparticles (SERS nanotags). The oligo encoding of the KRAS G12V mutant sequence could be identified by using a portable Raman spectrometer where the characteristic spectra of SERS nanotags indicate the presence of mutant targets. The Asy-PCR/SERS method showed high specificity and sensitivity for identifying as few as 0.1% mutant alleles of KRAS G12V mutation from non-target sequences. Using colorectal polyp biopsies, we demonstrated that Asy-PCR/SERS assay could distinguish KRAS G12V (c.35G > T) and KRAS G12D (c.35G > A) which occur at the same nucleotide location. As KRAS G12V is a driver oncogene in other cancers including lung, pancreatic, ovarian and endometrial cancers, the proposed assay shows great potential for application in additional tumor streams.

Platelet-rich plasma (PRP) is a platelet-based application used to treat osteoarthritis (OA) clinically. The co-stimulatory molecule CD226 is expressed in T cells, NK cells, and also platelets. However, exact effects of CD226 on platelets and whether its expression level influences PRP efficacy are largely unknown. Here, CD226fl/flPF4-Cre mice were obtained from mating CD226 fl/fl mice with PF4-Cre mice. Blood samples and washed platelets were collected from the mice eyeballs to undergo routine blood tests and transmission electron microscopy. Differentially expressed proteins were detected by iTRAQ-based proteomics analysis. Animal OA models were established through surgical destabilization of the medial meniscus (DMM) for C57BL/6 wildtype mice, followed by PRP injection to evaluate the effects of platelet CD226 on PRP efficacy. The results showed that deletion of platelet CD226 increased the number of megakaryocytes (MKs) in bone marrow (BM) but reduced MKs in spleen, combined with significantly decreased platelet amounts, α-granule secretion, and reduced immature platelets; indicating that absence of platelet CD226 may disrupt MK/platelet homeostasis and arrested platelet release from MKs. Sequencing analysis showed abnormal ribosomal functions and much downregulated proteins in the absence of platelet CD226. Autophagy-related proteins were also reduced in the CD226-absent MKs/platelets. Moreover, deletion of platelet CD226 diminished the protective effects of PRP on DMM-induced cartilage lesions in mice, and PDGF restored it. Therefore, deficiency of platelet CD226 inhibited platelet maturation, secretion, and normal ribosomal functions, which may lead to depressed PRP efficacy on OA, suggesting that CD226 is required to regulate platelet growth, functions, and its application.

Transcranial direct current stimulation (tDCS) is increasingly used in pain treatment. tDCS targeting both primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) may modulate the descending pain inhibitory system, however, it remains controversial regarding the optimal stimulation region for pain modulation. Therefore, this study aimed to explore the effects of high-definition anodic stimulation of M1 and DLPFC on conditioned pain modulation (CPM) and pain thresholds and establish a preferred stimulation setting. Twenty-six healthy adults were randomly assigned to M1-tDCS, DLPFC-tDCS, or sham-tDCS groups. During the three sessions, each participant received an active or sham stimulation of 2 mA for 20 min, with at least 3 days’ interval between sessions. Quantitative sensory tests were performed to obtain pressure pain threshold (PPT), cold pain threshold (CPT), and CPM before and after the tDCS intervention. Only M1-tDCS significantly increased CPM in healthy individuals compared with sham control (P = 0.004). No statistically significant difference was found in PPT and CPT between tDCS vs. sham control (P > 0.05). Our findings further support the important role of M1 as a target in pain regulation. Further large-scale, multicenter studies in chronic pain populations are needed to validate the alterations of distinct target brain regions related to pain and thus for an optimal target stimulation strategy in pain management.

Wangwang Yan,1,2,&ast; Yanling Yu,1,2,&ast; Yafei Wang,1 Xue Jiang,1,2 Ruihan Wan,1,3 Chang Ji,1,4 Le Shi,1 Xueqiang Wang,2 Yuling Wang1 1Department of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou City, Guangdong Province, People’s Republic of China; 2Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, People’s Republic of China; 3Department of Sport Rehabilitation, Shenyang Sport University, Shenyang City, Liaoning Province, People’s Republic of China; 4Postgraduate Research Institute, Guangzhou Sport University, Guangzhou City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueqiang WangDepartment of Sport Rehabilitation, Shanghai University of Sport, 188 Hengren Road, Shanghai, 200438, People’s Republic of ChinaEmail wangxueqiang@sus.edu.cnYuling WangDepartment of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, People’s Republic of ChinaEmail wangyul@mail.sysu.edu.cnBackground: Low back pain (LBP) is a highly prevalent musculoskeletal disorder that contributes to the greatest degree of disability worldwide. It has become a very serious public health problem that has attracted considerable research interest. The number of publications associated with LBP and physical activity (PA) is gradually increasing. Nevertheless, few studies have utilised visualisation in analysing the general aspects of this field. Therefore, we aimed to provide a systematic overview of global scientific research related to low back pain and physical activity from 2000 to 2020. It has significant benefits in terms of providing researchers with the status and trends of research on low back pain and physical activity.Methods: Publications on Science Citation Index-Expanded of Web of Science from 2000 to 2020 were searched, and publications relevant to LBP and PA were analysed using Citespace and SPSS. Analyses mainly included cooperation amongst authors, countries and institutions; co-occurrence analysis of keywords; and co-citation analysis of references, revealing productive researchers and contributing institutions tracking the status and trend of research fields.Results: Results of linear regression analysis showed that the number of publications on LBP and PA studies increased significantly (p< 0.001). The subject categories predominantly focused on orthopaedics (2579, 26.54%), rehabilitation (2544, 26.18%) and sport sciences (2015, 25.44%). The United States had the highest number of published papers (2700, 27.789%) and citations (86, 958). In terms of the number of publications, amongst the top 20 journals, Spine contributed the most, whilst the British Journal of Sports Medicine had the highest impact factor (IF2019, 12.022). The University of Sydney had the highest number of publications (330 publications). Maher published the most papers (123 papers) and had the highest H-index (41). Several citation articles and keywords (such as aerobic, obesity and fear-avoidance beliefs) can be used to provide frontier clues for research on LBP and PA.Conclusion: The results of our study may provide information, such as research trends and frontiers of research and collaborating partners, institutions and countries, on LBP and PA.Keywords: low back pain, physical activity, research trends, Web of Science

Cancer is a dynamic disease with heterogenic molecular signatures and constantly evolves during the course of the disease. Single cell proteomic analysis could offer a suitable pathway to monitor cancer cell heterogeneity and deliver critical information for the diagnosis, recurrence, and drug-resistant mechanisms in cancer. Current standard techniques for proteomic analysis such as ELISA, mass spectrometry, and Western blots are time-consuming, expensive, and often require fluorescence labeling that fails to provide accurate information about the multiple protein expression changes at the single cell level. Herein, we report a surface-enhanced Raman spectroscopy-based simple microfluidic device that enables the screening of single circulating tumor cells (CTC) in a dynamic state to precisely understand the heterogeneous expression of multiple protein biomarkers in response to therapy. It further enables identifying intercellular heterogeneous expression of CTC surface proteins which would be highly informative to identify the cancer cells surviving treatment and potentially responsible for drug resistance. Using a bead and cell line-based model system, we successfully detect single bead and single cell spectra when flowed through the device. Using SK-MEL-28 melanoma cells, we demonstrate that our system is capable of monitoring heterogeneous expressions of multiple surface protein markers (MCSP, MCAM, and LNGFR) before and during drug treatment. Integrating a label-free electrochemical system with the device, we also monitor the expression of an intracellular protein (here, BRAFsupV600E/sup) under drug treatment. Finally, we perform a longitudinal study with 15 samples from five different melanoma patients who underwent therapy. We find that the average expression of receptor proteins in a patient fails to determine the therapy response particularly when the disease progresses. However, single CTC analysis with our device shows a high level of intercellular heterogeneity in the receptor expression profiles of patient-derived CTCs and identifies heterogeneity within CTCs. More importantly, we find that a fraction of CTCs still shows a high expression of these receptor proteins during and after therapy, indicating the presence of resistant CTCs which may evolve after a certain time and progress the disease. We believe this automated assay will have high clinical importance in disease diagnosis and monitoring treatment and will significantly advance the understanding of cancer heterogeneity on the single cell level.

BACKGROUND AND OBJECTIVE Mindfulness-based interventions (MBIs) have been recently applied in pain management and cancer care. However, inconsistencies exist concerning the effectiveness of MBIs on pain control among cancer patients. Therefore, this study aimed to examine the efficacy of MBIs on pain in cancer patients via a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS Databases (MEDLINE, PubMed, Embase, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched using key terms related to pain, cancer and mindfulness. The primary outcome was pain intensity. Standardized mean difference (SMD) of each outcome with 95% confidence interval (95% CI) was calculated. The quality of evidence was assessed by GRADE assessment. RESULTS Ten RCTs with 843 participants were included. Significant pooled effects of MBIs on pain intensity were found at both short-term (SMD = -0.19, 95% CI [-0.33 to -0.04]) and long-term (SMD = -0.20, 95% CI [-0.35 to -0.05]) follow-up, whereas no significance was observed for pain interference. In subgroup analyses, significant intervention effects were only seen in clinic-based MBIs compared to remote MBIs, and pooled effects of MBIs in attenuating pain were discovered relative to passive rather than active comparators. GRADE ratings showed moderate certainty of evidence in MBIs for pain intensity but low for pain interference. CONCLUSIONS The efficacy of MBIs in reducing pain intensity among cancer patients was revealed in this meta-analysis, albeit with a small effect size. Future research is warranted to optimize mindfulness treatment for pain control in cancer patients with high methodological quality and a large sample size. SIGNIFICANCE The effect of MBIs on pain in cancer patients was demonstrated in our analysis, albeit with small effect sizes. High-quality RCTs are needed to verify the efficacy of MBIs on cancer patients or survivors with pain complaints. Future trials should take into account the specific pain outcome measures (pain intensity or pain interference), the approach of intervention provision (clinic-based or remote MBI, group or individual practice), the duration and frequency of interventions and the comparators (passive or active control arms).

Background: The lack of effective biomarkers for screening gastric cancer (GC) and premalignant lesions (PMLs) is a significant roadblock in the prevention and early intervention of GC. We aimed to identify noninvasive biomarkers to improve the screening of high-risk populations. Methods: We evaluated 25,000 adults residing in Wuwei. We collected baseline characteristics, GC risk indicators, including trefoil factors (TFF1–3), endoscopy diagnosis, and pathological information. We analyzed the data to determine the association of risk biomarkers with the progression of GC and the prediction capacities of these biomarkers using odds ratio (OR)-adjusted models and receiver operating characteristic (ROC) curve analyses. Results: TFF1 and TFF2 serum levels showed incremental changes from the PMLs to the GC group, with the highest serum TFF3 levels reported in the intestinal metaplasia group. TFF1 and TFF2 had significant predictive values in the PMLs and GC in the three OR-adjusted models but not in the non-atrophic gastritis group. Similar results were obtained after adjusting for all biomarkers and risk factors wherein the ORs (95 % confidence intervals) of TFF1 and TFF2 in the GC group were 2.71 (1.57–4.67) and 2.87 (1.75–4.71), respectively (P

The sensitive and simultaneous detection of cytokines will provide new insights into the physiological process and disease pathways due to the complex nature of cytokine networks. However, the key challenge is the lack of probes that can simultaneously detect multiple cytokines in a single sample. In this contribution, we proposed an alternative approach for sensitive cytokine detection in a multiplex manner by the use of a new set of surface-enhanced Raman spectroscopy (SERS) nanotags. Typically, the newly designed SERS nanotags are composed of gold nanoparticles as the core, tuneable Raman molecules as the reporters, and a thin silver layer as the shell. As demonstrated through rigorous numerical simulations, enhanced Raman signal is achieved due to a strong localization of light in the 0.2 nm thin, optically deep-subwavelength region between the Au core and the Ag shell. Sensitive detection of cytokines is realized by forming a sandwich immunoassay. The detection limit is down to 4.5 pg mL-1 (S/N = 3). The specificity of the assay is proved as negligible signals were detected for the false targets. Furthermore, multiple cytokines are simultaneously detected in a single assay from the secretion of B-lymphocyte cell line (Raji) after concanavalin A (Con A) stimulation. The results indicate that our method holds a significant potential for sensitive and multiplexed detection of cytokines and offers the opportunity for future applications in clinical settings.

Energy and environmental are always two major challenges for the sustainable development of the modern human being. For avoiding the serious environmental pollution caused in the fabrication process of porous carbon, a popular energy storage material, we reported a facile, green and activating agent free route hereby directly carbonizing a special biomass, Glebionis coronaria. A nitrogen doped hierarchical porous carbon with a specific surface area of up to 1007 m2 g−1 and a N doping content of up to 2.65 at.% was facilely fabricated by employing the above route. Benefiting from the peculiarly hierarchical porous morphology, enhanced wettability and improved conductivity, the obtained material exhibits superior capacitance performance, which capacitance reaches up to 205 F g−1 under two-electrode configuration, and no capacitance loss is observed after 5000 cycles. Meanwhile, the capacitance retention of the obtained material arrives up to 95.0% even under a high current density of 20 A g−1, illuminating its excellent rate capability. The fabricated nitrogen-doped hierarchical porous carbon with larger capacitance than commercial activated carbon, excellent rate capability and cycle stability is an ideal cost-efficient substitution of commercial activated carbon for supercapacitor application.

Removal of pyrite from coals is very important to reduce the emission of SO2 during coal combustion. The selective flotation of pyrite from coal is challenging due to the hydrophobic nature of both coal and pyrite particles. The surface properties of coal vary significantly with the degree of coalification. The present paper investigates the flotation behavior of pyrite from sub-bituminous and meta-bituminous coal which has different ranks and surface properties. XRD, XPS, contact angle, UV–visible spectroscopy, SEM and zeta potential measurements were used to characterize their differences in mineralogy and surface chemistry. The classical first-order model and the potential flow model were used for flotation kinetic studies and to back-calculate the induction times, respectively. Efficient selective flotation of pyrite from the sub-bituminous and meta-bituminous coal was observed in the presence of potassium amyl xanthate collector and starch depressant. The flotation recoveries of pyrite from the sub-bituminous coal and the meta-bituminous coal were over 95%, with pyrite grade of over 95% in the concentrates.

T-cells play a major role in host defense mechanisms against many diseases. With the current growth of immunotherapy approaches, there is a strong need for advanced technologies to detect and characterize these immune cells. Herein, we present a simple approach for the isolation of antigen specific T-cells from the complex biological sample based on T-cell receptor (TCR) and peptide major histocompatibility complex (pMHC) interaction. Subsequently, we characterize those antigen specific T-cells by profiling TCR expression heterogeneity. Our approach utilizes an alternating current electrohydrodynamic (ac-EHD) based microfluidic platform for isolation and surface enhanced Raman scattering (SERS) for TCR expression profiling. The use of ac-EHD enables specific isolation of T-cells by generating a nanoscopic shear force at the double layer of the sensing surface which enhances the frequency of pMHC and TCR interactions and consequently shears off the nonspecific targets. TCR expression profiling of the isolated T-cells was performed by encoding them with SERS-labelled pMHCs followed by SERS detection in bulk as well as in single T-Cell. In proof-of-concept experiments, 56.93 ± 7.31% of the total CD4+T-cells were captured from an excess amount of nonspecific cells (e.g., PBMCs) with high specificity and sensitivity (0.005%). Moreover, TCR analysis data using SERS shows the heterogeneity in the T-cell receptor expression which can inform on the activation status of T-cells and the patient’s response to immunotherapy. We believe that this approach may hold potential for numerous applications towards monitoring immune status, understanding therapeutic responses,and effective vaccine development.

This paper reports a celery-derived nitrogen doped microporous carbon fabricated by a one-step self-activation method. The fabricated samples inherit the developed water transport system in biological tissue of celery, and exhibits hierarchic porous structure with opened micropores, which specific surface area reaches up to 1186 m2 g−1, and the average micropore diameter arrives 0.94 nm. The nitrogen heteroatoms doping enhances the wettability, conductivity and surface activity of the fabricated samples, improves the electrolyte accessibility in micropores, and thus induces superior capacitive performance. The capacitance of the fabricated samples reaches up to 245 F g−1. Meanwhile, the device capacitance of the assembled coin-type symmetric supercapacitors reaches 54.0 F g−1, over 93.1% of initial capacitance is retained as the current density improves from 0.5 to 20 A g−1, and no apparent decline for initial capacitance is observed after 5000 times charge/discharge cycles, illuminating the superior charge storage capability, excellent rate capability and perfect cycle performance of the celery-derived nitrogen doped microporous carbon. In consideration of the huge yield of celery all over the world, the celery-derived nitrogen doped microporous carbon with high specific surface area and superior capacitive performance is expected to be a sustainable large-scale substitution for commercial activated carbon.