Search

Aberrant angiogenesis is a hallmark of cancer and is critically associated with tumor progression. Perivascular cells are essential components of blood vessels, and the role of tumor perivascular cell-derived extracellular vesicles (TPC-EVs) in angiogenesis remains elusive. In the present study, using genetic mouse models and pharmacological inhibitors, we found that ablation of perivascular cells inhibited angiogenesis in allografted colorectal cancer tumors. Further studies demonstrated that TPC-EVs promoted the proliferation, migration, invasion, viability, and tube formation of HUVECs. They also facilitated vessel spouting in rat aortic rings and induced neovascularization in chick chorioallantoic membranes (CAMs). Silencing of Gas6 or blockade of the Axl pathway suppressed TPC-EV-induced angiogenesis in vitro and ex vivo. Moreover, inhibition of the Gas6/Axl signaling pathway impaired TPC-EV-mediated angiogenesis in vivo. Our findings present a deeper insight into the biological functions of TPCs and TPC-EVs in tumor angiogenesis and demonstrate that TPC-EV-derived Gas6 could be an attractive and innovative regulator of tumor angiogenesis.

(R,S)-ketamine elicits rapid-acting and sustained antidepressant actions in treatment-resistant patients with depression. (R)-ketamine produces longer-lasting antidepressant effects than (S)-ketamine in rodents; however, the precise molecular mechanisms underlying antidepressant actions of (R)-ketamine remain unknown. Using isobaric Tag for Relative and Absolute Quantification, we identified nuclear receptor-binding protein 1 (NRBP1) that could contribute to different antidepressant-like effects of the two enantiomers in chronic social defeat stress (CSDS) model. NRBP1 was localized in the microglia and neuron, not astrocyte, of mouse medial prefrontal cortex (mPFC). (R)-ketamine increased the expression of NRBP1, brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element binding protein (p-CREB)/CREB ratio in primary microglia cultures thorough the extracellular signal-regulated kinase (ERK) activation. Furthermore, (R)-ketamine could activate BDNF transcription through activation of CREB as well as MeCP2 (methyl-CpG binding protein 2) suppression in microglia. Single intracerebroventricular (i.c.v.) injection of CREB-DNA/RNA heteroduplex oligonucleotides (CREB-HDO) or BDNF exon IV-HDO blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. Moreover, microglial depletion by colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. In addition, inhibition of microglia by single i.c.v. injection of mannosylated clodronate liposomes (MCLs) significantly blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. Finally, single i.c.v. injection of CREB-HDO, BDNF exon IV-HDO or MCLs blocked the beneficial effects of (R)-ketamine on the reduced dendritic spine density in the mPFC of CSDS susceptible mice. These data suggest a novel ERK-NRBP1-CREB-BDNF pathways in microglia underlying antidepressant-like effects of (R)-ketamine.

Objective. Serratus anterior plane block (SAPB) provides effective thoracic analgesia. This systematic review and meta-analysis was conducted to assess the safety and efficacy of SAPB for postoperative analgesia after breast surgery. Methods. A systematic literature search was performed using Embase, PubMed, Web of Science, and the Cochrane Library for eligible randomised controlled trials. The primary outcomes involved the administration of intraoperative and postoperative opioids. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence for making recommendations. Results. Overall, 13 studies comprising 826 patients met the inclusion criteria (412 in the SAPB group and 414 in the control group). Patients treated with SAPB exhibited a significantly lower postoperative opioid consumption (mean difference, −38.51 mg of oral morphine equivalent; 95% confidence interval (CI), −60.97 to −16.05; P < 0.01 ; I2 = 100%), whereas no difference was observed in the intraoperative opioid consumption (mean difference, −9.85 mg of oral morphine equivalent; 95% CI, −19.52 to −0.18; P = 0.05 ; I2 = 94%). In addition, SAPB significantly decreased the occurrence of postoperative nausea and vomiting (risk ratio, 0.32; 95% CI, 0.19–0.55; P < 0.05 ;I2 = 38%) and reduced pain scores during the postoperative period (1 h: standardised mean difference (SMD), −1.23; 95% CI, −2.00 to −0.45; I2 = 92%; 2 h: SMD, −0.71; 95% CI, −1.00 to −0.41; I2 = 48%; 4 h: SMD, −1.52; 95% CI, −2.77 to −0.27; I2 = 95%; 6 h: SMD, −0.80; 95% CI, −1.51 to −0.08; I2 = 81%; 8 h: SMD, −1.12; 95% CI, −1.98 to −0.27; I2 = 92%; 12 h: SMD, −0.78; 95% CI, −1.21 to −0.35; I2 = 83%; and 24 h: SMD, −0.71; 95% CI, −1.20 to −0.23; I2 = 87%; P < 0.05 for all). Conclusion. SAPB was safe and effective after breast surgery to relieve postsurgical pain. However, additional well-developed trials are required to validate these findings.

Oxidative stress is one of the major causes leading to male infertility including asthenozoospermia. Hydrogen sulfide (H2S) has been widely recognized to be a potent antioxidant whose role is partially implemented by protein S-sulfhydration. However, protein S-sulfhydration has not been reported in germ cells. Therefore, we investigated whether asthenozoospermia could be associated with sperm protein S-sulfhydration. S-sulfhydrated proteins in human sperm were enriched via biotin-switch assay and analyzed using LC-MS/MS spectrometry. Two hundred forty-four S-sulfhydrated proteins were identified. Importantly, we validated that sperm histones H3.1 and H3.3 were the S-sulfhydrated proteins. Their S-sulfhydrated amino acid residue was Cysteine111. Abundances of S-sulfhydrated H3 (sH3) and S-sulfhydrated H3.3 (sH3.3) were significantly down-regulated in asthenozoospermic sperm, compared with the fertile controls, and were significantly correlated with progressive motility. Retinoic acid (RA) up-regulated level of sH3.3 in primary round spermatids and the C18-4 cells (a mouse spermatogonial stem cell line). Overexpression of the mutant H3.3 (Cysteine111 was replaced with serine) affected expression of 759 genes and raised growth rate of C18-4 cells. For the first time, S-sulfhydration H3 and H3.3 were demonstrated in the present study. Our results highlight that aberrant S-sulfhydration of H3 is a new pathophysiological basis in male infertility. Supplementary Information The online version contains supplementary material available at 10.1007/s10815-021-02314-x.

China is facing increasing ground-level ozone (O3) along with the reduction of particulate matter since the implementation of the Air Pollution Prevention and Control Action Plan (APPCAP) in 2013. High-level O3 poses adverse effects to ecosystems by inhibiting the growth of crops and other plants in addition to human health effects. The capture of atmospheric carbon dioxide by plants is also weakened due to O3 stress effect. In recent years, studies have been conducted to evaluate the potential risk of O3 in agricultural production in China with different methods and focuses and the results are not consistent for comparison and policy-making. In this paper, we first briefly reviewed the levels of O3 pollution in China in recent years, and the evaluation indicators for analyzing O3 impacts on crops as well as their applicability. Then, methods for determining O3 flux and the progress in dry deposition of O3 in farmlands were presented. We also introduced some recent advances in evaluating losses of crop yield caused by O3 exposure. Finally, in view of the shortcomings of current research, prospects for future research were suggested.

Objective: Coronavirus disease 2019 (COVID-19) was associated with a higher risk of arrhythmia in infected patients. However, there are no reports about the effect of the ongoing pandemic on arrhythmias in the non-infected population. We measured the arrhythmia burden in a non-infected population with cardiac implantable devices. Methods: The arrhythmia burden during the COVID-19 pandemic was compared to a 6-month interval in the pre-COVID-19 period. The COVID-19 pandemic was divided into high-risk (17 January 2020 to 16 March 2020) and low-risk periods (17 March 2020 to 17 July 2020) according to whether there were locally infected patients. Arrhythmia burdens were compared among the pre-COVID-19, high-risk, and low-risk periods. Results: A total of 219 patients with 1859 episodes were included. We observed a larger proportion of patients with atrial fibrillation (AF) during the COVID-19 pandemic (38.36% vs 26.03%, p = 0.006). There was not significantly more ventricular arrhythmia during the COVID period than the pre-COVID-19 period (p > 0.05). During the high-risk period, daily frequency of non-sustained ventricular tachycardia (NSVT) (0.0172, 0.0475 vs 0.0109, 0.0164, p < 0.05), atrial tachycardia (AT) (0.0345, 0.0518 vs 0.0164, 0.0219 p < 0.05) and AF (0.0345, 0.0432 vs 0.0164, 0.0186, p < 0.05) and daily duration of NSVT (0.1982, 0.2845 vs 0.0538, 0.1640 p < 0.05) were higher and longer than those in the pre-COVID-19 period. Regression modeling showed that the impact of COVID-19 pandemic lead to an increased onset of AF (odds ratio 2.465; p < 0.01). Patients with paroxysmal AF who had undergone a previous radiofrequency ablation had a lower burden of AF (incidence 21.43% vs 55.00%, P = 0.049, daily frequency 0.0000, 0.0027 vs 0.0000, 241.7978, P = 0.020) during the pandemic. Conclusion: The COVID-19 pandemic contributed to a higher burden of arrhythmias in non-infected patients. Patients would experience a lower burden of AF following radiofrequency ablation treatment, and this effect persisted during the pandemic.

Based on the novel allosteric site of deoxyhypusine synthase (DHPS), two series of 30 novel 5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-amine derivatives as DHPS inhibitors were designed and synthesized. Among them, compound 8m, with the best DHPS inhibitory potency (IC50 = 0.014 μM), exhibited excellent inhibition against melanoma cells, which was superior to that of GC7. Besides, molecular docking and molecular dynamics (MD) simulations further proved that compound 8m was tightly bound to the allosteric site of DHPS. Flow cytometric analysis and enzyme-linked immunosorbent assay (ELISA) showed that compound 8m could inhibit the intracellular reactive oxygen species (ROS) level. Furthermore, by western blot analysis, compound 8m effectively activated caspase 3 and decreased the expressions of GP-100, tyrosinase, eIF5A2, MMP2, and MMP9. Moreover, both Transwell analysis and wound healing analysis showed that compound 8m could inhibit the invasion and migration of melanoma cells. In the in vivo study, the tumor xenograft model showed that compound 8m effectively inhibited melanoma development with low toxicity.

Kawasaki disease (KD) causes cardiovascular system injury in children. However, the pathogenic mechanisms of KD have not been well defined. Recently, strong correlation between aberrant microRNAs and KD nosogenesis has been revealed. A role of microRNA-197-3p (miR-197-3p) in the pathogenesis of KD is identified in the present study. Cell proliferation assay showed human coronary artery endothelial cells (HCAECs) were suppressed by serum from KD patients, which was correlated with high levels of miR-197-3p in both KD serum and HCAECs cultured with KD serum. The inhibition of HCAECs by miR-197-3p was confirmed by cells expressing miR-197-3p mimic and miR-197-3p inhibitor. Comparative proteomics analysis and Ingenuity Pathway Analysis (IPA) revealed TIMP3 as a potential target of miR-197-3p, which was demonstrated by western blot and dual-luciferase reporter assays. Subsequently, by detecting the endothelium damage markers THBS1, VWF, and HSPG2, the role of miR-197-3p/TIMP3 in KD-induced damage to HCAECs was confirmed, which was further validated by a KD mouse model in vivo. The expressions of miR-197-3p and its target, TIMP3, are dramatically variational in KD serum and HCAECs cultured with KD serum. Increased miR-197-3p induces HCAECs abnormal by restraining TIMP3 expression directly. Hence, dysregulation of miR-197-3p/TIMP3 expression in HCAECs may be an important mechanism in cardiovascular endothelium injury in KD patients, which offers a feasible therapeutic target for KD treatment.

Sulforaphane (SFN) is an organic isothiocyanate and an NF-E2-related factor-2 (Nrf2) inducer that exerts prophylactic effects on depression-like behavior in mice. However, the underlying mechanisms remain poorly understood. Brain-derived neurotrophic factor (BDNF), a neurotrophin, is widely accepted for its antidepressant effects and role in stress resilience. Here, we show that SFN confers stress resilience via BDNF upregulation and changes in abnormal dendritic spine morphology in stressed mice, which is accompanied by rectifying the irregular levels of inflammatory cytokines. Mechanistic studies demonstrated that SFN activated Nrf2 to promote BDNF transcription by binding to the exon I promoter, which is associated with increased Nrf2, and decreased methyl-CpG binding protein-2 (MeCP2), a transcriptional suppressor of BDNF, in BV2 microglial cells. Furthermore, SFN inhibited the pro-inflammatory phenotype and activated the anti-inflammatory phenotype of microglia, which was associated with increased Nrf2 and decreased MeCP2 expression in microglia of stressed mice. Hence, our findings support that Nrf2 induces BDNF transcription via upregulation of Nrf2 and downregulation of MeCP2 in microglia, which is associated with changes in the morphology of damaged dendritic spines in stressed mice. Meanwhile, the data presented here provide evidence for the application of SFN as a candidate for the prevention and intervention of depression.

Background The COVID-19 pandemic has lasted for more than 1 year, causing far-reaching and unprecedented changes in almost all aspects of society. This study aimed to evaluate the long-term consequences of the COVID-19 pandemic on depression and anxiety, and explore the factors associated with it. Methods A cross-sectional study using an online survey was conducted to assess mental health problems from February 2 to February 9, 2021 by using patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7). The insomnia severity index (ISI), demographic data and COVID-19 related variables were measured by a self-designed questionnaire. The factors associated with depressive and anxiety symptoms were identified by Pearson chi-square test and binary logistic regression analysis. Results In the study that 1171 participants enrolled, the overall prevalence of depressive and anxiety symptoms among general people was 22.6 and 21.4% respectively in the present study. Living alone was a potential risk factor for depressive symptoms, while regular exercises was a potential protective factor. The prevalence of depressive and anxiety symptoms was significantly associated with the severity of insomnia symptoms and the negative feelings about pandemic. Conclusion COVID-19 pandemic- related chronic stress has brought about profound impacts on long-term mental health in the general population. The level of insomnia and a negative attitude towards the pandemic are significantly correlated with unfavorable mental health. However, we failed to found a significant association of age and gender with the mental health symptoms, although they were recognized as well-established risk factors during the outbreak by some other studies. This discrepancy may be because the acute and chronic effects of the pandemic are influenced by different factors, which reminds that more attention should be paid to the intrinsic psychological factors and physical reactions towards COVID-19.

Qi Qi,* Xuemeng Qian,* Xinfang Zhu, Jiajing Cai, Rong Xia, Qi Zhang Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi Zhang; Rong XiaDepartment of Transfusion Medicine, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, People’s Republic of ChinaEmail friday0451@163.com; xiarongcn@126.comPurpose: Blood loss may be corrected with red blood cell transfusion, but may ultimately contribute to negative impacts. This study was a retrospective analysis to assess the impact of perioperative blood transfusion on hospital stay days in liver cancer patients.Methods: We retrospectively examined data from patients with primary liver cancer who underwent curative resection. Patients were divided into perioperative blood transfusion (PBT) and non-PBT groups. Data were given as means and SDs for continuous variables and as counts and percentage for categorical variables. The correlation between blood transfusion and hospital stay days was analyzed by Fisher’s exact test. Multivariable logistic regression analyses were used to identify independent predictors of length of hospital stays.Results: Totally 206/1031 patients (20.3%) were given perioperative transfusion. The mean length of hospital stay was 17.8 days in PBT and 13.9 days in non-PBT groups. Our multivariable logistic regression showed transfusion, total bilirubin, indirect bilirubin, and the ratio of albumin to bilirubin were all indicators of the length of hospital stay days. Perioperative transfusion was also associated with prolonged length of hospital stays (95% CI: 0.395– 0.811, p = 0.002). Transfusion also affected intrinsic coagulation factors (activated partial thromboplastin time, fibrinogen, platelet), inflammatory index (neutrocyte to lymphocyte ratio, monocyte), albumin and bilirubin levels.Conclusion: Perioperative transfusion of blood was associated with a significantly increased length of hospital stays probably via changing intrinsic coagulation and inflammatory factors and bilirubin levels in plasma.Keywords: primary liver cancer, transfusion, length of hospital stays, bilirubin, coagulation factor, inflammatory factor

Background Procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) are a group of enzymes that can mediate the hydroxylation of lysyl to hydroxylysine and participate in the formation of stabilized collagen. Evidence has demonstrated that PLODs are involved in the steps of tumor progression, including proliferation, invasion, and metastasis. However, limited information is available on the function of PLOD1/2/3 in lung cancer. In this study, we investigated the expression patterns and prognostic values of PLODs in patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods The Oncomine database and UALCAN were used to analyze the mRNA expression levels of PLOD family members in non-small cell lung cancer (NSCLC). The prognostic values of PLODs were investigated by the Kaplan–Meier Plotter database. We collected 33 patients with lung cancer to further verify the expression profiles and prognostic values of PLODs. The Kaplan-Meier method was used to perform survival curves, and the log-rank test was performed to evaluate the differences in survival. According to the GSE31210 databset, univariate and multivariate analyses were performed to identify whether PLODs were independent prognostic indicators for survival. Meanwhile, we investigated the mutations, potential biological functions and immune relevance of PLODs on the basis of the cBioPortal, Metascape and TIMER databases respectively. Results We found that the mRNA and protein expression levels of PLODs in NSCLC tissues were higher than those in normal lung tissues. High PLOD1/2/3 expression had significant relevance to poor survival in LUAD but not in LUSC. In addition, the GSE31210 dataset showed that PLOD1 and PLOD3 were independent risk factors for relapse-free survival and overall survival (OS) in LUAD. We observed a high alteration rate of PLODs in LUSC patients, and the genetic alterations of PLODs had significant relevance to favorable OS. Furthermore, we observed that PLODs were significantly associated with tumor immunity in lung cancer. The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the functions of the PLODs focused on cell cycle, DNA replication, and glycolysis/gluconeogenesis in LUAD. Conclusions These results indicated that PLODs were highly expressed in lung cancer and may be suitable prognostic markers.

Background Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, clearly distinguishing benign from malignant lung nodules at an early stage is of great significance. However, determining the kind of lung nodule which is more prone to lung cancer remains a problem worldwide. Methods A total of 480 patients with pulmonary nodule data were collected from Shandong, China. We assessed the clinical characteristics and computed tomography (CT) imaging features among pulmonary nodules in patients who had undergone video‐assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018. Preliminary selection of features was based on a statistical analysis using SPSS. We used WEKA to assess the machine learning models using its multiple algorithms and selected the best decision tree model using its optimization algorithm. Results The combination of decision tree and logistics regression optimized the decision tree without affecting its AUC. The decision tree structure showed that lobulation was the most important feature, followed by spiculation, vessel convergence sign, nodule type, satellite nodule, nodule size and age of patient. Conclusions Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population., Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, it is of great significance to clearly distinguish between benign and malignant lung nodules at early stages. However, what kind of lung nodules are more prone to lung cancer is still a worldwide problem. In this study, 458 cases with pulmonary nodules data were collected from Shandong, China. We assessed the clinical characteristics and low‐dose computed tomography (LDCT) imaging features among pulmonary nodules in patients who had undergone video‐assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018 to determine the machine learning models using multiple algorithms and select the best decision tree model. Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population.

Objective: To investigate the association between serum HIF-1α,β-catenin levels and the vascular calcification in the rat model of chronic kidney disease（CKD） vascular calcification. Methods: 30 SD male rats were randomly divided into normal control group (CON group, n = 10) and CKD vascular calcification group (CKD group, n = 20). Rats in calcification group were fed with adenine combined with high phosphorus diet. At the end of the 6th week, the blood and urine of the two groups were collected to detect renal function, calcium,phosphorus and 24-hour urinary protein, the renal tissue was stained with HE, the aorta of rats was stained with Von Kossa and calcium content was determined, and the levels of HIF-1 α and β-catenin in serum were detected by ElISA method. Results: compared with CON group, 24-hour urinary protein, blood BUN, Scr, P, Ca × P, aortic calcium content, serum HIF-1 α and β-catenin levels were significantly increased and serum calcium decreased in CKD group (P < 0.05); Glomerular atrophy, renal tubule dilatation and interstitial fibrosis were seen in CKD group, Von Kossa staining of calcified nodules in aorta showed more black substance deposition. The levels of serum HIF-1 α, β-catenin and serum P, Ca × P were positively correlated with the content of calcium in rat aorta. Conclusion: the levels of serum HIF-1 α and β-catenin are significantly increased in patients with vascular calcification in CKD, and they are significantly related to the degree of aortic calcification.

Inhibition of protein fibrillation process with nanomaterials is a promising strategy to combat neurodegenerative diseases. Copper-based nanomaterials have been seldom utilized in fibrillation inhibiting research due to Copper ions are generally considered as accelerators of fibrosis. Here, we proposed ultra-small Zn doped Cu2S (Zn:Cu2S) QDs as inhibitors of human insulin (HI) fibrosis. ThT, DLS, CD and TEM confirm that Zn:Cu2S QDs effectively inhibited insulin fibrosis in a dose-dependent manner with lag phase time extended (beyond 13-time by Zn:Cu2S QDs of 1 mg·mL−1), final fibril formation and the conversion from α-helix to β-sheet reduced. Additionally, thermodynamics analyzed results reveal that the HI fluorescence quenching process is static quenching dominated, and the Zn:Cu2S QDs inhibit HI fibrosis mainly through specific electrostatic interaction with oligomers. The positively charged amino acid residues of oligomers bind to the negatively charged Zn:Cu2S QDs, which prevents the self-assembly of the oligomers from growing into mature fibers to enhance the stability of the protein. Unlike free Copper ions, the as-prepared QDs show an excellent inhibition in HI fibrillation, breaking through the bottleneck of copper-based materials in inhibiting protein fibrosis and providing a potential strategy to inhibit protein fibrosis in-situ by biosynthesizing copper-based fibrosis inhibitors.

Metastasis is the main cause of mortality in patients with cancer. Epithelial–mesenchymal transition (EMT), a crucial process in cancer metastasis, is an established target for antimetastatic drug development. LFG-500, a novel synthetic flavonoid, has been revealed as a potential antitumor agent owing to its various activities, including modulation of EMT in the inflammatory microenvironment. Here, using a transforming growth factor beta (TGF-β)-induced EMT models, we found that LFG-500 inhibited EMT-associated migration and invasion in human breast cancer, MCF-7, and lung adenocarcinoma, A549, cell lines, consistent with the observed downregulation of YAP activity. Further studies demonstrated that LGF-500-induced suppression of YAP activation was mediated by integrin-linked kinase (ILK), suggesting that the ILK/YAP axis might be feasible target for anti-EMT and antimetastatic treatments, which was verified by a correlation analysis with clinical data and tumor specimens. Hence, our data support the use of LGF-500 as an antimetastatic drug in cancer therapy and provide evidence that the ILK/YAP axis is a feasible biomarker of cancer progression and a promising target for repression of EMT and metastasis in cancer therapy.

Neurodegenerative disorders, including spinal cord injury (SCI), result in oxidative stress-induced cell damage. Morroniside (MR), a major active ingredient of the Chinese herb Shan Zhu Yu, has been shown to ameliorate oxidative stress and inflammatory response. Our previous study also confirmed that morroniside protects SK-N-SH cell line (human neuroblastoma cells) against oxidative impairment. However, it remains unclear whether MR also plays a protective role for oligodendrocytes that are damaged following SCI. The present study investigated the protective effects of MR against hydrogen peroxide (H2O2)-induced cell death in OLN-93 cells. MR protected OLN-93 cells from H2O2-induced injury, attenuated H2O2-induced increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and blocked the reduction of mitochondrial membrane potential (MMP) induced by H2O2. MR enhanced the activity of the antioxidant enzyme superoxide dismutase (SOD) and suppressed H2O2-induced downregulation of the antiapoptotic protein Bcl-2 and activation of the proapoptotic protein caspase-3. Finally, we found that LY294002, a specific inhibitor of the PI3K/Akt pathway, inhibited the protective effect of MR against H2O2-induced OLN-93 cell injury in the MTT and TUNEL assays. LY294002 also inhibited the expression of SOD and Bcl-2, and increased the expression of iNOS and c-caspase-3 induced by MR treatment. MR exerts protective effects against H2O2-induced OLN-93 cell injury through the PI3K/Akt signaling pathway-mediated antioxidative stress and antiapoptotic activities. MR may provide a potential strategy for SCI treatment or other related neurodegeneration.

Background: The ultimate validation of a clinical marker for Alzheimer’s disease (AD) is its association with AD neuropathology. Objective: To identify clinical measures that predict pathology, we evaluated the relationships of the picture version of the Free and Cued Selective Reminding Test (pFCSRT + IR), the Mini-Mental State Exam (MMSE), and the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) to Braak stage. Methods: 315 cases from the clinicopathologic series at the Knight Alzheimer’s Disease Research Center were classified according to Braak stage. Boxplots of each predictor were compared to identify the earliest stage at which decline was observed and ordinal logistic regression was used to predict Braak stage. Results: Looking at the assessment closest to death, free recall scores were lower in individuals at Braak stage III versus Braak stages 0 and I (combined) while MMSE and CDR scores for individuals did not differ from Braak stages 0/I until Braak stage IV. The sum of free recall and total recall scores independently predicted Braak stage and had higher predictive validity than MMSE and CDR-SB in models including all three. Conclusion: pFCSRT + IR scores may be more sensitive to early pathological changes than either the CDR-SB or the MMSE.

Background Compared with traditional physical therapy for stroke patients, lower extremity exoskeletons can provide patients with greater endurance and more repeatable and controllable training, which can reduce the therapeutic burden of the therapist. However, most exoskeletons are expensive, heavy or require active power to be operated. Therefore, a lighter, easy to wear, easy to operate, low-cost technology for stroke rehabilitation would be a welcome opportunity for stroke survivors, caregivers and clinicians. One such device is the Kickstart Walk Assist system and the purpose of this study was to determine feasibility of using this unpowered exoskeleton device in a sample of stroke survivors. Methods Thirty stroke survivors were enrolled in the study and experienced walking with the Kickstart exoskeleton device that provided spring-loaded assistance during gait. After 5 days of wearing the exoskeleton, participants were evaluated in the two states of wearing and not wearing the exoskeleton. Outcome measures included: (a) spatio-temporal gait measures, (b) balance measures and (c) exoskeleton-use feedback questionnaire. Results In comparison to not wearing the device, when participants wore the Kickstart walking system, weight bearing asymmetry was reduced. The time spent on the 10-m walk test was also reduced, but there was no difference in the timed-up-and-go test (TUGT). Gait analysis data showed reduction in step time and double support time. Stroke survivors were positive about the Kickstart walking system’s ability to improve their balance, speed and gait. In addition, their confidence level and willingness to use the device was also positive. Conclusions These findings show the feasibility of using the Kickstart walking system for improving walking performance in stroke survivors. Our future goal is to perform a longer duration study with more comprehensive pre- and post-testing in a larger sample of stroke survivors. Trial registration Chinese Clinical Trial Registry, ChiCTR2000032665. Registered 5 May 2020—Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=53288

Background Wilson disease is a rare, disabling, neurological genetic disease. Biomarkers of brain damage are less well developed. Objective The aim of this study was to evaluate the utility of plasma glial fibrillary acidic protein as a biomarker for neurological involvement in patients with Wilson disease. Methods This prospective cross-observational study compared plasma glial fibrillary acidic protein concentration among different subtypes of patients with Wilson disease and healthy control subjects. Plasma glial fibrillary acidic protein levels were measured in 94 patients and 25 healthy control subjects. Patients were divided into two subtypes: patients with neurological manifestations (n = 74) or hepatic manifestations (n = 20). Results Median levels of plasma glial fibrillary acidic protein were significantly elevated in patients with neurological manifestations (143.87 pg/mL) compared with those with hepatic manifestations (107.50 pg/mL) and healthy control subjects (86.85 pg/mL). Receiver operating characteristic curve revealed that a plasma glial fibrillary acidic protein cutoff value of 128.8 pg/mL provides sufficient sensitivity (80.0%) and specificity (63.5%) to differentiate patients with neurological manifestations from those with hepatic manifestations. Conclusions Plasma glial fibrillary acidic protein may serve as a biomarker for distinguishing different subtypes of Wilson disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Gene regulatory networks play pivotal roles in our understanding of biological processes/mechanisms at the molecular level. Many studies have developed sample-specific or cell-type-specific gene regulatory networks from single-cell transcriptomic data based on a large amount of cell samples. Here, we review the state-of-the-art computational algorithms and describe various applications of gene regulatory networks in biological studies.基因调控网络对在分子水平上理解生物过程和机制起着至关重要的作用。很多研究基于单细胞转录组数据中的大量细胞样本，开发了一系列算法构建样本特异或细胞类型特异的基因调控网络。该文系统回顾了目前最新的基于单细胞转录组数据构建基因调控网络的算法，特别是一个细胞数据构建一个网络的理论和方法(CSN: cell-specific network)，与现有的单个细胞型(cell type)的基因调控网络不同，CSN是一个细胞构建一个基因调控网络的方法，该文进一步描述了其在生物学研究中的各种应用。.

Background With an aging population, China is facing a huge burden of elderly patients with drug resistant tuberculosis (DR-TB), which has become a significant obstacle for the global TB control. There is still little study on DR-TB in the elderly in China so far. Thus, more research on the epidemiological characteristics and trend of primary DR-TB among the elderly will be necessary. Methods A retrospective study was conducted in Shandong, China from 2004 to 2019. We collected 12,661 primary TB cases, of which 4368 elderly (≥60 years) primary TB cases were involved. Clinical characteristics including age, sex, cavity, smoking, drinking, comorbidity and drug susceptibility data were collected from 36 TB prevention and control institutions of Shandong Province. Sputum samples were collected by each surveillance site, and examined in the TB Reference Laboratory of SPCH. Descriptive statistical analysis, chi-square and linear regression were used for analyzing. Results Among 4368 elderly patients with primary TB, the DR-TB and multi-resistant tuberculosis (MDR-TB) accounted for 17.19% and 2.29%, respectively. During 2004-2019, the proportions of MDR-TB, polydrug resistant tuberculosis (PDR-TB), rifampin (RFP)-resistance increased by 160.00%, 18.18%, 231.82%, respectively and the rate of DR-TB among elderly patients with primary cavitary TB increased by 255%. Among the elderly with primary DR-TB during 2004-2019, the proportion of male (from 85.19 to 89.06), cavity (from 7.41 to 46.88), RFP-resistance (from 3.70 to 21.88), and streptomycin (SM)-resistance (from 37.04 to 62.5) increased significantly (P

Background Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people’s health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence. Methods By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006–2017. Data were retrieved from the China Information System for Disease Control and Prevention. Results Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are − 0.0015682, − 0.0028132 and − 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017. Conclusion We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of “difficult and expensive medical treatment”. In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.

Background Nutrients involved in one-carbon metabolism may play a key role in pancreatic carcinogenesis. The aim of this study was to examine the association between pancreatic cancer risk and intake or blood levels of vitamins B6, B12 and methionine via meta-analysis. Methods A systematic search was performed in PubMed, Web of Knowledge and Chinese National Knowledge Infrastructure (CNKI) up to April 2020 to identify relevant studies. Risk estimates and their 95% confidence intervals (CIs) were retrieved from the studies and combined by a random-effect model. Results A total of 18 studies were included in this meta-analysis on the association of vitamin B6, B12 and methionine with pancreatic cancer risk. The combined risk estimate (95% CI) of pancreatic cancer for the highest vs lowest category of vitamin B6 intake and blood pyridoxal 5′-phosphate (PLP, active form of vitamin B6) levels was 0.63 (0.48–0.79) and 0.65 (0.52–0.79), respectively. The results indicated a non-linear dose-response relationship between vitamin B6 intake and pancreatic risk. Linear dose–response relationship was found, and the risk of pancreatic cancer decreased by 9% for every 10 nmol/L increment in blood PLP levels. No significant association were found between pancreatic cancer risk and vitamin B12 intake, blood vitamin B12 levels, methionine intake and blood methionine levels. Conclusion Our study suggests that high intake of vitamin B6 and high concentration of blood PLP levels may be protective against the development of pancreatic cancer. Further research are warranted to confirm the results.

Imatinib mesylate is a tyrosine kinase inhibitor and used as the first-line medication for chronic myeloid leukaemia. Herein, we report two rare cases of hyperpigmentation of the palatal mucosa associated with imatinib mesylate therapy to treat chronic myeloid leukaemia in patients of Chinese ethnicity. A diffuse, bluish-grey lesion located on the hard palate was observed in both patients, and incisional biopsies were performed. Histopathological findings showed deposition of melanin pigments within the lamina propria with no increased melanocytes numbers within epithelium and lamina propria. The histopathologic findings and clinical history were consistent with the diagnosis of drug-induced oral melanosis. Clinicians should be cognizant that hyperpigmentation of the palatal mucosa is a rare side effect of imatinib mesylate therapy and include it as a possible differential diagnosis in oral melanosis cases.

Coal tar pitch (CTP) with high carbon content and wide source of raw materials was an excellent precursor for the preparation of porous carbons (PCs). CTP was composed of polycyclic aromatic hydrocarbons (PAHs) with complex molecular size and chemical structure, the separation of CTP into several fractions with relatively narrow molecular weight by solvent extraction was of significance for CTP utilization. In this paper, CTP was treated by single-solvent extraction (carbon disulfide, acetone and ethyl acetate), and the six fractions were used as raw materials to prepare PCs as electrode material for electric double layer capacitor. The fractions were well characterized and the effect of mass distribution of different narrow fractions on structure property and electrochemical performance of the PCs was studied. The PCs prepared by carbon disulfide extract, acetone raffinate and ethyl acetate extract, containing more PAHs, exhibited the excellent specific capacitance performance in comparison with its residual components. The remarkable performance might contribute in the enhanced transport of electrolyte ions via the molecular graphene structure of PAHs. Additionally, the PC prepared by carbon disulfide raffinate showed outstanding cycling performance (99.7% at 2 A g-1 after 15,000 cycles) which was related to its unique layered porous structure.

Dyslipidemia is a risk factor for cardiovascular diseases and type 2 diabetes. Several adipokines play important roles in modulation of blood lipids. Metrnl is a recently identified adipokine, and adipose Metrnl participates in regulation of blood triglyceride (TG). In this study, we generated Metrnl global, intestine-specific and liver-specific knockout mice, and explored the effects of Metrnl on serum lipid parameters. Global knockout of Metrnl had no effects on serum lipid parameters under normal chow diet, but increased blood TG by 14%, and decreased total cholesterol (TC) by 16% and high density lipoprotein cholesterol (HDL-C) by 24% under high fat diet. Nevertheless, intestine-specific knockout of Metrnl did not alter the serum lipids parameters under normal chow diet or high fat diet. Notably, liver-specific knockout of Metrnl decreased HDL-C by 24%, TC by 20% and low density lipoprotein cholesterol (LDL-C) by 16% without alterations of blood TG and nonesterified fatty acids (NEFA) under high fat diet. But deficiency of Metrnl in liver did not change VLDL secretion and expression of lipid synthetic and metabolic genes. We conclude that tissue-specific Metrnl controls different components of blood lipids. In addition to modulation of blood TG by adipose Metrnl, blood HDL-C is regulated by liver Metrnl.

Objective: The aim of the present study was to evaluate the effects of ethyl acetate extract of Polygonum orientale L. (POE) on ameliorating postmenopausal osteoporosis in ovariectomized (OVX) rats...

Background The prognostic value of platelet distribution width (PDW) is different in various malignancies. The purpose of this study was to identify the relationship between preoperative PDW and survival in patients with non‐small cell lung cancer (NSCLC). Methods Optimal cutoff values of PDW were confirmed using a receiver operating characteristic (ROC) curve. The Kaplan‐Meier method and log‐rank test were used to estimate disease‐free survival (DFS) and overall survival (OS). Univariate and multivariate Cox regression models were used for prognostic analysis. The likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare two models of the TNM staging system and the PDW‐TNM staging system (combination of PDW and the TNM staging system). Results Survival analysis indicated that the disease‐free survival (DFS) and overall survival (OS) of patients with PDW > 12.65 were both significantly longer than those of patients with PDW ≤ 12.65. Multivariate analysis showed that PDW was an independent prognostic factor for DFS and OS. After the two prediction models were established, further LRT analysis showed that the PDW‐TNM model had a better ability to assess patient prognosis. Conclusions PDW might act as an independent risk factor to predict progression and prognosis. Preoperative PDW combined with the TNM staging system showed a better ability to assess the prognosis of NSCLC patients. Key points Our study focused on the prognostic value of preoperative PDW in 750 patients with NSCLC. We also analyzed preoperative PDW in different stages and histological subtypes systematically. A model built by preoperative PDW combined with the TNM staging system had a better prognostic ability. LRT was used to calculate values of the goodness of fit between the model and the TNM staging system.

BACKGROUND: Thyroid transcription factor 1 (TTF-1), which is usually expressed by lung adenocarcinomas and small cell carcinomas, is usually used to distinguish adenocarcinoma and small cell carcinoma from cells of another type of lung cancer. We examined the association between TTF-1 expression and overall survival between patients with stage IV pulmonary adenocarcinoma to investigate the role of TTF-1 as a predictive and/or prognostic tumor marker in patients with advanced lung adenocarcinomas. METHODS: Analysis of the clinicopathologic features, treatment regimens, and overall survival of 209 lung adenocarcinoma patients who had been detected for TTF-1 expression and received consecutive treatments in the Affiliated Hospital of Qingdao University. RESULTS: TTF-1 expression was positive in 166 (79%) and negative in 43 (21%) patients who were reviewed. Moreover, there was no significant difference between the clinicopathologic features of TTF-1 positive and TTF-1 negative tumors. In the multivariable review, the overall survival of TTF-1 positive tumor patients was significantly longer than that of TTF-1 negative tumor patients [22.7 vs. 11.8 months (P

What is already known about this topic? After the type 2 strain of the live, attenuated poliovirus vaccine was withdrawn globally in 2016, any identification of a type 2 poliovirus is a Public Health Emergency of International Concern. A vaccine-derived type 2 poliovirus (VDPV2) was identified in Sichuan, prompting an urgent, comprehensive investigation and response. What is added by this report? Type 2 monovalent, live, attenuated oral poliovirus vaccine (mOPV2) is being used to respond to the numerous VDPV2 outbreaks seen around the world. In contrast, the response in Sichuan used Sabin strain inactivated poliovirus (sIPV) to stop circulation of the VDPV2. In the 6 months following the vaccination response, there have been no VDPV2s detected in Sichuan, despite extensive search. What are the implications for public health practices? Further search for the VDPV2 must continue in order to determine whether transmission has been stopped. The ongoing investigation and response to the Sichuan VDPV2 is providing evidence to the Global Polio Eradication Initiative on managing VDPV2 outbreaks.

Mammalian target of rapamycin (mTOR) is upregulated in a high percentage of glioblastomas. While a well-known mTOR inhibitor, rapamycin, has been shown to reduce glioblastoma survival, the role of mitochondria in achieving this therapeutic effect is less well known. Here, we examined mitochondrial dysfunction mechanisms that occur with the suppression of mTOR signaling. We found that, along with increased apoptosis, and a reduction in transformative potential, rapamycin treatment significantly affected mitochondrial health. Specifically, increased production of reactive oxygen species (ROS), depolarization of the mitochondrial membrane potential (MMP), and altered mitochondrial dynamics were observed. Furthermore, we verified the therapeutic potential of rapamycin-induced mitochondrial dysfunction through co-treatment with temzolomide (TMZ), the current standard of care for glioblastoma. Together these results demonstrate that the mitochondria remain a promising target for therapeutic intervention against human glioblastoma and that TMZ and rapamycin have a synergistic effect in suppressing glioblastoma viability, enhancing ROS production, and depolarizing MMP.

ObjectiveTo explore the factors associated with antenatal care (ANC) visits.DesignA secondary data analysis from cross-sectional studies was conducted.SettingSub-Saharan Africa.Participants56 002 women aged 15–49 years in Ghana (3224), Kenya (10 981), Malawi (9541), Namibia (2286), Rwanda (4416), Senegal (6552), Tanzania (5536), Uganda (7979) and Zambia (5487) were analysed.Outcomes4+ANC visits.ResultsOverall, 55.52% (95% CI: 55.11% to 55.93%) of women made 4+ANC visits. The highest 4+ANC visits were in Ghana (85.6%) and Namibia (78.9%), and the lowest were in Senegal (45.3%) and Rwanda (44.5%). Young women 15–19 years had the lowest uptake of 4+ANC visits. Multivariable analysis indicated that the odds of 4+ANC visits were 14% lower among women from rural areas compared with those living in towns (adjusted OR (AOR) 0.86; 95% CI: 0.81 to 0.91). This difference was significant in Kenya, Malawi, Senegal and Zambia. However, in Zambia, the odds of 4+ANC visits were 48% higher (AOR 1.48; 95% CI: 1.2 to 1.82) among women from rural compared with urban areas. Women with higher educational level had more than twofold higher odds of 4+ANC visits in seven of the nine countries, and was significant in Kenya, Malawi, Rwanda and Zambia. Compared with the poorest household wealth category, odds of 4+ANC visits increased by 12%, 18%, 32% and 41% for every 20% variation on the wealth quantile. Women in their first-time pregnancy had higher odds of 4+ANC visits compared with others across all countries, and women who had access to media at least once a week had a 22% higher probability of 4+ANC visits than women who had no access to media (AOR 1.22, 95% CI: 1.15 to 1.29).ConclusionThe number of ANC visits was considered to be inadequate with substantial variation among the studied countries. Comprehensive interventions on scaling uptake of ANC are needed among the low-performing countries. Particular attention should be given to women of low economic status and from rural areas.

Background: Postoperative cognitive dysfunction (POCD) is a common surgical complication in elderly patients undergoing hip and knee replacement. Electroacupuncture (EA) may have a protective effect on postoperative cognitive function, but relevant evidence remains uncertain.Objective: To systematically evaluate the evidence of EA for the prevention of POCD after total joint arthroplasty.Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, and Chinese Biomedical Literature Database (CBM) databases were searched until May 1, 2021. Randomized controlled trials (RCTs) in which patients undergoing hip and knee replacement pretreated with EA for preventing POCD were included. The risk of bias was assessed by the Cochrane Collaboration tool. Meta-analysis was performed using Review Manager version 5.4.Results: A total of 11 RCTs with 949 patients were identified. Meta-analysis showed that compared with controls, EA pretreatment significantly reduced the incidence of POCD at 1, 3, and 7 days and 3 and 6 months after the operation. EA was also superior in improving the Mini-Mental State Examination (MMSE) scores on the third postoperative day, but not on the first postoperative day. Neuron-specific enolase (NSE) and interleukin-1β (IL-1β) in the EA group were significantly lower than that in the control group. There was no difference in S100β between the EA group and the control group. Compared to the control group, tumor necrosis factor-α (TNF-α) levels were not significantly lower in the EA group at postoperative hour 0, while significantly decreased at postoperative hours 24 and 48.Conclusion: Our results suggest that EA pretreatment is an effective adjunctive therapy for reducing the incidence of POCD for patients receiving total joint replacement surgery. Its effect was embodied in improving the MMSE scores and NSE, IL-1β, and TNF-α levels, whereas it had no significant effect on S100β levels. Meanwhile, the benefits of EA for improving POCD need further strengthening and support from more large-scale, high-quality, and good-homogeneity RCTs.Systematic Review Registration:https://osf.io/xb3e8.

Abnormal production and degradation of amyloid beta (Aβ) in the brain lead to oxidative stress and cognitive impairment in Alzheimer’s disease (AD). Cirsium japonicum var. maackii (CJM) is widely used as an herbal medicine and has antibacterial and anti-inflammatory properties. This study focused on the protective effect of the ethyl acetate fraction from CJM (ECJM) on Aβ25-35-induced control mice. In the T-maze and novel object recognition test, ECJM provided higher spatial memory and object recognition compared to Aβ25-35 treatment alone. In the Morris water maze test, ECJM-administered mice showed greater learning and memory abilities than Aβ25-35-induced control mice. Additionally, ECJM-administered mice experienced inhibited lipid peroxidation and nitric oxide production in a dose-dependent manner. The present study indicates that ECJM improves cognitive impairment by inhibiting oxidative stress in Aβ25-35-induced mice. Therefore, CJM may be useful for the treatment of AD and may be a potential material for functional foods.

A meta-analysis was carried out in this study by summarizing relevant research to evaluate the relationship between rs2107538 polymorphism in the chemotactic chemokine ligand 5 (CCL5) gene and tuberculosis (TB) susceptibility. Published studies were retrieved from PubMed, Embase, and CNKI databases using the keywords ‘CCL5’, ‘TB’, and ‘polymorphism’. Nine studies involving 2584 patients with TB and 2265 controls were included in the current meta-analysis. The combined results suggested that the CCL5 rs2107538 polymorphism was correlated with TB susceptibility (recessive model: OR = 1.45, 95% CI = 1.02–2.07). Subgroup analysis according to race indicated that such correlation could be detected in Caucasians (CT versus CC: OR = 1.53, 95% CI = 1.20–1.95; dominant model: OR = 1.58, 95% CI = 1.25–1.99), but not in East Asian, South Asian, and South African populations. In conclusion, the results of our meta-analysis suggest that CCL5 rs2107538 polymorphism might contribute to the risk of TB, especially in Caucasians. Well-designed studies with more subjects will be required for further validation of these results.

Purpose: Maytansine (DM1) is a potent anticancer drug and limited in clinical application due to its poor water solubility and toxic side effects. Zein is widely used in nano drug delivery systems due to its good biocompatibility. In this study, we prepared DM1-loaded zein nanoparticles (ZNPs) to achieve tumor targeting and reduce toxic side effects of DM1. Methods: ZNPs were prepared by phase separation and Box-Behnken design was used to optimize the formulation. Then, confocal fluorescence microscope and flow cytometry were used to determine cellular uptake of ZNPs. A549 cells were cultured in vitro to study cytotoxicity and used to establish tumor xenografts in nude mice. Biodistribution and antitumor activity of ZNPs were performed in vivo experiments. In addition, we also performed histological and immunohistochemical examinations on tumors and viscera. Results: The optimal prescription was obtained by using 120 μL zein added to 2 mL water under stirring in 300 rpm. The encapsulation efficiency and drug loading were 82.97 ± 0.80% and 3.32 ± 0.03%, respectively. We found that DM1-loaded ZNPs have a strong inhibitory effect on A549 cells, which stemmed from the ability of ZNPs to enhance cellular uptake. Furthermore, we demonstrated that DM1-loaded ZNPs exhibits a better antitumor efficacy than DM1, which tumor inhibition rate were 97.3% and 92.7%, respectively. The biodistribution revealed that ZNPs could targeted to tumor. Finally, we confirmed by histological that DM1-loaded ZNPs are nontoxic. Conclusion: DM1-loaded ZNPs have considerable antitumor activity. Thus, DM1-loaded ZNPs are a promising treatment of non-small cell lung cancer.

Prolonged strenuous postures in occupational context may lead to low back pain. Avoiding such occurrences is known to help prevent low back pain episodes or may contribute to recovery. This research concerns wearable sensing technology to support posture monitoring for the prevention of occupational low back pain and, more specifically, how smart garments can help nurses avoid prolonged strenuous postures at work. We introduce BackUp, a system comprising of a smart shirt connected to a smartphone application that provides feedback and advice on low back posture, and we describe its design and implementation. We report on a series of studies that contributed to its development: an anthropometric study (N = 60) to decide on the placement of sensors on the lower spine; a brief field study aimed at evaluating user experience and attitudes towards the shirt (N = 17), and a second field study intended to assess its effectiveness in helping nurses avoid prolonged strenuous postures at work (N = 13). These studies demonstrate how smart clothing can support posture feedback in real life conditions. While the results from the field studies are encouraging regarding the potential of this technology, further research is needed to establish the durability of the behaviour modification achieved through smart garments.

Yanqi Qi,&ast; Jiawen Xu,&ast; Zhe Lin,&ast; Yijing Tao, Fenglei Zheng, Yujia Wang, Yameng Sun, Songling Fu, Wei Wang, Chunhong Xie, Yiying Zhang, Fangqi Gong Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangqi GongDepartment of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No. 3333 Binsheng Road, Hangzhou, 310052, People’s Republic of ChinaTel/Fax +86-571-88873008Email gongfangqi@zju.edu.cnIntroduction: Kawasaki disease (KD) is an acute febrile systemic vasculitis, but the etiology remains unknown. We studied serum levels of CD147, DcR3, and IL33 in different stages of KD to explore the value of CD147, DcR3, and IL33 in the pathophysiology of KD.Methods: We measured serum levels of CD147, DcR3, and IL33 by enzyme-linked immunosorbent assay (ELISA) at different stages with 71 KD patients and 66 healthy control children. We apply for network tools GeneMANIA and Cytoscape APP to analyze the functions of these pro-inflammatory factors at the gene and protein level.Results: Serum levels of CD147, DcR3, and IL33 were significantly increased in KD patients before IVIG treatment. Serum levels of CD147, DcR3, and IL33 gradually decreased over time after the treatment of IVIG. Eight cases were IVIG non-responders, while nine KD patients got CALs, but they did not overlap. And there were no statistical differences between group IVIG responders and IVIG non-responders or between groups without CALs and with CALs. We explored the functions of CD147, DcR3, and IL33 from GeneMANIA and Cytoscape APP and found these third pro-inflammatory factors were coexpressed, physical interactions, genetic interactions with other KD-related factors.Conclusion: CD147, DcR3, and IL33 are involved in the pathophysiology of KD, which provides novel evidence for diagnosing and treating KD with their inhibitors.Keywords: Kawasaki disease, coronary artery lesions, CD147, DcR3, IL33, PI3K/AKT pathway

Tai Chi Chuan (TCC) is assumed to exert beneficial effects on functional brain activity and cognitive function in elders. Until now, empirical evidence of TCC induced intra-regional spontaneous neural activity and inhibitory control remains inconclusive. Whether the effect of TCC is better than that of other aerobic exercises is still unknown, and the role of TCC in younger adults is not yet fully understood. Here we used resting-state functional MRI (fMRI) to investigate the effects of 8-week TCC (n = 12) and brisk walking (BW, n = 12) on inhibitory control and fractional amplitude of low-frequency fluctuations (fALFF). The results found that TCC had significant effects on inhibitory control performance and spontaneous neural activity that were associated with significantly increased fALFF in the left medial superior frontal gyrus (Cohen’s d = 1.533) and the right fusiform gyrus (Cohen’s d = 1.436) and decreased fALFF in the right dorsolateral superior frontal gyrus (Cohen’s d = 1.405) and the right paracentral lobule (Cohen’s d = 1.132).TCC exhibited stronger effects on spontaneous neural activity than the BW condition, as reflected in significantly increased fALFF in the left medial superior frontal gyrus (Cohen’s d = 0.862). There was a significant positive correlation between the increase in fALFF in the left medial superior frontal gyrus and the enhancement in inhibitory control performance. The change in fALFF in the left medial superior frontal gyrus was able to explain the change in inhibitory control performance induced by TCC. In conclusion, our results indicated that 8 weeks of TCC intervention could improve processing efficiency related to inhibitory control and alter spontaneous neural activity in young adults, and TCC had potential advantages over BW intervention for optimizing spontaneous neural activity.

Background Lung adenocarcinoma (LUAD) is a malignant tumor with a high fatality rate and poor overall survival, while molecular targets diagnosing and alleviating lung cancer remain inadequate. Methods In this article, we highlighted the upregulation of microRNA‐423‐3p (miR‐423‐3p) in LUAD, especially in smokers aged over 40, and revealed that the high expression of miR‐423‐3p was significantly associated with smoker, age, and pathologic stage of LUAD patients. Results Moreover, overexpressing miR‐423‐3p could facilitate LUAD cell proliferation, invasion, adhesion, and epithelial–mesenchymal transition (EMT) process, while depleted miR‐423‐3p caused repressive influence upon it. Mechanically, we identified that miR‐423‐3p could activate FAK signaling pathway through binding to the 3'‐UTR of cytochrome B reductase 1 (CYBRD1). Furthermore, we demonstrated that CYBRD1 was lowly expressed in LUAD, and miR‐423‐3p overexpression could rescue the impairment of LUAD cell proliferation, invasion, adhesion, and EMT caused by CYBRD1 depletion. Noticeably, miR‐423‐3p depletion efficiently hindered LUAD tumor growth in vivo. Conclusion Collectively, our findings demonstrated that miR‐423‐3p/CYBRD1 axis could be regarded as a promising biomarker to alleviate the poor LUAD prognosis., miR‐423‐3p facilitates LUAD cell proliferation, invasion, adhesion, and EMT. (A) qRT‐PCR was performed for the measurement of miR‐423‐3p in LUAD cell lines (NCI‐H1299 and NCI‐H157) and human bronchial epithelial cell line 16HBE. (B) For functional validation, transfection was achieved in NCI‐H1299 cells with miR‐423‐3p mimic plasmid, and in NCI‐H157 cells with miR‐423‐3p inhibitor, qRT‐PCR was utilized to examine the transfection efficacy. (C) CCK‐8 was performed to detect the proliferation rate of NCI‐H1299 and NCI‐H157 cells. Wound‐healing (D) and Transwell (E) assays were introduced for the cell migration and invasion analyses. Western blotting (F) and adhesion (G) assays were, respectively, employed for the detection of EMT‐related proteins and adhesive capacity. *p

The heparan sulfate (HS) mimetic pixatimod (PG545) is a highly potent inhibitor of angiogenesis, tumor growth, and metastasis currently in clinical trials for cancer. PG545 has also demonstrated potent antiviral activity against numerous HS-dependent viruses, including SARS-CoV-2, and shows promise as an antiviral drug for the treatment of COVID-19. Structurally, PG545 consists of a fully sulfated tetrasaccharide conjugated to the steroid 5α-cholestan-3s-ol. The reported synthesis of PG545 suffers from a low yield and poor selectivity in the critical glycosylation step. Given its clinical importance, new efficient routes for the synthesis of PG545 and analogues were developed. Particular attention was given to improving the key glycosylation step by using more stable protecting groups and optimized glycosyl donors.

An excessive high-fat/energy diet is a major cause of obesity and linked complications, such as non-alcoholic fatty liver disease (NAFLD). Betaine has been shown to effectively improve hepatic lipid metabolism. However, the mechanistic basis for this improvement is largely unknown. Herein, integration of mRNA sequencing and ribosome footprints profiling (Ribo-seq) was used to investigate the means by which betaine alleviates liver lipid metabolic disorders induced by a high-fat diet. For the transcriptome, gene set enrichment analysis demonstrated betaine to reduce liver steatosis by up-regulation of fatty acid beta oxidation, lipid oxidation, and fatty acid catabolic processes. For the translatome, 574 differentially expressed genes were identified, 17 of which were associated with the NAFLD pathway. By combined analysis of transcriptome and translatome, we found that betaine had the greater effect on NAFLD at the translational level. Further, betaine decreased translational efficiency (TE) for IDI1, CYP51A1, TM7SF2, and APOA4, which are related to lipid biosynthesis. In summary, this study demonstrated betaine alleviating lipid metabolic dysfunction at the translational level. The transcriptome and translatome data integration approach used herein provides for a new understanding of the means by which to treat NAFLD.