Search

Abstract Class IIa histone deacetylases (Class IIa HDACs) play critical roles in regulating essential cellular metabolism and inflammatory pathways. However, dissecting the specific roles of each class IIa HDAC isoform is hindered by the pan‐inhibitory effect of current inhibitors and a lack of tools to probe their functions beyond epigenetic regulation. In this study, a novel PROTAC‐based compound B4 is developed, which selectively targets and degrades HDAC7, resulting in the effective attenuation of a specific set of proinflammatory cytokines in both lipopolysaccharide (LPS)‐stimulated macrophages and a mouse model. By employing B4 as a molecular probe, evidence is found for a previously explored role of HDAC7 that surpasses its deacetylase function, suggesting broader implications in inflammatory processes. Mechanistic investigations reveal the critical involvement of HDAC7 in the Toll‐like receptor 4 (TLR4) signaling pathway by directly interacting with the TNF receptor‐associated factor 6 and TGFβ‐activated kinase 1 (TRAF6‐TAK1) complex, thereby initiating the activation of the downstream mitogen‐activated protein kinase/nuclear factor‐κB (MAPK/NF‐κB) signaling cascade and subsequent gene transcription. This study expands the insight into HDAC7's role within intricate inflammatory networks and highlights its therapeutic potential as a novel target for anti‐inflammatory treatments.

The fabric‐based pneumatic exosuit is now a hot research topic because it is lighter and softer than traditional exoskeletons. Existing research focuses more on the mechanical properties of the exosuit (e.g., torque and speed), but less on its wearability (e.g., appearance and comfort). This work presents a new design concept for fabric‐based pneumatic exosuits: volume transfer, which means transferring the volume of pneumatic actuators beyond the garment's profile to the inside. This allows for a concealed appearance and a larger stress area while maintaining adequate torques. In order to verify this concept, a fabric‐based pneumatic exosuit is developed for knee extension assistance. Its profile is only 26 mm and its stress area wraps around almost half of the leg. A mathematical model and simulation is used to determine the parameters of the exosuit, avoiding multiple iterations of the prototype. Experiment results show that the exosuit can generate a torque of 7.6 Nm at a pressure of 90 kPa and produce a significant reduction in the electromyography activity of the knee extensor muscles. It is believed that volume transfer can be utilized prevalently in future fabric‐based pneumatic exosuit designs to achieve a significant improvement in wearability.

Abstract Aim The study aimed to explore learning achievement and students' satisfaction with a blended learning (BL) electrocardiogram (ECG) education programme in undergraduate nursing education. Design This was a quasi‐experimental post‐test design. Methods The study was conducted during semester one of the academic year 2020/2021. Participants were divided into two groups: the BL group and face‐to‐face (FTF) group. The BL group received the newly designed BL programme. The FTF group received the traditional learning methods. Post‐test measures of the study variables such as knowledge, study time and satisfaction were conducted. Chi‐square (χ2) test was used to evaluate categorical variables. The Mann–Whitney test was used to analyse continuous variables. Results Participants in BL group had significantly higher scores in ECG interpretation and total score. No significant differences in foundational knowledge between the two groups were found. Study time was significantly longer in the BL group. Regarding satisfaction, significant differences were found in structure rationality and promotion of self‐learning.

Abstract Objective To investigate the effects of the apolipoprotein E (APOE) gene on oxygen saturation and cerebral perfusion in the early stages of traumatic brain injury (TBI). Methods This study included 136 consecutive TBI patients and 51 healthy individuals. The APOE genotypes of all subjects were determined using quantitative fluorescence polymerase chain reaction (QF‐PCR). Regional cerebral oxygen saturation (rScO2) of patients with TBI and normal subjects was monitored using near‐infrared spectroscopy (NIRS). Computed tomography (CT) perfusion was used to obtain cerebral perfusion in patients with TBI and normal subjects. Results In the TBI group, the rScO2 of APOEε4 carriers (53.06 ± 6.87%) was significantly lower than that of non‐carriers (58.19 ± 5.83%, p 5.75 s, Marshall CT Class, and GCS were independent risk factors for early poor prognosis in patients with TBI. Conclusion Both cerebral perfusion and cerebral oxygen were significantly impaired after TBI, and low cerebral perfusion and hypoxia were related to poor prognosis of patients with TBI. Compared with APOE ε4 non‐carriers, APOE ε4 carriers not only had poorer cerebral perfusion and cerebral oxygen metabolism but also worse prognosis in the early stages of TBI. Furthermore, a negative correlation was observed between the rSCO2 and MTT levels. In addition, both CT perfusion scanning (CTP) and NIRS are reliable for monitoring the condition of patients with TBI in the neurological intensive care unit (NICU).

Abstract Background The surgical indications and therapeutic strategies for early‐stage multifocal and recurrent hepatocellular carcinoma (rHCC) remain controversial. This study compared the long‐term outcome of patients with recurrent and multifocal HCC meeting the Barcelona Clinic Liver Cancer (BCLC) stage A with repeat hepatectomy (RH) and RH combined with intraoperative radiofrequency ablation (RFA). Methods A total of 109 consecutive patients with intrahepatic early‐stage multifocal rHCC within BCLC stage A following RH or RH + RFA were retrospectively collected from April 2010 to May 2020. Propensity score matching, subgroup analysis, and univariate and multivariate analyses were performed. Overall survival after recurrence (rOS) and recurrence‐free survival after recurrence (rRFS) were calculated by Kaplan–Meier analysis. Results The 1‐, 3‐, and 5‐year rOS and rRFS of the combination group and the RH group were similar (p = .699; p = .587, respectively). The similar results also appeared in matched population. Subgroup analyses indicated that there was no significant difference between patients with two tumors and three tumors, but the RH group was associated with better rRFS than the combination group for patients whose tumors were located in the same lobe (p = .045). Multivariate analysis revealed that time to recurrence (TTR) ≤ 2 years and intrahepatic metastasis (IM) pathologically were independent risk factors. Conclusions For multifocal rHCC patients meeting the BCLC stage A, tumor which is difficult to be surgically resected could be treated by RFA in order to avoid complications or bleeding. Tumors which were located in the same lobe may be more suitable to be treated by RH alone.

Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA‐binding protein WD repeat and HMG‐box DNA‐binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non‐NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP‐seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC.

Abstract The efficiency of many clean technologies, such as urea fuel cells, hydrogen production from urea‐containing water splitting, and sewage treatment, and so forth, is restricted due to the sluggish kinetics of the urea oxygen reaction (UOR). Mo‐doped Ni‐based catalysts are excellent for UOR because of the synergistic effect between Ni and Mo. However, such applications have indeed been hampered by a lack of mechanistic comprehension. Here, we fabricate Mo‐Ni(OH)2 nanosheets for efficient UOR electrocatalysis with activity at least twice higher than Ni(OH)2 nanosheets. Various in situ characterizations including Raman, differential electrochemical mass spectrometry and Fourier transform infrared spectroscopy reveals that the doping of Mo lowers the onset potential required for Ni2+/Ni3+ conversion and promotes the coupling of the N–N bond inside the molecule and the fracture of the double bond between C and O in the urea molecule. In addition, an entirely flexible direct urea fuel cell with the Mo‐Ni(OH)2 electrocatalyst delivers a maximum output power density of 0.78 mW cm−2 and complete flexibility for the first time. Our research significantly promotes the mechanistic understanding of UOR electrocatalysis and its applications.

Aberrant expression of members of the proteasome subunit beta (PSMB) family (including PSMB2, PSMB4, PSMB7 and PSMB8) has been reported in hepatocellular carcinoma (HCC). However the role of PSMB5 in HCC is unclear. To address this issue, we examined the expression of PSMB5 in HCC tissues using the The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus databases. A quantitative real‐time PCR and immunohistochemistry were performed to validate the expression of PSMB5 in HCC. The survival mutation status and immune cell infiltration of PSMB5 were also evaluated in HCC. We then examined the effect of knocking down PSMB5 expression through RNA interference in the HCC cell line Huh7. High expression of PSMB5 was observed in HCC tissues and was associated with poor prognosis. PSMB5 expression and clinical characteristics were then incorporated to build a prognostic nomogram. We observed that PSMB5 expression was closely related to the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cell macrophages and neutrophils. Moreover silencing of PSMB5 in Huh7 significantly suppressed cell proliferation and migration at the same time as increasing apoptosis. Inhibition of the phosphatidylinositol‐3‐kinase/Akt/mechanistic target of rapamycin pathway was observed after PSMB5 downregulation in Huh7 cells. Our findings suggest that PSMB5 may promote the proliferation of HCC cells by inactivating the phosphatidylinositol‐3‐kinase/Akt/mechanistic target of rapamycin signaling pathway and thus PSMB5 may have potential as a biomarker for diagnosis and prognosis of HCC.

Abstract With the development of modern tokamak devices, the magnetic interference problem has become increasingly serious. On considering the International Thermonuclear Experimental Reactor (ITER), for example, the stray magnetic field around the tokamak device will be over 200 mT. To ensure the reliable operation of the electrical and electronic equipment installed around the tokamak, the magnetic immunity test becomes a mandatory requirement. Generally, a set of coils is employed to realize the required test field. Since the coil power loss and conductor mass are proportional to the dimension and intensity of the test field, optimization design is of great significance. This paper presents the multi‐objective optimization design of a large‐scale high‐intensity homogeneous magnetic field coil system. The analytical model of the multi‐coil system is proposed, and the constrained multi‐objective optimization model is established based on the non‐dominated sorting genetic algorithm. Taking the ITER test coil as an example, the optimization design is performed and the Pareto‐front is figured out. The designed four‐coil system enables the magnetic field immunity tests for equipment within 1 m side‐length at a highest test level of 275 mT with a magnetic field inhomogeneity of 1.05. The validity of the proposed model is verified by the finite element analysis and experimental tests.

Abstract Aim To evaluate the prevalence and influencing factors of anxiety and depression symptoms in surgical nurses during the COVID‐19 epidemic in Anhui, China. Methods A cross‐sectional, multic'entre quantitative study was conducted among surgical nurses in Anhui province. SAS, SDS and SSRS scales were used for the investigation. Data were collected between 3 March 2020 to 19 March 2020. Results A total of 3,492 surgical nurses completed the survey. The average level of anxiety and depression of surgical nurses were higher than that of the Chinese norm. Levels of social support for surgical nurses were significantly negatively associated with the degree of anxiety and depression. Fertility status, participation in care for COVID‐19 patients, likelihood of being infected with COVID‐19 and social support were significantly influencing surgical nurses’ anxiety degree. Similarly, these characteristics were significantly associated with the odds of depression symptoms in surgical nurses. Conclusion These findings suggest that targeted psychological interventions to promote mental health of surgical nurses need to be immediately implemented.

Abstract Aims/Introduction Hyperglycemia, hypoglycemia, and blood glucose fluctuation are associated with the outcome in critically ill patients, but the target of blood glucose control is debatable especially in patients with diabetes regarding the status of blood glucose control before admission to ICU. This study aimed to investigate the association between the glycemic gap which is calculated as the mean blood glucose level during the first 7 days after admission to ICU minus the A1C‐derived average glucose and the outcome of critically ill patients with diabetes. Method This study was undertaken in two intensive care units (ICUs) with a total of 30 beds. Patients with diabetes who were expected to stay for more than 24 h were enrolled, the HbA1c was tested within 3 days after admission and converted to the A1C‐derived average glucose (ADAG) by the equation: ADAG = [(HbA1c * 28.7) – 46.7 ] * 18‐1, arterial blood glucose measurements were four per day routinely during the first 7 days after admission, the APACHE II score within the first 24 h, the mean blood glucose level (MGL), standard deviation (SD), and coefficient of variation (CV) during the first 7 days were calculated for each person, the GAPadm and GAPmean were calculated as the admission blood glucose and MGL minus the ADAG, respectively, the incidence of moderate hypoglycemia (MH) and severe hypoglycemia (SH), the total dosage of glucocorticoids and average daily dosage of insulin within 7 days, the duration of renal replacement therapy (RRT), ventilator‐free hours, and non‐ICU stay days within 28 days were also collected. The enrolled patients were divided into a survival group and a nonsurvival group according to survival or not at 28 days and 1 year after admission, and the relationship between parameters derived from blood glucose and mortality in the enrolled critically ill patients was explored. Results Five hundred and two patients were enrolled and divided into a survival group (n = 310) and a nonsurvival group (n = 192). It was shown that the two groups had a comparable level of HbA1c, the nonsurvivors had a greater APACHE II, MGL, SD, CV, GAPadm, GAPmean, and a higher incidence of hypoglycemia. A lesser duration of ventilator‐free, non‐ICU stay, and a longer duration of RRT were recorded in the nonsurvival group, who received a lower carbohydrate intake, a higher daily dosage of insulin and glucocorticoid. GAPmean had the greatest predictive power with an AUC of 0.820 (95%CI: 0.781–0.850), the cut‐off value was 3.60 mmol/L (sensitivity 78.2% and specificity 77.3%). Patients with a low GAPmean tended to survive longer than the high GAPmean group 1 year after admission. Conclusions Glycemic GAP between the mean level of blood glucose within the first 7 days after admission to ICU and the A1C‐derived average glucose was independently associated with a 28 day mortality of critically ill patients with diabetes, the predictive power extended to 1 year. The incidence of hypoglycemia was associated with mortality either.

Abstract Purpose To expand the mutation spectrum of patients with familial exudative vitreoretinopathy (FEVR) disease. Participants 74 probands (53 families and 21 sporadic probands) with familial exudative vitreoretinopathy (FEVR) disease and their available family members (n = 188) were recruited for sequencing. Methods Panel‐based targeted screening was performed on all subjects. Before sanger sequencing, variants of LRP5, NDP, FZD4, TSPAN12, ZNF408, KIF11, RCBTB1, JAG1, and CTNNA1 genes were verified by a series of bioinformatics tools and genotype–phenotype co‐segregation analysis. Results 40.54% (30/74) of the probands were sighted to possess at least one etiological mutation of the nine FEVR‐causative genes. The etiological mutation detection rate was 37.74% (20/53) in family‐attainable probands while 47.62% (10/21) in sporadic cases. The diagnosis rate of patients in the early‐onset subgroup (≤5 years old, 45.4%) is higher than that of the children or adolescence‐onset subgroup (6–16 years old, 42.1%) and the late‐onset subgroup (≥17 years old, 39.4%). A total of 36 etiological mutations were identified in this study, comprising 26 novel mutations and 10 reported mutations. LRP5 was the most prevalent mutant gene among the 36 mutation types with a percentage of 41.67% (15/36). Followed by FZD4 (10/36, 27.78%), TSPAN12 (5/36, 13.89%), NDP (4/36, 11.11%), KIF11 (1/36, 2.78%), and RCBTB1 (1/36, 2.78%). Among these mutations, 63.89% (23/36) were missense mutations, 25.00% (9/36) were frameshift mutations, 5.56% (2/36) were splicing mutations, 5.56% (2/36) were nonsense mutations. Moreover, the clinical pathogenicity of these variants was defined according to American College of Medical Genetics (ACMG) and genomics guidelines: 41.67% (15/36) were likely pathogenic variants, 27.78% (10/36) pathogenic variants, 30.55% (11/36) variants of uncertain significance. No etiological mutations discovered in the ZNF408, JAG1, and CTNNA1 genes in this FEVR cohort. Conclusions We systematically screened nine FEVR disease‐associated genes in a cohort of 74 Chinese probands with FEVR disease. With a detection rate of 40.54%, 36 etiological mutations of six genes were authenticated in 30 probands, including 26 novel mutations and 10 reported mutations. The most prevalent mutated gene is LRP5, followed by FZD4, TSPAN12, NDP, KIF11, and RCBTB1. In total, a de novo mutation was confirmed. Our study significantly clarified the mutation spectrum of variants bounded up to FEVR disease.

Abstract Alkali burn is a potentially blinding corneal injury. During the progression of alkali burn‐induced injury, overwhelmed oxidative stress in the cornea triggers cell damage, including oxidative changes in cellular macromolecules and lipid peroxidation in membranes, leading to impaired corneal transparency, decreased vision, or even blindness. In this study, we identified that ferroptosis, a type of lipid peroxidation‐dependent cell death, mediated alkali burn‐induced corneal injury. Ferroptosis‐targeting therapy protected the cornea from cell damage and neovascularization. However, the specific ferroptosis inhibitor ferrostatin‐1 (Fer‐1) is hydrophobic and cannot be directly applied in the clinic. Therefore, we developed Fer‐1‐loaded liposomes (Fer‐1‐NPs) to improve the bioavailability of Fer‐1. Our study demonstrated that Fer‐1‐NPs exerted remarkable curative effects regarding corneal opacity and neovascularization in vivo. The efficacy was comparable to that of dexamethasone, but without appreciable side effects. The significant suppression of ferroptosis (induced by lipid peroxidation and mitochondria disruption), inflammation, and neovascularization might be the mechanisms underlying the therapeutic effect of Fer‐1‐NPs. Moreover, the Fer‐1‐NPs treatment showed no signs of cytotoxicity, hematologic toxicity, or visceral organ damage, which further confirmed the biocompatibility. Overall, Fer‐1‐NPs provide a new prospect for safe and effective therapy for corneal alkali burn.

Abstract Background The aim of this study was to determine the specific side detection rate of the sentinel lymph node biopsy and the accuracy in predicting lymph node metastasis in early stage cervical cancer. Methods A systematic search of databases was performed from the inception of the databases to 27 June 2020. Studies of cervical cancer patients with FIGO stage FIGO ⅠA~ⅡB, evaluating the sentinel lymph node biopsy with blue dye, technetium 99, combined technique (blue dye with technetium 99) or indocyanine green with a reference standard of systematic pelvis lymph node dissection or clinical follow‐up were included. Stata12.0 and Meta‐Disc 1.4 were used for the meta‐analysis. Results Of 2825 articles found, 21 studies (2234 women) were eventually included. Out of 21 studies, 20 met the detection rate evaluation criteria and six were included for sensitivity meta‐analysis. Due to heterogeneity, it was inappropriate to pool all studies. The pooled specific side detection rates were 85% in tumors up to 2 cm, 67% in tumors over 2 cm, 75.2% for blue dye, 74.7% for technetium 99, 84% for combined technique, and 85.5% for indocyanine green. The sentinel lymph node biopsy had a pooled specific side sensitivity of 88%. Adverse effects of sentinel lymph node biopsy appear minimal for most patients and are mainly related to the injection of blue dye. Conclusions Sentinel lymph node biopsy using a tracer with a high detection rate and ultrastaging is highly accurate and reliable when limited to seriously selected patients, with satisfactory bilateral lymph node mapping and where enough cases for learning curve optimization exist. Indocyanine green sentinel lymph node mapping seems to be a superior sentinel lymph node mapping technique compared to other methods at present.

Abstract Background The feasibility of pneumothorax following low‐dose CT‐guided puncture lung biopsy in different severities of COPD has not been reported. Methods The data of the patients with pulmonary lesion who underwent low‐dose CT‐guided lung biopsy by one experienced operator in our hospital from January 1st to September 30th in 2019 were retrospectively collected. They were divided into COPD group and non‐COPD group. The risk factors, incidence and severity of pneumothorax with the severity of COPD and changes in MMRC score, treatment way and discharge time after pneumothorax were assessed. Results Two hundred and nineteen patients were retrospectively enrolled in this study with 64 in the COPD group and 155 in the non‐COPD group. The average age, MMRC score and the incidence of pneumothorax after biopsy were significantly higher in the COPD group (64.7 ± 1.27 years, 1.02 ± 0.13, 31.3%) than in the non‐COPD group (58.8 ± 1.16 years, 0.35 ± 0.06, 17.4%, P 0.05). Conclusion Although the incidence of pneumothorax after low dose CT‐guided lung biopsy is increased in COPD, there was no difference in the severity of pneumothorax amongst the different severities of COPD and it is well‐tolerated without increasing medical burden.

This project attempts to clarify the expression of MUS81 in castration-resistant prostate cancer (CRPC) and the effect on drug sensitivity to Olaparib. We collected clinical surgical samples of patients who were suffering from benign prostatic hyperplasia (BPH), common prostate cancer (PCa), and castration-resistant prostate cancer (CRPC) and detected the expression of MUS81 in healthy prostate epithelial cells, PCa cells, and androgen-independent PCa cells. We subsequently performed CCK-8 assays, flow cytometry, and Transwell invasion and migration assay to determine the proliferation, apoptosis, invasion, and metastasis abilities of transfected CRPC cells as well as drug toxicity of Olaparib to CRPC cells. The expression of MUS81 indicated marked upregulation in PCa and CRPC tissues, compared with the level of MUS81 in BPH tissues. MUS81 silencing inhibited the proliferation of CRPC cells and promoted their sensitivity to Olaparib. MUS81 silencing in CRPC cells remarkably accelerated cell apoptosis and greatly inhibited cell invasion and metastasis after Olaparib administration. MUS81 silencing in CRPC cells has significantly enhanced the sensitivity of cells to Olaparib, which provides evidence for the prediction of Olaparib resistance in CRPC cells by the MUS81 gene and is expected to become a promising gene target in CRPC therapy.

In order to investigate the bearing capacity of H-shaped honeycombed steel web composite columns with rectangular concrete-filled steel tube flanges (STHCCs) subjected to eccentrical compression load, 33 full-scale STHCCs were designed with the eccentricity(e), the slenderness ratio (λ), the cubic compressive strength of concrete(fcuk), the thickness of the steel tube flange (t1), the thickness of honeycombed steel web (t2), diameter-depth ratio (d/hw), space-depth (s/hw), and the yield strength of the steel tube (fy) as the main parameters. Considering the nonlinear constitutive model of concrete and simplified constitutive model of steel, the finite element (FE) model of STHCCs was established by ABAQUS software. By comparison with the existing test results, the rationality of the constitutive model of materials and FE modeling was verified. The numerical simulation of 33 full-scale STHCCs was conducted, and the influence of different parameters on the ultimate eccentrical compression bearing capacity was discussed. The results show that the cross-sectional stress distribution basically conforms to the plane-section assumption. With the increase in e, λ, and d/hw, the ultimate eccentrical compression bearing capacity of the full-scale STHCCs decreases, whereas it gradually increases with the increase in fcuk, t1, t2, s/hw, and fy. By introducing bias-stress stability coefficient (φ), the calculation formula of full-scale STHCCs under eccentrical compression is proposed by statistical regression, which can lay a foundation for the popularization and application of these types of composite columns in practical engineering.

The online-to-offline (O2O) meal delivery mode in which takeout meals are ordered online and delivered offline is recently emerging. The fast delivery of huge meal orders for time-sensitive customers imposes great challenges on O2O meal delivery platforms. This study establishes a two-stage solution for meal delivery routing optimization with the objective of maximizing time-sensitive customer satisfaction. In the first stage, a large number of meal orders are hierarchically classified and merged into delivery bundles based on the nearest pickup location rule by applying the hierarchical agglomerative clustering (HAC) algorithm, to increase fast meal delivery efficiency. In the second stage, a genetic algorithm (GA) is applied to solve the cluster-based delivery routing optimization model to find an optimal delivery route for meal orders in each delivery bundle. The numerical simulation results verify that the two-stage routing optimization solution is effective to schedule timely meal delivery and improve customer time satisfaction. The comparison of the results indicates the superiority of the proposed two-stage solution with HAC and GA on customer satisfaction while ensuring the delivery of all orders within 60 minutes. The sensitivity analysis shows the impact of time-sensitive customer heterogeneity on meal delivery satisfaction. This research has significant managerial insights for fast delivery services of O2O meal delivery platforms.

Abstract Background Cervical cancer (CC) is the second leading cause of cancer death among women worldwide. Epigenetic regulation of gene expression through DNA methylation and hydroxymethylation plays a pivotal role during tumorigenesis. In this study, to analyze the epigenomic landscape and identify potential biomarkers for CCs, we selected a series of samples from normal to cervical intra‐epithelial neoplasia (CINs) to CCs and performed an integrative analysis of whole‐genome bisulfite sequencing (WGBS‐seq), oxidative WGBS, RNA‐seq, and external histone modifications profiling data. Results In the development and progression of CC, there were genome‐wide hypo‐methylation and hypo‐hydroxymethylation, accompanied by local hyper‐methylation and hyper‐hydroxymethylation. Hydroxymethylation prefers to distribute in the CpG islands and CpG shores, as displayed a trend of gradual decline from health to CIN2, while a trend of increase from CIN3 to CC. The differentially methylated and hydroxymethylated region‐associated genes both enriched in Hippo and other cancer‐related signaling pathways that drive cervical carcinogenesis. Furthermore, we identified eight novel differentially methylated/hydroxymethylated‐associated genes (DES, MAL, MTIF2, PIP5K1A, RPS6KA6, ANGEL2, MPP, and PAPSS2) significantly correlated with the overall survival of CC. In addition, no any correlation was observed between methylation or hydroxymethylation levels and somatic copy number variations in CINs and CCs. Conclusion Our current study systematically delineates the map of methylome and hydroxymethylome from CINs to CC, and some differentially methylated/hydroxymethylated‐associated genes can be used as the potential epigenetic biomarkers in CC prognosis.

Abstract Background The clinical features and outcomes of subacute sclerosing panencephalitis (SSPE) in younger children are different from those of adults, leading easily to misdiagnosis during the early stage. So far, there are limited data related to SSPE in preschool children. Methods In order to summarize the clinical data and evolution of SSPE in preschool children and to expand the phenotypes of SSPE, the medical charts of preschool patients diagnosed with SSPE were retrospectively reviewed and analyzed; the clinical outcomes of the enrolled cases were evaluated and followed up. Results Overall, we included three cases in the study. Their onset age was 5 years and 2 months, 4 years and 3 months, and 4 years and 2 months, respectively. All patients presented drop attacks or jerks as the onset symptom, and one patient had concurrent gait disturbance. Atypical periodic complexes on electroencephalography (EEG) were recorded in all patients. The brain magnetic resonance imaging (MRI) findings of two cases showed demyelinating lesions predominantly on the white matter. The neurological conditions of all cases deteriorated rapidly. Two children died at 21 months and 6 months after onset, respectively. The other case progressively developed vegetative status and akinetic mutism within 4 months. Conclusions In younger children, the characteristic features of SSPE may be seizures and gait instability as onset manifestations, atypical periodic complexes on EEG, and rapid worsening of neurological conditions.

Modeling and understanding human grasp functionality are fundamental in prosthetics, robotics, medicine, and rehabilitation, since they contribute to exploring motor control mechanism, evaluating grasp function, and designing and controlling prosthetic hands or exoskeletons. However, there are still limitations in providing a comprehensive and quantitative understanding of hand grasp functionality. After simultaneously considering three significant and essential influence factors in daily grasping contained relative position, object shape, and size, this paper presents the tolerance grasping to provide a more comprehensive understanding of human grasp functionality. The results of joint angle distribution and variance explained by PCs supported that tolerance grasping can represent hand grasp functionality more comprehensively. Four synergies are found and account for 93%±1.5% of the overall variance. The ANOVA confirmed that there was no significant individual difference in the first four postural synergies. The common patterns of grasping behavior were found and characterized by the mean value of postural synergy across 10 subjects. The independence analysis demonstrates that the tolerance grasping results highly correlate with unstructured natural grasping and more accurately correspond to cortical representation size of finger movement. The potential for exploring the neuromuscular control mechanism of human grasping is discussed. The analysis of hand grasp characteristics that contained joint angle distribution, correlation, independence, and postural synergies, presented here, should be more representative to provide a more comprehensive understanding of hand grasp functionality.

Abstract Global food trade has become an increasingly crucial element for feeding the world's population. Enhancing bilateral or multilateral trust in food safety in international food trade is not only important for promoting the sustainable development of trade but is also beneficial for cooperation when facing a global food crisis. However, highly credible traceability systems (TSs) for the cross‐border movement of food are still absent in many countries and regions. Blockchain is regarded as a promising technology that can help build trust for transparency and security issues. In this paper, an interconnected conceptual traceability framework based on blockchain is proposed in order to increase trust in food safety during food trade. Taking the food trade between China and the European Union as an example, a conceptual framework is designed in order to take full advantage of existing TSs in these two locations, and the features of logistical flow, data flow, and blockchain flow are analyzed. Considering the data capacity and data privacy level, a hybrid data storage method combining on‐chain and off‐chain is adopted. Smart contracts according to the features of cross‐border food trade—including the recording of exportation data, exporter inspection data, shipment data, importer inspection data, importation data, and tracing queries—are packaged and deployed to a blockchain network. An effective operation mechanism involving the distribution of related rights for different roles is presented. The blockchain‐based TS framework has the advantages of enhancing bilateral trust in cross‐border food trade, providing a flexible and intelligent technical framework, and having effective operability. Future challenges, such as data security, special smart contracts, and consensus mechanisms, and interoperability with other systems, are discussed.

The nature of biosensing is a biochemical reaction. DNA‐based chemical reaction networks (DNA‐CRNs) as a powerful programming language for describing behaviors of chemical reactions have shown great potential in designs and applications of biosensors. Due to their programmability, modularity, and versatility of the DNA strand, the performance of different detection strategies can be improved mainly by the rational design of DNA‐CRNs. Herein, an overview of the fundamental theory and biosensing processes of DNA‐CRNs is provided. Various detection strategies of DNA‐CRNs are introduced, either in a simple low‐order reaction model or in a complicated high‐order reaction type, in combination with some typical cases for the different detection purposes. In addition, an overview of the recent development of DNA‐CRNs for monitoring the cell microenvironment is presented, which is of significance to uncover some specific cell behaviors and functions. Finally, the roles of DNA‐CRNs in the rational design of high‐performance biosensors are summarized by pointing out the remaining challenges that impede the precise biosensing using DNA‐CRNs in complicated biological environments.

A highly sensitive and selective sensor for isobutyraldehyde (IBD) is demonstrated based on intensive cataluminescence (CTL) emission from the surface of nanosized Sm2O3 particles. The characteristics and optimum conditions for the CTL sensor, including the working temperature, wavelength, and flow rate, were investigated in detail. Under the optimized experimental conditions, the CTL intensity varied linearly with the concentration of IBD, in the two-order-of-magnitude range of 0.015–3.9 μg/mL, with a correlation coefficient (r) of 0.99991 and a limit of detection (LOD), at a signal-to-noise ratio (S/N = 3) of 4.6 ng/mL. The sensor was quite specific: butyraldehyde, methanol, ethanol, acetone, formaldehyde, acetaldehyde, benzene, ethylbenzene, and cumene could not produce significant CTL intensities; specifically, butyraldehyde, ethanol, acetone, and acetaldehyde produced low CTL intensities, with values that were 3.8%, 2.8%, 0.60%, and 0.57% that of IBD. As a test of sensor stability, we found that the relative standard deviation (RSD) of 30 measurements of the CTL at an IBD concentration of 1.6 μg/mL within a period of 72 h was 2.2%, indicating good stability and long service life of the sensor. The sensor was tested against spiked samples containing IBD, and recoveries between 89.7% and 97.4% were obtained with an RSD of 6.1%–8.6%. The performance of the sensor indicated its utility for practical sample analysis.

Objective. To explore the clinical characteristics of patients with different severity in the early outbreak of COVID-19, hoping to provide reference for clinical diagnosis and treatment. Methods. We retrospectively analyzed the clinical data of 95 COVID-19 patients in Wuhan Red Cross Hospital of China from January 17 to February 13, 2020. All patients were investigated with epidemiological questionnaires. Outcomes were followed up until April 1, 2020. Results. There were 53 males and 42 females, aged 22–84 years (mean 57.3 years). Clinical classification included 54 cases of common type, 27 cases of severe type, and 14 cases of critical type. Six patients had been exposed to the local Huanan seafood market. There were 38 clusters of COVID-19, including 27 family clusters and 11 work unit clusters. Common symptoms included fever (86 (90.5%) of 95), cough (73 (76.8%)), and fatigue (50 (52.6%)). Laboratory findings showed that the most common abnormalities were lymphopenia (75 (78.9%)), elevated D-dimer (60 (63.2%)), and elevated C-reactive protein (56 (58.9%)) on admission. All patients had abnormal chest computed tomography, showing patchy shadows or ground-glass opacities. Severe and critical cases were older, more likely to have shortness of breath, more likely to have underlying comorbidities, and more likely to have abnormal laboratory findings than common cases. The prognosis of patients with different degrees of severity was significantly different. All common and severe patients (100%) were cured and discharged from the hospital, while 10 (71.4%) of 14 critical patients died. Conclusions. COVID-19 has fast transmission speed and high pathogenicity. We must assess the severity of the disease and take corresponding treatment measures as early as possible.

Abstract Introduction Fine particulate matter (PM2.5) is closely associated with many neurological disorders including neurodegenerative disease, stroke, and brain tumors. However, the toxic effects of PM2.5 on neurodevelopment remain unclear. In this study, we aimed to determine the neurotoxic effects of early postnatal exposure to PM2.5 in immature and mature rats. Methods We exposed neonatal rats to PM2.5 (2 or 10 mg/kg body weight) through intranasal instillation from postnatal day (PND) 3–15, once a day. Emotional and cognitive development were evaluated using the elevated plus maze, forced swimming, and Morris water maze tests. Hippocampal tissue was collected and subjected to transmission electron microscopy observation and western blot analysis. Results Rats had lower body weight after exposure to high dose of PM2.5. The behavioral test results indicated that high‐dose PM2.5 exposure led to increased anxiety‐like symptoms in immature and mature rats, apparent depressive‐like behaviors in mature rats, and impaired spatial learning and memory abilities in immature rats, and low‐dose PM2.5 exposure increased anxiety‐like behaviors in immature rats. Further, high‐dose PM2.5 exposure contributed to fewer synapses, thinner postsynaptic density, and shorter active zone in immature and mature rats, and also decreased expressions of synaptophysin (SYP), growth associated protein‐43 (GAP43), and postsynaptic density‐95 (PSD95) in immature rats, SYP and PSD95 in mature rats. Moreover, low‐dose PM2.5 exposure diminished the expression of PSD95 in immature rats. In addition, high‐dose PM2.5 exposure reduced brain‐derived neurotrophic factor (BDNF) expression and cAMP response element binding protein (CREB) phosphorylation in both immature and mature rats, and low‐dose PM2.5 exposure lessened BDNF expression and CREB phosphorylation in immature rats. Conclusions Our findings indicate that PM2.5 impairs emotional and cognitive development by disrupting structural synaptic plasticity, possibly via the CREB/BDNF signaling pathway.

Abstract Background and purpose A higher Totaled Health Risks in Vascular Events (THRIVE) score has been shown to predict poor functional outcome in patients with acute ischemic stroke (AIS) and anterior circulation large vessel occlusions undergoing thrombectomy treatment. We attempted to evaluate the value of the THRIVE score in predicting the outcome of thrombectomy treatment in AIS patients with basilar artery occlusion (BAO). Methods A total of 68 AIS patients with BAO who underwent thrombectomy treatment from May 2014 to August 2018 were included in the present study. Multivariable logistic regression was performed to determine the predictive value of the THRIVE score for poor functional outcome (defined as modified Rankin Scale score ≥ 3), all‐cause mortality, and hemorrhage transformation (HT) at 3 months. Results A total of 42 (61.8%) participants experienced poor functional outcomes, 25 (36.8%) patients died from all causes, and 21 (30.9%) patients had HT during the 3‐month follow‐up. Multivariable logistic regression showed that a higher THRIVE score was significantly associated with poor functional outcome (odds ratio [OR] 5.86, 95% confidence interval [CI], 2.28–14.91, p 5; sensitivity, 88.5%; specificity, 83.3%, p = .007) and all‐cause mortality (AUC = 0.768; cutoff > 5; sensitivity, 92.0%; specificity, 65.1%, p = .018). Conclusions A high THRIVE score was independently associated with an increased risk of poor functional outcome and all‐cause mortality in AIS patients with BAO who underwent thrombectomy treatment. Moreover, the THRIVE score appeared to be a better predictor of clinical outcome than the NIHSS score.

Huang-Lian Jie-Du decoction (HLJDD) has been used to treat cardiovascular and cerebrovascular disease for many years in China. Currently, the determination of effect components in HLJDD is focusing either on the formula or on the extract, while quantification of that in biological samples is scarce, especially simultaneous determination of multicomponent. In this paper, a rapid, specific, and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous determination of seven main active constituents, i.e., baicalin, baicalein, wogonoside, wogonin, berberine, palmatine, jatrorrhizine in rat plasma. The method was also successfully applied to a quantitative study after oral administration of HLJDD at different doses of 1.5, 3, and 6 g/kg body weight to high fat-induced atherosclerosis rats. The analytes were detected by ESI source and multiple reactions monitoring (MRM) using positive scanning mode. The blood was collected from the abdominal aorta of rats at predetermined time and preprepared with icariin and tetrahydropalmatine as internal standards (IS). Sample preparation was achieved by protein precipitation (PPT). The validation parameters (linearity, sensitivity, intra-/interday precision and accuracy, extraction recovery, and matrix effect) were within acceptable ranges, and biological extracts were stable during the entire storing and preparing process. And the result of determination of HLJDD-containing plasma, baicalin, baicalein, wogonoside, and wogonin could be highly detected in a dose-dependent manner while berberine, jatrorrhizine, and palmatine were determined in a very low level and in a dose-independent mode. Thus, the established method was sensitive enough and successfully applied to the determination of seven effective components in plasma taken from 24 high fat-induced atherosclerosis rats after oral administration of three dosages of HLJDD.

The characteristics of porosity and permeability in tight clastic rock reservoir have significant difference from those in conventional reservoir. The increased exploitation of tight gas and oil requests further understanding of fluid performance in the nanoscale pore-throat network of the tight reservoir. Typical tight sandstone and siltstone samples from Ordos Basin were investigated, and rate-controlled mercury injection capillary pressure (RMICP) and nuclear magnetic resonance (NMR) were employed in this paper, combined with helium porosity and air permeability data, to analyze the impact of pore-throat structure on the storage and seepage capacity of these tight oil reservoirs, revealing the control factors of economic petroleum production. The researches indicate that, in the tight clastic rock reservoir, largest throat is the key control on the permeability and potentially dominates the movable water saturation in the reservoir. The storage capacity of the reservoir consists of effective throat and pore space. Although it has a relatively steady and significant proportion that resulted from the throats, its variation is still dominated by the effective pores. A combination parameter (ε) that was established to be as an integrated characteristic of pore-throat structure shows effectively prediction of physical capability for hydrocarbon resource of the tight clastic rock reservoir.

BackgroundBreastfeeding confers substantial benefits to child health and has also been associated with lower risk of maternal cardiovascular diseases (CVDs) in later life. However, the evidence on the effects of CVD is still inconsistent, especially in East Asians, in whom the frequency and duration of breastfeeding significantly differ from those in the West. Methods and ResultsIn 2004–2008, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30 to 79 years from 10 diverse regions across China. During 8 years of follow‐up, 16 671 incident cases of coronary heart disease and 23 983 cases of stroke were recorded among 289 573 women without prior CVD at baseline. Cox regression yielded adjusted hazard ratios (HRs) and 95% CIs for incident CVD by breastfeeding. Overall, ≈99% of women had given birth, among whom 97% reported a history of breastfeeding, with a median duration of 12 months per child. Compared with parous women who had never breastfed, ever breastfeeding was associated with a significantly lower risk of CVD, with adjusted HRs of 0.91 (95% CI, 0.84–0.99) for coronary heart disease and 0.92 (95% CI, 0.85–0.99) for stroke. Women who had breastfed for ≥24 months had an 18% (HR, 0.82; 0.77–0.87) lower risk of coronary heart disease and a 17% (HR, 0.83; 0.79–0.87) lower risk of stroke compared with women who had never breastfed. Among women who ever breastfed, each additional 6 months of breastfeeding per child was associated with an adjusted HR of 0.96 (95% CI, 0.94–0.98) for coronary heart disease and 0.97 (95% CI, 0.96–0.98) for stroke. ConclusionsAmong Chinese women, a history of breastfeeding was associated with an ≈10% lower risk of CVD in later life and the magnitude of the inverse association was stronger among those with a longer duration of breastfeeding.

Superoxide dismutase is an important antioxidant enzyme extensively existing in eukaryote, which scavenges reactive oxygen species (ROS) and plays an essential role in stress tolerance of higher plants. A full-length cDNA encoding Cu/Zn SOD was cloned from leaves of Gynura bicolor DC. by rapid amplification of cDNA ends (RACE). The full-length cDNA of Cu/Zn SOD is 924 bp and has a 681 bp open reading frame encoding 227 amino acids. Bioinformatics analysis revealed that belonged to the plant SOD super family. Cu/Zn SODs of the Helianthus annuus, Mikania micrantha, and Solidago canadensis var. scabra all have 86% similarity to the G. bicolor Cu/Zn SOD. Analysis of the expression of Cu/Zn SOD under different treatments revealed that Cu/Zn SOD was a stress-responsive gene, especially to 1-MCP. It indicates that the Cu/Zn SOD gene would be an important gene in the resistance to stresses and will be helpful in providing evidence for future research on underlying molecular mechanism and choosing proper postharvest treatments for G. bicolor.

The high-dimensional features of defective bearings usually include redundant and irrelevant information, which will degrade the diagnosis performance. Thus, it is critical to extract the sensitive low-dimensional characteristics for improving diagnosis performance. This paper proposes modified kernel marginal Fisher analysis (MKMFA) for feature extraction with dimensionality reduction. Due to its outstanding performance in enhancing the intraclass compactness and interclass dispersibility, MKMFA is capable of effectively extracting the sensitive low-dimensional manifold characteristics beneficial to subsequent pattern classification even for few training samples. A MKMFA- based fault diagnosis model is presented and applied to identify different bearing faults. It firstly utilizes MKMFA to directly extract the low-dimensional manifold characteristics from the raw time-series signal samples in high-dimensional ambient space. Subsequently, the sensitive low-dimensional characteristics in feature space are inputted into K-nearest neighbor classifier so as to distinguish various fault patterns. The four-fault-type and ten-fault-severity bearing fault diagnosis experiment results show the feasibility and superiority of the proposed scheme in comparison with the other five methods.

Energy shortfalls are becoming more and more serious all over the world, and worldwide governments have tried to promote the development of biofuels in order to mitigate the climatic impacts of massive fossil fuel consumption. Since the land is the main input factor of the bioenergy production, the development of biofuels will inevitably lead to change of the land use structure and allocation and thereby affect the climate system. With Central Europe as the study area, this study explored the impacts of land use/land cover change (LUCC) on climate under the influence of demand of bioenergy production for land resources. First, the land use structure from 2010 to 2050 is simulated with the Agriculture and Land Use model in MiniCam. The result indicates that the main conversion will be mainly from grassland and forest to cropland and from cropland to grassland. Then the Dynamics of Land System model was used to spatially simulate the LUCC in the future. The impacts of LUCC on the climate were analyzed on the basis of simulation with the Weather Research and Forecasting (WRF) model. The climate change will be characterized by the increase of latent heat flux and temperature and the decrease of precipitation.

One of the key factors responsible for the development of type 2 diabetes is the loss of functional pancreatic β cells. This occurs due to a chronic exposure to a high fatty acid environment. ER stress is caused by an accumulation of irreversible misfold or unfold protein: these trigger the death of functional pancreatic β cells. PPARδ is an orphan nuclear receptor. It plays a pivotal role in regulating the metabolism of dietary lipids and fats. However, the correlation between PPARδ of fatty acids and ER stress of pancreatic β cells is not quite clear till date. Here, we show that PPARδ attenuates palmitate-induced ER stress of pancreatic β cells. On the other hand, PPARδ agonist inhibits both abnormal changes in ER structure and activation of signaling cascade, which is downstream ER stress. Further, we illustrate that PPARδ attenuates palmitate-induced ER stress by promoting fatty acid oxidation through treatment with etomoxir, an inhibitor of fatty acid oxidation. It dramatically abolishes PPARδ-mediated inhibition of ER stress. Finally, we show that PPARδ could protect pancreatic β cells from palmitate-induced cell death and dysfunction of insulin secretion. Our work elucidates the protective effect of PPARδ on the fatty-acid-induced toxicity of pancreatic β cells.

This paper presents a novel mathematical model with multidrug-resistant (MDR) and undetected TB cases. The theoretical analysis indicates that the disease-free equilibrium is globally asymptotically stable if R0