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Events including antibody‒antigen affinity, internalization, trafficking and lysosomal proteolysis combinatorially determine the efficiency of antibody–drug conjugate (ADC) catabolism and hence the toxicity. Nevertheless, an approach that conveniently identifies proteins requisite for payload release and the ensuing toxicity for mechanistic studies and quality assessment is lacking. Considering the plethora of ADC candidates under development, we developed a target-responsive subcellular catabolism (TARSC) approach that examines ADC catabolism and probes changes in response to targeted interferences of proteins of interest. We firstly applied TARSC to study the commercial T-DM1 and the biosimilar. We recorded unequivocal catabolic behaviors regardless of the absence and presence of the targeted interferences. Their negligible differences in TARSC profiles agreed with their undifferentiated anti-tumoral efficacy according to further in vitro viability and in vivo tumor growth assays, highlighting TARSC analysis as a useful tool for biosimilarity assessment and functional dissection of proteins requisite for ADC catabolism. Additionally, we employed TARSC to investigate the catabolic behavior of a new trastuzumab–toxin conjugate. Collectively, TARSC can not only characterize ADC catabolism at (sub)cellular level but also comprehensively determine which protein targets affect payload release and therapeutic outcomes. Future use of TARSC is thus anticipated in early-stage screening, quality assessment and mechanistic investigations of ADCs., Graphical abstract The TARSC approach, characterizing ADC catabolism at (sub)cellular level and comprehensively determining which protein targets affect payload release and hence the therapeutic outcomes, is anticipated to support ADC development.Image 1

Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction. Protocatechuic aldehyde (PCA) is a major phenolic acid in Chinese herb Danshen (Salvia miltiorrhiza root). This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2 (PKM2) function to protect cardiomyocytes. In rats subjected to isoprenaline, PCA attenuated heart injury and protected cardiomyocytes from apoptosis. Through DARTS and CETSA assays, we identified that PCA bound and promoted PKM2 nuclear translocation in cardiomyocytes exposed to oxygen/glucose deprivation (OGD). In the nucleus, PCA increased the binding of PKM2 to β-catenin via preserving PKM2 acetylation, and the complex, in cooperation with T-cell factor 4 (TCF4), was required for transcriptional induction of genes encoding anti-apoptotic proteins, contributing to rescuing cardiomyocyte survival. In addition, PCA ameliorated mitochondrial dysfunction and prevented mitochondrial apoptosis dependent on PKM2. Consistently, PCA increased the binding of PKM2 to β-catenin, improved heart contractive function, normalized heart structure and attenuated oxidative damage in mice subjected to artery ligation, but the protective effects were lost in Pkm 2-deficient heart. Together, we showed that PCA regulated nuclear PKM2 function to rescue cardiomyocyte survival via β-catenin/TCF4 signaling cascade, suggesting the potential of pharmacological intervention of PKM2 shuttle to protect the heart.

This study investigated neurologic changes in patients with dry eye (DE) by functional magnetic resonance imaging (fMRI) and to used regional homogeneity (ReHo) analysis to clarify the relationship between these changes and clinical features of DE. A total of 28 patients with DE and 28 matched healthy control (HC) subjects (10 males and 18 females in each group) were enrolled. fMRI scans were performed in both groups. We carried out ReHo analysis to assess differences in neural activity between the 2 groups, and receiver operating characteristic curve (ROC) analysis was performed to evaluate the performance of ReHo values of specific brain areas in distinguishing DE patients from HCs. The relationship between average ReHo values and clinical characteristics was assessed by correlation analysis. ReHo values of the middle frontal gyrus, inferior frontal gyrus, and superior frontal gyrus were significantly lower in DE patients compared to HCs. The ROC analysis showed that ReHo value had high accuracy in distinguishing between DE patients and HCs (P

The new heterocyclic compound 2-((6-chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl) thiazole-5-carboxamide (1), designed using 2-chloro-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (2) as start material, was successfully obtained via multistep synthesis route and finally characterized by IR (infrared radiation), 1H NMR (nuclear magnetic resonance), and single crystal X-ray crystallography. The inhibitory effect of compound 1 on human breast tumor cell line BS524 was further explored. The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and IC50 (half maximal inhibitory concentration) values suggested that compound 1 has significant anti-proliferation activity on BS524 cells and with low side effect. Then, serial experiments, such as the Annexin V-FITC/PI assay, TUNEL staining and autophagy detection revealed that compound 1 could inhibit cell proliferation via induce cells apoptosis, and the apoptosis is induced by (reactive oxygen species) ROS generation in BS524 cells.

The switch from using only trivalent oral polio vaccine (tOPV) to sequential schedules combining inactivated poliovirus vaccine (IPV) and bivalent oral polio vaccine (bOPV) for polio vaccination will cause changes to mucosal immunity against polio in infants, which plays an important role in preventing the poliovirus spread. Here, we analyzed mucosal immunity against poliovirus in the intestine during different sequential vaccination schedules. We conducted clinical trials in Guangxi Province, China on 1,200 2-month-old infants who were randomly assigned to one of three vaccination schedule groups: IPV-bOPV-bOPV, IPV-IPV-tOPV, and IPV-IPV-bOPV, with vaccine doses administered at 8, 12, and 16 weeks of age. Stool samples were collected from 10% of participants in each group before administration of the second vaccine doses and at 1, 2, and 4 weeks after the administrations of the second and third vaccine doses. Immunoglobulin A (IgA) in the stool samples was measured to analyze the mucosal immune response in the intestine. Because of the absence of poliovirus type 2 in bOPV, the vaccination schedule of IPV-IPV-bOPV did not sufficiently raise intestinal mucosal immunity against poliovirus type 2, although some cross-immunity was seen. The level of intestinal mucosal immunity was related to shedding status; shedders could produce intestinal mucosa IgA more quickly. The intestinal mucosal immunity level was not related to serum neutralizing antibody level. In the combined sequential vaccination schedule of IPV and bOPV, the risk of circulating vaccine-derived poliovirus type 2 (cVDPV2) may be increased owing to insufficient intestinal mucosal immunity against poliovirus type 2.

To compare the clinical results of patients with low rectal cancer who underwent skin bridge loop ileostomy and traditional loop ileostomy, and provide clinical evidence for choosing a better ostomy method. We retrospectively collected data of 118 patients with rectal cancer who underwent low anterior resection and loop ileostomy. To investigate the patients characteristics, postoperative stoma-related complications and the frequency of exchanged ostomy bags. The differences of these indicators between the two groups of patients who underwent skin bridge loop ileostomy and traditional loop ileostomy were compared. The Visual Analog Scale (VAS) score of the skin bridge loop ileostomy group was lower than that of the traditional ileostomy loop group (P P P

Background The effect of postsurgical radiotherapy (PSRT) among T1-3 gallbladder cancer (GBC) patients with one to three lymph node metastases remains controversial. The aim of this study was to assess the impact of PSRT on gallbladder cancer-specific survival (GBCSS) in patients with stage IIIB. Methods The data of GBC patients were obtained from the American Surveillance, Epidemiology, and End Results (SEER) Data resources between 2004 and 2015. Then, a 1:1 propensity score matching (PSM) method was performed. GBCSS was compared among all patients. Subgroup analysis was conducted to identify patients who would benefit from PSRT. Results 726 AJCC (8th edition) stage IIIB GBC patients were included. PSRT failed to improve GBCSS (p = 0.168). Male sex, tumor size ≥ 4 cm and absence of chemotherapy were independent negative prognostic factors. No significant survival benefit from PSRT was found in any subgroup. Conclusions PSRT provides no survival benefit for IIIB GBC.

Objective The present study aimed to determine the diagnostic value of prenatal chromosomal microarray analysis (CMA) for fetuses with several indications of being at high risk for various conditions. Materials and methods This retrospective analysis included 1256 pregnancies that were prenatally evaluated due to high-risk indications using invasive CMA. The indications for invasive prenatal diagnosis mainly included ultrasound anomalies, high-risk for maternal serum screening (MSS), high-risk for non-invasive prenatal tests (NIPT), family history of genetic disorders or birth defects, and advanced maternal age (AMA). The rate of clinically significant genomic imbalances between the different groups was compared. Results The overall prenatal diagnostic yield was 98 (7.8%) of 1256 pregnancies. Clinically significant genomic aberrations were identified in 2 (1.5%) of 132 patients with non-structural ultrasound anomalies, 36 (12.7%) of 283 with structural ultrasound anomalies, 2 (4.5%) of 44 at high-risk for MSS, 38 (26.6%) of 143 at high-risk for NIPT, 11 (3.8%) of 288 with a family history, and 7 (2.1%) of 328 with AMA. Submicroscopic findings were identified in 29 fetuses, 19 of whom showed structural ultrasound anomalies. Conclusion The diagnostic yields of CMA for pregnancies with different indications greatly varied. CMA could serve as a first-tier test for structural anomalies, especially multiple anomalies, craniofacial dysplasia, urinary defects, and cardiac dysplasia. Our results have important implications for genetic counseling.

BACKGROUND Diabetes is a common chronic disease. Given the increasing incidence of diabetes, more individuals are affected by diabetic optic neuropathy (DON), which results in decreased vision. Whether DON leads to abnormalities of other visual systems, including the eye, the visual cortex, and other brain regions, remains unknown. AIM To investigate the local characteristics of spontaneous brain activity using regional homogeneity (ReHo) in patients with DON. METHODS We matched 22 patients with DON with 22 healthy controls (HCs). All subjects underwent resting-state functional magnetic resonance imaging. The ReHo technique was used to record spontaneous changes in brain activity. Receiver operating characteristic (ROC) curves were applied to differentiate between ReHo values for patients with DON and HCs. We also assessed the correlation between Hospital Anxiety and Depression Scale scores and ReHo values in DON patients using Pearson correlation analysis. RESULTS ReHo values of the right middle frontal gyrus (RMFG), left anterior cingulate (LAC), and superior frontal gyrus (SFG)/left frontal superior orbital gyrus (LFSO) were significantly lower in DON patients compared to HCs. Among these, the greatest difference was observed in the RMFG. The result of the ROC curves suggest that ReHo values in altered brain regions may help diagnose DON, and the RMFG and LAC ReHo values are more clinically relevant than SFG/LFSO. We also found that anxiety and depression scores of the DON group were extremely negatively correlated with the LAC ReHo values (r = -0.9336, P < 0.0001 and r = -0.8453, P < 0.0001, respectively). CONCLUSION Three different brain regions show ReHo changes in DON patients, and these changes could serve as diagnostic and/or prognostic biomarkers to further guide the prevention and treatment of DON patients.

Background In rare instances, primary liver cancer can be associated with intraocular metastasis (IOM). Aim To investigate the correlation between a diverse range of clinical characteristics and IOM in diabetic patients with primary liver cancer, and to determine potential risk factors in predicting IOM. Methods We recruited a total of 722 diabetic patients with primary liver cancer. The differences between the IOM and non-intraocular metastasis (NIOM) groups in these patients were assessed using the chi-squared test and Student's t-test. Binary logistic regression analysis was subsequently used to determine risk factors. Finally, the diagnostic value of IOM in this cohort with primary liver cancer was analyzed by receiver operating characteristic (ROC) curve analysis. Results In all, 13 patients had IOM. There were no remarkable intergroup differences with respect to age, sex, histopathological sub-types, or blood biochemical parameters. However, the IOM group had significantly higher alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) values than the NIOM group. Binary logistic regression identified AFP and CA125 to be significant risk factors for IOM in diabetic patients with primary liver cancer. ROC curve analysis showed that the area under the curve values for AFP and CA125 were 0.727 and 0.796, with the cut-off values of 994.20 ng/mL and 120.23 U/mL, respectively. The sensitivity and specificity for AFP were 92.3% and 59.9%, while those for CA125 were 84.6% and 70.1%, respectively. Conclusion Elevated AFP and CA125 represent significant risk factors for IOM in diabetic patients with primary liver cancer.

Invasive ductal carcinoma (IDC) is a major type of breast cancer. Ocular metastasis (OM) in IDC is rarely seen, but patients with OM often have a poor prognosis. Furthermore, OM is difficult to detect in the early stages by common imaging examinations. In the present study, we tried to figure out the risk factors of OM in IDC and evaluate their diagnostic values for early detection. There were 1192 IDC patients who were divided into two groups according to ocular metastasis involved in this study. Clinical parameters of those patients were used to detect differences. The binary logistic regression test was then used to determine the risk factors of OM in IDC. Furthermore, ROC curves of both single and combined risk factors were established to examine their diagnostic values. The incidence of axillary lymph node metastases was significantly higher in the OM group (p = 0.002). Higher carbohydrate antigen 153 (CA153), lower apolipoprotein A1 (ApoA1), and hemoglobin (Hb) were risk factors for OM in IDC (p, The study provided a new method in the preventive diagnosis of distant metastasis in breast cancer. Risk factors CA153, ApoA1, and Hb could be used in clinical practice to predict OM in patients with IDC.

Aim Despite initiatives to increase elderly patients' access to surgical treatments, the prevalence and impact of postoperative infectious complications (PICs) in elderly patients in China are poorly described. The aim of our study was to describe PICs and associated mortality in elderly patients undertaking elective surgery in China. Methods We analyzed data about elderly patients from China during the International Surgical Outcomes Study (ISOS), a 7-day prospective cohort study of outcomes after elective surgery in in-patient adults. All elderly patients (age ≥60 years) from 28 hospitals in China included in the ISOS study were included in this study as well. A review of 2014 elderly patients who underwent elective surgery in April 2014 was conducted. Results Of 2014 elderly patients, 209 (10.4%) developed at least one postoperative complication. Infectious complications were most frequent, affecting 154 patients (7.6%); there was one death, or 0.6% 30-day mortality, which was a significantly higher rate than among patients without PICs (0%). The most frequent infectious complication was superficial surgical-site infection (3.3%). The length of hospital stay was longer in elderly patients with PICs than in those without PICs. Moreover, a total of 142 elderly patients (7.1%) were routinely sent to critical care after surgery, of whom 97 (68.3%) developed PICs. Compared to elderly patients admitted to a standard ward, those admitted to critical care immediately after surgery had a higher postoperative complication rate and critical care admission rate to treat complications. Conclusions The present prospective, multicentre study found that 7.6% of elderly patients in China had PICs after elective surgery that could prolong hospital stay and increase 30-day mortality. The clinical effectiveness of admission to critical care after surgery on elderly patients is not identified. Initiatives to increase elderly patients' access to surgical interventions should also enhance safe perioperative care to reduce PICs in China.

Guar gum-derived galactomannan (GGGM) has been widely used in the food industry for a long time and its adverse impacts have been scarcely reported. Galactomannan is considered to have a structure similar to the surface components of certain pathogens, and the present study was thus conducted to investigate if oral administration of GGGM could cause physiological effects that were hypothesized to be related to intestinal inflammatory responses. The results showed that oral administration of GGGM resulted in compromises on growth performance, an increase of the relative weight of spleen and epididymal fat, and an elevation of the α1-acid glycoprotein content in both serum and livers of mice. With regard to energy metabolism-related indices, the activities of intestinal lactic dehydrogenase and succinic dehydrogenase were all increased by the GGGM treatment in both in vivo and in vitro experiments, the latter of which also showed an elevation in the consumption of reducing sugar by intestinal epithelial cells along with a reduced viability of these cells in response to the GGGM treatment. Notably, the GGGM treatment triggered intestinal inflammatory responses that were evidenced by the increased expression of intestinal inflammatory cytokines such as TNF-α and IL-6 both in vivo and in vitro, which were at least partially responsible for the increased energy expenditure in the intestine and the retardation of growth. The results of this study could expand our knowledge of GGGM administration and provide integrated insights into the consumption of GGGM-containing foods.

Objective. In order to further study the changes of cerebral functional connectivity in patients with toothache (TA), this study used the resting-state functional magnetic resonance imaging (rs-fMRI) technique and degree centrality (DC) analysis method. Methods. Eighteen TA patients (8 males, 10 females) and 18 healthy individuals of similar age, sex, and educational levels were recruited as healthy controls (HCs) to take part in the study, and all underwent rs-fMRI examination. And DC technology was used to compare the state of their cerebral spontaneous functional activity. In order to compare the average DC values of the TA group and HC group, we used independent two-sample t -test and receiver operating characteristic (ROC) curve to compare the difference of DC values between the two groups, so as to distinguish the accuracy of TA diagnosis. Finally, we also carry out Pearson’s linear regression analysis. Results. The TA group showed higher DC values in the right lingual gyrus (RLG), right precentral gyrus, and left middle temporal gyrus (LMTG) than HCs. Moreover, ROC curve analysis indicated that the area under the curve (AUC) of each cerebral region studied had high accuracy. In addition, linear analysis indicated that the DC values of the RLG were positively correlated with the Hospital Anxiety and Depression Scale (HADS) ( r = 0.844 , p < 0.001 ), and the DC values of the LMTG were positively correlated with the visual analogue scale (VAS) ( r = 0.723 , p < 0.001 ). Conclusion. TA generates abnormal changes in the intrinsic activity patterns of pain-related and vision-related areas of the cerebral cortex, which will be beneficial to reveal the underlying neuropathic mechanisms.

To investigate the effects of microwave ablation (MWA) on visible benign thyroid nodules (BTN) with different internal characteristics.A total of 51 cases with 53 visible BTN were treated by ultrasound-guided percutaneous MWA. The 53 nodules were classified into three categories according to the internal characteristics, which were simple solid, mainly solid and mainly cystic nodules. Ultrasound examinations were performed to evaluate the volume shrinkage rations during follow-up. The thyroid functions and the cervical cosmetic scores were evaluated. The complications were observed during and after ablation.A total of 53 symptomatic BTN were treated by MWA completely. The average volume of the nodules was 11.68 ± 10.16 ml, the volume reduction rates (VRR) at 1st, 3rd, 6th, 12th, and 18th months after ablation were 0.29 ± 0.27, 0.46 ± 0.25, 0.67 ± 0.19, 0.83 ± 0.10, and 0.92 ± 0.10, respectively. The VRR was significantly different among the three categories of lesions (MWA of visible BTN is safe and effective, and the short-time ablation effect is significantly different due to the internal characteristics of the nodule.

Metabolic syndrome is a clustering of metabolic disorder with unclear molecular mechanism. Increasing studies have found that the pathogenesis and progression of metabolic syndrome are closely related to inflammation. Here, we report celastrol, a traditional Chinese medicine, can improve high fat diet-induced metabolic syndrome through suppressing resistin-induced inflammation. Mechanistically, celastrol binds to adenylyl cyclase associated protein 1 (CAP1) and inhibits the interaction between CAP1 and resistin, which restrains the cyclic adenylate monophosphate (cAMP)–protein kinase A (PKA)–nuclear factor kappa-B (NF-κB) signaling pathway and ameliorates high fat diet-induced murine metabolic syndrome. Knockdown of CAP1 in macrophages abrogated the resistin-mediated inflammatory activity. In contrast, overexpression of CAP1 in macrophages aggravated inflammation. Taken together, our study identifies celastrol, which directly targets CAP1 in macrophages, might be a promising drug candidate for the treatment of inflammatory metabolic diseases, such as metabolic syndrome., Graphical abstract In obesity, adipose tissue generates resistin, which binds to CAP1 on macrophages and activates the cAMP–PKA–NF-κB signaling pathway and promotes proinflammatory cytokines expression. These factors further aggravate inflammation, insulin resistance, and hepatic steatosis. Celastrol ameliorates metabolic syndrome via binding to CAP1 and inhibiting its interaction with resistin.Image 1

Supplemental Digital Content is available in the text., Background: In an era of antibiotic resistance, modified dual therapy has been paid much attention because of simple drug composition and low resistance of amoxicillin. However, its eradication rate as a first-line regimen remains controversial. This study is to evaluate the efficacy and safety of modified dual therapy for the initial treatment of Helicobacter pylori (H. pylori) infection compared with mainstream first-line therapies. Methods: PubMed, the Cochrane Library, and Embase were searched for randomized clinical trials evaluating the efficacy and safety of modified dual therapy as the initial treatment for H. pylori eradication compared with guideline-recommended first-line therapies. A meta-analysis was conducted using Review Manager 5.3 and dichotomous data were estimated by the risk ratio (RR) with the 95% confidence interval (CI). We also performed subgroup analysis according to control groups and studies with antibiotic susceptibility tests. Results: Eight studies including 1672 patients with H. pylori infection met the selection criteria and were assessed. The meta-analysis demonstrated that modified dual therapy achieved similar efficacy [85.83% vs. 86.77%, RR 0.99 (95% CI, 0.95-1.03), intention-to-treat analysis; 89.53% vs. 90.45%, RR 0.99 (95% CI, 0.96-1.02), per-protocol analysis] and compliance [95.77% vs. 95.56%, RR 1.00 (95% CI, 0.98-1.02)] compared with recommended first-line regimens. In addition, there were no significant differences in comparing the eradication rate of modified dual therapy with clarithromycin triple therapy, bismuth quadruple therapy, and concomitant therapy, respectively. Subgroup analysis based on the studies with antibiotic susceptibility tests also confirmed a similar efficacy. However, modified dual therapy showed fewer adverse effects [8.70% vs. 22.38%, RR 0.39 (95% CI, 0.28-0.54)], with a significant difference (P

Leptographium panxianense and L. puerense are proposed as new taxa based on sequence data and morphological characters. The phylogenetic analyses based on ITS2-partial LSU rDNA region, β-tubulin and elongation factor 1-α genes showed that L. panxianense and L. puerense formed well-supported clades and were closely related to L. yunnanense, L. wushanense and L. conjunctum, and then nested within the L. lundbergii complex. The two species differ in their conidial size and shape. The conidia of L. panxianense are larger than those of L. puerense while the conidial shape of L. puerense is more ovovoid. The optimal growth temperature of both L. panxianense and L. puerense is at 20 °C, which is different from those of L. yunnanense, L. wushanense and L. conjunctum. Comparison of sequence data and morphological characters confirmed the placement of the two undescribed taxa in the genus of Leptographium.

The migration sources and pathways of Sogatella furcifera (Horváth) in topologically complex regions like Yunnan, China, and adjacent montane areas have long been a challenging task and a bottleneck in effective pest forecast and control. The present research reinvestigated this issue using a combination of mtDNA and long‐term historical wind field data in an attempt to provide new insights. Genetic analyses showed that the 60 populations of S. furcufera collected across Myanmar, Thailand, Laos, Vietnam, Yunnan, Guizhou, and Sichuan lack genetic structure and geographic isolation, while spatial analysis of haplotype and diversity indices discovered geographic relevance between populations. Migration rate analysis combined with high‐resolution 10‐year wind field analysis detected the following migration sources, pathways, and impacted areas which could explain the outbreak pattern in Yunnan. (a) Dominating stepwise northward migrations originated from northern Indochina, southern Yunnan, and central‐eastern Yunnan, impacting their northern areas. (b) Concurring summer–autumn southward (return) migration originated from nearly all latitude belts of Sichuan and Yunnan mainly impacting central and southern Yunnan. (c) Regular eastward and summer–autumn westward migrations across Yunnan. The northward migration reflects the temporal rhythm of gradual outbreaks from the south to the north in a year, while the return migration may explain the repeated or very severe outbreaks in the impacted areas. To form a better pest forecast and control network, attention must also be paid to the northern part of Yunnan to suppress the impact of return migration in summers and autumns.

Background Glioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms. Methods Microarray analyses were performed to explore the lncRNAs/miRNAs/genes with differential expression in glioma. NCK1-AS1 levels in glioma tissues and normal brain tissues, and in glioma cell lines and normal human glial cells were identified. The interactions among NCK1-AS1, miR-138-2-3p and TRIM24 were validated through luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Gain- and loss-of functions of NCK1-AS1, miR-138-2-3p and TRIM24 were performed to identify their roles in the behaviors of glioma cells. The activity of the Wnt/β-catenin pathway was measured. In vivo experiments were performed as well. Results High expression of NCK1-AS1 was found in glioma tissues and cells, especially in U251 cells. Online predictions and the integrated experiments identified that NCK1-AS1 elevated the TRIM24 expression through sponging miR-138-2-3p, and further activated the Wnt/β-catenin pathway. Artificial silencing of NCK1-AS1 or up-regulation of miR-138-2-3p led to inhibited proliferation, invasion and migration but promoted cell apoptosis of U251 cells, while up-regulation of TRIM24 reversed these changes, and it activated the Wnt/β-catenin pathway. The in vitro results were reproduced in in vivo experiments. Conclusions Our study suggested that NCK1-AS1 might elevate TRIM24 expression and further activate the Wnt/β-catenin pathway via acting as a ceRNA for miR-138-2-3p. Silencing of NCK1-AS1 might inhibit the progression of glioma.

An outbreak of a novel coronavirus disease (i.e., COVID-19) has been recorded in Wuhan, China since late December 2019, which subsequently became pandemic around the world. Although COVID-19 is an acutely treated disease, it can also be fatal with a risk of fatality of 4.03% in China and the highest of 13.04% in Algeria and 12.67% Italy (as of 8th April 2020). The onset of serious illness may result in death as a consequence of substantial alveolar damage and progressive respiratory failure. Although laboratory testing, e.g., using reverse transcription polymerase chain reaction (RT-PCR), is the golden standard for clinical diagnosis, the tests may produce false negatives. Moreover, under the pandemic situation, shortage of RT-PCR testing resources may also delay the following clinical decision and treatment. Under such circumstances, chest CT imaging has become a valuable tool for both diagnosis and prognosis of COVID-19 patients. In this study, we propose a weakly supervised deep learning strategy for detecting and classifying COVID-19 infection from CT images. The proposed method can minimise the requirements of manual labelling of CT images but still be able to obtain accurate infection detection and distinguish COVID-19 from non-COVID-19 cases. Based on the promising results obtained qualitatively and quantitatively, we can envisage a wide deployment of our developed technique in large-scale clinical studies., 21 pages, 7 figures

Highlights • Electrode-generated currents exhibit several limitations when used to suppress seizure in clinical practice. • Magnetic stimulation provides enhanced biocompatibility, efficiency, and consistency over implanted electrode. • Clinical cases that utilize magnetic fields for epilepsy treatment are effective and relatively safe. • Current understanding of the cellular mechanisms underlying magnetic control of epileptic circuitry is insufficient. • In vivo and in vitro animal models are developed for neurological studies pertaining to the magnetic suppression of seizure., Non-invasive brain tissue stimulation with a magnetic coil provides several irreplaceable advantages over that with an implanted electrode, in altering neural activities under pathological situations. We reviewed clinical cases that utilized time-varying magnetic fields for the treatment of epilepsy, and the safety issues related to this practice. Animal models have been developed to foster understanding of the cellular/molecular mechanisms underlying magnetic control of epileptic activity. These mechanisms include (but are not limited to) (1) direct membrane polarization by the magnetic field, (2) depolarization blockade by the deactivation of ion channels, (3) alteration in synaptic transmission, and (4) interruption of ephaptic interaction and cellular synchronization. Clinical translation of this technology could be improved through the advancement of magnetic design, optimization of stimulation protocols, and evaluation of the long-term safety. Cellular and molecular studies focusing on the mechanisms of magnetic stimulation are of great value in facilitating this translation.

Electric currents can produce quick, reversible control of neural activity. Externally applied electric currents have been used in inhibiting certain ganglion cells in clinical practices. Via electromagnetic induction, a miniature-sized magnetic coil could provide focal stimulation to the ganglion neurons. Here we report that high-frequency stimulation with the miniature coil could reversibly block ganglion cell activity in marine mollusk Aplysia californica, regardless the firing frequency of the neurons, or concentration of potassium ions around the ganglion neurons. Presence of the ganglion sheath has minimal impact on the inhibitory effects of the coil. The inhibitory effect was local to the soma, and was sufficient in blocking the neuron’s functional output. Biophysical modeling confirmed that the miniature coil induced a sufficient electric field in the vicinity of the targeted soma. Using a multi-compartment model of Aplysia ganglion neuron, we found that the high-frequency magnetic stimuli altered the ion channel dynamics that were essential for the sustained firing of action potentials in the soma. Results from this study produces several critical insights to further developing the miniature coil technology for neural control by targeting ganglion cells. The miniature coil provides an interesting neural modulation strategy in clinical applications and laboratory research.

Isodon lophanthoides var. graciliflorus is a folk medicinal herb that is distributed in tropical and subtropical Asia. In this study, the complete plastome of I. lophanthoides var. graciliflorus was assembled and annotated. The plastome is 152,195 bp in length, consisting of a large single-copy (LSC) region of 83,095 bp, a small single-copy (SSC) region of 17,699 bp, and two inverted repeat (IR) regions of 25,701 bp, each. It has 113 genes, including 80 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. The overall GC content of the plastome is 37.6%. Phylogenetic analysis showed that I. lophanthoides var. graciliflorus was sister to Isodon serra.

Background: Oral breathing can cause morphological changes in the oral and maxillofacial regions. Aims: To investigate whether oral breathing affected structural changes in bone tissues. Study Design: Animal experimentation. Methods: A total of 48 8-day-old male Sprague−Dawley rats were divided into two groups: a breathing group and a sham (control) group. All Sprague−Dawley rats were killed at 7 weeks after unilateral nostril obstruction modeling. Then, structural changes in bone tissues were detected by micro-computed tomography, and the expression levels of receptor activator of nuclear factor-κB, osteoprotegerin, and receptor activator of nuclear factor-κB ligand in the signal pathway of bone metabolism within the local alveolar bone and serum of rats were detected by reverse transcription-quantitative polymerase chain reaction and Western blotting. Results: The results showed that receptor activator of nuclear factor-κB ligand and receptor activator of nuclear factor-κB levels in bone tissues and serum in the oral breathing group were higher than those in the control group [Maxillary alveolar bone: receptor activator of nuclear factor-κB ligand (pRNA=0.009, pprotein=0.008), receptor activator of nuclear factor-κB (pRNA=0.008, pprotein=0.009); Mandibular alveolar bone: receptor activator of nuclear factor-κB ligand (pRNA=0.047, pprotein=0.042), receptor activator of nuclear factor-κB (pRNA=0.041, pprotein=0.007); Serum: receptor activator of nuclear factor-κB ligand (pRNA

BACKGROUND The presence of mucinous component has been indicated to have a prognostic value in adenocarcinoma. However, little is known regarding the clinicopathological characteristics and prognosis of hilar cholangiocarcinoma (HC) with mucinous component (HCM). METHODS Between January 1996 and December 2014, a total of 61 HCM patients who underwent curative-intent resection at West China Hospital were retrospectively reviewed. The clinicopathological characteristics and survival of these patients were compared with a large cohort of 217 surgically resected conventional HC patients during the same period. RESULTS The clinicopathological characteristics of HCM were distinct from conventional HC, including higher CA19-9 levels, larger tumor sizes, less differentiation, and a high frequency of liver parenchyma invasion, portal vein invasion, and lymphovascular invasion. HCM patients showed significantly worse recurrence-free survival (13.4 vs 23.9 months; P = .011) and overall survival (18.2 vs 32.1 months; P = .019) compared with conventional HC patients. Multivariate analysis confirmed liver parenchyma invasion, N stage, surgical margin, and histological grade as independent prognostic factors influencing overall survival in HCM patients. CONCLUSION HCM showed distinct clinicopathological features, more aggressive biological behaviors, and poor prognosis in comparison with conventional HC. Therefore, the mucinous component is an adverse prognostic factor for HC.

Ureteral injury is an intractable complication in gynecological cancer surgeries. Identifying risk factors can ensure safety of the ureters intraoperatively. A narrow pelvis is known to exert extra difficulties in pelvic surgeries. However, whether pelvic dimension can affect the risk of ureteral injury in gynecological cancer surgeries is poorly understood. We aimed to evaluate the association between pelvic dimension and the risk of ureteral injury during gynecological cancer surgeries. All patients who had undergone gynecological cancer surgeries were searched from January 2011 to July 2017. We included patients with ureteral injury who had available data of abdominal and pelvic computed tomography for measuring pelvic dimensions. Multivariate condition logistic analysis was used to identify the risk factors independently correlated with ureteral injury in gynecological cancer surgeries. A total of 43 cases with 86 controls were included in this study. We discovered that a longer anteroposterior diameter of the mid-pelvis (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01–1.13, P = 0.019) and a shorter transverse diameter of the mid-pelvis (OR 0.92, 95% CI 0.86–0.98, P = 0.013) were associated with ureteral injury in gynecological cancer surgeries. In laparoscopic analysis, a longer anteroposterior diameter of the mid-pelvis (OR 1.11, 95% CI 1.00–1.24, P = 0.041) was a risk factor for ureteral injury. In the analysis of open surgery, a longer transverse diameter of the mid-pelvis (OR 0.79, 95% CI 0.66–0.93, P = 0.006) was a protective factor for ureteral injury. This study demonstrated that mid-pelvis dimensions were associated with ureteral injury, but the observed differences were too small. In addition, pelvic inlet dimensions did not appear to relate with ureteral injury. Thus, these pelvimetry measures could not be beneficial in assessing the risk of ureteral injury in gynecological cancer surgeries.

A novel Gram-stain-negative, facultatively anaerobic, oxidase-negative, catalase-positive bacillus, designated WD2A32T, was isolated from a marine solar saltern in the coast of Weihai, Shandong Province, PR China. Strain WD2A32T grew optimally at 37–40 °C (range, 20–45 °C) and pH 7.0–7.5 (range, 6.5–8.0) and was tolerant to 6–8 % (w/v) NaCl (range, 2–12 %). The 16S rDNA of strain WD2A32T was most similar (93.5 %) to that of Rhodovibrio salinarum DSM 9154T (the type species of the genus Rhodovibrio ), followed by Limimonas halophila DSM 25584T (92.4 %; the type species of the genus Limimonas ). The similarities to the type strains of the genera Pelagibius and Limibacillus were less than 91.0 %. The draft genome sequence of strain WD2A32T contained 72 contigs (>507 bp) of 4 237 996 bp with a DNA G+C content of 65.5 mol%. The major polar lipids of strain WD2A32T were phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and unidentified aminolipids; major cellular fatty acids were summed feature 8 (C18 : 1ω7c/C18 : 1ω6c) and C19 : 0 cyclo ω8c; the major respiratory quinone was Q-10. On the basis of the results from chemotaxonomic, physiological and biochemical analyses, strain WD2A32T represents a novel species of a novel genus in the family Rhodospirillaceae , for which the name Ferruginivarius sediminum gen. nov., sp. nov. has been proposed. The type strain is WD2A32T (=KCTC 52888T=MCCC 1H00201T).

The aim of this research was to determine the underlying mechanism of activating transcription factor 3 (ATF3) on cell proliferation, invasion, migration and epithelial‐mesenchymal transition (EMT). The differentially expressed mRNAs in cholangiocarcinoma (CC) and its adjacent tissues were screened by microarray analysis, and the expression of ATF3 was detected through Quantitative real time polymerase chain reaction (qRT‐PCR) and Western blot. The expression of EMT markers and p53‐related proteins was analysed by Western blot. Analyses using the Cell Counting Kit‐8 and TUNEL were performed to assess the rate of apoptosis and cell proliferation. Scratch wound and transwell assays were performed to study cell migration and invasion. Activating transcription factor 3 was restrained in CC cell lines and tissues and inhibited EMT while activating the p53 signalling pathway. Knockdown of ATF3 promoted cell proliferation but reduced the rate of apoptosis by inhibiting p53 signalling. Cell migration and invasion can be strengthened by ATF3 through activating the p53 signalling pathway.

Hui Ye,1 Meiling Duan2 1Department of Galactophore, Linyi Central Hospital of Shandong, Linyi, 276400, China; 2Department of Respiratory One, Linyi Central Hospital of Shandong, Linyi, 276400, China Introduction: Forkhead box (FOX) N2 (FOXN2), a member of FOX protein family, has been reported to play critical roles in some types of cancers. However, the expression and function of FOXN2 in breast cancer remain unclear. Methods: In the present work, we explored the detailed molecular mechanism of FOXN2 in breast cancer. We performed RT-qPCR and Western blotting analysis to detect the expression of FOXN2 in breast cancer. Colony formation assay, CCK-8 assay, wound healing assay, and Transwell assay were used to determine the effect of FOXN2 on cell proliferation, migration, and invasion in breast cancer. Results: Our results demonstrated that FOXN2 was downregulated in breast cancer tissues and cell lines. Downregulation of FOXN2 was correlated with tumor size, pathological grade, and lymph node metastasis. The in vitro experiments revealed that the ectopic expression of FOXN2 significantly suppressed the proliferation, migration, and invasiveness of breast cancer cells, and inhibition of FOXN2 promoted the proliferation, migration, and invasiveness of breast cancer cells. Moreover, inhibition of FOXN2 facilitated epithelial–mesenchymal transition (EMT) through regulation of SLUG. Conclusion: Taken together, our results showed for the first time that FOXN2 plays an essential role in cell proliferation and invasion. Thus, FOXN2 may be an attractive therapeutic target for the treatment of breast cancer. Keywords: FOXN2, proliferation, EMT, SLUG, breast cancer

Mitochondrial trans-2-enoyl-CoA reductase (MECR) is a protein-coding gene, and the protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFASII). Numerous studies have shown disorder of lipid metabolism is closely related with malignance, especially in liver cancer. Through pre-experiment, we found that the expression of MECR gene was highly expressed in hepatocelluar carcinoma (HCC) cell lines in vitro. This suggests that the MECR gene may play a role of oncogene in HCC. Therefore, we conducted a preliminary experimental study on the role of MECR gene in HCC cells in vitro. Objective to explore whether the MECR gene can affect the malignant biological behavior of HCC. We selected HCC cell line BEL-7404 as experimental cell, which involves the highest expression of MECR in the pre-experiment. We constructed MECR knockdwon lentivirus vector, and then infected HCC cell lines to down-regulate MECR expression, and establish negative control group (NC). Through various experiments of cytology, our study showed that knockdown of MECR inhibited cell proliferation and colony formation, promoted apoptosis, and inhibited metastasis in HCC cell lines BEL-7404. MECR might serve as a novel gene therapeutic target for the treatment of HCC. Further study is needed to elucidate the signaling pathway through which MECR functions in HCC.

Si-Wen Tan,1,2,* Guo-Qian Cai,3,* Qiu-Yu Li,1,* Yu Guo,3 Yi-Cong Pan,1 Li-Juan Zhang,1 Qian-Min Ge,1 Hui-Ye Shu,1 Xian-Jun Zeng,3 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China; 2The First Clinical Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comXian-Jun ZengDepartment of Radiology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88694639Email 375135747@qq.comPurpose: Previous research suggests that diabetic optic neuropathy (DON) can cause marked anatomical and functional variations in the brain, but to date altered functional synchronization between two functional hemispheres remains uncharacterized in DON patients. Voxel mirrored homotopic connectivity (VMHC) is a voxel-based method to evaluate the synchronism between two mirrored hemispheric by determining the functional connectivity between each voxel in one hemisphere and its counterpart. In this study, we aim to assess abnormal changes in interhemispheric functional connectivity in DON patients via the VMHC method.Methods: The study included 28 adult DON patients (12 male, 16 female) and 28 healthy controls (12 male, 16 female) who were closely matched for sex and age. Participants were examined using resting-state functional magnetic resonance imaging. The VMHC method was applied to investigate the abnormal state in bilateral hemispheres in DON patients and the same regions in healthy controls, as well as the receiver operating characteristic (ROC) curves were used to evaluate characteristics. Associations between altered VMHC values in distinct cerebral regions and clinical features were assessed via correlational analysis.Results: Markedly lower VMHC values were evident in the right temporal inferior, the left temporal inferior, the right mid-cingulum, the left mid-cingulum, the right supplementary motor region, and the left supplementary motor region in DON patients compared with healthy controls. ROC curve analysis suggested that the application of VMHC is reliable for the diagnosis of DON.Conclusion: Anomalous interhemispheric functional connectivity in specific brain areas caused by DON may indicate neuropathologic mechanisms of vision loss and blurry vision in patients with DON.Keywords: diabetes, diabetic optic neuropathy, magnetic resonance imaging, resting-state functional MRI

Aim: We conducted a systematic review of high-quality randomized controlled trials (RCTs) to assess the efficacy and safety of Chinese herbal medicine (CHM) for the treatment of chemotherapy-induced leukopenia (CIL).Methods: Eight electronic databases were searched from the date of inception to November 4, 2020 for high-quality RCTs that met the requirements of at least four key domains of the Cochrane risk of bias (RoB) tool. RevMan 5.3 was applied for the meta-analysis.Results: Fourteen RCTs involving 1,053 patients were included. The pooled results showed that CHM + chemotherapy exerted greater beneficial effects on white blood cell (WBC), neutrophil (NEU), hemoglobin (Hb), and platelet (PLT) counts in addition to the Karnofsky performance scale (KPS) score, but showed no significant difference on granulocyte colony-stimulating factor (G-CSF) dosage compared with chemotherapy alone. Placebo (PBO) + chemotherapy and CHM + chemotherapy groups showed no significant differences in terms of reduction of the incidence of neutropenia. CHM + chemotherapy was superior to Western medicine (WM) + chemotherapy in improving the WBC count, KPS, infection amount, G-CSF use rate, and incidence of leukopenia. In addition, no severe adverse events were observed in the 14 RCTs.Conclusion: CHM in combination with chemotherapy could effectively improve the clinical symptoms of CIL when compared with chemotherapy alone or Western medicine + chemotherapy, except when comparing with PBO + chemotherapy. While CHMs were generally safe for clinical use and exerted no severe side effects in the 14 RCTs, high-quality RCTs with larger sample sizes are essential to reduce study heterogeneity.

The association between the efficacy of mobile health and the occurrence and development of coronary heart disease (CHD) is still unclear. Mobile health can alleviate the risk factors for CHD. PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, WanFang, and VIP databases were searched from inception through May 28, 2020. Randomized controlled trials of the effect of mobile health in alleviating the risk factors of CHD's occurrence and development were included. Risks of bias were assessed by two independent reviewers by using the RevMan 5.3, GRADEpro, and RoB2.0 to generate findings. Meta‐analyses were performed to investigate the effects of mobile health on risk factors for CHD. Subgroup analyses were conducted. Sixteen randomized controlled trials, including 3898 patients with CHD, were included. Meta‐analysis results showed that mobile health can reduce BMI (mean difference [MD] = − 1.24, 95% CI = − 2.02 to − 0.45, p

Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of their high content of miR-106b-5p, which blocks Mitofusin 2 (Mfn2). In a mouse model of NAFLD-associated sepsis, TREM2 deficiency accelerated the initial progression of NAFLD and subsequent susceptibility to sepsis. Conversely, overexpression of TREM2 in liver macrophages improved hepatic energy supply and sepsis outcome. This study demonstrates that NAFLD is a risk factor for sepsis, providing a basis for precision treatment, and identifies hepatocyte-macrophage metabolic coordination and TREM2 as potential targets for future clinical trials.

Yan-Chang Yang,1,* Qiu-Yu Li,2,* Min-Jie Chen,2 Li-Juan Zhang,2 Meng-Yao Zhang,1 Yi-Cong Pan,2 Qian-Min Ge,2 Hui-Ye Shu,2 Qi Lin,2 Yi Shao2 1Department of Ophthalmology, Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang 330006, Jiangxi, People’s Republic of China; 2Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang 330006, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, 17 Yongwaizheng Street, Donghu, Nanchang, Jiangxi 330006, People’s Republic of ChinaEmail freebee99@163.comPurpose: The percent amplitude of fluctuation (PerAF) method was used to study the changes in neural activities and functions in specific brain regions of patients with a retinal detachment (RD).Patients and Methods: In this study, we recruited 15 RD patients (nine males and six females) and 15 healthy controls (HCs) matched for gender, age, and weight. All participants were scanned with resting functional magnetic resonance imaging (rs-fMRI). The PerAF method was then used for data analysis to evaluate and detect changes in neural activity in relevant brain regions. Receiver operating characteristic (ROC) curve analysis was used to evaluate the two groups.Results: The PerAF signal values of the right fusiform gyrus and the left inferior temporal gyrus of RD patients were significantly higher than those of HCs. This may indicate changes in neural activity and function in the related brain regions. The anxiety and depression scores of hospital anxiety and depression scale (HADS) and the durations in RD patients were positively correlated with the PerAF values of the left inferior temporal gyrus.Conclusion: In this study, we demonstrated that there were significant changes in the PerAF values in specific areas of the brain in patients with RD. The change of PerAF values represent the changes of BOLD signal intensity, which reflect the hyperactivity or weakening of specific brain regions in RD patients, which are helpful to predict the development and prognosis of RD patients, and play an important role in the early diagnosis of RD. In addition, according to the results, changes in neural activity in specific brain regions of RD patients increase the risk of brain dysfunction related diseases, which may help to understand the pathological mechanism of vision loss in RD patients.Keywords: retinal detachment, the percent amplitude of fluctuation, resting-state, functional magnetic resonance imaging, hospital anxiety and depression scale

Cancer cells exhibit different metabolic patterns compared to their normal counterparts. Although the reprogrammed metabolism has been indicated as strong biomarkers of cancer initiation and progression, increasing evidences suggest that metabolic alteration tuned by oncogenic drivers contributes to the occurrence and development of cancers rather than just being a hallmark of cancer. With this notion, targeting cancer metabolism holds promise as a novel anticancer strategy and is embracing its renaissance during the past two decades. Herein we have summarized the most recent developments in omics technology, including both metabolomics and proteomics, and how the combined use of these analytical tools significantly impacts this field by comprehensively and systematically recording the metabolic changes in cancer and hence reveals potential therapeutic targets that function by modulating the disrupted metabolic pathways.

Recurrent aphthous stomatitis (RAS) is the most common disease of oral mucosa, which almost attacks each individual once in their lifespan. Although plenty of factors have been suggested to play a role in the pathogenesis of RAS, the aetiology of RAS is still controversial, which might lead to limited clinical therapies in accordance with each RAS patient. This review mainly illustrates recent advances in potential causes associated with RAS in detail. Deeper comprehension of the aetiology of RAS will support doctors and researchers to make a better management of RAS patients and to discover new treatments. The aetiology of RAS is complicated, hence we should take a comprehensive view into its aetiology, with multiple potential factors being considered. Sample collection of RAS patients have greatly limited the progress in the aetiology of RAS. A research model of multiagency cooperation can help achieve perfect sample collection of year-round and multiposition.

Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implantation. However, it is unknown if miniature coils could be effective in axonal blockage and, if so, what the underlying mechanisms are. Here we demonstrate that a submillimeter magnetic coil can reversibly block action potentials in the unmyelinated axons from the marine mollusk Aplysia californica. Using a multi-compartment model of the Aplysia axon, we demonstrate that the miniature coil causes a significant local depolarization in the axon, alters activation dynamics of the sodium channels, and prevents the traveling of the invading action potentials. With improved biocompatibility and capability of emitting high-frequency stimuli, micro coils provide an interesting alternative for electric blockage of axonal conductance in clinical settings.

Objective: To determine the effects of an improved method of peri-pin membrane immobilization in tibial Gustilo type III fracture treated with vacuum sealant drainage (VSD) combined with an external fixator. Method: A biliary T tube of suitable size and type was cut into a certain long arm and cross arm which wrapping around a pin to improving traditional peri-pin VSD method. Eighty-six cases of Gustilo type III tibial fracture admitted from January 2016 to December 2019 were prospectively treated, of which 43 cases were treated using a traditional method of VSD (Traditional group) and 43 cases in which VSD treatment was enhanced (Improved group). The 2 groups were compared by some clinical indexes. Statistical software was then used for data analysis. P

This study investigated the effects of dietary selenium-enriched yeast (Se yeast) supplementation on the laying performance, egg quality, plasma antioxidant balance, and egg selenium (Se) content in laying Longyan ducks. A total of 480 32-week-old ducks were randomly divided into four dietary treatments, each consisting of six replicates of 20 ducks. The dietary treatments were a control basal diet and basal diets with supplementation of 0.05, 0.15, and 0.25 mg Se/kg via Se yeast. The analyzed Se contents of the four diets were 0.15, 0.21, 0.36, and 0.43 mg Se/kg, respectively. Dietary Se yeast supplementation had no apparent effects on laying performance and egg quality (p > 0.05), but it improved the antioxidant balance of ducks, as inferred by greater glutathione peroxidase and catalase activities, and decreased the malondialdehyde content in plasma of ducks (p < 0.05). It was suggested that the Se content in the basal diet containing 0.15 mg/kg of Se requirement is adequate for productive performance, but not for the antioxidant balance of laying ducks. Besides that, the Se contents in the yolk, albumen, and whole egg increased linearly as the Se supplementation levels increased. With more feeding days, the Se contents in the yolk and whole egg from non-Se-yeast-supplemented ducks increased linearly (p < 0.05), while those from Se-yeast-supplemented ducks showed a quadratic relationship (p < 0.05). In conclusion, the Se content of the basal diet at 0.15 mg/kg was adequate for laying performance and egg quality traits in laying ducks. Dietary Se yeast supplementation is beneficial to improve the antioxidant balance of laying ducks and increase the Se deposition in eggs for producing Se-enriched eggs. Based on the quadratic model or the quadratic broken-line model analyses, supplemental 0.19 mg Se/kg via Se yeast, with a total equivalent of 0.34 mg Se/kg in the diet, could provide the optimum antioxidant balance in laying ducks. Dietary supplementation of 0.25 mg Se/kg via Se yeast, with a total equivalent of 0.40 mg Se/kg in the diet, could lead to achieving the desired Se content in the whole egg.

NADPH is a pivotal cofactor that maintains redox homeostasis and lipogenesis in cancer cells and interference with NADPH production is a promising approach for treating cancer. However, how normal and cancer cells differentially exploit NADPH-producing pathways is unclear, and selective approaches to targeting NADPH are lacking. Here, we show that the assayed cancer cell lines preferentially depend on ME1-mediated NADPH production. ME1 knockdown increases intracellular ROS levels and impairs lipogenesis in cancer cells, leading to retarded proliferation and increased anoikis, while sparing normal cells. Notably, ME1 interference ultimately resulted in adaptive upregulation of mitochondrial IDH2 dependent of AMPK-FoxO1 activation to replenish the NADPH pool and mitigate cytosolic ROS. Combining ME1 ablation and IDH2 inhibition drastically reduces intracellular NADPH and prevents resistance to ME1 interference, resulting in increased apoptosis and impeded tumor growth and metastasis. This study demonstrates that cytosolic ME1 integrated with mitochondrial IDH2 is essential for tumor growth and metastasis, thereby highlighting the blockade of metabolic compensation by disrupting mitochondrial-cytosol NADPH transport as a promising approach to selectively targeting NADPH in cancer cells that rely on NADPH-driven antioxidant systems., Graphical abstract Image 1, Highlights • NADPH is vital in mitigating ROS stress and supporting lipogenesis in cancer cells. • Certain cancer cells preferentially depend on ME1-mediated NADPH production route. • ME1 knockdown adaptively upregulates IDH2 dependent of AMPK-FoxO1 axis. • Compensatory IDH2 contributes to replenish the NADPH pool and mitigates ROS. • Combined targeting ME1 and IDH2 depletes NADPH and inhibits tumor growth and metastasis.

It is necessary to create novel, efficacious and harmless therapeutic strategy for lung cancer treatment. The application of nanoemulsion to specifically suppress cancer progression in the tumor microenvironment would be an effective therapy. Neobavaisoflavone (Neo) is an isoflavone isolated from Psoralea corylifolia L, possesses striking anti-inflammatory and anti-cancer effects. In our stduy, Neo significantly reduced reactive oxygen species (ROS) generation in the activated myofibroblast. Furthermore, a novel Neo nanoemulsion (nano-Neo) was prepared to improve Neo solubility and bioavailability. Nano-Neo showed more effectively anti-proliferative role in lung cancer cells. In addition, in vivo analysis further demonstrated that nano-Neo could effectively suppress tumor growth compared to the free Neo-treated mice without noticeable damage to major organs. Furthermore, nano-Neo treatment markedly reduced extracellular matrix (ECM) deposition in tumor samples by repressing transforming growth factor-β (TGF-β)/SMADs signaling pathway. Meanwhile, the activated immune microenvironment in tumor tissues was dramatically improved by nano-Neo through reducing regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) infiltration, as well as improving the count of natural killer (NK) cells and M2 macrophage phenotype switch to pro-inflammatory M1. In addition, we found that the prepared nano-Neo exerted promising tumor targeting efficiency with improved pharmacokinetic properties. Therefore, the novel approach to prepare nano-Neo introduced here might provide an effective strategy for lung cancer treatment with few adverse effects.

Theacrine, i.e., 1,3,7,9-tetramethyluric acid, is one of the major purine alkaloids found in leaf of a wild tea plant species Camellia kucha Hung T. Chang. Theacrine has been attracted great attentions academically owing to its diverse health benefits. Present review examines the advances in the research on the health beneficial effects of theacrine, including antioxidant effect, anti-inflammatory effect, locomotor activation and reducing fatigue effects, improving cognitive effect, hypnotic effect, ameliorating lipid metabolism and inhibiting breast cancer cell metastasis effect. The inconsistent results in this research field and further expectations were also discussed.

To review the clinic value and severity assessment of serum substance P (SP) concentration in children with different degrees of traumatic brain injury (TBI) through analyzing correlations with outcomes.One hundred thirty-nine children with TBI who were diagnosed and treated at Nanjing Medical University for longer than 72 hours between June 2017 and 2019 were analyzed. Blood samples were obtained within 24 hours after TBI to measure SP concentration. The endpoint was discharge mortality. Thirty healthy children composed the control group. Comparative analyses of differences in SP concentration were conducted for the different groups. Both the Sequential Organ Failure Assessment (SOFA) scores and Pediatric Clinical Illness Score (PCIS) were measured on admission and used in univariate and multivariate analyses.The serum SP (89.10 ± 64.32) pmol/L) level in the case group was significantly higher than that in the control group (21.84 ± 2.09) pmol/L (t = 5.71, P0.05). The serum SP (182.81 ± 58.39) pmol/L) level in the deceased group was significantly higher than that in the survival group (59.93 ± 27.90) pmol/L (t = 16.52, P0.05). A negative correlation existed between serum SP concentration and Glasgow Coma Scale score in the severe, moderate, and mild groups (r = -0.72, P0.05). Serum SP concentration was identified as an independent risk factor for mortality (odds ratio1, 95% confidence interval = 1.04-1.28, P0.01). Receiver operating characteristic curve analysis suggested that serum SP concentration had the same calibrating power as SOFA and PCIS in discriminating the risk of death of children.Serum SP concentration was associated with severity in children with TBI, and extremely high levels indicated a poor prognosis.

Background We aimed to analyse multiple factors in the prediction of risk of postoperative recurrent vitreous haemorrhage (RVH) for non-clearing vitreous haemorrhage in patients with diabetic retinopathy (DR) who underwent sutureless vitrectomy with 23- (23G) or 25-gauge (25G) narrow-gauge systems. Methods A retrospective consecutive case series design was used. DR patients who underwent sutureless vitrectomy for non-clearing vitreous haemorrhage between June 2017 and October 2019 were enrolled. All operations were performed at a tertiary hospital. Patient demographics and risk factors, including age, gender, duration of diabetes, preoperative fasting blood sugar levels (FBSL), systolic blood pressure (SBP), serum creatinine (Cr), urea, triamcinolone acetonide (TA), electrical coagulation, air-fluid exchange, pan-retinal photocoagulation status (PRP), anti-vascular endothelial growth factor drug (anti-VEGF), and other factors, were recorded. Patients were divided into two groups based on the timing of their postoperative RVH: immediate postoperative RVH (within 2 weeks after operation) and delayed postoperative RVH (beyond 2 weeks after operation). Results Overall, 167 eyes (167patients) were enrolled. Seventy eyes were underwent 23G and 25G sutureless vitrectomy performed in 97 eyes, respectively. Postoperative RVH developed in 18 eyes (25.7%) in Group 23G and in 20 eyes (21.6%) in Group 25G (P = 0.540). Of these, 3 eyes (4.3%) had severed RVH in Group 23G compared with 5 eyes (5.2%) in Group 25G (P = 0.584). Delayed postoperative RVH occurred in 6 eyes (8.6%) in Group 23G and 8 eyes (8.2%) in Group 25G (P = 0.789). A binomial logistic regression analysis revealed that age, duration of diabetes, and Cr level were significantly associated with RVH in both Group 23G (P Conclusions The incidence and severity of RVH were 25.7 and 4.3%, respectively, in Group 23G and 21.6 and 5.2%, respectively, in Group 25G. Thus, the 23G sutureless vitrectomy approach was as safe as the 25G sutureless vitrectomy approach for treating vitreous haemorrhage in patients with DR. A younger age, shorter duration of diabetes, and higher Cr levels were risk factors for postoperative RVH in sutureless vitrectomy.

The embryonic development of the pancreas originates from dorsal and ventral anlagen, and the pancreatic cancer arising from dorsal or ventral pancreas may have different clinical pathology features. This study aims to explore whether there are differences in clinicopathological features and prognosis of pancreatic head carcinoma arising from dorsal or ventral pancreas. Between January 2014 and February 2018, 101 patients with resectable pancreatic head cancer who underwent pancreaticoduodenectomy in our institution were retrospectively reviewed. The patients were assigned into 2 groups according to tumor location on preoperative imaging materials (computed tomography/magnetic resonance imaging [CT/MRI]), and the clinicopathological features and prognosis were retrospectively analyzed in view of the embryonic development of the pancreas. Among these patients with pancreatic head cancer, 42 patients had tumors arising from dorsal pancreas (D group) and 59 patients had tumors arising from ventral pancreas (V group). The frequency of lymph node (LN) metastasis around the common hepatic artery (CHA) and hepatoduodenal ligament lymph nodes in the D group was higher than that in the V group (45.2% vs 10.2%, P = .001). And the rate of LN metastasis in the superior mesenteric artery (SMA) region in the V group is higher than that in the D group (32.2% vs 4.8%, P = .002). The D group was more likely to invade the common bile duct (78.6% vs 59.3%, P = .042) and duodenum (71.4% vs 44.1%, P = .006) than the V group. In addition, the survival outcome of V group was better than D group (median overall survival [OS], 15.37 months vs 10.53 months, P = .048, median DFS 9.73 months vs 5.93 months, P = .046). The clinicopathological features of pancreatic head carcinoma arising from dorsal or ventral pancreas are different, and the pancreatic head carcinoma arising from ventral pancreas has a better survival outcome.

Detailed extraction of retinal vessel morphology is of great significance in many clinical applications. In this paper, we propose a retinal image segmentation method, called MAU-Net, which is based on the U-net structure and takes advantages of both modulated deformable convolution and dual attention modules to realize vessels segmentation. Specifically, based on the classic U-shaped architecture, our network introduces the Modulated Deformable Convolutional (MDC) block as encoding and decoding unit to model vessels with various shapes and deformations. In addition, in order to obtain better feature presentations, we aggregate the outputs of dual attention modules: the position attention module (PAM) and channel attention module (CAM). On three publicly available datasets: DRIVE, STARE and CHASEDB1, we have achieved superior performance to other algorithms. Quantitative and qualitative experimental results show that our MAU-Net can effectively and accurately accomplish the retinal vessels segmentation task.

Introduction Mucinous carcinoma (MC) of the breast is a special histological type of breast cancer. Clinicopathological characteristics and genomic features of MC is not fully understood. Materials and methods 186,497 primary breast cancer patients from SEER database diagnosed with invasive ductal carcinoma (IDC) or MC were included. 801 primary IDC or MC patients from TCGA cohort were included for transcriptomic and genomic analysis. Results MC patients were older, had lower tumor grade and T and N stage, higher hormone receptor positive proportions and lower HER2 positive proportions than IDC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of MC patients was significantly better than IDC patients (P, Highlights • Mucinous breast carcinoma is a distinct histological subtype with better prognosis. • The clinicopathological characteristics of mucinous breast carcinoma contributed to its good prognosis. • Transcriptomic and genomic features of mucinous breast carcinoma contributed to its formation.

Liquor distiller's grains with solubles (LDGS) is high in yield and rich in crude fiber and crude protein, which suggests that LDGS might be developed and used as unconventional feedstuff for ducks. The aim of this study was to investigate the effects of sources and levels of LDGS on growth performance, carcass characteristics, serum parameters, and intestinal morphology of Cherry Valley ducks from 15 to 42 D of age. A total of 3,300 15-day-old male ducks were randomly assigned into a 1 plus 2 × 5 factorial design including 2 different sources of LDGS (unfermented LDGS [ULDGS] and fermented LDGS [FLDGS]) at 5 levels (4, 8, 12, 16, and 20%) for 4 wk. Each treatment group included 6 pens with 50 ducks per pen. Levels of dietary LDGS and the interaction between sources and levels of LDGS had no effect on final body weight, average daily feed intake (ADFI), average daily gain, or feed-to-gain ratio (F:G) of ducks from day 15 to 42 (P > 0.05). Compared with dietary ULDGS, dietary FLDGS increased final body weight (P < 0.05) and ADFI (P < 0.05) and decreased the F:G (P = 0.03). The levels of LDGS and interaction effect between levels and sources of LDGS had no effect on carcass characteristics (P > 0.05). Regardless of the inclusion level, ducks fed with diets containing FLDGS had a higher percentage of thigh muscle (P < 0.01) than birds fed with diets containing ULDGS. Sources of dietary LDGS, levels of dietary LDGS, and their interaction had no effect on serum biochemistry parameters (P > 0.05) and intestinal morphology, including villus height, crypt depth, and villus height-to-crypt depth ratio (P > 0.05). In conclusion, the inclusion of LDGS in the diet at levels up to 20% had no negative effect on the growth performance, carcass characteristics, serum parameters, and intestinal morphology of ducks. Compared with ULDGS, FLDGS increased final body weight, ADFI, and thigh muscle yield and decreased the F:G of ducks. Therefore, LDGS, especially with fermentation, could be developed as an unconventional feedstuff resource for ducks from 15 to 42 D of age.