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After the emergence of COVID-19 in 2019, it has now become a pandemic. COVID-19 has brought painful disasters to people all over the world. It not only threatens lives and health but also induces economic crises. At present, promising methods to eradicate COVID-19 mainly include drugs and vaccines. Enzyme inhibitors have always been a reliable strategy for the treatment of related diseases. Scientists worldwide have worked together to study COVID-19, obtained the structure of key SARS-CoV-2 associated enzymes, and reported the research of inhibitors of these enzymes. This article summarizes COVID-19-related enzyme inhibitors' recent development, mainly including 3CLpro, PLpro, TMPRSS2, and RdRp inhibitors, hoping to provide valuable weapons in the ensuing battle against COVID-19.

AIM: To evaluate the long-term effect of foldable capsular vitreous body (FCVB) in the treatment of severe ocular rupture to provide a practical basis for clinical selection. METHODS: A total of 26 patients (26 eyes), 23 men and 3 women, with severe ocular rupture who underwent FCVB implantation between March 2018 and September 2018 were retrospectively analysed. All open ocular wounds located in zone III, with preoperative visual acuity grade IV and above (Snellen less than 4/200). The best corrected visual acuity (BCVA), intraocular pressure (IOP), cornea, anterior chamber, iris, lens, choroid, and retina were evaluated before and after the surgery. The subjective feeling and the location of FCVB were also assessed. RESULTS: The average age of the 26 patients was 36y (20-60y). Postoperative follow-up was from 10 to 14mo. At the end of follow up, BCVA was light perception (LP) in 10 cases, no light perception (NLP) in 13 cases, hand motions (HM) in 3 cases. IOP was 11±5 mm Hg. Corneal degeneration was in 3 cases and corneal endothelial dystrophy was in 7 cases. Shallow anterior chamber was in 8 cases and hyphema was in 8 cases. Organized membrane in the pupil was in 14 cases. Epiphora occurred in 3 cases. FCVB drainage tube exposed in 3 cases. All FCVBs were in their normal location and no rejection occurred. CONCLUSION: FCVB implantation is a long-term effective treatment and may provide a practical selection for severe ocular rupture.

Background Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. Methods A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. Results 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. Conclusions Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

A comprehensive dynamics simulation has been presented in a quad-beam optic fiber with intersection arrangement. As the offset distance changes, the motion type of dielectric micro-particle could transform from trapping to orbital rotation. Finally, they would be repelled far away from the trapping center due to weak centripetal forces. Different from dual-beam optic fiber configuration, this intersection arrangement has much stronger trapping force to attract the suspending particles. Moreover, the cross optical trapping having misalignment could generate a vortex field with symmetric characteristics, which cause the particles carrying out circular orbital movement. This novel optic fiber arrangement is conducive to the application of particle manipulation and provides more technical support in integrated microfluidic chip.

Background To analyze the rule of traditional Chinese medicine in the treatment of acute pancreatitis (AP). Methods Using machine learning technology and artificial intelligence, we collected 516 traditional Chinese medicine compounds for treating AP in the recent past 20 years, and analyzed the application of Chinese medicine in the field of AP. The data set was established by the ingredients of each prescription and its corresponding effectiveness. 90% of the data was divided into the training set, and the remaining 10% of the data was used as the test set. We employed random forest method to build a model to predict the efficacy of the prescriptions in the treatment of AP. The R-squared score and mean absolute error was used to evaluate the model's performance. Results The most frequently used drugs were rhubarb, Radix Bupleuri, Fructus Aurantii Immaturus, and Mirabilite. Rhubarb and Rhizoma Corydalis had the greatest curative effect. The random forest model that fit all data showed that its R-squared score reached 0.8021. And the results predicted on the test set showed that the R-squared score reached 0.7318. Conclusions Soothing the liver, promoting qi, clearing heat, removing obstructions of organs, activating blood, and resolving stagnation are the treatment methods for AP.

Background Z score utility is emphasized in classifying coronary artery lesions in Kawasaki disease patients. The present study is the largest such multicenter Chinese pediatric study about coronary artery diameter reference values and Z score regression equation to date. It is useful in Chinese pediatric echocardiography. Methods A multicenter cohort was assembled, which consisted of 852 healthy children between 1 month and 17 years of age, ten children were excluded because their ultrasound images were not clear, or lost in following up. Diameters of the right coronary artery, left coronary artery, and left anterior descending coronary artery were assessed using echocardiography. Data were body surface area (BSA)-corrected using BSA calculated via either the Stevenson BSA formula or the Haycock BSA formula. Coronary artery diameter reference values and Z score regression equations were established for use in the Chinese pediatric population. Results No difference was observed between coronary artery diameter data corrected using BSAste or BSAhay. Of the five assessed regression models, the exponential model exhibited the best fit and was therefore selected as the basis for derivation of the SZ method. When comparing Z scores, those produced by the SZ method conformed to the standard normal distribution, while those produced by the D method did not. In addition, there was a statistically significant difference between Z scores produced by the SZ and D methods (P Conclusions Coronary artery diameter reference values for echocardiography were successfully established for use in the Chinese pediatric population, and a Z score regression equation more suitable for clinical use in this population was successfully developed.

Development of sensors uniting different sensing principles is in line with the concept of reliable, comprehensive, and diversified equipment construction. However, the current exploration in this field is obstructed by compromise of reaction conditions and inevitable mutual interference arising from different sensing modes. This work reported a closed bipolar electrode (c-BPE) strategy for dual-modality detection or dual-target detection. To this end, a c-BPE sensing platform installed in physically separated anode and cathode compartments was well designed and carefully optimized. If luminol was present in the anode section and Prussian blue (PB) was at the cathode part, single stimulation could realize electrochemiluminescence (ECL) from luminol at the anode and conversion of PB to Prussian white (PW) at the cathode. The latter reaction helped elevate the ECL signal and also prepared for colorimetric detection as color change from PW to PB under the trigger of oxidant (like H2O2) was used to track the content of the oxidant. Thus, dual signals were obtained for dual-modality detection of single target or the detection of different targets was realized at different poles. Detection of glucose was carried out to validate the application for dual-modality detection, while VLDL/AChE and NADH/H2O2 assays illustrated the potential of dual-target detection. The proposed platform possesses outstanding sensing performance including selectivity, repeatability, long-term stability, accuracy, and so forth. This work implements a breakthrough in designing dual-mode sensors and is expected to present a rational basis for development of a diversified sensing platform.

Background/Objectives Enucleation is an effective surgical method to treat pancreatic insulinoma, however, the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) is high. We aim to investigate the risk factors for CR-POPF which have not been well characterized and develop effective methods to prevent CR-POPF after enucleation. Methods This retrospective cohort study included 161 patients diagnosed with insulinoma from June 2016 to July 2020 in Peking Union Medical College Hospital. The risk factors for CR-POPF were evaluated and the role of prophylactic pre-operative pancreatic stent to prevent the occurrence of CR-POPF after enucleation of pancreatic insulinoma were explored. Results A cohort of 161 insulinoma cases were reviewed. The CT or MRI imaging reports could be tracked in 108 cases. A total of 96 patients underwent surgery, while 81 experienced pancreatic enucleation. Univariate and multivariate analyses showed that the distance from insulinoma to the main pancreatic duct (MPD) ≤2 mm was an independent risk factor for CR-POPF (p = 0.003, OR = 6.011, 95% Cl 1.852–19.512). The pre-operative pancreatic stent substantially reduced the incidence of CR-POPF in patients with tumor located in proximity to (distance ≤2 mm) the MPD (CR-POPF of the stented group vs the non-stented group: 37.5% vs 71.4%, p = 0.028). Conclusions The distance from insulinoma to MPD ≤2 mm is a predictive factor for CR-POPF after enucleation. Pancreatic duct stenting may benefit patients with insulinoma in proximity to the MPD by enabling a lower CR-POPF rate, so it should be considered before the enucleation of the insulinoma in proximity to the MPD (distance ≤2 mm).

Today, cancer still poses a serious threat to human, but there is no exact cure. Therefore, exploring to accomplish high therapeutic performance is a challenging and urgent task. Since the nanoparticles unique properties were discovered, they have displayed promising potential for more effective therapies and have been widely used in photodynamic therapy (PDT) and radiation therapy (RT). However, some special properties of the tumour microenvironment (TME) have seriously affected the therapeutic outcomes, so the modulation of the TME becomes critical. Manganese dioxide (MnO2), as a transition metal oxide, has been widely used in biomedical fields with special physical and chemical properties, especially in regulating the TME. Furthermore, MnO2 has widely applications in various cancer treatments, such as PDT, chemodynamic therapy (CDT), immunotherapy, and some specific collaborative treatment. Herein, we reviewed the recent applications of MnO2 modified nanomaterials in tumour therapies and theranostics, including TME regulation, controlled drug loading/delivery/release, and imaging.

This study aims to compare the effectiveness of video and paper materials used for teach-back education on the first insulin injection for patients with diabetes. The study enrolled 110 patients hospitalized for diabetes who had received education on their first insulin injection in the endocrinology department. The patients were divided into an intervention group ( n = 55) and a control group ( n = 55) using convenience sampling. Video materials were employed for the teach-back education of the intervention group, while paper materials were employed for the teach-back education of the control group. We compared cases who answered correctly to the common parts (selection and management of injection devices, selection and rotation of injection sites, proper use of injection angles and pinching, insulin storage, injection-related complications and their prevention, selection of the correct needle length, and safe disposal of needles after use) for the first time, the number of educational sessions and total education duration between the two groups and employed the “ My View on Insulin” questionnaire to survey the two groups before and 28 days after the intervention. The intervention group had a shorter total education duration than the control group, a difference that was statistically significant ( p .05); however, both groups scored significantly higher than before the intervention, a difference that was statistically significant ( p

Background Though BRCA1 mutation is the most susceptible factor of breast cancer, its prognostic value is disputable. Here in this study, we use a novel method which based on whole-genome analysis to evaluate the chromosome instability (CIN) value and identified the potential relationship between CIN and prognosis of breast cancer patients with germline-BRCA1 mutation. Materials and methods Sanger sequencing or a 98-gene panel sequencing assay was used to screen for BRCA1 germline small mutations in 1151 breast cancer patients with high-risk factors. MLPA assay was employed to screen BRCA1 large genomic rearrangements in familial breast cancer patients with BRCA1 negative for small mutations. Thirty-two samples with unique BRCA1 germline mutation patterns were further subjected to CIN evaluation by LPWGS (low-pass whole-genome sequencing) technology. Results Firstly, 113 patients with germline BRCA1 mutations were screened from the cohort. Further CIN analysis by the LPWGS assay indicated that CIN was independent from the mutation location or type of BRCA1. Patients with high CIN status had shorter disease-free survival rates (DFS) (HR = 6.54, 95% CI 1.30–32.98, P = 0.034). The TP53 copy loss was also characterized by LPWGS assay. The rates of TP53 copy loss in CIN high and CIN low groups were 85.71% (12/14) and 16.67% (3/18), respectively. Conclusion CIN-high is a prognostic factor correlated with shorter DFS and was independent with the germline BRCA1 mutation pattern. Higher CIN values were significantly correlated with TP53 copy loss in breast cancer patients with germline BRCA1 mutation. Our results revealed a reliable molecular parameter for distinguishing patients with poor prognosis from the BRCA1-mutated breast cancer patients.

BACKGROUND AND AIM Gastrointestinal stromal tumors (GISTs) are among the most common submucosal tumors in the stomach that require therapeutic intervention. We aim to identify the predictors of technical difficulty during endoscopic resection of gastric GIST and to investigate follow-up outcomes. METHODS Patients with gastric GISTs were reviewed from June 2009 to June 2020 at Zhongshan Hospital. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed. A nomogram was developed and validated internally and externally. RESULTS A total of 628 GISTs were finally analyzed. The difficulty was experienced in 66 cases. GISTs size (2-3 cm: OR 2.431 P = 0.018 and > 3 cm: OR 9.765 P

In this study, an ultra-broadband orbital angular momentum (OAM) mode generator based on a phase-modulated helical long period fiber grating (HLPG) working at highradial order cladding mode is firstly proposed and numerically demonstrated. The proposed phase-only modulation method can considerably facilitate the HLPG’s fabrication by eliminating the grating’s apodization, which is extremely difficult to realize in the screw-type grating. Meanwhile, the proposed method provides more flexibilities in the design of HLPGs. As a typical example, a first-order OAM (OAM −1) mode generator with a bandwidth of ~63 nm, a conversion efficiency of ~100%, and purity of ~ 91% has been numerically demonstrated. Moreover, an OAM −1 mode generator with a bandwidth of ~469 nm, a conversion efficiency of ~100%, and purity of ~ 91% has been successfully obtained, covering all bands of fiber communication, i.e., o riginal- (O-), extended- (E-), short- (S-), conventional- (C-), long- (L-), and ultralong- (U-) wavelength bands, which, based on our knowledge, are the best results reported to date among those of the HLPG-based OAM mode generators. The proposed component may find potential applications in the OAM mode division multiplexing (MDM) system combined with the wavelength division multiplexing technique.

Background Thymic epithelial tumors (TETs) are rare malignant neoplasms originating from thymic epithelial cells. The current treatment for localized TETs is surgical removal. However, 20-30% of thymomas and 70-80% of thymic carcinomas are unresectable, recurrent, or metastatic at the time of detection. The standard therapy for these patients is chemotherapy, but the effect is limited. With a deeper understanding of tumor immunity, immunotherapy for various cancers has rapidly developed. Antibodies against cytotoxic T-lymphocyte antigen-4, programmed death-1, and programmed death-ligand 1 have been approved for the treatment of many solid tumors. Compared with traditional treatments, these immune checkpoint inhibitors (ICIs) have better efficacy and lower toxicity. Recently, ICIs have been used more enthusiastically in the treatment of TETs. However, due to the unique biological characteristics of the thymus, immunotherapy usually causes severe immune-related adverse events (irAEs). Most previous studies on immunotherapy in TETs had small sample sizes and reported diverse conclusions. Methods We collected relevant studies in PubMed during the last five years and analyzed the available data to discuss the efficacy and safety of ICIs in TETs. Results According to 14 previous studies in the past five years, all TETs showed expression of programmed death-ligand 1, while thymic carcinomas showed 100% expression. The best median progression-free survival (mPFS) among the five studies was 6.5 months, and the best median overall survival (mOS) was 24.9 months. In addition, the most common irAEs were myasthenic symptoms, liver enzyme elevation, and elevated creatine phosphokinase levels. Conclusions ICIs can be used in TET treatment, especially for thymic carcinomas, in the absence of standard second-line treatment. However, more attention should be paid to irAEs.

In recent year, optic-fiber optical tweezers were considered as a valuable manipulated tool, allowing for trapping and sorting numerous interest microparticles in biological and microfluidic application. Especially for dual optic-fiber array with misalignment, vortex optical field can be utilized to cause particle realizing periodic orbital rotation, contributing to measure unknown parameters such as torque, viscosity, and angular momentum. Yet, this optic-fiber array with several misalignments creating more vortex fields remains an interesting work for a large range of microparticle trapping and rotation. Therefore, motion profiles of particle exerting by four optic-fibers forming quad-beam were studied by changing offset distance in our numerical model. Compared to dual beam, the array of such four optic-fibers has much more controllable variables, reflecting the asymmetric radial distance relevant to particle. Herein, these motion characteristics relevant to microparticle have been simulated based on ray optics approximation. Finally, dynamic simulations imply that quad-beam can generate two or more vortexes inducing particle to move in orbital rotation, which have revealed different rotational radius, direction, and velocity. As a results, this optic-fiber array may be readily implemented in cellular trapping and manipulation, exploring biophysical properties of different types of cell.

It remains extremely challenging to build three-dimensional photonic crystals with complete photonic bandgaps by simple and experimentally realizable colloidal building blocks. Here, we demonstrate that particle softness can enhance both the self-assembly of pyrochlore- and perovskite-like lattice structures from simple deformable triblock Janus colloids and their photonic bandgap performances. Dynamics simulation results show that the region of stability of pyrochlore lattices can be greatly expanded by appropriately increasing softness, and the perovskite lattices are unexpectedly obtained at enough high softness. Photonic calculations show that the direct pyrochlore lattices formed from overlapping soft triblock Janus particles exhibit even larger photonic bandgaps than the ideal nonoverlapping pyrochlore lattice, and proper overlap arising from softness can also dramatically improve the photonic properties of the inverse pyrochlore and perovskite lattices. Our study offers a new and feasible self-assembly path toward three-dimensional photonic crystals with large and robust photonic bandgaps.

Polymer-stabilised blue-phase liquid crystal (PS-BPLC) is a soft artificial three-dimensional photonic crystal (PC) functional material for optics and optoelectronics because of its superior optica...

Community detection for Location-based Social Networks (LBSNs) has been received great attention mainly in the field of large-scale Wireless Communication Networks. In this paper, we present a Differential Privacy Latent Trajectory cOmmunity Discovering (DP-LTOD) scheme, which obfuscates original trajectory sequences into differential privacy-guaranteed trajectory sequences for trajectory privacy-preserving, and discovers latent trajectory communities through clustering the uploaded trajectory sequences. Different with traditional trajectory privacy-preserving methods, we first partition original trajectory sequence into different segments. Then, the suitable locations and segments are selected to constitute obfuscated trajectory sequence. Specifically, we formulate the trajectory obfuscation problem to select an optimal trajectory sequence which has the smallest difference with original trajectory sequence. In order to prevent privacy leakage, we add Laplace noise and exponential noise to the outputs during the stages of location obfuscation matrix generation and trajectory sequence function generation, respectively. Through formal privacy analysis, we prove that DP-LTOD scheme can guarantee $\epsilon$ e -differential private. Moreover, we develop a trajectory clustering algorithm to classify the trajectories into different kinds of clusters according to semantic distance and geographical distance. Extensive experiments on two real-world datasets illustrate that our DP-LTOD scheme can not only discover latent trajectory communities, but also protect user privacy from leaking.

Background Phimosis is one of the most common diseases in children. Early selection of appropriate treatment for phimosis in children is beneficial to the development of their reproductive organs and significantly improves the prognosis of phimosis in children. Although traditional circumcision is the most widely used, it has many disadvantages, including postoperative bleeding and incision infection, pain, obvious scars on the surgical incision, and unsatisfactory appearance. In addition, there is much controversy regarding treatment options and timing at home and abroad. Surgical procedures such as circumcision and cerclage for children with excessively long foreskin will greatly affect the normal life of children after the operation. Young children need general anesthesia, but this anesthesia carries a great risk. Aim To design a new children phimosis dilatation retractor for children phimosis. Methods The children phimosis was dilated with an elastic dilation frame, in order to expand the foreskin mouth and expose the penis head, and after that, the phimosis was cured. Results A new type of phimosis dilatation retractor was designed, which can gently dilate the prepuce at multiple angles and in multiple directions at the same time. It has obtained the national patent for clinical application. Conclusion The phimosis dilatation retractor based on the principle of elastically expanding the prepuce can achieve the purpose of expanding the phimosis. The clinical application shows that the effect of the children phimosis retractor is significant, which is worth promoting.

Background Rosai-Dorfman disease (RDD) is a rare benign proliferative disease whose etiology is not clear and may be related to infection or unexplained immune dysfunction. The authors present a case of RDD with lung involvement in a 10-year-old patient. Case summary A 10-year-old girl found that her left cervical lymph nodes were enlarged for more than 7 mo, and the largest range was about 6.5 cm × 5.9 cm × 8.1 cm. Cervical magnetic resonance imaging showed multiple masses in the left neck, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. A malignant tumor, with a high possibility of lymph node metastasis, was initially considered. At the same time, lung computed tomography showed multiple nodules of different sizes scattered on both sides of the lung, with uniform internal density. Thus, a possible metastatic tumor was considered. Finally, RDD was diagnosed by pathology and immunohistochemistry. According to the antibiogram, clindamycin was administered for 2 wk, and prednisone acetate was administered for 7 wk. Nine months later, the ulcer in the left neck was better than before, but the imaging showed that the lesion was not controlled. Conclusion The diagnosis of RDD cannot be made by a single tool and its treatment is a long-term exploratory process. Follow-up is necessary.

Ligustrazine, an alkaloid extracted from the traditional Chinese herbal medicine Ligusticum Chuanxiong Hort, has been clinically applied to treat the cerebrovascular diseases. Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD). Memory deficits can be caused by Hhcy via pathologies of AD-like tau and amyloid-β (Aβ) in the hippocampus. Here, we investigated whether homocysteine (Hcy) can induce AD-like pathologies and the effects of ligustrazine on these pathologies. The Hcy rat model was constructed by 14-day Hcy injection via vena caudalis, and rats were treated with daily intragastric administration of ligustrazine at the same time. We found that the pathologies of tau and Aβ were induced by Hcy in the hippocampus, while the Hcy-induced tau hyperphosphorylation and Aβ accumulation could be markedly attenuated by simultaneous ligustrazine treatment. Our data demonstrate that ligustrazine may be used as a promising neuroprotective agent to treat the Hcy-induced AD-like pathologies.

Background The pancreatic immune‐related adverse event (irAE) is a rare but increasingly occurrence disease with limited knowledge, which was associated with the use of immune checkpoint inhibitors (ICIs). Methods In this case series study of pancreatic irAE patients, clinical and radiological manifestations are summarized. Baseline and post‐treatment fecal microbiota of immune‐related acute pancreatitis (irAP) patients were analyzed by the 16 s rDNA amplicon sequencing method. Results A total of six patients were enrolled into the study, and the onset of pancreatic irAEs occurred a median of 105 days after a median of 4.5 cycles with immune checkpoint inhibitors (ICIs). All patients had an effective response to ICIs. Abdominal pain was the main clinical manifestation. Serum amylase (sAMY) and lipase (sLIP) had dynamic changes parallel to clinical severity. Contrast‐enhanced computed tomography (CT) did not accurately reveal the level of inflammation. However, magnetic resonance imaging (MRI) was a sensitive imaging method which showed decreased and increased signal intensity of pancreatic parenchyma in T1‐weighted fat‐saturated and diffusion‐weighted imaging, respectively. Glucocorticoids were the main treatment with a rapid initial effect followed by a slow improvement. After reinitiation of ICI therapy, pancreatic irAEs either deteriorated, remained stable or the patient developed severe pancreatic β‐cell destruction without irAP recurrence. The baseline microbiota of irAP had low Bacteroidetes/Firmicutes ratio at phylum level, low relative abundance of Alistipes, Bacteroides and high Lachnospiraceae at genus level, compared to levels of pancreatic β‐cell destruction and post‐treatment of irAP. Conclusions Pancreatic irAE patients had corresponding abdominal pain and increase in sAMY/sLIP. MRI was found to be an ideal imaging modality. Treatment with glucocorticoids were the main approach. The microbiota showed relative changes at baseline and during treatment., Following onset and glucocorticoid treatment of severe immune‐related acute pancreatitis (irAP) (A), the serum amylase and lipase had parallel changes with the clinical conditions (B). The contrast‐enhanced CT did not accurately reveal the inflammation level; however, the MRI including T1‐weighted fat‐saturated, diffusion‐weighted image and magnetic resonance cholangiopancreatography clarified the radiological characteristics and dynamic changes of irAP (C). Correspondingly, the microbiota had relative changes at baseline and during treatment (D).

Objective This study aims to evaluate the performance of convolutional neural networks (CNNs) trained with resting-state functional magnetic resonance imaging (rfMRI) latency data in the classification of patients with pediatric epilepsy from healthy controls. Methods Preoperative rfMRI and anatomic magnetic resonance imaging scans were obtained from 63 pediatric patients with refractory epilepsy and 259 pediatric healthy controls. Latency maps of the temporal difference between rfMRI and the global mean signal were calculated using voxel-wise cross-covariance. Healthy control and epilepsy latency z score maps were pseudorandomized and partitioned into training data (60%), validation data (20%), and test data (20%). Healthy control individuals and patients with epilepsy were labeled as negative and positive, respectively. CNN models were then trained with the designated training data. Model hyperparameters were evaluated with a grid-search method. The model with the highest sensitivity was evaluated using unseen test data. Accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve were used to evaluate the ability of the model to classify epilepsy in the test data set. Results The model with the highest validation sensitivity correctly classified 74% of unseen test patients with 85% sensitivity, 71% specificity, F1 score of 0.56, and an area under the receiver operating characteristic curve of 0.86. Conclusions Using rfMRI latency data, we trained a CNN model to classify patients with pediatric epilepsy from healthy controls with good performance. CNN could serve as an adjunct in the diagnosis of pediatric epilepsy. Identification of pediatric epilepsy earlier in the disease course could decrease time to referral to specialized epilepsy centers and thus improve prognosis in this population.

In this paper, we introduce an ultra-sensitive optical sensing platform based on the parity-time-reciprocal scaling (PTX)-symmetric non-Hermitian metasurfaces, which leverage exotic singularities, such as the exceptional point (EP) and the coherent perfect absorber-laser (CPAL) point, to significantly enhance the sensitivity and detectability of photonic sensors. We theoretically studied scattering properties and physical limitations of the PTX-symmetric metasurface sensing systems with an asymmetric, unbalanced gain-loss profile. The PTX-symmetric metasurfaces can exhibit similar scattering properties as their PT-symmetric counterparts at singular points, while achieving a higher sensitivity and a larger modulation depth, possible with the reciprocal-scaling factor (i.e., X transformation). Specifically, with the optimal reciprocal-scaling factor or near-zero phase offset, the proposed PTX-symmetric metasurface sensors operating around the EP or CPAL point may achieve an over 100 dB modulation depth, thus paving a promising route toward the detection of small-scale perturbations caused by, for example, molecular, gaseous, and biochemical surface adsorbates. [Image: see text]

Stress urinary incontinence (SUI) is defined as involuntary urine leakage during physical activities that increase the intra-abdominal pressure on the bladder. We studied bone marrow stem cell (BMSC) secretome-induced activation of anterior vaginal wall (AVW) fibroblasts and its ability to accelerate SUI recovery following vaginal distention (VD) in a rat model of birth trauma using BMSC-conditioned medium (BMSC-CM) and concentrated conditioned medium (CCM). BMSC-CM enhanced the proliferation, migration, and collagen synthesizing abilities of fibroblasts. Differentially expressed genes in BMSC-CM-induced fibroblasts were mainly enriched for cell adhesion, extracellular fibril organization and angiogenesis. Treatment with the JAK2 inhibitor AG490 reversed BMSC-CM-induced activation of the JAK2/STAT4 pathway. Periurethral injection with BMSC-CCM markedly enhanced the abdominal leak point pressure (LPP) in rats after VD. Histological analysis revealed increased numbers of fibroblasts, improved collagen fibers arrangement and elevated collagens content in the AVW of rats receiving BMSC-CCM. These findings suggest the BMSC secretome activates AVW fibroblasts and contributes to the functional and anatomic recovery of simulated birth trauma-induced SUI in rats.

BACKGROUND: Identifying sex‐related differences is critical for enhancing our understanding of factors that may impact prognosis and advance treatments in Huntington's disease (HD). OBJECTIVES: To investigate if sex‐related differences exist in clinical HD. METHODS: Longitudinal study of the Enroll‐HD database. Manifest HD patients were included in the analysis (N = 8401). Linear mixed models were used to assess motor, behavioral, and cognitive functioning over a series of four annual visits, and compared male and female HD gene carriers. RESULTS: HD patients showed significant sex‐dependent differences in motor, cognitive, and behavioral symptoms. Both sexes had worsened motor symptoms over the course of four visits, but there was a significant disparity between sexes, with females consistently presenting with more symptoms than males. For behavioral symptoms, specifically depressive symptoms, females had significantly more depressive symptoms, although self‐reported symptoms in both sexes became less severe throughout time. CONCLUSIONS: Our analyses suggest that women have worse symptoms than men during the course of HD.

In recent decades, much attention has been given to cyclopropyl scaffolds, which commonly exist in natural products and synthetic organic molecules. Clinical drug molecules with cyclopropyl rings are an area of focus in therapeutic research due to their interesting chemical properties and unique pharmacology activity. These molecular drugs against different targets are applicable in some therapeutic treatment fields including cancer, infection, respiratory disorder, cardiovascular and cerebrovascular diseases, dysphrenia, nervous system disorders, endocrine and metabolic disorders, skin disease, digestive disorders, urogenital diseases, otolaryngological and dental diseases, and eye diseases. This review is a guide for pharmacologists who are in search of valid preclinical/clinical drug compounds where the progress, from 1961 to the present day, of approved marketed drugs containing cyclopropyl scaffold is examined.

The problem of effluent total nitrogen (TN) at most of the wastewater treatment plants (WWTPs) in China is important for meeting the related water quality standards, even under the condition of high energy consumption. To achieve better prediction and control of effluent TN concentration, an efficient prediction model, based on controllable operation parameters, was constructed in a sequencing batch reactor process. Compared with previous models, this model has two main characteristics: ① Superficial gas velocity and anoxic time are controllable operation parameters and are selected as the main input parameters instead of dissolved oxygen to improve the model controllability, and ② the model prediction accuracy is improved on the basis of a feedforward neural network (FFNN) with algorithm optimization. The results demonstrated that the FFNN model was efficiently optimized by scaled conjugate gradient, and the performance was excellent compared with other models in terms of the correlation coefficient (R). The optimized FFNN model could provide an accurate prediction of effluent TN based on influent water parameters and key control parameters. This study revealed the possible application of the optimized FFNN model for the efficient removal of pollutants and lower energy consumption at most of the WWTPs.

ObjectiveTo analyze the association between peri-ictal brainstem posturing semiologies with postictal generalized electroencephalographic suppression (PGES) and breathing dysfunction in generalized convulsive seizures (GCS).MethodsIn this prospective, multicenter analysis of GCS, ictal brainstem semiology was classified as (1) decerebration (bilateral symmetric tonic arm extension), (2) decortication (bilateral symmetric tonic arm flexion only), (3) hemi-decerebration (unilateral tonic arm extension with contralateral flexion) and (4) absence of ictal tonic phase. Postictal posturing was also assessed. Respiration was monitored with thoracoabdominal belts, video, and pulse oximetry.ResultsTwo hundred ninety-five seizures (180 patients) were analyzed. Ictal decerebration was observed in 122 of 295 (41.4%), decortication in 47 of 295 (15.9%), and hemi-decerebration in 28 of 295 (9.5%) seizures. Tonic phase was absent in 98 of 295 (33.2%) seizures. Postictal posturing occurred in 18 of 295 (6.1%) seizures. PGES risk increased with ictal decerebration (odds ratio [OR] 14.79, 95% confidence interval [CI] 6.18–35.39,p< 0.001), decortication (OR 11.26, 95% CI 2.96–42.93,p< 0.001), or hemi-decerebration (OR 48.56, 95% CI 6.07–388.78,p< 0.001). Ictal decerebration was associated with longer PGES (p= 0.011). Postictal posturing was associated with postconvulsive central apnea (PCCA) (p= 0.004), longer hypoxemia (p< 0.001), and Spo2recovery (p= 0.035).ConclusionsIctal brainstem semiology is associated with increased PGES risk. Ictal decerebration is associated with longer PGES. Postictal posturing is associated with a 6-fold increased risk of PCCA, longer hypoxemia, and Spo2recovery. Peri-ictal brainstem posturing may be a surrogate biomarker for GCS severity identifiable without in-hospital monitoring.Classification of EvidenceThis study provides Class III evidence that peri-ictal brainstem posturing is associated with the GCS with more prolonged PGES and more severe breathing dysfunction.

To gain insights into the role of testosterone in the development of atherosclerosis and its related metabolic pathways, we applied a proton nuclear magnetic resonance (1H NMR)-based metabolomics approach to investigate urine metabolic profiles in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM) and castrated male pigs with testosterone replacement (CMT). Our results showed that testosterone deficiency significantly increased atherosclerotic lesion areas, intima-media thickness, as well as serum lipid levels in the CM pigs. Moreover, seventeen significantly changed metabolites were identified in both IM vs. CM and CMT vs. CM groups. Among these, seven were shared between the two comparative groups and were all significantly reduced in the urine of the CM group but rescued in the CMT group. In addition, the correlation analysis demonstrated that several metabolites, including niacinamide, myo-inositol, choline and 3-hydroxyisovalerate, were negatively correlated with atherosclerotic lesion areas. Our study demonstrated that testosterone deficiency accelerated early AS formation in HFC diet-fed pigs, which involved several metabolites predominantly related to lipid metabolism, inflammation, oxidative stress and endothelial disorders. Our results reveal potential pathways in the pathogenesis of atherosclerosis caused by testosterone deficiency and HFC diet.

Diabetes mellitus (DM) is a metabolic disease, and diabetes patients have long-term higher blood sugar levels than standard. Most people with diabetes have complications that greatly affect their standard of living. Patients with type 2 DM occupy the vast majority of all diabetes patients. Glucagonlike peptide-1 (GLP-1) secreted by intestinal enteroendocrine L-cells is a small molecule polypeptide, which is glucose concentration-dependent and can effectively reduce blood glucose concentration. Dipeptidyl peptidase-4 (DPP-4) is an important target for the treatment of type 2 DM because it can degrade GLP-1. DPP-4 inhibitors can enhance the blood glucose lowering effect of GLP-1 by inhibiting DPP-4. This article summarizes the development of DPP-4 inhibitors from 2015 to 2019, and can provide helpful information for the discovery of novel DPP-4 inhibitors in the future.

ObjectiveTo determine whether machine learning (ML) algorithms can improve the prediction of delayed cerebral ischemia (DCI) and functional outcomes after subarachnoid hemorrhage (SAH).MethodsML models and standard models (SMs) were trained to predict DCI and functional outcomes with data collected within 3 days of admission. Functional outcomes at discharge and at 3 months were quantified using the modified Rankin Scale (mRS) for neurologic disability (dichotomized as good [mRS ≤ 3] vs poor [mRS ≥ 4] outcomes). Concurrently, clinicians prospectively prognosticated 3-month outcomes of patients. The performance of ML, SMs, and clinicians were retrospectively compared.ResultsDCI status, discharge, and 3-month outcomes were available for 399, 393, and 240 participants, respectively. Prospective clinician (an attending, a fellow, and a nurse) prognostication of 3-month outcomes was available for 90 participants. ML models yielded predictions with the following area under the receiver operating characteristic curve (AUC) scores: 0.75 ± 0.07 (95% confidence interval [CI] 0.64–0.84) for DCI, 0.85 ± 0.05 (95% CI 0.75–0.92) for discharge outcome, and 0.89 ± 0.03 (95% CI 0.81–0.94) for 3-month outcome. ML outperformed SMs, improving AUC by 0.20 (95% CI −0.02 to 0.4) for DCI, by 0.07 ± 0.03 (95% CI −0.0018 to 0.14) for discharge outcomes, and by 0.14 (95% CI 0.03–0.24) for 3-month outcomes and matched physician's performance in predicting 3-month outcomes.ConclusionML models significantly outperform SMs in predicting DCI and functional outcomes and has the potential to improve SAH management.

Background Pancreatic cancer with ovarian metastases is rare and easily misdiagnosed. Most patients are first diagnosed with ovarian cancer. We report a rare case of ovarian metastases secondary to pancreatic adenocarcinoma. We also review the literature to analyze the clinical characteristics of, diagnostic methods for, and perioperative management strategies for this rare malignancy. Case summary A 48-year-old woman with an abdominal mass presented to our hospital. Computed tomography revealed lesions in the pancreas and lower abdomen. Radiological examination and histological investigation of biopsy specimens revealed either an ovarian metastasis from a pancreatic neoplasm or two primary tumors, with metastasis strongly suspected. The patient simultaneously underwent distal pancreatectomy plus splenectomy by a general surgeon and salpingo-oophorectomy with hysterectomy by a gynecologist. Histological examination of the surgical specimen revealed a pancreatic adenocarcinoma (intermediate differentiation, mucinous) and a metastatic mucinous adenocarci-noma in the ovary. Conclusion For this rare tumor, surgical resection is the most effective treatment, and the final diagnosis depends on tumor pathology.

We propose here a fully-passive wireless liquid sensor using a harmonic transponder, which comprises a dual-band microstrip antenna reconfigured by different types of liquids injected in a fluidic cavity. Different from traditional radio-frequency (RF) backscatter sensors, the proposed harmonic-transponder sensor (or harmonic sensor) receives frequency-hopped RF monotones and backscatters their second harmonics, with the peak frequency shifted by dielectric properties of liquid mixtures. This microstrip antenna has a hybrid-feed structure, of which an outer split-ring patch exhibits a narrow-band TM310 mode at the fundamental frequency ( ${f}_{0}$ ) and an inner elliptical patch displays a wideband resonance centered at the second-harmonic frequency ( $2{f}_{0}$ ), achieved with hybridization of TM $_{e110}$ and TM $_{o110}$ modes. In particular, the outer split-ring patch is loaded with a fluidic channel system to tune the resonance frequency of the TM $_{3}10$ mode ( ${f}_{0}$ ). We demonstrate that the type of liquid mixture filling in the fluidic cavity can be clearly perceived by reading the peak received signal strength indicator (RSSI) in the spectrum of second harmonics. Our results show the potential for deploying this passive wireless sensor in noisy environments that include clutters, multiple reflections, jamming, and crosstalks.

Aging is associated with dysfunction of the gut microbiota-immune-brain axis, a major regulatory axis in both brain health and in central nervous system (CNS) diseases. Antigen presenting cells (APCs) play a major role in sensing changes in the gut microbiota and regulation of innate and adaptive immune responses. APCs have also been implicated in various chronic inflammatory conditions, including age-related neurodegenerative diseases. The increase in chronic low-level inflammation seen with aging has also been linked to behavioral decline. Despite their acknowledged importance along the gut microbiota-immune-brain axis, there is limited evidence on how APCs change with aging. In this study, we examined age-related changes in myeloid APCs in the gut, spleen, and brain as well as changes in the gut microbiota and behavioral phenotype in mice ranging in age from 2 months up to 32 months of both sexes. Our data show that the number of peripherally-sourced myeloid APCs significantly increases with advanced aging in the brain. In addition, our data showed that age-related changes in APCs are subset-specific in the gut and sexually dimorphic in the spleen. Our work highlights the importance of studying myeloid APCs in an age-, tissue-, and sex-specific manner.

In this article, we design and experimentally demonstrate a flexible, low-profile harmonic transponder sensor, capable of performing multiplexed fluidic sensing. The harmonic transponder comprises multiple reconfigurable electrically small antennas (ESAs) integrated with microfluidic channels for receiving radio frequency (RF) signals at the fundamental frequencies ( $f_{0}$ ), as well as a broadband microstrip monopole for retransmitting the second-harmonic signal ( $2~f_{0}$ ) to a sniffer. Such a frequency orthogonality can help suppressing possible echoes, clutters, and crosstalks in the rich-scattering environment. We show that injection of different liquid samples into a microfluidic channel, which tunes the operating frequency of an ESA, can be precisely recognized by analyzing the shift of peak second-harmonic received signal strength indicator (RSSI) in the frequency-hopping spread spectrum (FHSS). We also demonstrate the possibility of performing rapid and multiplexed noncontact detection with the proposed harmonic transponder sensor. We envision that this battery-free and lightweight multiplexing wireless sensor may benefit various Internet-of-Things (IoTs) and healthcare applications, such as rapid contactless point-of-care (POC) and drive-through tests.

The goal of this study was to compare the efficacy and safety of needle-knife fistulotomy (NKF) to that of conventional cannulation methods (CCMs) when used for primary biliary access in patients with duodenal papillary tumors. Consecutive patients who had duodenal papillary tumors and who underwent endoscopic retrograde cholangiopancreatography (ERCP) were retrospectively enrolled. Successful cannulation rates, cannulation and procedure times, and the prevalence of adverse events were compared between the NKF and CCM groups. A total of 404 patients (NKF, n = 124; CCM, n = 280) with duodenal papillary tumors were included. The primary and overall cannulation rates were 92.1% (372/404) and 96.0% (388/404), respectively. Compared to CCMs, NKF was associated with a significantly higher successful cannulation rate (99.2% versus 88.9%, P

Background Micropapillary-predominant adenocarcinoma (MPA) of the lung is associated with extensive lymph node involvement and rapid terminal metastasis. However, this subtype has been recognized for only a few years, and there have been few studies of the molecular mechanisms associated with its highly invasive behaviors. Methods The present study utilized immunohistochemical staining of surgically resected tissue blocks of MPA and lepidic-predominant lung adenocarcinoma to quantify the expression of specific biological markers in the WNT/β-catenin pathway and evaluate their influence on the lymph nodes invasion of these two types of lung adenocarcinomas. Results Our findings revealed that disruption of the cell membrane cadherin-catenin complex, which weakens the tumor cell adherence of MPA, was caused by the dissociation of β-catenin from the cadherin-catenin complex and the subsequent accumulation of β-catenin in the cytoplasm. This caused abnormal activation of the WNT/β-catenin pathway. We also found that Wnt-1-specific overexpression and Axin1 inhibition in MPA could explain the redistribution and cytoplasmic retention of β-catenin. Collectively, these findings suggest that an abnormality in the WNT/β-catenin pathway could enhance the invasiveness of MPA through the overexpression of Wnt-1 and downregulation of Axin1 molecules. Conclusions Our data support the need for further research regarding the WNT/β-catenin pathway and the need to develop novel targeted therapies for restoration of tumor cell adherence and improvement of the prognosis of MPA.

Cyclin-dependent kinases 4 and 6 (CDK4/6) along with their upstream/downstream components are pivotal regulators for the cell cycle progression. The dysfunction of CDK4/6 is the common feature and promoting factor in various cancer types. In-depth research on CDK4/6 inhibitors has afforded therapeutic agents, while new challenges and ideas are emerging concomitantly.This review focuses on patent publications related to CDK4/6 inhibitors which could be utilized for anti-cancer purposes during the period 2015-2019.The increasingly comprehensive and thorough understanding of CDK4/6 inhibitors facilitates them to break through the current limitations. Hence the utilization of CDK4/6 inhibitors for cancer therapy in the near future is likely to be performed in diverse forms and for distinct purposes. Selectivity over kinases is still crucial to new agent development but shall be prudently dealt with. The gradually revealing of resistance and adverse events proposed another issue that calls for new tackling strategies.

Background The psoas major (PM) can support the lumbar spine and plays an important role in lumbar movement and maintaining lumbar curvature. Purpose To analyze morphological changes of PM and its relation with the severity of adolescent idiopathic scoliosis (AIS). Material and Methods The study was conducted on patients with AIS (age range = 10–18 years) with primary lumbar scoliosis. The cross-sectional area (CSA) of the PM at the L1–L5 levels were measured. The CSA of the PM in patients with AIS was compared with the average CSA of the PM in age-matched controls. The difference in PM at the apical vertebrae level was compared with the Cobb angle to determine the association between PM imbalance and severity of scoliosis. Results The CSA of the PM was larger on the concave side than the convex side at the apical vertebrae level and other lumber levels. Patients with a larger Cobb angle had statistically higher PM imbalance at the apical vertebrae level. The CSA of the PM on both the concave and convex sides of patients with AIS were larger than the average CSA of controls aged 16–18 years; however, there was no significant difference between patients with AIS and controls aged 10–15 years. Conclusion There is a significant PM imbalance in patients with AIS before skeletal maturity, and the imbalance is related to the severity of scoliosis. The morphology of PM changed with the progression of scoliosis.

Patent foramen ovale (PFO) is a potential conduit for paradoxical embolization to the systemic atrial circulation of a thrombus originating in the venous system. In a selected group of subjects, the prevalence of deep vein thrombosis (DVT) was assessed. Subjects were identified if they underwent magnetic resonance venography (MRV) pelvis and lower extremity doppler (LE-VDU) for assessment of DVT with PFO. The primary outcome measure was to report the number of patients with paradoxical embolization as their suspected etiology of stroke due to the presence of DVT, which then will be considered as determined stroke. Others with determined stroke diagnosis were reported using Treatment of Acute Stroke Trial (TOAST) criteria. At discharge, those without etiology of their stroke were grouped under embolic stroke of undetermined source (ESUS). We further analyzed the prevalence of DVT by age group, ≤ 60 years vs > 60 years to describe if the prevalence is higher with younger age and to evaluate if higher Risk of Paradoxical Embolism (ROPE) score will have higher number of DVTs compared to lower ROPE scores. Of the 293, 19 (7%) were strokes due to paradoxical embolism. At discharge, determined stroke were 54% vs ESUS were 46%. The overall prevalence of DVT was 19 (7%); MRV-pelvis 13 (4%), and LE-VDU was 9 (3%). No significant difference was noted using both modalities. However, in multivariable regression analysis, a trend suggested an association between pelvic thrombi and high ROPE score as the etiology of stroke; OR 3.56 (0.98, 12.93); p = 0.054. Detection of DVT was not associated with PFO, high ROPE scores or young age. Our data indicate an over-reliance of testing for DVT, particularly MRV pelvis with contrast, in patients with PFO. Clinical studies are needed to identify other factors predictive of DVT in patients with ischemic stroke and PFO.

Purpose Myocardial ischemia/reperfusion injury (IRI) induces cardiomyocytes death and leads to loss of cardiac function. Circular RNAs (circRNA) have gain increasing interests in modulating myocardial IRI. In this study, we aim to investigate the role and exact mechanism of circTLK1 in the pathogenesis of myocardial IRI. Methods Myocardial IRI was developed in mice with measuring hemodynamic parameters and the activity of serum myocardial enzymes to evaluate cardiac function. HE and TTC staining were performed to assess infarct area. Expression patterns of circTLK1 and miR-214 were investigated using qRT-PCR assay. Gene expression of circTLK1, miR-214 or RIPK was altered by transfecting with their overexpression or knockdown vectors. The apoptosis of cardimyocytes was assessed by TUNEL staining and Caspase-3 activity analysis. Apoptosis-related markers Bcl-2, Bax, and caspase3, as well as TNF-α signals were determined by western blotting. The interactions of circTLK1/miR-214 and miR-214/RIPK1 were verified using luciferase reporter assay. RNA immunoprecipitation (RIP) was subjected to further definite the direct binding of circTLK1/miR-214. The regulatory network of circTLK1/miR-214/RIPK1 was further validated in vivo. Results circTLK1 was an up-regulated circRNA found in a myocardial IRI mouse model. Mice with silencing circTLK1 significantly alleviated the impaired cardiac function indexes and decreased infarct area, thus attenuating the pathogenesis of myocardial IRI. Knockdown of circTLK1 dramatically decreased cardiomyocytes apoptosis, which was determined by apoptosis-related proteins. miR-214 was identified as a downstream effector to reverse circTLK1-mediated damage effects in myocardial IRI. miR-214 could directly target RIPK1 via binding to its' 3′-UTR. Overexpression of RIPK1 led to impaired cardiac function indexes, increased infarct area, and cell apoptosis, which abolished the protective effects of miR-214. The TNF signaling pathway was demonstrated to be involved in the circTLK1/miR-214/RIPK1 regulatory network in myocardial IRI. Conclusion Taken together, our study revealed an up-regulated circRNA, circTLK1, could exacerbate myocardial IRI via targeting miR-214/RIPK1-mediated TNF signaling pathway, which may provide therapeutic targets for treatment.

INTRODUCTION: Stroke is a sexually dimorphic disease. While women account for more stroke deaths, recent data show that after adjusting for age and pre-stroke functional status, mortality is higher in men. Immune responses are key determinants of stroke outcome and may differ by sex. This study examined sex differences in central and peripheral T cell immune responses, systemic effects on gut permeability and microbiota diversity and behavioral outcomes after stroke in aged mice. We hypothesized that there are sex differences in the immune response to stroke in aged animals. METHODS: C57BL/6N mice (20-22 months) were subjected to 60 min middle cerebral artery occlusion, or sham surgery. T cells were quantified in brain and blood at 3, 7 and 15 days (d) post-stroke by flow cytometry. Peripheral effects on gut permeability and microbiota diversity, as well as neurological function were assessed up to 14d, and at 21d (cognitive function) post-stroke. Brain glial fibrillary acidic protein (GFAP) expression was evaluated at 42d post-stroke. RESULTS AND DISCUSSION: Mortality (50% vs 14%, p

Background DNA damage is one of the critical contributors to the occurrence and development of some cancers. APEX1 and APEX2 are the most important molecules in the DNA damage, and APEX1 has been identified as a diagnostic and prognostic biomarker in liver hepatocellular carcinoma (LIHC). However, the expression of APEX2 and its functional mechanisms in LIHC are still unclear. Aim To examine the expression of APEX2 and the potential mechanism network in LIHC. Methods We conducted a pan-cancer analysis of the expression of APEX1 and APEX2 using the interactive TIMER tool. GEO datasets, including GSE14520, GSE22058, and GSE64041, were used to compare the APEX2 expression level in tumor tissues and adjacent non-tumor tissues. Then, we calculated the 5-year survival rate according to the web-based Kaplan-Meier analysis. We included the TCGA liver cancer database in GSEA analysis based on the high and low APEX2 expression, showing the potential mechanisms of APEX2 in LIHC. After that, we conducted Pearson correlation analysis using GEPIA2. Next, we performed quantitative polymerase chain reaction (qPCR) assay to examine the APEX2 levels in normal liver cell line LO2 and several liver cancer cell lines, including HepG2, Huh7, SMMC7721, and HCCLM3. APEX2 in HCCLM3 cells was knocked down using small interfering RNA. The role of APEX2 in cell viability was confirmed using CCK-8. Dual-luciferase reporter assay was performed to examine the promoter activity of CCNB1 and MYC. Results APEX1 and APEX2 are both highly expressed in the tumor tissues of BLCA, BRCA, CHOL, COAD, ESCA, HNSC, LIHC, LUAD, LUSC, READ, and STAD. APEX2 overexpression in LIHC was validated using GSE14520, GSE22058, and GSE64041 datasets. The survival analysis showed that LIHC patients with high expression of APEX2 had a lower overall survival rate, even in the AJCC T1 patients. High level of APEX2 could indicate a lower overall survival rate in patients with or without viral hepatitis. The GSEA analysis identified that kinetochore and spindle microtubules are the two main cellular components of APEX2 in GO Ontology. APEX2 was also positively associated with molecular function regulation of chromosome segregation and DNA replication. The results of KEGG analysis indicated that APEX2 expression was positively correlated with cell cycle pathway and pro-oncogenic MYC signaling. Pearson correlation analysis showed that APEX2 had a significant positive correlation with CCNB1 and MYC. APEX2 level was higher in liver cancer cell lines than in normal liver LO2 cells. Small interfering RNA could knock down the APEX2 expression in HCCLM3 cells. Knockdown of APEX2 resulted in a decrease in the viability of HCCLM3 cells as well as the expression and promoter activity of CCNB1 and MYC. Conclusion APEX2 is overexpressed in LIHC, and the higher APEX2 level is associated with a worse prognosis in overall survival. APEX2 is closely involved in the biological processes of chromosome segregation and DNA replication. APEX2 expression is positively correlated with the pro-oncogenic pathways. Knockdown of APEX2 could inhibit the cell viability and CCNB1 and MYC pathways, suggesting that APEX2 is an oncogene in LIHC, which could be a potential pharmaceutic target in the anti-tumor therapy.

In this study, a new energy efficient welding method called flux bands constricting arc (FBCA) welding was presented. A real-time electrical signal acquisition system and a high-speed camera system were proposed to understand the arc stability in FBCA welding. In ultra-narrow gap groove, the arc voltage and welding current in gas metal arc welding and FBCA welding experiments with various groove gaps (4–10 mm) were acquired. The dynamic characteristics, probability distributions, scatter graphs, and coefficients of variations of voltage and current during welding were adopted to determine the arc stability. Results indicate that flux bands considerably improve the arc stability in the ultra-narrow gap (

An electrically switchable band-edge laser has been demonstrated in a dye-doped polymer-stabilised blue phase liquid crystal. The light intensity of the laser can be tuned in three-dimensional spac...