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Magic-angle twisted bilayer graphene (TBG) has attracted significant interest recently due to the discoveries of diverse correlated and topological states. In this work, we study the phonon properties in magic-angle TBG based on many-body classical potential and interatomic forces generated by a deep neural network trained with data from

Due to the worldwide epidemic of allergic disease and a cure nowhere in sight, there is a crucial need to explore its pathophysiological mechanisms. As allergic disease has been associated with gut dysbiosis, we searched for a possible mechanism from the perspective of the molecular interface between host and microbiota with concurrent metabolomics and microbiome composition analysis. Sprague-Dawley rats were injected with Artemisia pollen extract to stimulate a hyper reaction to pollen. This hyper reaction decreased the circulation of valine, isoleucine, aspartate, glutamate, glutamine, indole-propionate (IPA), and myo-inositol, and reduced short-chain fatty acids (SCFAs) in feces. Several beneficial genera belonging to Ruminococcaceae, Lachnospiraceae, and Clostridiales declined in the model group, whereas Helicobacter and Akkermansia were only expressed in the model group. Furthermore, the expression of intestinal claudin-3 and liver fatty acid binding protein was downregulated in the model group and associated with metabolic changes and bacteria. Our results suggest that alterations in amino acids as well as their derivatives (especially valine, and IPA which is the reductive product of tryptophan) , SCFAs, and the gut microbiome (specifically Akkermansia and Helicobacter) may disrupt the intestinal barrier function by inhibiting the expression of claudin proteins and affecting the mucus layer, which further results in hay fever.

Deep regional hyperthermia might have an additional effect on radiotherapy in treating locally advanced rectal cancer (LARC). This study aimed to investigate the role of hyperthermia combined with modern preoperative concurrent chemoradiotherapy (CRT) for LARC.From 2012 to 2018, 152 consecutive patients with LARC treated with neoadjuvant chemoradiation were enrolled and analyzed retrospectively. Pelvic radiotherapy (45-50 Gy) was delivered as volumetric modulated arc therapy (VMAT), concurrently with capecitabine chemotherapy. Fifty patients received hyperthermia combined with CRT (HCRT group) twice a week. Treatment response and outcomes were compared between the two groups. Furthermore, the relationships between peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) in response to hyperthermia were analyzed.Patients treated with hyperthermia had a significantly higher T-downstaging rate than those without hyperthermia (82.0Hyperthermia can improve preoperative treatment response in LARC. Pretreatment NLR may be a predictive factor for hyperthermia.

In histopathology, doctors identify diseases by characterizing abnormal cells and their spatial organization within tissues. Polarization microscopy and supervised learning have been proved as an effective tool for extracting polarization parameters to highlight pathological features. Here we present an alternative approach based on unsupervised learning to group polarization-pixels into clusters, which correspond to distinct pathological structures. For pathological samples from different patients, it is confirmed that such unsupervised learning technique can decompose the histological structures into a stable basis of characteristic microstructural clusters, some of which correspond to distinctive pathological features for clinical diagnosis. Using hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) samples, we demonstrate how the proposed framework can be utilized for segmentation of histological image, visualization of microstructure composition associated with lesion, and identification of polarization-based microstructure markers that correlates with specific pathology variation. This technique is capable of unraveling invisible microstructures in non-polarization images, and turn them into visible polarization features to pathologists and researchers.

Berberine (BBR) is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes, hyperlipidemia and inflammation. Due to the low oral bioavailability of BBR, its mechanism of action is closely related to the gut microbiota. This study focused on the CYP51 enzyme of intestinal bacteria to elucidate a new mechanism of BBR transformation by demethylation in the gut microbiota through multiple analytical techniques. First, the docking of BBR and CYP51 was performed; then, the pharmacokinetics of BBR was determined in ICR mice in vivo, and the metabolism of BBR in the liver, kidney, gut microbiota and single bacterial strains was examined in vitro. Moreover, 16S rRNA analysis of ICR mouse feces indicated the relationship between BBR and the gut microbiota. Finally, recombinant E. coli containing cyp51 gene was constructed and the CYP51 enzyme lysate was induced to express. The metabolic characteristics of BBR were analyzed in the CYP51 enzyme lysate system. The results showed that CYP51 in the gut microbiota could bind stably with BBR, and the addition of voriconazole (a specific inhibitor of CYP51) slowed down the metabolism of BBR, which prevented the production of the demethylated metabolites thalifendine and berberrubine. This study demonstrated that CYP51 promoted the demethylation of BBR and enhanced its intestinal absorption, providing a new method for studying the metabolic transformation mechanism of isoquinoline alkaloids in vivo., Graphical abstract Image 1, Highlights • The demethylation metabolism of natural drugs difficult to absorb through the gut microbiota was first reported. • Six different methods were presented to explain the metabolic mechanism of natural isoquinoline alkaloids. • The findings provided a new idea for studying the mechanism of drug metabolism of gut microbiota.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)—the cellular receptor of SARS-CoV-2—into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with exceptionally high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was successfully developed as an inhaled formulation that achieves appropriate aerodynamic properties for respiratory system delivery, and we found that aerosol inhalation of HH-120 significantly reduced viral loads and lung pathology scores in golden Syrian hamsters infected by the SARS-CoV-2 wild-type strain and the Delta variant. Our study presents a breakthrough for the inhalation delivery of large biologics like HH-120 (molecular weight ~ 1000kDa) and demonstrates that HH-120 can serve as a highly efficacious, safe, and convenient agent against all SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 will be efficacious against additional emergent coronaviruses.

Background and aimsThe prevalence of metabolic syndrome (MS), wich mainly including hypertension, hyperglycemia, hyperlipidemia, remains high, and the safety and antibody response of inactivated coronavirus disease 2019 (COVID-19) vaccination in patients with metabolic syndrome (MS) is still inconsistency, therefore it is necessary to explore the safety and antibody responses of inactivated COVID-19 vaccination in MS patients in clinical practice.Methods157 adults patients who were suffering from MS and 117 health controls (HC) at an interval of at least 21 days after full-course (2nd dose) vaccination were enrolled. The safety of inactivated COVID-19 vaccination was evaluated through collected adverse events (AEs) by questionnaire. The immunogenicity of included participant to inactivated COVID-19 vaccination was represented by serum seropositivity rate of anti-receptor binding domain (RBD) IgG, SARS-CoV-2 neutralizing antibodies (CoV-2 Nab) and titers of anti-RBD IgG, CoV-2 Nab. The B cells, mainly including RBD-specific B cells, RBD-specific memory B cell (MBC), RBD+ resting MBC cells, RBD+ activated MBC cells, RBD+ atypical MBC cells (atyMBCs), and RBD+ intermediate MBC cells, were also analyzed.ResultsIn terms of safety, all AEs in MS patients were mild and self-limiting, and the incidence was comparable to that of HC participants, with overall AEs within seven days reported in 9.6% (15/157) of 3H and 11.1% (13/117) of HC. Both groups experienced no serious adverse events. As for immunogenicity of MS patients to inactivated COVID-19 vaccination, compared with health controls, the seroprevalence of anti-RBD IgG and CoV-2 Nab was significantly decreased in MS patients (p = 0.000, p = 0.003, respectively), while the titers of anti-RBD IgG (AU/ml) and CoV-2 Nab (μg/ml) were also significant lower in MS patients (p = 0.014, p = 0.002, respectively). As for frequencies of B cells, MS patients had lower frequencies of RBD-specific B cells, RBD+ resting MBCs, and RBD+ intermediate MBCs (p = 0.003, p = 0.000, p = 0.000, respectively), but had a higher frequencies of RBD+ atypical MBCs (p = 0.000) than HC. In comorbidity number subgroups analysis of MS, except frequencies of RBD+ resting MBC cells, RBD+ activated MBC cells and RBD+ intermediate MBC cells had significant difference among three groups (p = 0.035, p = 0.042, p = 0.046, respectively), antibody response had no significant difference among 1H, 2H, and 3H groups (p > 0.05). And took 70 years old as a boundary, also no statistically significant differences (p > 0.05) were found in age subgroups. Lastly, comprehensive analysis in MS patients indicated that interval time after 2nd dose vaccine was the statistical significant factor which impacting antibody response in MS individuals.ConclusionsInactivated COVID-19 vaccines were well-tolerated, but induced a poorer antibody response against SARS-CoV-2 in MS patients comparing to HC participants. Patients with MS should therefore be more proactive in receiving inactivated COVID-19 vaccine, and a booster vaccination may be considered necessary.Clinical trial registrationhttps://clinicaltrials.gov/, identifier: NCT05043246.

BackgroundAdolescents are at high risk of Internet addiction (IA). Previous studies have shown that the occurrence of IA may be associated with childhood trauma and social support to varying degrees. This study aimed to investigate the pathogenesis of IA in adolescents. Further, to explore the potential mediating role of social support in childhood trauma and IA. This study provides theoretical support for future interventions targeting IA in adolescents.MethodsThis study used a descriptive cross-sectional design. The Childhood Trauma Questionnaire (CTQ), Social Support Rating Scale (SSRS), and Young’s Internet Addiction Test (IAT) were used to conduct an anonymous questionnaire survey among randomly selected adolescents aged less than 18 years old in two cities in southern Anhui Province. Descriptive statistics and correlation analysis were used to test the correlation between IA and other variables. A binary logistic regression model was used to explore the influencing factors of IA. Multiple regression models were examined with process macro and bootstrapping to confirm significant mediating effects.ResultsA total of 844 adolescents, equally divided between males and females, participated in this study, and the prevalence of IA in the region was 23.0%. Through the mediation test, the direct effect of childhood trauma on IA was 0.20 (95% CI [0.12, 0.27], p < 0.001), and the mediating effect of social support on childhood trauma and IA was 0.09 (95% CI [0.06, 0.14]).ConclusionThe study showed that childhood trauma significantly affected the incidence of IA in adolescents. Social support had a significant mediating effect on childhood trauma and IA and attenuated its negative effects.

In recent years, machine learning has gradually been applied to building energy-saving designs to reduce the time consumption of the optimization screening stage. However, since most of the existing research scholars come from the fields of computers and engineering, the application of machine learning technology mostly involves complex programming as well as software in the field of engineering, which requires multiple software to be coupled to achieve. In view of the differences between disciplines and the high learning threshold, these theories are difficult to apply and promote in practical work in the field of architecture. In this regard, this paper focuses on the improvement of methods, based on the Grasshopper platform, proposes a detached energy-saving residential form generation design method and process, to explore the optimal energy-saving building form in a more concise and efficient way. Based on this new method, on the basis of verifying its feasibility through a residential building case, two machine learning algorithms, neural network (ANN) and support vector machine (SVM), are compared and studied, and the applicability of these two algorithms in different building performance indicators is further discussed. The results show that the ANN model has the highest accuracy and is more suitable for the prediction of building energy consumption; in view of the simple and fast operation of SVM, it is more suitable for comfort prediction with relatively low accuracy requirements. By combining the above two machine learning methods, work efficiency can be improved while satisfying the prediction of relevant performance indicators. This method can help architects quickly search for the best building energy-saving form design scheme in the scheme design stage and provide data support and information feedback for architects in design conception and deepening.

The objective is to explore the value of preoperative geriatric nutritional risk index (GNRI) in evaluating long-term prognosis in elderly locally advanced rectal cancer (LARC) patients who accepted neoadjuvant chemoradiotherapy (NCRT) and to compare GNRI with established nutritional markers, including prognostic nutritional index (PNI) and controlling nutritional status (CONUT) score.Preoperative GNRI was retrospectively assessed in 172 LARC patients aged ≥ 60 years who underwent radical resection after NCRT at two centers. Optimal cutoff value of GNRI was determined by X-tile program. The association of GNRI with clinicopathological parameters and nutritional markers was analyzed. The survival ability of markers was evaluated using time-dependent receiver-operating characteristic (ROC) curve analysis. Finally, survival analysis was performed using Kaplan-Meier and Cox regression analysis.GNRI was highly correlated with nutritional markers. An optimal cutoff value for the GNRI was 96. In the time-dependent ROC curve, GNRI demonstrated a stable predictive ability for both disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that GNRI was the only nutritional marker that independently predicted DFS (HR 2.457, 95% CI 1.066-5.665, P = 0.035) and OS (HR 9.002, 95% CI 3.100-26.146, P 0.001). As an additional benefit, GNRI was able to stratify survival in subgroups of ypTNM and tumor response.Preoperative GNRI is a promising predictor of long-term survival for elderly LARC patients undergoing NCRT, superior to the established nutritional markers.

Radiotherapy is an effective treatment for certain patients with muscle-invasive bladder cancer and radio-sensitivity detection plays a vital role during bladder cancer radio treatment because radiotherapy responses have profound influences on a patient’s prognosis. Although several potential biomarkers were investigated to assess the radio-response of bladder cancer, studies on detecting radio-sensitivity based on morphological characteristics of cancer cells at the single-cell level are rare. In fact, morphological parameters are vital characteristics of cells that could provide direct information to infer the physiological statuses of cells and evaluate the response of cells to the external stimulations. In this study, digital holographic microscopy was applied to quantify morphological parameters of bladder cancer cells (HT-1376) at the single-cell level and their alterations after exposure to four different radiation doses, i.e., 0 Gy (control), 4, 8, and 12 Gy. Based on the reconstructed phase images, four morphological parameters of cells, namely, cell phase volume (CPV), cell projected area (CPA), cell average phase height (CAPH), and cell maximum phase height (CMPH), were quantitatively calculated. The results show that the change rates of CPV, CAPH, and CMPH were increased with the radiation dose rising, while the change rate of CPA was decreased with the radiation dose increasing. Moreover, the change rates of CPV, CPA, CAPH, and CMPH were different between control group and 12 Gy treated group. The results demonstrate that morphological characteristics have the potential to be utilized to estimate the radio-sensitivity of bladder cancer cells, and it may provide new perspectives to establishing label-free methods to detect radio-sensitivity and guide radiotherapy in bladder cancer.

IntroductionPrimary intrathoracic liposarcoma is extremely rare, and most published series lack genetic analyses. The aim of our study is to better understand the clinicopathologic and genetic features of these rare lesions.Materials and methodsForty-three primary intrathoracic liposarcomas were identified and most cases were analyzed by systematic genetic studies, including fluorescence in situ hybridization (FISH), whole-exome sequencing (WES), and Sanger sequencing.ResultsThis series included 27 males and 16 females (ratios, 1.68:1) aged 24-73 years (median, 53 years). Tumors mainly occurred in the mediastinum (n=23, 53.5%), followed by pleural cavity (n=16, 37.2%) and lung (n=4, 9.3%). The study included 21 well-differentiated liposarcomas (WDLs), 19 dedifferentiated liposarcomas (DDLs), 2 myxoid pleomorphic liposarcomas (MPLs) and 1 pleomorphic liposarcoma (PL), without identification of myxoid liposarcoma. FISH analysis identified MDM2 amplification in 17 of 18 WDLs (94.4%) and all DDLs (16/16, 100.0%). The MDM2-nonamplified WDL was CDK4-nonamplified but FRS2-amplified. WES and Sanger sequencing found somatic TP53 mutation in the 2 MPLs. Follow-up information was available for 33 of 38 cases (86.8%). Thirteen patients (39.4%) showed no evidence of disease, 10 patients (30.3%) were alive with disease, and 8 patients (24.2%) died of disease. Fourteen cases developed recurrence and 1 with metastasis.ConclusionsWDL/DDL was the overwhelming subtype in this location, followed by MPL and PL. Analysis of the FRS2 gene, in combination with MDM2 and other genes of 12q13-15, may more precisely characterize WDL/DDLs. MPL is the most fatal subtype of this site. Further studies are needed to explore the role of TP53 in the pathogenesis of MPL.

Background The factors related to psychological sub-health (PSH) have been widely described, but the research on the mechanism behind the complex relationship between childhood trauma and PSH is limited. This study investigated the current situation and risk factors of PSH among Chinese adolescents. And further, explore whether Internet addiction (IA) plays a potential mediating effect in childhood trauma and PSH. Methods The study was conducted in October 2020 in Anhui Province, China. The PSH state of 866 adolescents was investigated, including demographic information such as gender, age, and grade. Childhood trauma, IA, and PSH were measured by the Childhood Trauma Questionnaire Short Form (CTQ-SF), Young’s Internet Addiction Test (IAT), and the Multidimensional Sub-health Questionnaire of Adolescents (MSQA). The mediating effect is further verified by the structural equation model (SEM). Results In this study, 866 adolescents were selected as subjects, and the proportion of male and female is roughly equal. The prevalence of PSH in adolescents was 25.8%, and left-behind children, boarding, or adolescents who have had non-suicidal self-injury (NSSI) are more likely to have PSH. Through the mediation test, the direct effect of childhood trauma on PSH was 0.23 (95% CI [4.91,9.00],p <0.001), and the mediating effect of IA on childhood trauma and PSH was 0.07 (95% CI [1.42, 3.32],p <0.001). and the proportion of them is 75.14% and 24.86% respectively. Conclusions Childhood trauma has direct and indirect effects on PSH, and IA plays a mediating effect in the indirect effect. Therefore, clarifying these relationships helps formulate and implement effective interventions to improve psychological health (PH) in Chinese adolescents.

Survival improvement of colorectal liver metastasis (CRLM) benefits from systemic therapy and metastasis-directed local therapy. Stereotactic ablative body radiotherapy (SABR), as a new efficient metastasis-directed local therapy with a systematic impact, plays a vital role in CRLM multidisciplinary treatment. SABR leads to a dramatic immunological change in the tumor microenvironment (TME) via differential activation of cytoprotective and cytotoxic pathways in malignant and non-malignant cells, in addition to direct tumor cell death. The synergy of SABR and immunotherapy might increase the abscopal response rate of out-field lesions by targeting different steps of the immune-mediated response, in addition to direct intratumoral cell death. The clinical treatment and efficacy of SABR, its influence on TME, and potential molecular underpinnings of which are the topic of this review.

The incidence of pediatric liposarcoma is rare and most published cases lack systematic genetic analyses. We present clinicopathologic and genetic features of 23 liposarcomas aged

The sex ratio is an important factor affecting the economic benefits of duck groups in the process of hemp duck breeding. However, the current manual counting method is inefficient, and the results are not always accurate. On the one hand, ducks are in constant motion, and on the other hand, the manual counting method relies on manpower; thus, it is difficult to avoid repeated and missed counts. In response to these problems, there is an urgent need for an efficient and accurate way of calculating the sex ratio of ducks to promote the farming industry. Detecting the sex ratio of ducks requires accurate counting of male ducks and female ducks. We established the world’s first manually marked sex classification dataset for hemp ducks, including 1663 images of duck groups; 17,090 images of whole, individual duck bodies; and 15,797 images of individual duck heads, which were manually captured and had sex information markers. Additionally, we used multiple deep neural network models for the target detection and sex classification of ducks. The average accuracy reached 98.68%, and with the combination of Yolov5 and VovNet_27slim, we achieved 99.29% accuracy, 98.60% F1 score, and 269.68 fps. The evaluation of the algorithm’s performance indicates that the automation method proposed in this paper is feasible for the sex classification of ducks in the farm environment, and is thus a feasible tool for sex ratio estimation.

Nodular fasciitis (NF) rarely occurs in infants aged < 2 years although cranial fasciitis develops predominantly in this age group. Histologically, NF may present high cellularity and brisk mitoses, but atypical forms are generally absent. Here, we report a NF in a 22-month-old Chinese boy. Microscopically, the lesion was manifested as cellular variant of NF. Notably, atypical mitotic figures including multipolar form were identified. Immunohistochemically, the neoplastic cells showed strong positivity for smooth muscle actin. Fluorescence in situ hybridization analysis revealed an unbalanced rearrangement of USP6, along with the USP6 increased copies. Subsequent next-generation sequencing-based technology revealed a novel PAFAH1B1-USP6 fusion gene as well as unusual fusion point on USP6 (exon 9). To the best of our knowledge, this is the only reported case with overt atypical mitosis. This case is also the first published example of genetically confirmed infant NF. Additionally, PAFAH1B1-USP6 fusion has never been described in NF.

Objective To describe the clinical characteristics of renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and bland thrombus (BT), and to evaluate the influence of BT on surgical treatment and cancer‐specific survival (CSS) of RCC with VTT. Methods We retrospectively reviewed clinical data of 123 patients with RCC and VTT, who underwent surgical treatment in our center between February 2015 and May 2018. Patients were divided into the BT group (21 patients) and non‐BT group (102 patients). Chi‐square and Mann‐Whitney U test were used for categorical and continuous variables respectively. Univariable log‐rank tests and multivariable Cox regressions were conducted to evaluate the prognostic significance of each variable. Kaplan‐Meier plots were performed to evaluate the influence of BT. Results In the delayed phase of enhanced magnetic resonance imaging (MRI), BT and VTT had difference. Patients were divided according to the relative position of BT: proximal end BT (one patients), contralateral renal vein BT (two patients), distal end BT (12 patients), and multiple BT (six patients). The average length of BT was 8.4 ± 5.8 cm (range: 0.6‐20.0 cm). Patients with BT had longer operative time (P = .001), more surgical blood loss (P = .004), higher proportion of open surgery (P = .006), more postoperative complications (P = .011). BT (hazard ratio [HR] = 3.323, P = .007) were independent risk factors for poor prognosis. Conclusions In the delayed phase of enhanced MRI, BT showed no obvious enhancement, while VTT usually showed enhancement. This was an important basis for preoperative imaging diagnosis of BT. The presence of BT increases the difficulty of surgery, and is correlated with adverse survival outcomes in patients with RCC and VTT., MRI is an important examination for RCC patients with VTT and BT. BT has adverse influence on surgical treatment and survival.

The removal of heavy metals in waste pickling acid by iron powder reduction was studied. The effects of reaction time, reaction temperature and dosage of iron powder on the removal efficiency of Zn, Cr, Ni and Pb in waste pickling acid were investigated. The results showed that, the removal rate of Cr tended to be stable after 2 h of reaction under magnetic stirring. After 4 hours, the removal rate of Zn,Ni and Pb tended to be stable. The temperature was increased from 20°C to 90 °C, the removal rates of Ni and Pb could be increased by 9.09% and 11.6%, while the removal rates of Zn and Cr were only increased by 1.15% and 2.85%; Increasing the dosage of iron powder was beneficial to the removal of heavy metals in waste pickling acid, and the combined amount of free acid in the waste acid would affect the removal efficiency of heavy metals. The research results had important guiding significance for the practical application of iron powder reduction method in the heavy metal purification project of waste pickling acid.

The progression of hyperuricemia disease is often accompanied by damage to renal function. However, there are few studies on hyperuricemia nephropathy, especially its association with intestinal flora. This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition. The results showed that amino acid metabolism was disturbed with serine, glutamate and glutamine being downregulated whilst glycine, hydroxyproline and alanine being upregulated. The combined glycine, serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00. Imbalanced intestinal flora was also observed. Flavobacterium, Myroides, Corynebacterium, Alcaligenaceae, Oligella and other conditional pathogens increased significantly in the model group, while Blautia and Roseburia, the short-chain fatty acid producing bacteria, declined greatly. At phylum, family and genus levels, disordered nitrogen circulation in gut microbiota was detected. In the model group, the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation. The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy. Hence, modulation of gut microbiota or targeting at metabolic enzymes, i.e., urease, could assist the treatment and prevention of this disease., Graphical abstract The combination of metabolomics and 16S rRNA analysis revealed a panel of metabolites and bacterial strains changing with the progression of hyperuricemia nephropathy. In the case of disease, nitrogen circulation in the gut microbiota was dysregulated with enhanced urate decomposition pathway and urea liver-intestinal circulation, causing kidney damage.Image 1

Bifidobacteria is an important microbe that inhabits the human gut. It is capable of metabolizing complex compounds in the human diet. Albiflorin, an antidepressant natural product from Radix Paeoniae Alba in China, is difficult to absorb after oral administration, and its metabolism has been proven to be closely related to the gut microbiota. In this study, we demonstrated in vitro that several Bifidobacteria species were able to convert albiflorin to benzoic acid, and four esterases (B2, B3, B4, and BL) from Bifidobacterium breve and Bifidobacterium longum were found through genome mining and modeled by SWISS-MODEL. B2 and B3 presented the strongest albiflorin metabolism ability. The optimal conditions, including temperature, buffer, and pH, for the conversion of albiflorin by the four esterases were investigated. Furthermore, the effect of esterase on the metabolism of albiflorin in vivo was confirmed by transplanting bacteria containing esterase B2. This study demonstrated the vital role of esterases from Bifidobacteria in the metabolism of natural compounds containing ester bonds, which could contribute to the development of new enzymes, microbial evolution, and probiotic adjuvant compounds for treatment.

ObjectiveCardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI) despite advances in care. This study aims to derive and validate a risk score for in-hospital development of CS in patients with AMI.MethodsIn this study, we used the Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome (CCC–ACS) registry of 76,807 patients for model development and internal validation. These patients came from 158 tertiary hospitals and 82 secondary hospitals between 2014 and 2019, presenting AMI without CS upon admission. The eligible patients with AMI were randomly assigned to derivation (n = 53,790) and internal validation (n = 23,017) cohorts. Another cohort of 2,205 patients with AMI between 2014 and 2016 was used for external validation. Based on the identified predictors for in-hospital CS, a new point-based CS risk scheme, referred to as the CCC–ACS CS score, was developed and validated.ResultsA total of 866 (1.1%) and 39 (1.8%) patients subsequently developed in-hospital CS in the CCC–ACS project and external validation cohort, respectively. The CCC–ACS CS score consists of seven variables, including age, acute heart failure upon admission, systolic blood pressure upon admission, heart rate, initial serum creatine kinase-MB level, estimated glomerular filtration rate, and mechanical complications. The area under the curve for in-hospital development of CS was 0.73, 0.71, and 0.85 in the derivation, internal validation and external validation cohorts, respectively.ConclusionThis newly developed CCC–ACS CS score can quantify the risk of in-hospital CS for patients with AMI, which may help in clinical decision making.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT02306616.

The factors associated with non-suicidal self-injury (NSSI) of adolescents have been widely researched. However, the underlying mechanism of the relationship between childhood trauma and NSSI is limited. This study aimed to explore the risk factors for NSSI among Chinese adolescents. Our hypothesis was that psychological sub-health (PSH) played a mediating role between childhood trauma and NSSI. The Childhood Trauma Questionnaire, the Multidimensional Sub-health Questionnaire of Adolescent, and the self-report NSSI were used to measure childhood trauma, PSH, and NSSI. Structural equation model (SEM) was performed to verify our hypothesis. The results showed that 33.9% of the participants in our survey had engaged in NSSI in the past year. Adolescents who were left-behind children or in primary schools were more likely to engage in NSSI. Additionally, 56.2% of the participants had moderate to severe childhood trauma, and 26.1% of the participants had PSH. Furthermore, childhood trauma and PSH would increase the risk of NSSI by 2 times (B = 0.79, p < 0.01) and 5 times (B = 1.64, p < 0.01), respectively. SEM was established (p = 0.512) and the goodness-of-fit indices were examined (CMIN/DF = 0.892; GFI = 0.997; AGFI = 0.992; NFI = 0.991; RFI = 0.980; IFI = 1.00; TLI = 1.00; CFI = 1.00; RMSEA < 0.001). The SEM indicated that childhood trauma positively predicted NSSI both directly and indirectly through PSH. PSH has been confirmed to have partial mediating effects between childhood trauma and NSSI. The assessment of PSH may be an operable and effective method to screen and predict NSSI. Meanwhile, the intervention of childhood trauma and PSH may effectively prevent and reduce the occurrence of NSSI among adolescents.

Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO production in the gut microbiota and treat atherosclerosis. Effects of BBR on TMAO production in the gut microbiota, as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacterial, HFD-fed animals and atherosclerotic patients, respectively. We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase (CutC) and flavin-containing monooxygenase (FMO) in the gut microbiota. This action was performed by BBR’s metabolite dihydroberberine (a reductive BBR by nitroreductase in the gut microbiota), via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway. Oral BBR decreased TMAO production in animal intestine, lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters. Moreover, 21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2% after oral BBR (0.5 g, bid) for 4 months (*P n = 21); whereas the plaque score in patients treated with rosuvastatin plus aspirin, or clopidogrel sulfate or ticagrelor (4 months, n = 12) increased by 1.9%. TMA and TMAO in patients decreased by 38 and 29% in faeces (*P P P P

Conventional energy-integration black-white X-ray imaging lacks spectral information of X-ray photons. Although X-ray spectra (energy) can be distinguished by photon-counting technique typically with CdZnTe detectors, it is very challenging to be applied to large-area flat-panel X-ray imaging (FPXI). Herein, we design multi-layer stacked scintillators of different X-ray absorption capabilities and scintillation spectrums, in this scenario, the X-ray energy can be discriminated by detecting the emission spectra of each scintillator, therefore the multispectral X-ray imaging can be easily obtained by color or multispectral visible-light camera in one single shot of X-ray. To verify this idea, stacked multilayer scintillators based on several emerging metal halides were fabricated in the cost-effective and scalable solution process, and proof-of-concept multi-energy FPXI were experimentally demonstrated. The dual-energy X-ray image of a bone-muscle model clearly showed the details that were invisible in conventional energy-integration FPXI. By stacking four layers of specifically designed multilayer scintillators with appropriate thicknesses, a prototype FPXI with four energy channels was realized, proving its extendibility to multispectral or even hyperspectral X-ray imaging. This study provides a facile and effective strategy to realize energy-resolved flat-panel X-ray imaging.

With the rapid development of complex equipment, such as airplanes, the appropriate design of the human-machine interface is often upgraded, thus emerged many methods to evaluate whether such an upgrade is effective. Most researches focus on the time accumulation effect of the human state during the interaction to evaluate the interface. However, in the aviation application, the performance of the pilot’s instantaneous reactions also reveals the design efficiency of the interface, since the difficulty level of obtaining the useful information would severely influence the reaction time in some voice command tasks or emergency situations. Besides, there are so many flight scenarios that are impossible to be simulated in experiments or in a laboratory environment. Also, voice commands are too numerous to be traversed simulated. This paper introduced predicted auditory reaction time as an index to evaluate human-machine interface design. The proposed method has two advantages. On the one hand, it effectively measures the pilot’s auditory reaction time based on the eye movement tracking; thus, the data can be taken in flight task scenarios, and the experiment would not cause interference to the subjects. On the other hand, a prediction model is proposed, in which the pilot’s reaction time under more generalized voice command can be estimated based on a small-size sample set.

Background The fibroblast growth factor receptor substrate 2 (FRS2) gene is located close to MDM2 and CDK4 within the 12q13-15 chromosomal region. FRS2 gene was recently found to be consistently amplified in atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDL) and dedifferentiated liposarcoma (DDL), suggesting the detection of FRS2 amplification could be a diagnostic tool for ALT/WDL/DDLs. However, the expression of FRS2 protein and diagnostic value of FRS2 immunohistochemistry (IHC) has not been evaluated in a large cohort of ALT/WDL/DDLs. Methods A SNOMED search of hospital surgical pathology files from January 2007 to July 2020 identified 182 ALT/WDL/DDLs with available materials. FRS2 fluorescence in situ hybridization (FISH) and IHC were performed on 182 ALT/WDL/DDLs and 64 control samples. The expression of FRS2 was also compared with that of classic immunomarkers (MDM2 and CDK4) of this tumor entity. Results This study included 91 ALT/WDLs and 91 DDLs. The FISH results showed 172 of 182 (94.5%) cases were FRS2-amplified, and 10 cases were FRS2-nonamplified. Immunostaining results showed 171 (94.0%) ALT/WDL/DDLs were positive for FRS2 and 11 cases (6.0%) were FRS2-immunonegative. In 172 FRS2-amplified cases, 166 (96.5%) were FRS2-immunopositive, and 6 (3.5%) were negative. Among 10 FRS2-nonamplified ALT/WDL/DDL cases, 5 cases were FRS2-immunonegative, and 5 tumors displayed 1+ staining for this marker. In 64 control cases, none of them exhibited FRS2 amplification. Forty-seven (73.5%) control cases were negative for FRS2 immunostaining, while 17 cases (26.5%) were FRS2-immunopositive. Fifteen of these false positive samples (15/17, 88.2%) showed 1+ positivity and only 2 cases (2/17, 11.8%) displayed 2+ positivity. In ALT/WDL/DDLs, the sensitivity of FRS2 immunostaining was slightly lower than MDM2 (FRS2 vs. MDM2: 94.0% vs 100.0%) and CDK4 (FRS2 vs. CDK4: 94.0% vs 97.0%). However, the specificity of FRS2 (73.5%) was slightly higher than that of MDM2 (67.8%) and CDK4 (64.4%). Conclusion This study indicated that FRS2 IHC had relatively good consistency with FRS2 FISH, suggesting that FRS2 immunostaining could be utilized as an additional screening tool for the diagnosis of ALT/WDL/DDL. It must be emphasized that MDM2/CDK4/FRS2 especially MDM2 FISH remains the gold standard and the most recommended method to diagnose this entity.

There is great interest in the development of micromotors which can convert energy to motion in sub-millimeter dimensions. Micromachines take the micromotor concept a step further, comprising complex systems in which multiple components work in concert to effectively realize complex mechanical tasks. Here we introduce light-driven micromotors and micromachines that rely on optoelectronic tweezers (OET). Using a circular micro-gear as a unit component, we demonstrate a range of new functionalities, including a touchless micro-feed-roller that allows the programming of precise three-dimensional particle trajectories, multi-component micro-gear trains that serve as torque- or velocity-amplifiers, and micro-rack-and-pinion systems that serve as microfluidic valves. These sophisticated systems suggest great potential for complex micromachines in the future, for application in microrobotics, micromanipulation, microfluidics, and beyond., Light-driven micromotors can convert energy to motion in sub-millimeter dimensions. Here, the authors extend this concept and introduce reconfigurable micromachines with multiple components, driven by optoelectronic tweezers, and demonstrate new functionalities.

Objectives The objective of this study was to evaluate the efficacy and safety of CT-guided radioactive 125I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma (HNSTS) after surgery and external beam radiotherapy. Methods and Materials From December 2006 to February 2018, 25 patients with locally recurrent HNSTS after surgery and external beam radiotherapy were enrolled. All the patients successfully underwent CT-guided 125I seed implantation. The primary end points included the objective response rate (ORR) and local progression-free survival (LPFS). The secondary end points were survival (OS) and safety profiles. Results After 125I seed implantation, the ORR was 76.0%. The 1-, 3-, and 5-year LPFS rates were 65.6%, 34.4%, and 22.9%, respectively, with the median LPFS of 16.0 months. The 1-, 3-, and 5-year OS rates were 70.8%, 46.6%, and 34.0%, respectively, with the median OS of 28.0 months. Furthermore, univariate analyses showed that the recurrent T stage and histological grade were prognostic factors of LPFS, whereas only the histological grade was a predictor of OS. The major adverse events were skin/mucosal toxicities, which were generally of lower grade (≤Grade 2) and were well tolerated. Conclusions Radioactive 125I seed implantation could be an effective and safe alternative treatment for locally recurrent HNSTS after failure of surgery and radiotherapy. Recurrent T stage and histological grade were the main factors influencing the efficacy.

Multifunctionality is an essential feature for the application of soft actuators in the fields of soft robotics, flexible electronics, and energy generators. Accordingly, liquid crystal polymer networks (LCNs) afford a promising platform for designing multifunctional soft actuators due to their reversible, programmable, and multi-stimuli-responsive shape changing behaviors via the self-organization of liquid crystals. Although the introduction of functional components (e.g. conductive and magnetic fillers) has been considered to be an effective approach to exploit multifunctional LCN soft actuators, it remains a great challenge to integrate a particular role of functional components while maintaining inherent shape changing capabilities of LCNs. Herein, we report a facile method to achieve multifunctional LCN soft actuators by directly injecting the desired functional component in the liquid state into LCN tubular actuators. In our design, the LCN tubular actuators prepared via the mechanical programming process act as a structural framework, providing reversible shape changing behaviors with a large strain both in length and inner diameter. To introduce conductive functionality, liquid metals (LMs) are selected as the functional component due to their ultrahigh conductivity and controllable melting point. The multifunctional LCN soft actuators elegantly couple ultrahigh conductivity of the LMs and original shape changing behaviors of the LCN tubular actuators and are demonstrated as a thermal-responsive electrical switch.

To ascertain the safety and efficacy of radioactive iodine-125 seed implantation (RISI) for the treatment of thoracic tumors.Clinical patients with primary or metastatic tumors in the chest treated with RISI were analyzed. The RISI process included the following stages: preoperative planning, template design and 3D printing, CT-guided RISI assisted by a template, and postoperative dosimetric verification. The prescribed dose was ≥ 80 Gy. The main analytic measures were the local control (LC) rate and toxicity.From April 2015 to July 2018, a total of 92 patients, including 41 with lung cancer and 51 with lung metastases, were analyzed. The median lesion diameter was 5 cm. The median postoperative D90 was 142.6 Gy. The median follow-up was 10.7 months. The overall survival rates at 1 year and 3 years were 59.7% and 22.2%, respectively. The LC rates at 1 year and 3 years were 64.9% and 32.8%, respectively. The LC rates at 3 years for patients with D90 140 Gy and D90 140 Gy were 23.1% and 54.3%, respectively (P = 0.014). The LC rate of metastatic lung cancer was more favorable than that of primary lung cancer. The multivariate analyses showed that the dose and lesion type were independent factors for LC (P 0.05). No factors were related to OS. The incidence of pneumothorax and hemoptysis was 35.8% and 3.2%, respectively. Few cases of radiotherapy-related toxicity effects were observed.RISI may be safe and efficacious and is associated with few complications during the treatment of thoracic tumors. If patients need local treatment and surgery or radiotherapy is not available, RISI could be considered.

Purpose We compared the three-dimensional printed non-coplanar template (3DPNCT) plans with 3D-printed coplanar template (3DPCT) plans for radioactive seed implantation (RSI) in lung cancer and explored the differences between the two technologies. Material and methods 33 patients with peripheral lung cancer that received 3DPCT-assisted RSI in our department between June 2017 and February 2018 were analyzed. A 3DPNCT plan was re-designed for all patients. The prescribed dose and seed activity in the new plan were the same as the 3DPCT plan. The data in the two plans were compared, including seed number, needle number, number of needles needed to cross the ribs, and dosimetry parameters. Dosimetry parameters included D90, Dmean, MPD (minimum peripheral dose), V100, V150, CI (conformity index), EI (external index), HI (homogeneity index) of target volume, D2cc of spinal cord and aorta, and V20 of affected side lung. We used a paired t-test and two groups of related non-parameters tests to examine statistical significance. A p value < 0.05 was considered statistically significant. Results We found no significant difference in dosimetry parameters (p > 0.05), except MPD. The mean MPD of the 3DPNCT plan was significantly higher than the 3DPCT plan (88.5 Gy and 81.8 Gy, respectively, p = 0.017). The number of needles used in the 3DPNCT plan and the number of needles needed to cross the ribs were significantly less compared with the 3DPCT plan (p = 0.000). Conclusions The dose distributions of the two 3DPCT plans were similar. 3DPNCT plan had a higher dose in target volume margin, with fewer needles and fewer breaks to the ribs.

Body area network (BAN) is a key technology of solving telemedicine, where protecting security of vital signs information becomes a very important technique requirement. The traditional encryption methods are not suitable for BANs due to the complex algorithm and the large consumption. This paper proposes a new encryption method based on the QRS complex of the ECG signal, which adopts the vital signs from the BAN system to form the initial key, utilizes the LFSR (Linear Feedback Shift Register) circuit to generate the key stream, and then encrypts the data in the BANs. This new encryption method has the advantages of low energy consumption, simple hardware implementation, and dynamic key updating.

Summary Background To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. Methods This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18–75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3–4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio ClinicalTrials.gov , number NCT00793962 . Findings Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2–81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8–10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4–10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI −3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p Interpretation Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. Funding National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.

The COVID-19 pandemic has led to thinking about the response to sudden-onset disasters, for which the transportation resilience of urban areas is crucial. The purpose of paper is to provide a graded assessment of urban transportation resilience to help city managers target policies and plans. Wuhan, the first city in China to be severely hit by COVID-19, was selected as the case study for this research. Based on an extensive survey of the travel characteristics of residents in central urban areas, the concept of “travel mode shift” was combined to classify residents into four modes, including non-motorized conventional travel, non-motorized over-distance travel, motorized adaptable travel and motorized non-substitutable travel. The potential transportation stoppages in different levels of epidemic impact were then divided into three scenarios, corresponding to each of the city’s three levels of transportation resilience. The concept of MWD (Maximum Willingness Distance) in active travel mode was further developed, which was divided into WMWD (Walking Maximum Willingness Distance) and RMWD (Riding Maximum Willingness Distance). Finally, a hierarchical assessment model of urban transportation resilience is developed based on the MWD distance threshold. Besides, the average income level of urban residents was also included in the assessment system. The following research conclusions were drawn: (1) The degree of transportation resilience in Wuhan showed an “S-curve” relationship with RMWD, with thresholds at RMWD = 2.5 km, 11 km and 23 km respectively. (2) The resilience of transportation in the suburbs of the city was weaker than in the city center, and the gap between the two increases as the RMWD increases, but the share of motorized transportation in short distance trips in the city center was still higher than desirable. (3) The upper-income groups in the city had more flexible travel options, while the lower income groups were less resilient to travel. Based on the results of the study, it is recommended that city managers can identify areas of low resilience and critical distance thresholds that may lead to sudden changes in transportation resilience in the event of a sudden disaster. This will lead to the development of improved policies. The special needs of socially disadvantaged groups should also be taken more into account in this process.

Sarcopenia is a systemic disease with progressive and generalized skeletal muscle dysfunction defined by age-related low muscle mass, high content of muscle slow fibers, and low muscle function. Muscle phenotypes and sarcopenia risk are heritable; however, the genetic architecture and molecular mechanisms underlying sarcopenia remain largely unclear. In recent years, significant progress has been made in determining susceptibility loci using genome-wide association studies. In addition, recent advances in omics techniques, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, offer new opportunities to identify novel targets to help us understand the pathophysiology of sarcopenia. However, each individual technology cannot capture the entire view of the biological complexity of this disorder, while integrative multi-omics analyses may be able to reveal new insights. Here, we review the latest findings of multi-omics studies for sarcopenia and provide an in-depth summary of our current understanding of sarcopenia pathogenesis. Leveraging multi-omics data could give us a holistic understanding of sarcopenia etiology that may lead to new clinical applications. This review offers guidance and recommendations for fundamental research, innovative perspectives, and preventative and therapeutic interventions for sarcopenia.

The division and prediction of river basins provide important theoretical support for mountain torrents, flow direction control and governance. This paper takes Shuangliu District of Chengdu as the main research area. The experiment is supported by the elevation data of Fuhe River in Huanglongxi Town, Yong’an Town, Shuangliu District of Chengdu from 2020 to 2021. By constructing the model database, dividing the spatial unit of the basin and predicting the river trend, the arcswat model for the River Basin of Shuangliu District of Chengdu is established. The results show that the preliminary watershed area obtained by introducing elevation image analysis is the best. In the follow-up test, by combining the calculated results of hydrological system characteristics in the database with the weather data obtained from the world weather database, it better fitted the water conditions of Shuangliu area and showed excellent performance.

It has been reported that monoamine neurotransmitters can be produced by gut microbiota, and that several related metabolites of amino acids in these pathways are associated with nervous system (NVS) diseases. Herein, we focused on three pathways, namely, phenylalanine (Phe), tryptophan (Trp), and glutamic acid (Glu), and established an underivatized liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the quantification of nineteen monoamine neurotransmitters and related metabolites in the gut microbiota. The neurotransmitters and related metabolites included Phe, tyrosine (Tyr), l-dopa (Dopa), dopamine (DA), 3-methoxytyramine, Trp, hydroxytryptophan, 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), kynurenine (KN), kynurenic acid (KYNA), melatonin, tryptamine (TA), indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), indolyl-3-propionic acid (IPA), Glu, gamma-aminobutyric acid (GABA), and acetylcholine (Ach). A fluoro-phenyl bonded column was used for separation, and the mobile phase consisted of methanol:acetonitrile (1:1) and water, with 0.2% formic acid in both phases. The compounds exhibited symmetric peak shapes and sufficient sensitivity under a total analysis time of 8.5 min. The method was fully validated with acceptable linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The results showed that neurotransmitters, such as Dopa, DA, 5-HT, GABA, and Ach, were present in the gut microbiota. The metabolic pathway of Trp was disordered under depression, with lower levels of 5-HT, 5-HIAA, KN, KYNA, TA, ILA, IAA, IPA, and Glu, and a higher ratio of KYNA/KN. In addition, some first-line NVS drugs, such as sertraline, imipramine, and chlorpromazine, showed regulatory potential on these pathways in the gut microbiota.

Monolithic fault detection methods have low accuracy for comprehensive faults detection, because they can only detect specific type of faults. Therefore, it is necessary to study the combination of fault detection methods to improve the detection accuracy. In this paper, based on the fault propagation on component-based aerospace embedded software architecture, we analyze occur reasons, manifestations and effects of instruction-, component- and system-level faults whose root cause is single event upset (SEU) which is the main reason of aerospace embedded software, and propose a hierarchical fault model to specify characteristics of the three levels faults. And based on the hierarchical fault model, a hierarchical detection method is proposed to combine the three levels monolithic fault detection methods. The experimental results show that the hierarchical fault detection method has higher fault detection accuracy than the monolithic fault detection methods for comprehensive faults detection.

Twisted graphene systems have draw significant attention due to the discoveries of various correlated and topological phases. In particular, recently the alternating twisted trilayer graphene is discovered to exhibit unconventional superconductivity, which motivates us to study the electronic structures and possible interesting correlation effects of this class of alternating twisted graphene systems. In this work we consider generic alternating twisted multilayer graphene (ATMG) systems with $M$-$L$-$N$ stacking configurations, in which the $M$ ($L$) graphene layers and the $L$ ($N$) layers are twisted by an angle $\theta$ (-$\theta$). Based on analysis from a simplified $\textbf{k}\!\cdot\!\textbf{p}$ model approach, we analytically derive generic partition rules for the low-energy electronic structures, which exhibit various intriguing band dispersions including one pair of flat bands, two pairs of flat bands, as well as flat bands co-existing with with Dirac cones, quadratic bands, or more generally $E(\mathbf{k})\!\sim\!k^J$ dispersions ($J$ is positive integer) for each spin and valley. Such unusual non-interacting electronic structures may have unconventional correlation effects. Especially for a mirror symmetric ATMG system with two pairs of flat bands (per spin per valley), we find that Coulomb interactions may drive the system into a state breaking both time-reversal and mirror symmetries, which can exhibit a novel type of orbital magnetoelectric effect due to the interwining of electric polarization and orbital magnetization orders in the symmetry-breaking state.

Background: To assess the efficacy and prognosis of computed tomography (CT)-guided 125I radioactive seeds implantation brachytherapy (RSI-BT) for recurrent nasopharyngeal carcinoma (NPC) after external beam radiotherapy (EBRT). Methods: Thirty-one patients with recurrent NPC (forty-one lesions) after EBRT from February 2003 to January 2019 were enrolled in this retrospective study. The work-follow of CT-guidance RSI-BT was: indication selection, patient set-up and immobilization on CT couch, CT-simulation, preoperative planning, prescription doses (PD) definition of 110-160Gy, seed implantation, postoperative dosimetric evaluation and postoperative follow-up. Median radioactivity of RSI was 0.43 (range 0.22-0.79, average 0.61) mCi. Median actuarial number of 125I seeds was 24 (range 3-83, average 37). Median value of post-operative D90 was 118.5 (range 62.4-246, average 136.2) Gy. Local control (LC) and overall survival (OS) were investigated for their relationship with the prognosis. The adverse events were evaluated by the Radiation Therapy Oncology Group (RTOG) classification criteria. Results: Median follow-up was 41.9 (range 2.1-60.2, average 44.1) months. Median LC was 35.8 (range 2.1-60.2, average 34.9) months. LC at 1-, 3- and 5-year was 71.3%, 41.9% and 27.9%, respectively. Median OS was 22.6 (range 2.1~60.2, average 27.1) months. OS at 1-, 3- and 5-years was 57.7%, 23.8% and 11.9%, respectively. Univariate analysis suggested that sex (P=0.037) and frequency of previous EBRT (P=0.001) were prognostic factors influencing LC. Moreover, univariate analysis also suggested that frequency of previous EBRT (P=0.012) was prognostic factors influencing OS. Prevalence of side effects (≥grade 3) was 6.5%. Conclusion: 125I RSI-BT was a safe and feasible salvage treatment for recurrent NPC after EBRT. Key words: recurrent nasopharyngeal carcinoma; External beam radiotherapy; 125I seed implantation brachytherapy; overall survival; local control; side effects.