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Abstract Background Surgical treatment for renal cell carcinoma (RCC) and inferior vena cava (IVC) tumor thrombus (TT) is difficult, and the postoperative complication rate is high. This study aimed to explore the safety and oncologic outcomes of neoadjuvant stereotactic ablative body radiotherapy (SABR) combined with surgical treatment for RCC and IVC-TT. Methods Patients with RCC and IVC-TTs were enrolled in this study. All patients received neoadjuvant SABR focused on the IVC at a dose of 30 Gy in 5 fractions, followed by 2 ~ 4 weeks of rest. Then, radical nephrectomy and IVC tumor thrombectomy were performed for each patient. Adverse effects, perioperative outcomes, and long-term prognoses were recorded. Results From June 2018 to January 2019, 8 patients were enrolled—4 with Mayo grade II TT and 4 with Mayo grade III TT. Four (50%) patients had complicated IVC wall invasion according to CT/MRI. All patients received neoadjuvant SABR as planned. Short-term local control was observed in all 8 patients. Only Grade 1–2 adverse events were reported. In total, 3 (37.5%) laparoscopic surgeries and 5 (62.5%) open surgeries were performed. The median operation time was 359 (IQR: 279–446) min, with a median intraoperative bleeding volume of 750 (IQR: 275–2175) ml. The median postoperative hospital stay was 7 (5–10) days. With a 26-month (range: 5–41) follow-up period, the estimated mean overall survival was 30.67 ± 5.38 months. Conclusions This is the first preoperative radiotherapy study in Asia that focused on patients with TT. This study revealed the considerable safety of neoadjuvant SABR for RCC with IVC-TT. Trial registration This study was registered in the Chinese Clinical Trials Registry on 2018-03-08 (ChiCTR1800015118). For more information, please see the direct link ( https://www.chictr.org.cn/showproj.html?proj=25747 ).

Effectively incorporating technology into teaching and learning can be accomplished through the application of information and communication technology (ICT). Nonetheless, the extent to which ICT is employed in educational environments is heavily impacted by numerous factors. Teachers' ICT integration in China was investigated with the aim of identifying the specific factors that influence it. The research sample consists of 680 educators, and it highlights three primary elements that affect their adoption of ICT: attitudes, self-efficacy, and digital competence. Employing a partial least squares structural equation modeling (PLS-SEM) method, the results indicate that all three elements play a significant role in the effective integration of ICT by educators. The study also indicated the mediating effect of attitudes and digital competence. Furthermore, the research identified no substantial disparities in the factors based on sex or age, except for the correlation between self-efficacy and attitudes. By providing useful insights for the development of successful instructional designs that integrate ICT, this study contributed to the advancement and impact of educational technology.

Abstract 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.

C1q domain-containing (C1qDC) proteins are significant pattern recognition receptors in the innate immune system that play important roles in regulating immune responses in vertebrates and invertebrates. In this study, a gene encoding the fish C1qDC (designated CiC1ql2) from the grass carp Ctenopharyngodon idella was characterized for the first time. Like other reported C1ql proteins, CiC1ql2 contains a conserved C1q domain and a signal peptide at its 5′ end. Expression profile analysis revealed that CiC1ql2 was mostly expressed in the intestine but was expressed at low levels in the brain and gill. In vivo injection experiments directly revealed that CiC1ql2 exhibited strong responsiveness to Aeromonas hydrophila, Aeromonas veronii and pathogen-associated molecular pattern (PAMP) challenge, as indicated by the presence of lipopolysaccharide (LPS) and peptidoglycan (PGN), and that the expression of these genes was significantly upregulated in the intestine of C. idella. Additionally, the recombinant CiC1ql2 protein obviously promoted the agglutination of the gram-negative bacteria A. hydrophila and A. veronii and the gram-positive bacterium Bacillus subtilis, as shown by in vitro binding experiments. Moreover, CiC1ql2 protein injection experiment revealed that CiC1ql2 significantly enhanced the expression levels of classic complement genes (C3, C5, and C7) and inflammatory cytokines (TNF-α, IL-1β, and IL-8), while knockdown of CiC1ql2 decreased the expression of these immune-related genes. Taken together, our results suggested that CiC1ql2 could act as a pathogenic pattern recognition receptor involved in complement activation and that this might be related to the intestinal defense of C. idella against bacterial infection.

PurposeThis study analyzes the relationship of alexithymia, childhood trauma, and body investment to non-suicidal self-injury (NSSI) behaviors in adolescents with depressive disorder and whether they have predictive and diagnostic value for non-suicidal self-injury (NSSI) behaviors in adolescents with depressive disorder.Patients and methodsA total of 225 patients with a diagnosis of adolescent depressive disorder were included in the study and were divided into two groups according to the DSM-5 criteria: 98 cases without NSSI and 127 cases with NSSI. Compare the demographic data, 24-item Hamilton Depression Scale (HAMD-24), 20-item Toronto Alexithymia Scale (TAS-20), Childhood Trauma Questionnaire-Short Form (CTQ-SF), and Body Investment Scale (BIS) scores between two groups. Binary logistic regression was used to analyze the independent risk factors contributing to NSSI behaviors in adolescents with depression, and establish four predictive models. Based on the models’ predictive probability, the ROC curves were plotted to calculate the value of the predictive diagnostic effect.ResultsThe group without NSSI had lower scores than the group with NSSI on HAMD-24 total score, TAS-20 total score, difficulty identifying feelings, difficulty describing feelings, and externally focused thinking, as well as lower scores on CTQ-SF total score, physical neglect, emotional neglect, physical abuse, and emotional abuse. In contrast, the BIS total score, body image feelings and attitudes, body care, and body protection factor scores were higher for the group without NSSI. The BIS body care factor score and the CTQ-SF emotional abuse factor score were significantly linked with adolescents diagnosed with depressive disorder who exhibited NSSI behaviors. These results provide a good diagnostic model for adolescents with depressive disorder.ConclusionLow levels of body care and childhood emotional abuse may independently contribute to the implementation of NSSI in adolescents with depressive disorder. Body investment and childhood trauma are valuable in diagnosing and predicting NSSI behaviors and should be considered as potentially important factors in clinical treatment.

Based on Boyd’s “Observation Orientation-Decision-Action (OODA)” aerial combat theory and the principles of operational success, an analysis of the operational division patterns for cross-generational human-machine collaboration was conducted. The research proposed three stages in the development of aerial combat human-machine fusion intelligence: “Human-Machine Separation, Functional Coordination,” “Human-Machine Trust, Task Coordination,” and “Human-Machine Integration, Deep Fusion.” Currently, the transition from the first stage to the second stage is underway, posing challenges primarily related to the lack of effective methods guiding experimental research on human-machine fusion interaction and trust. Building upon the principles of decision neuroscience and the theory of supply and demand relationships, the study analyzed the decision-making patterns of human-machine fusion intelligence under different states. By investigating the correlations among aerial combat mission demands, dynamic operational limits of human-machine tasks, and aerial combat mission performance, a theoretical model of human-machine fusion interaction and trust was proposed. This model revealed the mechanistic coupling of human-machine interactions in aerial tasks, aiming to optimize the decision-making processes of human-machine systems to enhance mission performance. It provides methodological support for the design and application of intelligent collaborative interaction modes in aviation equipment.

Abstract 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 high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses.

Abstract The integration of Information and Communication Technology (ICT) can significantly improve teaching and learning outcomes, but various factors determine the degree to which ICT is integrated into educational practices. This study used quantitative methodology to examine four key factors that impact in-service teachers’ ICT integration and how they interact with each other. Data was collected through snowball sampling from 685 in-service teachers in Henan Province, China. Using partial least squares structural equation modeling (PLS-SEM), the study analyzed four factors from the Technology Acceptance Model 3 (TAM 3) and the Will-Skill-Tool model (WST model): attitudes (AT), self-efficacy (SE), digital competence (DC), and digital tools utilization (DTU). The findings revealed that all four elements exerted a noteworthy influence on the integration of ICT by in-service instructors. Meanwhile, attitudes, digital competence, and digital tools utilization have a mediating effect in this research. Additionally, the study examined how gender, age, and teaching experience influence these factors and ICT integration. The findings revealed that females exhibit higher levels of positive attitudes and digital competence than males, while teachers aged 31–35 years have stronger digital abilities, digital tool use, and ICT integration compared to younger or older teachers. Furthermore, teachers with less than three years of teaching experience exhibit significantly stronger attitudes, self-efficacy, digital competence, and ICT integration than those with more than ten years of experience. The implication of the study provides valuable insights for designing effective ICT-based instruction and developing teacher education and educational technology programs aimed at promoting ICT integration in the classroom.

Liposarcomas originating in the urinary bladder are extremely rare. Only six cases of bladder liposarcoma have been reported, and all have been described as myxoid liposarcomas. Notably, none of the patients underwent molecular testing. Here, we report a dedifferentiated liposarcoma (DDL) that occurred in the urinary bladder, primarily in a 69-year-old Chinese woman, with infrequent low-grade dedifferentiation. Computed tomography (CT) revealed an ill-defined solid mass in the anterior bladder wall. The patient underwent a partial bladder resection. Histologically, the tumor cells with mild-to-moderate nuclear atypia were arranged in fascicular and storiform patterns, mimicking a low-grade fibroblastic tumor. In addition, scattered small foci of typical lipoma-like well-differentiated components were identified. Immunohistochemically, the tumor tested positivity for MDM2, CDK4, and p16. Fluorescence in situ hybridization revealed MDM2 gene amplification in the neoplastic cells. Whole-exome sequencing showed that this tumor also harbored CDK4, TSPAN31, and JUN amplification. At the latest follow-up (85 months after surgery), the patient was alive, with no evidence of disease. To the best of our knowledge, this is the first example of a molecularly confirmed primary bladder liposarcoma and the first case of DDL at this site.

Abstract 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

Background 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.Methods and materials 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.Results Patients treated with hyperthermia had a significantly higher T-downstaging rate than those without hyperthermia (82.0 vs. 62.7%; p = .016). Hyperthermia was an independent favorable predictor of T-downstaging (odds ratio [OR] = 2.473; 95% confidence interval [CI] 1.050–5.826; p = .038). In the HCRT group, a pre-therapeutic elevated NLR (≥3) was associated with a higher T-downstaging rate (100.0 vs. 73.5%, p = .043). However, NLR was not associated with the T-downstaging rate in the CRT group. Five-year rates of locoregional recurrence-free survival (96.8 vs. 94.7%, p = .959), disease-free survival (DFS; 61.4 vs. 79.3%, p = .242), and overall survival (OS; 92.7 vs. 89.8%, p = .831) were not statistically different between the CRT and HCRT groups.Conclusions Hyperthermia can improve preoperative treatment response in LARC. Pretreatment NLR may be a predictive factor for hyperthermia.

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.

Summary: Ionic diodes constructed with asymmetric channel geometry and/or charge layout have shown outstanding performance in ion transport manipulation and reverse electrodialysis (RED) energy collection, but the working mechanism is still indistinct. Herein, we systematically investigated RED energy conversion of straight nanochannel-based bipolar ionic diode by coupling the Poisson-Nernst-Planck and Navier-Strokes equations. The effects of nanochannel structure, charging polarity, and symmetricity as well as properties of working fluids on the output voltage and output power were investigated. The results show that as high-concentration feeding solution is applied, the bipolar ionic diode-based RED system gives higher output voltage and output power compared to the unipolar channel RED system. Under optimal conditions, the voltage output of the bipolar channel is increased by ∼100% and the power output is increased by ∼260%. This work opens a new route for the design and optimization of high-performance salinity energy harvester as well as for water desalination.

Objectives Studies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study was to determine whether PD increased the risk of COPD and COPD-related clinical events.Design A systematic review and meta-analysis.Data sources PubMed, Ovid EMBASE and Ovid CENTRAL were searched from inception to 22 February 2023.Eligibility criteria for studies We included trials and observational studies evaluating association of PD with the risk of COPD or COPD-related events (exacerbation and mortality), with statistical adjustment for smoking.Data extraction and synthesis Two investigators independently extracted data from selected studies using a standardised Excel file. Quality of studies was evaluated using the Newcastle-Ottawa Scale. OR with 95% CI was pooled in a random-effect model with inverse variance method.Results 22 observational studies with 51 704 participants were included. Pooled analysis of 18 studies suggested that PD was weakly associated with the risk of COPD (OR: 1.20, 95% CI 1.09 to 1.32). However, in stratified and subgroup analyses, with strict adjustment for smoking, PD no longer related to the risk of COPD (adjusting for smoking intensity: OR: 1.14, 95% CI 0.86 to 1.51; smokers only: OR: 1.46, 95% CI 0.92 to 2.31; never smokers only: OR: 0.93, 95% CI 0.72 to 1.21). Moreover, PD did not increase the risk of COPD-related exacerbation or mortality (OR: 1.18, 95% CI 0.71 to 1.97) in the pooled result of four studies.Conclusions This study demonstrates PD confers no risk for COPD and COPD-related events when strictly adjusted by smoking. Large-scale prospective cohort studies with control of potential confounding factors are warranted to validate the present findings.

Surface-enhanced Raman scattering (SERS) is a cutting-edge technique for highly sensitive analysis of chemicals and molecules. Traditional SERS-active nanostructures are constructed on rigid substrates where the nanogaps providing hot-spots of Raman signals are fixed, and sample loading is unsatisfactory due to the unconformable attachment of substrates on irregular sample surfaces. A flexible SERS substrate enables conformable sample loading and, thus, highly sensitive Raman detection but still with limited detection capabilities. Stretchable SERS substrates with flexible sample loading structures and controllable hot-spot size provide a new strategy for improving the sample loading efficiency and SERS detection sensitivity. This review summarizes and discusses recent development and applications of the newly conceptual stretchable SERS substrates. A roadmap of the development of SERS substrates is reviewed, and fabrication techniques of stretchable SERS substrates are summarized, followed by an exhibition of the applications of these stretchable SERS substrates. Finally, challenges and perspectives of the stretchable SERS substrates are presented. This review provides an overview of the development of SERS substrates and sheds light on the design, fabrication, and application of stretchable SERS systems.

Abstract 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

Abstract Recently the alternating twisted trilayer graphene is discovered to exhibit unconventional superconductivity, which motivates us to study the electronic structures and possible correlation effects for this class of alternating twisted multilayer graphene (ATMG) systems. In this work we consider generic 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 θ (−θ). Based on analysis from a simplified k⋅p model approach, we derive generic partition rules for the low-energy electronic structures, which exhibit various band dispersions including two pairs of flat bands and flat bands co-existing with various gapless Fermionic excitations. For a mirror-symmetric ATMG system with doubled flat bands, we further find that Coulomb interactions may drive the system into a state with intertwined electric polarization and orbital magnetization orders, which can exhibit an interaction-driven orbital magnetoelectric effect.

BackgroundDue to the complex structure of the ventilation ducts in nuclear facilities, the concentration distribution of radionuclides such as aerosols in the ducts is uneven. The inhomogeneity of aerosol distribution brings great challenges to the sampling representativeness of radiation monitoring. In chemical processes, static stirring devices are commonly used to enhance the homogeneity of the product mix. However, this device has not been applied in the nuclear power field.PurposeAccordingly, this study aims to improve the mixing uniformity of aerosols in air supply pipelines by using static stirring devices, so as to provide a reference for the representativeness of radiation monitoring sampling.MethodsThe stirring effects of three different stirring devices were investigated through numerical simulations. The RNG k-ε model was used to simulate the gas phase flow field, and the discrete phase model (DPM) was employed in ANSYS CFX software to simulate the behavior of aerosol particles. Selection of the particle size of aerosols followed the recommendations in the sampling representative standards, with the specific size of 10 μm. The other boundary conditions in the simulation were based on the actual operating conditions of a nuclear power plant. As a result, the effects of different stirring devices on the flow field and aerosol concentration distribution were obtained.ResultsThe static stirring device can form strong swirls, thereby improving the uniformity of aerosol distribution. Increasing the twist angle of the blades and the proportion area of the inner blades strengthened the generated vortex field, further affecting the diffusion of aerosols. The static stirring device with an increased inner blade area exhibited a moderate swirl intensity, and better stirring effect than those of the other two structures. The coefficient of variation of the aerosol concentration decreased by 30.60%.ConclusionsInstalling a static stirring device in an air supply duct is a feasible method to improve the mixing uniformity of aerosols. Owing to the complex structure of ventilation ducts in nuclear facilities, the concentration distribution of radionuclides, such as aerosols, in the ducts is uneven. This inhomogeneous aerosol distribution poses significant challenges to the sampling representativeness of radiation monitoring. In chemical processes, static stirring devices are commonly used to enhance the homogeneity of the product mix. However, these devices have not yet been applied in the field of nuclear power.

Technology invention and implementation have resulted in long-term educational progress. This study aimed to identify the innovative strategies in determining the factors influencing in-service teachers' technology integration in China, focusing on the information and communication technology (ICT) integration. The sample consists of 685 in-service teachers. Four factors are found to influence in-service teachers' ICT integration: attitudes, self-efficacy, digital competence, and digital tools use. The results of the study utilizing the PLS-SEM approach demonstrated that all four factors have a substantial impact on in-service teachers' ICT integration and interact with each other. Meanwhile, attitudes, digital competence, and digital tools use have a mediating effect in this research. In addition, the study discussed the effects of gender, age, and teaching experience on influencing factors and ICT integration. This research provided beneficial insights for a successful design of instruction with ICT and contributed to innovative strategies for educational technology.

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.

BackgroundThe aim of this study was to investigate whether clinical and blood parameters can be used for predicting pathological complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).MethodsWe retrospectively enrolled 226 patients with LARC [allocated in a 7:3 ratio to a training (n = 158) or validation (n = 68) cohort] who received nCRT before radical surgery. Backward stepwise logistic regression was performed to identify clinical and blood parameters associated with achieving pCR. Models based on clinical parameters (CP), blood parameters (BP), and clinical-blood parameters (CBP) were constructed for comparison with previously reported Tan’s model. The performance of the four models was evaluated by receiver operating characteristic (ROC) curve analysis, calibration, and decision curve analysis (DCA) in both cohorts. A dynamic nomogram was constructed for the presentation of the best model.ResultsThe CP and BP models based on multivariate logistic regression analysis showed that interval, Grade, CEA and fibrinogen–albumin ratio index (FARI), sodium-to-globulin ratio (SGR) were the independent clinical and blood predictors for achieving pCR, respectively. The area under the ROC curve of the CBP model achieved a score of 0.818 and 0.752 in both cohorts, better than CP (0.762 and 0.589), BP (0.695 and 0.718), Tan (0.738 and 0.552). CBP also showed better calibration and DCA than other models in both cohorts. Moreover, CBP revealed significant improvement compared with other models in training cohort (P < 0.05), and CBP showed significant improvement compared with CP and Tan’s model in validation cohort (P < 0.05).ConclusionWe demonstrated that CBP predicting model have potential in predicting pCR to nCRT in patient with LARC.

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.

Abstract 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.

Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota–gut–brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ in vivo. The aims of our study were to assess the protective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool. In the current study, chronic oral administration of rotenone was utilized to induce a mouse model to mimic the pathological process of PD. Here we revealed that FLZ treatment alleviated gastrointestinal dysfunctions, motor symptoms, and dopaminergic neuron death in rotenone-challenged mice. 16S rRNA sequencing found that PD-related microbiota alterations induced by rotenone were reversed by FLZ treatment. Remarkably, FLZ administration attenuated intestinal inflammation and gut barrier destruction, which subsequently inhibited systemic inflammation. Eventually, FLZ treatment restored blood–brain barrier structure and suppressed neuroinflammation by inhibiting the activation of astrocytes and microglia in the substantia nigra (SN). Further mechanistic research demonstrated that FLZ treatment suppressed the TLR4/MyD88/NF-κB pathway both in the SN and colon. Collectively, FLZ treatment ameliorates microbiota dysbiosis to protect the PD model via inhibiting TLR4 pathway, which contributes to one of the underlying mechanisms beneath its neuroprotective effects. Our research also supports the importance of microbiota–gut–brain axis in PD pathogenesis, suggesting its potential role as a novel therapeutic target for PD treatment.

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.

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.

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.

We theoretically study the piezoelectric effects in moirè graphene systems. Since the strain couples to the electrons in the system as an effective vector field, which has opposite signs for the K and K^{′} valleys of graphene, its effects on the two valleys with opposite Chern numbers do not cancel out, but adds up. As a result, some components of the piezoelectric tensor (PET) in these systems, which typically have nontrivial topology in their flat bands, are nearly quantized in terms of the valley Chern numbers. The quantization of the PET is topologically protected by valley U(1) symmetry of the system. Such a conclusion is verified by numerical calculations of the in-plane piezoelectric response of hBN-aligned twisted bilayer graphene (TBG), twisted bilayer-monolayer graphene (TBMG), and twisted double bilayer graphene (TDBG) systems using both continuum model and atomistic tight-binding model. We propose that such nearly quantized piezoelectric response may serve as a direct experimental probe for the valley Chern numbers of the flat bands in moiré graphene systems.

Objective: To compare the operation complexity and prognosis of completely laparoscopic versus open radical nephrectomy and infrahepatic tumor thrombectomy. Methods: We reviewed and analyzed the clinical data of 87 patients with infrahepatic tumor thrombus from January 2015 to April 2019 retrospectively. Completely laparoscopic infrahepatic tumor thrombectomy was completed in 41 cases, and open surgery was completed in 46 cases. Results: All 41 patients successfully completed laparoscopic operation, and there were no cases of death during the operation. The completely laparoscopic group were older, had smaller renal tumor diameter, shorter median operation time, lower median intraoperative hemorrhage volume, and lower median transfusion volume of suspended red blood cells compared with open surgeries. The proportion of low-level tumor thrombus (Mayo I) in the completely laparoscopic group was higher (63.4%), while the proportion of low-level tumor thrombus in the open surgery group was lower (30.4%) (P = 0.002). The postoperative complications incidence of laparoscopic surgery was 19.5%, which was lower than that of open surgery (47.8%) (P = 0.004). The mean cancer-specific survival time of the laparoscopic surgery group was 36.6 ± 2.5 months, while that of the open surgery group was 32.3 ± 2.7 months (P = 0.277). There was no statistical difference between the two groups. Conclusion: Although completely laparoscopic radical nephrectomy and infrahepatic tumor thrombectomy is a challenging operation, it could be feasible and safely performed, especially in the hands of highly-experienced laparoscopic urologists for well selected cases.

Abstract The phenylalanine–tyrosine–dopa–dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (l-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H• through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of l-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The l-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut–brain dialog activated by BBR’s effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson’s disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of l-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal l-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of l-dopa in the gut microbiota through a vitamin-like effect.

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.

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.

Abstract 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.

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. KEY WORDS: Hyperuricemia, Renal function, Gut microbiota, Metabolomics, Urease

Remote sensing technology has the advantages of fast information acquisition, short cycle, and a wide detection range. It is frequently used in surface resource monitoring tasks. However, traditional remote sensing image segmentation technology cannot make full use of the rich spatial information of the image, the workload is too large, and the accuracy is not high enough. To address these problems, this study carried out atmospheric calibration, band combination, image fusion, and other data enhancement methods for Landsat 8 satellite remote sensing data to improve the data quality. In addition, deep learning is applied to remote-sensing image block segmentation. An asymmetric convolution-CBAM (AC-CBAM) module based on the convolutional block attention module is proposed. This optimization module of the integrated attention and sliding window prediction method is adopted to effectively improve the segmentation accuracy. In the experiment of test data, the mIoU, mAcc, and aAcc in this study reached 97.34%, 98.66%, and 98.67%, respectively, which is 1.44% higher than that of DNLNet (95.9%). The AC-CBAM module of this research provides a reference for deep learning to realize the automation of remote sensing land information extraction. The experimental code of our AC-CBAM module can be found at https://github.com/LinB203/remotesense.

Resonant frequency tracking control of electromagnetic acoustic transducers (EMATs) remains a challenge in terms of drifting working frequency and reduced conversion efficiency caused by working environment changes. This paper presents a fixed-time nonsingular integral terminal sliding mode (FT-NITSM) control strategy for resonant frequency tracking of EMATs to realize precise and high robustness resonant frequency tracking performance. Specifically, a FT-NITSM control method with fast convergence feature is developed and a resonant frequency tracking controller for EMATs is further designed to improve the convergence speed and tracking accuracy. Fixed time stability of the proposed frequency tracking control system is proved through Lyapunov function analysis. Moreover, numerical simulations demonstrate that the FT-NITSM control strategy can ensure precise tracking of the system’s operating frequency to its natural resonant frequency in less than 3 s with a tracking error of less than 0.01 × 104 Hz. With the maximum overshoot variation between −20 and 20 and error range in −5 and 5° at the steady state, the FT-NITSM control strategy can ensure the control system impedance angle θ being consistent and eventually bounded. This study provides a toolbox for the resonant frequency tracking control and performance improvement of EMATs.

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 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.

Abstract MicroRNAs are endogenous single-stranded non-coding small RNA molecules that can be secreted into the circulation and exist stably. They usually exhibit aberrant expression under different physiological and pathological conditions. Recently, differentially expressed circulating microRNAs were focused on as potential biomarkers for cancer screening. We herein review the role of circulating microRNAs for cancer diagnosis, tumor subtype classification, chemo- or radio-resistance monitoring, and outcome prognosis. Moreover, circulating microRNAs still have several issues hindering their reliability for the practical clinical application. Future studies need to elucidate further potential application of circulating microRNAs as specific and sensitive markers for clinical diagnosis or prognosis in cancers.

Abstract Background For the recurrence of head and neck cancer after operation and radiotherapy, the local control of radioactive seed implantation is good, and it has a certain palliative effect. This study aims to investigate the acute and late side effects of a three-dimentional printing non co-planar template (3D–PNCT) for computed tomography (CT)-guided radioactive 125I seed (RIS) implantation in recurrent cancer of the head and neck. Methods Between January 2016 and December 2016, forty-two patients with local recurrent malignant tumors of the head and neck received 3D–PNCT-assisted RIS implantation. The prescribed dose was 110–160 Gy. Preoperative planning design, production of individual guide plates, RIS implantation, postoperative dose evaluation, and follow-up were completed for all patients. Side effects in the skin, mucous membranes, blood and spinal cord were evaluated. Results All patients underwent surgery successfully. Duration of follow-up was 4–14 (median, of 8.5) months. The activity of a single RIS was 0.34–0.7 (median, 0.6) mCi. The number of RIS was 10–126 (median, 34). The number of implantation needles was 4–31 (median, 11). The mean D2cc (dose to the most exposed 2-cc volume) and D0.1cc (dose to the most exposed 0.1-cc volume) of the skin were 24.9 (7.1–85.5) and 47.5 (9.4–167.2), respectively, whereas those of the spinal cord were 8.4 (4.5–33.3) and 14.2 (13.6–63.0), mucosa were 35.1 (4.2–82.8) and 87.0 (6.6–214.1), parotid glands were 16.2 (12.8–19.7) and 29.8 (26.1–33.4) and those of the trachea were 17.9 (2.5–45.9) and 32.7 (3.9–83.9), respectively. No case had an acute reaction of grade ≥ 3. Three cases had a grade-1 skin reaction. Blood toxicity did not occur, nor spinal-cord injury. Xerostomia was not aggravated than that of before brachytherapy. One case had a grade-3 nerve response. Conclusions 3D–PNCT-assisted RIS implantation can provide good accuracy for positioning. For local recurrent malignant tumor of head and neck, there were no obvious adverse reactions.

Abstract Background The CRISPR/dCas9 system is a powerful tool to activate the transcription of target genes in eukaryotic or prokaryotic cells, but lacks assays in complex conditions, such as the biosynthesis of secondary metabolites. Results In this study, to improve the transcription of the heterologously expressed biosynthetic genes for the production of epothilones, we established the CRISPR/dCas9-mediated activation technique in Myxococcus xanthus and analyzed some key factors involving in the CRISPR/dCas9 activation. We firstly optimized the cas9 codon to fit the M. xanthus cells, mutated the gene to inactivate the nuclease activity, and constructed the dCas9-activator system in an epothilone producer. We compared the improvement efficiency of different sgRNAs on the production of epothilones and the expression of the biosynthetic genes. We also compared the improvement effects of different activator proteins, the ω and α subunits of RNA polymerase, and the sigma factors σ54 and CarQ. By using a copper-inducible promoter, we determined that higher expressions of dCas9-activator improved the activation effects. Conclusions Our results showed that the CRISPR/dCas-mediated transcription activation is a simple and broadly applicable technique to improve the transcriptional efficiency for the production of secondary metabolites in microorganisms. This is the first time to construct the CRISPR/dCas9 activation system in myxobacteria and the first time to assay the CRISPR/dCas9 activations for the biosynthesis of microbial secondary metabolites.

Abstract Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and it has been confirmed that increased low density lipoprotein cholesterol (LDL-C) is an independent risk factor for atherosclerosis. Recently, the increasing evidence has showed that hypertriglyceridemia is associated with incremental ASCVD risk. But the proatherogenic mechanism of triglyceride (TG) remains unclear. Therefore, this article focuses on the clinical studies and proatherogenic mechanism related to hypertriglyceridemia, in order to provide reference for the prevention and treatment of ASCVD.

Abstract Background Estrogen was reported to protect against obesity, however the mechanism remains unclear. We aimed to investigate the impact of 17β-estradiol (17β-E2) on triglyceride metabolism in adipocytes with or without lipopolysacchride (LPS) stimulating, providing novel potential mechanism for estrogen action. Methods 3T3-L1 adipocytes were cultured and differentiated into mature adipocytes in vitro. The differentiated 3T3-L1 cells were divided into six groups: (i) control group, treated with 0.1% DMSO alone; (ii) 17β-E2 group, treated with 1, 0.1, or 0.001 μM 17β-E2 for 48 h; (iii) 17β-E2 plus MPP group, pre-treated with 10 μM MPP (a selective ERα receptor inhibitor) for 1 h, then incubated with 1 μM 17β-E2 for 48 h; (iv) 17β-E2 plus PHTPP group, pre-treated with 10 μM PHTPP (a selective ERβ receptor inhibitor), then incubated with 1 μM 17β-E2 for 48 h; (v) LPS group, pre-treated with 100 ng/mL LPS for 24 h, then cells were washed by PBS for 3 times and incubated with 0.1% DMSO alone for 48 h; (vi) 17β-E2 plus LPS group, pre-treated with 100 ng/mL LPS for 24 h, then cells were washed by PBS for 3 times and incubated with 1 μM 17β-E2 for 48 h. The levels of triglyceride and adipose triglyceride lipase (ATGL) in differentiated 3T3-L1 cells and the concentrations of interleukin-6 (IL-6) in culture medium were measured. Results Comparing with control group, 1 μM and 0.1 μM 17β-E2 decreased the intracellular TG levels by about 20% and 10% respectively (all P 0.05). There was no significant difference in the triglyceride contents of differentiated 3T3-L1 cells among control group, LPS group and 17β-E2 + LPS group (all P > 0.05). ATGL expression in 17β-E2 group was significantly higher than control group (P

Abstract Background Microbial secondary metabolism is regulated by a complex and mostly-unknown network of global and pathway-specific regulators. A dozen biosynthetic gene clusters for secondary metabolites have been reported in myxobacteria, but a few regulation factors have been identified. Results We identified a transcription regulator Esi for the biosynthesis of epothilones. Inactivation of esi promoted the epothilone production, while overexpression of the gene suppressed the production. The regulation was determined to be resulted from the transcriptional changes of epothilone genes. Esi was able to bind, probably via the N-terminus of the protein, to an inverted repeat sequence in the promoter of the epothilone biosynthetic gene cluster. The Esi-homologous sequences retrieved from the RefSeq database are all of the Proteobacteria. However, the Esi regulation is not universal in myxobacteria, because the esi gene exists only in a few myxobacterial genomes. Conclusions Esi binds to the epothilone promoter and down-regulates the transcriptional level of the whole gene cluster to affect the biosynthesis of epothilone. This is the first transcription regulator identified for epothilone biosynthesis.

Paeoniflorin, the main component of Xiaoyao Wan, presents low oral bioavailability and unclear antidepressant mechanism. To elucidate the potential reasons for the low bioavailability of paeoniflorin and explore its antidepressant mechanism from the perspective of the gut microbiota, here, a chronic unpredictable depression model and forced swimming test were firstly performed to examine the antidepressant effects of paeoniflorin. Then the pharmacokinetic study of paeoniflorin in rats was performed based on the gut microbiota; meanwhile, the gut microbiota incubated with paeoniflorin in vitro was used to identify the possible metabolites of paeoniflorin. Molecular virtual docking experiments together with the specific inhibitor tests were applied to investigate the mechanism of paeoniflorin metabolism by the gut microbiota. Finally, the intestinal microbiota composition was analyzed by 16S rRNA gene sequencing technology. The pharmacodynamics tests showed that paeoniflorin had significant antidepressant activity, but its oral bioavailability was 2.32%. Interestingly, we found paeoniflorin was converted into benzoic acid by the gut microbiota, and was mainly excreted through the urine with the gut metabolite benzoic acid as the prominent excreted form. Moreover, paeoniflorin could also regulate the composition of the gut microbiota by increasing the abundance of probiotics. Therefore, the metabolism effect of gut microbiota may be one of the main reasons for the low oral bioavailability of paeoniflorin. Additionally, paeoniflorin can be metabolized into benzoic acid via gut microbiota enzymes, which might exert antidepressant effects through the blood–brain barrier into the brain.