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Large-tube forgings were formed using nine layers of continuous-casting billet made from 15CrNi3MoV alloy steel via additive forging. The interfacial microstructural evolution under different hot-compression bonding temperatures and strains was investigated using optical microscopy, scanning electron microscopy, and electron backscatter diffraction. The tensile properties of the hot-compression-bonded and tube-forged samples were also evaluated. The results showed that as the hot-compression bonding temperature and strain increased, the bonding interface gradually disappeared and the voids at the bonding interface closed. Finally, the interface was replaced with recrystallised grains. The tensile properties of the hot-compression-bonded samples at different temperatures and strains were identical. The tensile properties of the interface and base samples of the tube forging were comparable, and the fracture morphologies were consistent. The fracture position of the large tensile sample with a length of 1000 mm containing three original interfaces is the base, indicating the complete metallurgical bonding of the forging.

In the transactional processes within a multi-building microgrid system, it is imperative to safeguard stakeholders’ interests and ensure stable, economically efficient operation. Therefore, this paper proposes an integrated interactive control of distribution systems with multi-building microgrids based on game theory. Initially, an interactive framework encompassing superior power grids, distribution network operators, and multi-building microgrids is proposed. This framework establishes a master–slave game model between distribution network operators and multi-building microgrids. Additionally, it introduces the concept of Soft Open Points between building microgrids to enhance system operational safety while also reducing economic costs for distribution network operators. Subsequently, to maintain solution accuracy and optimality, it employs linearization and cone relaxation methods to transform the original model into a mixed-integer second-order cone programming model. Furthermore, it enhances an iterative search method and the price mechanism based on supply and demand ratios. The revised price mechanism serves to boost the participation of building microgrid users in energy regulation, while the iterative search method effectively resolves the equilibrium point of interest among all game participants. Finally, a simulation analysis is conducted on an IEEE-33 test system, and the effectiveness of the proposed strategy is verified by comparing three schemes.

Profile soil moisture (PSM), the soil water content in the whole soil layer, directly controls the major processes related to biological interaction, vegetation growth, and runoff generation. Its spatial heterogeneity, which refers to the uneven distribution and complexity in space, influences refined spatial management and decision-making in ecological, agricultural, and hydrological systems. Satellite instruments and hydrological models are two important sources of spatial information on PSM, but there is still a gap in understanding their potential mechanisms that affect spatial heterogeneity. This study is designed to identify the spatial heterogeneity and the driving factors of two PSM datasets; one is preprocessed from a satellite product (European Space Agency Climate Change Initiative, ESA CCI), and the other is simulated from a distributed hydrological model (the DEM-based distributed rainfall-runoff model, DDRM). Three catchments with different climate conditions were chosen as the study area. By considering the scale dependence of spatial heterogeneity, the profile saturation degree (PSD) datasets from different sources (shown as ESA CCI PSD and DDRM PSD, respectively) during 2017 that are matched in terms of spatial scale and physical properties were acquired first based on the calibration data from 2014–2016, and then the spatial heterogeneity of the PSD from different sources was identified by using spatial statistical analysis and the semi-variogram method, followed by the geographic detector method, to investigate the driving factors. The results indicate that (1) ESA CCI and DDRM PSD are similar for seasonal changes and are overall consistent and locally different in terms of the spatial variations in catchment with different climate conditions; (2) based on spatial statistical analysis, the spatial heterogeneity of PSD reduces after spatial rescaling; at the same spatial scale, DDRM PSD shows higher spatial heterogeneity than ESA CCI PSD, and the low-flow period shows higher spatial heterogeneity than the high-flow period; (3) based on the semi-variogram method, both ESA CCI and DDRM PSD show strong spatial heterogeneity in most cases, in which the proportion of C/(C0 + C) is higher than 0.75, and the spatial data in the low-flow period mostly show larger spatial heterogeneity, in which the proportion is higher than 0.9; the spatial heterogeneity of PSD is higher in the semi-arid catchment; (4) the first three driving factors of the spatial heterogeneity of both ESA CCI and DDRM PSD are DEM, precipitation, and soil type in most cases, contributing more than 50% to spatial heterogeneity; (5) precipitation contributes most to ESA CCI PSD in the low-flow period, and there is no obvious high contribution of precipitation to DDRM PSD. The research provides insights into the spatial heterogeneity of PSM, which helps develop refined modeling and spatial management strategies for soil moisture in ecological, agricultural, and hydrological fields.

In order to improve the inversion accuracy of stellar occultation data and to provide a reference for the selection of inversion methods with higher accuracy in the future, this study compared and analyzed the inversion effects of two different methods on the same set of data, which are the effective cross-section method and the onion-peeling method, respectively. Firstly, the inversion principle of the effective cross-section method is introduced in detail. The regularisation parameters and screening conditions for the observation data in the inversion process were clarified based on the ozone observation characteristics. Second, the algorithm was applied to invert the GOMOS observational data from 1 December 2002. The atmospheric radiative transmittance obtained from the observations was filtered, and the inversion results were compared with those obtained using the onion-peeling method. Third, the errors in the height distribution obtained by both methods were calculated using the GOMOS secondary results from 1 December 2002 as the reference value. Finally, the inversion errors of other trace components were computed to further validate the accuracy of the two methods. The results demonstrate that the effective cross-sectional method is more accurate for the inversion of ozone, particularly in low-altitude regions affected by refraction. The method achieved a maximum error of 1.2%, with an apparent magnitude of 2, an effective temperature greater than 10,000 K, and a regularisation parameter of 1015. Furthermore, when applying the same method to the inversion of nitrogen trioxide and calculating the error, it was observed that the results of both methods were comparable at altitude of 30–60 km, with an error value ranging from 0 to 2%. However, at approximately 25 km, the inversion accuracy of the onion-peeling method surpassed that of the effective cross-sectional method. This research provides a theoretical foundation for further investigation of the stellar occultation inversion method and enhancing the accuracy of inversions.

Structured light illumination is widely applied for surface defect detection due to its advantages in terms of speed, precision, and non-contact capabilities. However, the high reflectivity of metal surfaces often results in the loss of point clouds, thus reducing the measurement accuracy. In this paper, we propose a novel quaternary categorization strategy to address the high-reflectivity issue. Firstly, we classify the pixels into four types according to the phase map characteristics. Secondly, we apply tailored optimization and reconstruction strategies to each type of pixel. Finally, we fuse point clouds from multi-type pixels to accomplish precise measurements of high-reflectivity surfaces. Experimental results show that our strategy effectively reduces the high-reflectivity error when measuring metal surfaces and exhibits stronger robustness against noise compared to the conventional method.

Nutrients play important roles in the growth and development of most plant species. However, in perennial trees, the function of nutrients in different genotypes is poorly understood. Three different nutrient levels (low, sufficient, and high nutrient levels) were applied to two contrasting Eucalyptus urophylla cultivars (a high-growth cultivar ZQUA44 and a low-growth cultivar ZQUB15), and growth and expression levels were analyzed. Although the growth traits of both genotypes under nutrient starvation treatment were much lower than under abundant nutrients, tree height, crown width, and biomass of different ZQUA44 tissues were much higher than those of ZQUB15 at all three nutrient levels. Differentially expressed genes (DEGs) clustered into six subclusters based on their expression patterns, and functional annotation showed that the DEGs involved in glutathione metabolism and flavonoid biosynthesis may be responsible for nutrient starvation across different genotypes, while the DEGs involved in carotenoid biosynthesis and starch and sucrose metabolism may have a range of functions in different genotypes. The DEGs encoding the MYB-related family may be responsible for nutrient deficiency in all genotypes, while B3 may have different functions in different genotypes. Our results demonstrate that different genotypes may form different pathways to coordinate plant survival when they face abiotic stresses.

Abstract MXenes suffer from severe oxidation and progressive degradation in aqueous media due to its poor chemical stability. Herein, sodium dodecyl sulfate (SDS) is employed as an efficient protectant for long‐term storage of Ti3C2Tx‐MXene aqueous dispersion. Experimental data support SDS's capability to protect oxidation‐prone sites on Ti3C2Tx nanosheets, providing extended colloidal stability of up to 213 days. Concentration‐dependent anti‐oxidation effect articulates that 1.5 mg mL−1 is deemed as an ideal SDS dose for Ti3C2Tx to achieve optimal oxidation‐resistance in aqueous solution. Additionally, a chroma strategy is developed to instantly and precisely measure the oxidation degree of Ti3C2Tx. Adsorption‐driven anti‐oxidation efficacy of SDS is further confirmed by optimized conformations with interaction energies of SDS on termination‐free and surface‐defective Ti3C2Tx through multiscale simulations. This proposed route is a step forward in broadening the horizons of experimental and theoretical investigations of MXenes with promising implications for long‐term storage and reliable applications.

Background: Solid pseudopapillary neoplasms (SPNs) are uncommon tumors of low malignancy with a generally favorable prognosis, mostly originating from the pancreas. To date, 12 cases of SPNs with a primary ovarian origin (SPN–Os) have been reported globally, and their detailed characteristics have not been fully elucidated. Case description: We reported the 13th SPN-O case, which occurred in a 52-year-old woman with an 18.5 cm left ovarian mass. Four imaging methods, including ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography, were utilized before surgery. An elevated level of serum cancer antigen 125 was detected and a total hysterectomy plus bilateral salpingo-oophorectomy was performed. Microscopic examination revealed a typical solid pseudopapillary structure. The tumor cells were stained focally for pan-cytokeratin, synaptophysin, CD99 and CD10, while β-catenin, vimentin and CD56 were diffusely expressed. The Ki-67 proliferation index was 3%, and immunohistochemical (IHC) staining for chromogranin-A, inhibin-a, and E-cadherin was negative. No evidence of recurrence or metastasis was observed by clinical and imaging data during a 5-month postoperative follow-up. Conclusion: This is a report of an unusual case of a primary ovarian SPN with an up-to-date review of SPN-Os. A minimum combination of imaging methods and IHC stains was proposed for SPN-Os, which may prove beneficial in clinical practice.

Objectives This investigation sought to elucidate promising treatment modalities for rotator cuff tears (RCTs) by delving into the molecular machinations instigating the affliction. The focus was on differentially expressed genes (DEGs) linked to RCTs, and the exploration of their roles and operative pathways. Methods DEGs were discerned from GEO datasets, followed by the establishment of a protein-protein interaction (PPI) network. Subsequently, the network’s core genes were determined employing a Venn diagram. Enrichment analysis facilitated the unveiling of the biological roles and signal transduction pathways of these pivotal genes, thus shedding light on molecular strategies for RCT-targeted treatment. The Discovery Studio 2019 software was employed to sift through FDA-sanctioned drugs targeting these essential proteins. Moreover, the efficaciousness of these FDA-endorsed drugs vis-à-vis RCTs was corroborated by the construction of an in vivo animal model of the injury and the in vitro cultivation of tendon-derived stem cells. Results Bioinformatics outcomes revealed a significant overexpression of S100A1 and RASSF8 in RCT patients. The FDA drug repository indicated that Butanediamide has a selective affinity for S100A1 and RASSF8. Subsequent in vivo and in vitro experimentation demonstrated that Butanediamide could suppress S100A1 expression and bolster TDSC proliferation, thereby facilitating RCT healing. Conclusions S100A1 and RASSF8 are pivotal genes implicated in RCTs, and their roles have been elucidated. The FDA-approved compound, Butanediamide, may represent a prospective therapeutic agent for RCTs by targeting S100A1 and RASSF8, respectively.

Introduction: Treatment of relapsed or refractory acute myeloid leukemia (R/R AML) and myeloid sarcoma (MS) has presented challenges for decades. Studies on selinexor in combination with various standard or intensive chemotherapy regimens for the treatment of R/R AML have demonstrated promising results. This study aimed to evaluate the efficacy and safety of chemotherapy-free or low-dose chemotherapy regimens with selinexor for R/R AML and MS patients.Methods: Ten patients with R/R AML or MS who received chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor at Tongji Hospital from October 2021 to August 2022 were included in this study. The primary endpoint was overall response rate (ORR) and secondary endpoints included complete remission (CR), CR with incomplete hematological recovery (CRi), partial remission (PR), transplantation rate, and safety.Results: All patients were evaluable for response, achieving CR in four (40.0%) patients and CRi in two (20.0%) patients for a total CR/CRi of 60.0%. The ORR was 80.0% when patients with PR were included. Five (50.0%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after treatment with selinexor-containing regimens. At the end of the follow-up, seven (70.0%) patients were alive, and three patients died of transplant-related complications or disease progression. The most frequently reported nonhematologic adverse events (AEs) in patients were grade 1 or 2 asymptomatic hyponatremia.Conclusion: The chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor for R/R AML are feasible and tolerable and provide an opportunity for patients to receive transplantation.

The relationship between cancer and microorganisms has been extensively studied, with bacteria receiving more attention than fungi. However, fungi have been shown to play a significant role in cancer development and progression. Understanding the underlying mechanisms is crucial for identifying new avenues in prevention and treatment. To evaluate the current state of research on fungi and cancer, we conducted a comprehensive bibliometric analysis. Using the Web of Science Core Collection database, we searched for English-language articles published between 1998 and 2022. Analyzing the resulting publication data, we identified trends, patterns, and research gaps. Our analysis encompassed co-authorship networks, citation analysis, and keyword co-occurrence analysis. With 8283 publications identified, averaging 331.32 publications per year, our findings highlight China, the United States, India, Japan, and Germany as the top contributing countries. The Chinese Academy of Sciences, Sun Yat-Sen University, and University of São Paulo emerged as the most productive institutions. Key themes in the literature included “cancer,” “cytotoxicity,” “apoptosis,” “metabolites,” and “fungus.” Recent trends indicate increased interest in keywords such as “green synthesis,” “molecular docking,” “anticancer activity,” “antibacterial,” “anticancer,” and “silver nanoparticles.” Our study provides a comprehensive assessment of the current research landscape in the field of fungi and cancer, offering insights into collaborative networks, research directions, and emerging hotspots. The growing publication rate demonstrates the rising interest in the topic, while identifying leading countries, institutions, and research themes serves as a valuable resource for researchers, policymakers, and funders interested in supporting investigations on fungi-derived compounds as potential anti-cancer agents.

Summary: Background: Chronic liver diseases of all etiologies exist along a spectrum with varying degrees of hepatic fibrosis. Despite accumulating evidence implying associations between liver fibrosis and cognitive functioning, there is limited research exploring the underlying neurobiological factors and the possible mediating role of inflammation on the liver-brain axis. Methods: Using data from the UK Biobank, we examined the cross-sectional association of liver fibrosis (as measured by Fibrosis-4 score) with cognitive functioning and regional grey matter volumes (GMVs) while adjusting for numerous covariates and multiple comparisons. We further performed post-hoc preliminary analysis to investigate the mediating effect of C-reactive protein (CRP) on the association between liver fibrosis and both cognitive functioning and GMVs. Findings: We analysed behaviour from up to 447,626 participants (N ranged from 45,055 to 447,533 per specific cognitive metric) 37 years and older. 38,244 participants (age range 44–82 years) had GMV data collected at a median 9-year follow-up. Liver fibrosis showed significant associations with cognitive performance in reasoning, working memory, visual memory, prospective memory, executive function, and processing speed. Subgroup analysis indicated larger effects sizes for symbol digital substitution but smaller effect sizes for trail making in middle-aged people than their old counterparts. Neuroimaging analyses revealed significant associations between liver fibrosis and reduced regional GMVs, primarily in the hippocampus, thalamus, ventral striatum, parahippocampal gyrus, brain stem, and cerebellum. CRP levels were significantly higher in adults with advanced liver fibrosis than those without, indicating an elevated systemic inflammation. Moreover, the serum CRP significantly mediated the effect of liver fibrosis on most cognitive measures and regional GMVs in the hippocampus and brain stem. Interpretation: This study provides a well-powered characterization of associations between liver fibrosis, cognitive impairment, and grey matter atrophy. It also highlights the possibly mediating role of systemic inflammation on the liver-brain axis. Early surveillance and prevention of liver diseases may reduce cognitive decline and brain GMV loss. Funding: National Science Foundation, and National Institutes of Health.

ObjectiveCerebral white matter hyperintensity can lead to cerebral small vessel disease, MRI images in the brain are used to assess the degree of pathological changes in white matter regions. In this paper, we propose a framework for automatic 3D segmentation of brain white matter hyperintensity based on MRI images to address the problems of low accuracy and segmentation inhomogeneity in 3D segmentation. We explored correlation analyses of cognitive assessment parameters and multiple comparison analyses to investigate differences in brain white matter hyperintensity volume among three cognitive states, Dementia, MCI and NCI. The study explored the correlation between cognitive assessment coefficients and brain white matter hyperintensity volume.MethodsThis paper proposes an automatic 3D segmentation framework for white matter hyperintensity using a deep multi-mapping encoder-decoder structure. The method introduces a 3D residual mapping structure for the encoder and decoder. Multi-layer Cross-connected Residual Mapping Module (MCRCM) is proposed in the encoding stage to enhance the expressiveness of model and perception of detailed features. Spatial Attention Weighted Enhanced Supervision Module (SAWESM) is proposed in the decoding stage to adjust the supervision strategy through a spatial attention weighting mechanism. This helps guide the decoder to perform feature reconstruction and detail recovery more effectively.ResultExperimental data was obtained from a privately owned independent brain white matter dataset. The results of the automatic 3D segmentation framework showed a higher segmentation accuracy compared to nnunet and nnunet-resnet, with a p-value of

Vacuum preloading coupled with prefabricated vertical drains (PVDs) has been widely used to improve the property of the dredged slurry. However, the effect of PVD layout on slurry consolidation characteristics remains poorly understood. This study conducted two vacuum preloading model tests—with single and dual PVDs. Particle image velocimetry (PIV) was used to directly observe the slurry displacements and strain paths. The test results revealed that the slurry consolidation characteristics were similar under different PVD layouts in the early stage of vacuum preloading. However, in the mid-stage, the effect of dual PVDs led to a significant reduction and increased dispersion of the slurry horizontal displacement. This, in turn, resulted in a thinner clogging zone and a subsequent decrease in vacuum pressure loss. Consequently, the slurry near the PVDs experienced an extended period of consolidation deformation. During the later stage, the single PVD model test exhibited a distinct zone of both vertical and horizontal compression in the slurry, while under dual PVDs, the slurry primarily underwent vertical compression and horizontal extension. The study also provided the relationship between the clogging zone thickness and time, which provided a reference for theoretical consolidation calculations.

Relationship extraction is one of the important tasks of constructing knowledge graph. In recent years, many scholars have introduced external information other than entities into relationship extraction models, which perform better than traditional relationship extraction methods. However, they ignore the importance of the relative position between entities. Considering the relative position between entity pairs and the influence of sentence level information on the performance of relationship extraction model, this article proposes a BERT-PAGG relationship extraction model. The model introduces the location information of entities, and combines the local features extracted by PAGG module with the entity vector representation output by BERT. Specifically, BERT-PAGG integrates entity location information into local features through segmented convolution neural network, uses attention mechanism to capture more effective semantic features, and finally regulates the transmission of information flow through gating mechanism. Experimental results on two open Chinese relation extraction datasets show that the proposed method achieves the best results compared with other models. At the same time, ablation experiments show that PAGG module can effectively use external information, and the introduction of this module makes the Macro-F1 value of the model increase by at least 2.82%.

Objectives: This study aimed to evaluate the effects of factors related to periapical lesions (PALs) on sinus membrane thickening (SMT) in the Chinese population using cone-beam computed tomography (CBCT). Methods: In this retrospective study, CBCT images (n = 512) of maxillary sinuses of 446 patients were evaluated by two examiners for SMT and PALs, PAL size, and the distance between the maxillary sinus floor (MSF), and the PAL’s edge/root apex. The data were analyzed using analysis of variance, the Kruskal-Wallis test, χ2-test, and logistic regression. Results: A binary logistic regression model showed that the prevalence and severity of SMT > 2 mm were significantly associated with older age (>60 years) (odds ratio [OR]: 4.03, 95% confidence interval [CI]): 2.24–7.72, P 2 mm than did distance after adjusting for confounding factors, including age and sex (PALs: OR = 10.17 and 14.57, P

ObjectiveTo evaluate the prognostic value of common clinical inflammatory and nutritional indicators before treatment in patients with non-small cell lung cancer in the real world.MethodA total of 5,239 patients with pathologically confirmed non-small cell lung cancer from 2011 to 2018 in the Affiliated Cancer Hospital of Xinjiang Medical University were selected. Their inflammatory and nutritional indicators (RDW, PDW, NLR, LMR, NMR, PLR, SII, PNI, TP, ALB, CYRFA21-1, CEA, CA125, NSE, α1-globulin, α2-globulin, β1-globulin, β2-globulin, and γ-globulin) before treatment were collected. From the total number, 1,049 patients were randomly sampled (18 to 20% of patients each year) and used as the validation set; the remaining 4,190 patients were used as the training set. According to the eighth edition of the guidelines for the diagnosis, treatment, and stage risk stratification of lung cancer, the patients were divided into four groups: stage I/II operable, stage III operable, stage III inoperable, and stage IV. We used the X-tile software to intercept and classify the cut-off values of each index in the validation set. Univariate and multivariate Cox proportional-hazard regression were used to screen the independent risk factors affecting the prognosis of non-small cell lung cancer and establish a prognostic model for 1, 3, and 5 years. The validation set was used to verify its performance. Finally, the Kaplan–Meier curve was used to assess the survival rate, and the corresponding nomogram was established for clinical use.ResultsAfter screening, no effective indicators were found in the stage I/II operable group. RDW and CA125 were effective indicators for the stage III operable group (cut-off values were 14.1 and 9.21, respectively, compared with the low-value group; univariate HR was 2.145 and 1.612, and multivariate HR was 1.491 and 1.691, respectively). CYRFA21-1 and CA125 were effective prognostic indicators for the stage III inoperable group (cut-off values were 10.62 and 44.10, respectively, compared with the low-value group; univariate HR was 1.744 and 1.342, and multivariate HR was 1.284 and 1.304, respectively). CYRFA21-1, CA125, NLR, and α1-globulin were effective indicators of prognosis in stage IV (cut-off values were 3.07, 69.60, 4.08, and 5.30, respectively, compared with the low-value group; univariate HR was 1.713, 1.339, 1.388, and 1.539; and multivariate HR was 1.407, 1.119, 1.191, and 1.110, respectively). The model was constructed with the best validation power in stage IV patients (C-index = 0.733, 0.749, and 0.75 at 1, 3, and 5 years, respectively).ConclusionFor patients with stage III and IV non-small cell lung cancer, some inflammatory markers, serum tumor markers, and nutritional indicators are independent prognostic factors. Combined with the general data of patients, the constructed prognostic evaluation model has the best efficacy in patients with stage IV and can be widely used in clinical practice.

Abstract Chimeric antigen receptor (CAR)‐T cell therapy is a promising form of cancer immunotherapy that genetically modifies a patient's own T cells to express CARs for the specific recognition and eradication of cancer cells. Unfortunately, unlike the impressive advancements it achieves in hematologic cancer treatment, CAR‐T cell therapy has encountered obstacles in treating solid tumors such as high cost, inadequate tumor infiltration, and immunosuppressive tumor microenvironment. Recently, the regional administration of CAR‐T cells via hydrogel platforms has been investigated as a potential method to not only promote tumor infiltration, cell expansion, and anticancer efficacy of the CAR‐T cells but also provide a multifunctional platform to introduce additional therapeutic agents for achieving potentiated cancer therapy. In this perspective, different design strategies of CAR‐T cell delivery hydrogels are introduced. Besides, various types of therapeutic agents incorporated in the hydrogel platforms and diverse hydrogel formulations have been discussed. The current challenges and future research directions on CAR‐T cell delivery hydrogels are also proposed. It is hoped that this perspective can help future researchers develop new CAR‐T cell delivery hydrogels that can effectively fight against solid tumors.

IntroductionTo compare the accuracy of Artificial Intelligent Breast Ultrasound (AIBUS) with hand-held breast ultrasound (HHUS) in asymptomatic women and to offer recommendations for screening in regions with limited medical resources.Methods852 participants who underwent both HHUS and AIBUS were enrolled between December 2020 and June 2021. Two radiologists, who were unaware of the HHUS results, reviewed the AIBUS data and scored the image quality on a separate workstation. Breast imaging reporting and data system (BI-RADS) final recall assessment, breast density category, quantified lesion features, and examination time were evaluated for both devices. The statistical analysis included McNemar’s test, paired t-test, and Wilcoxon test. The kappa coefficient and consistency rate were calculated in different subgroups.ResultsSubjective satisfaction with AIBUS image quality reached 70%. Moderate agreements were found between AIBUS with good quality images and HHUS for the BI-RADS final recall assessment (κ = 0.47, consistency rate = 73.9%) and breast density category (κ = 0.50, consistency rate = 74.8%). The lesions measured by AIBUS were statistically smaller and deeper than those measured by HHUS (P < 0.001), though they were not significant in clinical diagnosis (all < 3 mm). The total time required for the AIBUS examination and image interpretation was 1.03 (95% CI (0.57, 1.50)) minutes shorter than that of HHUS per case.ConclusionModerate agreement was obtained for the description of the BI-RADS final recall assessment and breast density category. With image quality comparable to that of HHUS, AIBUS was superior for the efficiency of primary screening.

IntroductionGastric cancer is a highly heterogeneous malignant tumor of the digestive system. Anti-HER2 treatment can inhibit downstream signaling pathways and improve clinical treatment and outcomes in patients with HER2 protein overexpression. Currently, two standard methods for evaluating HER2 expression status are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). However, these low-throughput assays often produce discordant or equivocal results.MethodsIn this study, we presented a new HER2 protein detection method based on mass spectrometry selected reaction monitoring (MS-SRM) and validated the method. We conducted a retrospective study on 118 formalin-fixed paraffin-embedded (FFPE) tissues from patients with advanced gastric adenocarcinoma in northern China, and we compared the MS-SRM results with those from IHC and correlated them with FISH. ResultsWe established and validated the upper and lower detection limits (300-700 amol/μg) for abnormal HER2 protein expression in advanced gastric cancer. We also found that, among samples with mixed Lauren subtypes, those with a high level of HER2 expression had typical intestinal type features in pathology. DiscussionThis study demonstrated that the MS-SRM method can overcome the limitations and deficiencies of IHC, directly quantify the expression of HER2 protein in tumor cells and be used as a supplement to IHC. It has the potential to be used as a companion diagnosis for new drugs used to treat advanced gastric cancer. Large-scale clinical validation is required.

ABSTRACTDoxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.

Multi-objective genetic algorithms (MOGAs) are widely used for multi-reservoir systems’ optimization due to their high efficiency and fast convergence. However, the computational cost grows exponentially with the expansion of multi-reservoir systems and the increased dimensions of optimization problems, posing a great challenge to multi-reservoir operations. Therefore, it is important to find a suitable and efficient multi-objective algorithm for multi-reservoir system optimization. In this study, three representative MOGAs were selected, namely the Non-dominated Sorting Genetic Algorithm II (NSGA-II), Non-Dominated Sorting Genetic Algorithm III (NSGA-III), and Reference Vector Guided Evolutionary Algorithm (RVEA), and three multi-objective optimization models were then developed accordingly. Numerical experiments were conducted to evaluate the performance of these three algorithms for the optimization of a cascaded reservoir system. The results show that for the two-objective model, the non-dominant size generation rate (NDSGR) of NSGA-II is 1.66 and 4.01 times that of NSGA-III and RVEA, respectively. NSGA-II is more suitable for solving the optimization operation problem with two objectives. Based on the comprehensive evaluation, NSGA-III seems to be more appropriate for more than two objectives. These results emphasize the importance of using appropriate algorithms and provide further insights into the choice of algorithms for the optimization of hydropower systems. HIGHLIGHTS Development of MOGAs was reviewed.; Three representative MOGAs were selected, namely NSGA-II, NSGA-III, and RVEA, and three multi-objective optimization models were then developed accordingly for comparison.; Numerical experiments were conducted to evaluate the performance of representative MOGAs for optimization of a cascaded reservoir system.;

Abstract Background Tooth-colored onlays and partial crowns for posterior teeth have been used increasingly in clinics. However, whether onlays/partial crowns could perform as well as full crowns in the posterior region was still not evaluated thoroughly. Methods A literature search was conducted without language restrictions in Pubmed, Embase, Cochrane Central Register of Controlled Trial and Web of science until September 2021. RCTs, prospective and retrospective observational studies with a mean follow-up of 1 year were selected. Cochrane Collaboration’s tool was adopted for quality assessment of the RCT. The quality of observational studies was evaluated following Newcastle-Ottawa scale. The random-effects and fixed-effects model were employed for meta-analysis. Results Four thousand two hundred fifty-seven articles were initially searched. Finally, one RCT was identified for quality assessment and five observational studies for qualitative synthesis and meta-analysis. The RCT was of unclear risk of bias while five observational studies were evaluated as low risk. The meta-analysis indicated no statistically significant difference in the survival between onlays/partial crowns and full crowns after 1 year (OR = 0.55, 95% CI: 0.02-18.08; I2 = 57.0%; P = 0.127) and 3 years (OR = 0.65, 95% CI: 0.20-2.17; I2 = 0.0%; P = 0.747). For the success, onlays/partial crowns performed as well as crowns (OR = 0.58, 95% CI: 0.20-1.72; I2 = 0.0%; P = 0.881) at 3 years. No significant difference of crown fracture existed between the two methods (RD = 0.00, 95% CI: − 0.03-0.03; I2 = 0.0%; P = 0.972). Conclusions Tooth-colored onlays/partial crowns performed as excellently as full crowns in posterior region in a short-term period. The conclusions should be further consolidated by RCTs with long-term follow-up.

In order to investigate the regulation mechanism that exogenous putrescine (Put) treatments on reducing chilling injury of postharvest yellow melon fruits, ‘Xinmi No.3’ yellow melon fruits was used as material, and the effect that exogenous putrescine ( 0 and 2.0 mmol/L Put) treatments on the chilling injury were studied and reactive oxygen metabolism of yellow melon fruits under 5±0.5 ℃ temperature. The results showed that 2.0 mmol/L Put treatment could maintain higher level of superoxide dismutase (SOD) activity, furthermore, it could increase the activity of catalase (CAT), peroxidase (POD) and ascorbate peroxidase (APX) 2.3, 1.6, 1.2 times, respectively compared with CK at 21 days (Severe chilling injury), and reached to 30.06, 2.46 and 39.14 U·g−1 FW, respectively. It inhibited the accumulation of superoxide anion radical (O2·−) and hydrogen peroxide (H2O2), the activity of lipoxygenase (LOX) and the content of malondialdehyde (MDA) at 28~49 days significantly, thus, it could alleviate the damage of reactive oxygen species to cell membrane, and relieved the symptoms of chilling injury of ‘Xinmi No.3’ yellow melon fruits, delay the occurrence time of chilling injury by 7 d, the chilling injury index was only 0.27 until at the end of storage period, it lower than the control significantly. Therefore, the exogenous putrescine (Put) treatment can alleviate chilling injury of yellow melon is closely related to balance reactive oxygen metabolism.

In this paper, the simulation model of thermoelectric generator and maximum power point tracking control (MPPT) DC/DC circuit is set up from the theory and mathematical formula. On this basis, this paper completes the maximum power point tracking control by observation and disturbance method, constant voltage method, pure fuzzy control, constant voltage method combined with PI control and constant voltage method combined with single neuron PI control. In this paper, the above five methods are firstly simulated and compared. The maximum power point tracking accuracy and corresponding time of constant voltage method combined with PI control and constant voltage method combined with single neuron PI control are the best, and these two methods are selected for subsequent experimental verification in this paper. The intelligent control algorithm of constant voltage method combined with single neuron PI control has high maximum power point tracking accuracy, and can greatly reduce the disturbance degree of output power. The experimental tracking accuracy of the control strategy studied in this paper is between 99.3% and 99.4%. The experimental, simulation and theoretical results of the thermoelectric generator and its maximum power point tracking control algorithm in this paper are highly consistent, which can prove the rationality and correctness of the research in this paper.

Abstract The present study aimed to explore whether chromosomal polymorphisms (CPs) have negative effects on reproductive outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET)/frozen-thawing embryo transfer (FET)? We conducted a retrospective study consisting of 21,867 assisted reproductive technology treatment cycles, among which, fresh embryo transfer cycles accounted for 10,400, and the rest were FET cycles. According to karyotype of CPs, the former was grouped as: group 1 (male carrier, n = 425), group 2 (female carrier, n = 262), and group 3 (couple without CPs, n = 9713). Accordingly, FET cycles were divided into 3 groups: group 4 (male carrier, n = 298), group 5 (female carrier, n = 311), and group 6 (couple without CPs, n = 10,858). The embryo implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and early miscarriage rate (EMR) were compared among the groups. In fresh embryo transfer cycles after IVF/ICSI, there were no significant differences in the infertility duration, BMI, basal FSH, no. of oocyte, no. of 2PN, endometrial thickness on trigger day, serum E2, P, and LH level on trigger day (P > 0.05). The female age, no. of 2PN embryo cleavage, top-quality embryo, and no. of embryo transferred were significantly different among groups (P 0.05), but the female age, BMI, no. of embryo transferred were significantly different among groups (P > 0.05). The IR was 24.3%, 23.6% and 22.3% in group 4, 5, and 6, receptivity. The CPR was 31.8%, 30.9%, and 30.0%, the LBR was 23.8%,26.3%, and 23.8%, while the EMR was 12.6%, 13.1%, 14.4%, respectively. The IR, CPR, EMR, and LBR showed no significant differences among groups (P > 0.05). Binary logistic regression analysis indicated that female age, infertility duration, and no. of embryo transferred were independently factors affecting CPR and LBR after FET. The CPs were not associated with CPR and LBR after FET. The results suggested that uniparental carrying of CPs have no effects on the reproductive outcomes after IVF/ICSI-ET/FET. However, it is not clear whether both parents carrying CPs would affect pregnancy outcome.

Abstract Enhancer release and retargeting (ERR) events could activate disease-causing gene promoters for increasing the expression level of oncogenes. Meanwhile, class A orphan GPCRs (oGPCRs) are known as potential biomarkers or drug targets for various cancers, such as gastric cancer (GC). Hence, systemic investigation of ERR events for class A oGPCRs in GC could help to explore biomarkers for GC. In this study, ENCODE and GTEx eQTL data were utilized to define ERR events in GC. Only GPR35 was then detected that could be activated by ERR in GC based on these data and ChIP-seq. Then, activated GPR35 functional in GC cells were explored by flow cytometry, cell-based wound healing assay, Transwell migration assay, and M2 polarization of macrophages assay. Meanwhile, according to TCGA and GEO database, overall survival, immune-related gene expression, and immune cell infiltration level in different GPR35 expressions were calculated. Here, we found ERR event activate GPR35 results in GC cells proliferation and migration, and partly immune cells significance exhaustion (CD8 + T-cells and CD4 + memory T-cells) and/or infiltration (T-cells and macrophage). Meanwhile, high GRP35 level leads to a poor prognosis in GC patients, probably partly due to it promoting the immune infiltration level of macrophages and then inducing polarization of M2 macrophages. Notably, GPR35’s high expression in CTSB+ and CD68 + macrophage could be a genetic indicator for early warning of primary GC. Hence, our findings provide a novel activation approach for oGPCRs, and GPR35 could be determined as a new drugable receptor and early genetic indicator for GC.

Scientifically judging the current state of carbon emissions in China and each province is a logical starting point for judging whether carbon emissions will peak or not by 2030. Using the Tapio decoupling model, this paper examines the carbon emissions peaking states of 30 provinces in China. The results show that carbon emissions in seven provinces including Beijing, Tianjin, Shanghai, Jilin, Chongqing, Sichuan, and Heilongjiang have peaked; nine provinces including Zhejiang, Henan, Shaanxi, Hubei, Guizhou, Yunnan, Jiangsu, Hunan, and Qinghai have pseudo-peaks, that is, although carbon emissions have reached a peak for the moment, they may peak again in the future; carbon emissions in other provinces have not peaked. Further, this paper finds that the current emission reduction efforts are not enough to support the realization of the 2030 carbon emissions peaking goal through the Kaya model prediction. Among the provinces which have pseudo-peaks, Zhejiang, Guizhou, Shaanxi, and Jiangsu are more difficult to achieve peaking, while Henan, Hubei, Yunnan, and Qinghai perform better under the enhanced low-carbon scenario. Ningxia, Xinjiang, and Inner Mongolia are unlikely to reach their peaks in 2030 under any pre-set scenario.

With the increasing demands of consumers for product grade, the C2B model of high-grade e-commerce emerges as required. In order to solve the problem of coordination and cooperation between e-commerce platforms and manufacturers, and to further develop the C2B model of high-grade e-commerce, this paper studies the coordination of supply chain interests by establishing a differential game model considering product grade factors. By comparing the equilibrium solutions of differential games under different decision-making situations, a cooperative coordination mechanism is proposed. Next, the equilibrium solution is further analyzed by means of numerical simulation. Finally, the influence of several important parameters on the equilibrium solution is discussed through sensitivity analysis. It is found that (1) the supply chain parties have optimal quality behavior in the centralized decision-making situation, and the overall benefit is the greatest. (2) Compared with the Nash non-cooperative game, the optimal quality behavior of the dominant party remains unchanged, and the optimal quality behavior of the following party is enhanced after both parties move from the Stackelberg master-slave game, and the optimal profits of both parties, as well as the overall increase. (3) The cooperative coordination model can coordinate the quality behavior of both sides of the supply chain when the benefit distribution coefficient is within a specific range.

Abstract In this article, an adaptive fuzzy finite‐time fault‐tolerant control (FTC) scheme for uncertain non‐linear systems under sensor faults is proposed. Compared with the existing methods, the considered system contains unknown time‐varying fault parameters, uncertain non‐linear functions, and can guarantee the performance of the system in finite time. The coupling between fault parameters and actual states is solved by the fault parameters separation method. The fuzzy logic system (FLS) is used to approximate the unknown functions, and combining the backstepping technology an adaptive fault‐tolerant controller is designed. The finite‐time stability of the closed‐loop system is proved by the Lyapunov theory. At last, the numerical simulation and the real physical system simulation verified the effectiveness of the proposed scheme.

Abstract Objective Few studies have performed detailed ultrasound measurements of medial epicondyle‐olecranon (MEO) ligament that cause the entrapment of ulnar nerve. This study aims to comprehensively evaluate dynamic ultrasonographic characteristics of MEO ligament and ulnar nerve for clinical diagnosis and accurate treatment of cubital tunnel syndrome (CuTS). Methods Thirty CuTS patients (CuTS group) and sixteen healthy volunteers (control group) who underwent ultrasound scanning from October 2016 to October 2020 were retrospectively collected, with 30 elbows in each group. Primary outcomes were thickness at six points, length and width of MEO ligament. Secondary outcomes were thickness of ulnar nerve under MEO ligament at seven parts and the cross‐sectional area (CSA) of ulnar nerve at proximal end of MEO ligament (P0 mm). The thickness of MEO ligament and ulnar nerve in different points of each group was compared by one‐way ANOVA analysis with Bonferroni post hoc test, other outcomes were compared between two elbow positions or two groups using independent‐samples t test. Results Thickness of MEO ligament in CuTS group at epicondyle end, midpoint in transverse view, olecranon end, proximal end, midpoint in axial view, and distal end was 0.67 ± 0.31, 0.37 ± 0.18, 0.89 ± 0.35, 0.39 ± 0.21, 0.51 ± 0.38, 0.36 ± 0.25 at elbow extension, 0.68 ± 0.34, 0.38 ± 0.27, 0.77 ± 0.39, 0.32 ± 0.20, 0.48 ± 0.22, 0.32 ± 0.12 (mm) at elbow flexion, respectively. Compared with control group, they were significantly thickened except for proximal end at elbow flexion. MEO ligament thickness at epicondyle end and olecranon end was significantly larger than midpoint in two groups. No significant difference was found in length and width of MEO ligament among different comparisons. Ulnar nerve thickness at 5 mm proximal to MEO ligament (P5 mm, 3.25 ± 0.66 mm) was significantly increased than midpoint of MEO ligament (Mid), distal end of MEO ligament (D0 mm), 5 mm (D5 mm), 10 mm (D10 mm) distal to MEO ligament at extension in CuTS group. Compared with control group, ulnar nerve thickness at P5 mm in CuTS group was significantly increased at extension position, at D5 mm and D10 mm was significantly decreased at flexion position. CSA of ulnar nerve at extension position (14.44 ± 4.65 mm2) was significantly larger than flexion position (11.83 ± 3.66 mm2) in CuTS group, and CuTS group was significantly larger than control group at two positions. Conclusions MEO ligament in CuTS patients was thickened, which compressed ulnar nerve and caused its proximal end swelling. Ultrasonic image of MEO ligament thickness was a significant indicator for CuTS and can guide surgeons in selecting the appropriate treatment.

Abstract With the awareness of global environmental protection, the generation of photovoltaic (PV) power is increasing rapidly. Local voltage/Var control is widely studied to overcome the real‐time change in PV power generation. The stability condition of local controls is strictly dependent on the system information, and the control parameter is chosen considering both the stability condition and dynamic performance, which limits its scalability and makes the parameter setting difficult. In this work, the coupling between node voltages is separated in the prediction time, and a local voltage predictive control strategy is proposed to reduce the voltage deviation with respect to the reference voltage. The proposed control is implemented by using historical local data and current local measurements. The control parameter is the data length, which has less correlation with the system information, and the control performance is less sensitive to the control parameter. The proposed control can be regarded as a conventional local control with dynamic compensation, which improves the dynamic performance and the steady‐state error. The proposed local control is tested on a practical distribution system. The simulation result demonstrates the proposed control achieves better performance than the conventional local control under different application scenarios and weather conditions.

Background: Traditional full-incision double eyelid blepharoplasty has several significant disadvantages, including slow recovery and bilateral asymmetry, which results in high rates of patient dissatisfaction. These problems can be minimized using improved surgical techniques aimed at reducing tissue damage and bleeding, decreasing operation time, and especially at protecting the subcutaneous capillary network during the operation. We therefore aimed to guard the capillary network and reduce intraoperative bleeding using the practical technique of reverse orbicularis oculi muscle resection. Methods: Fifty cases of double eyelid blepharoplasty with traditional full-incision (group A) and 61 cases of reverse double eyelid blepharoplasty with a preserved capillary network (group B) were divided into two groups from October 1 to December 31, 2021 and from March 1 to May 31, 2022, respectively. The orbicularis oculi muscle was removed reversely from the front of the tarsal plate using double eyelid blepharoplasty, and the muscular membrane and subcutaneous capillary network were preserved. The operation time recorded in previous medical records was checked and compared with that of our novel technique. The recovery of double eyelid blepharoplasty was determined at 1, 4, and 12 weeks after the operation and patient satisfaction was also compared with that in previous medical records of patients in group A. Results: The reverse double eyelid blepharoplasty procedure was less complicated and easier to control than the traditional full-incision double eyelid blepharoplasty methodology. The average operation time of the double eyelid blepharoplasty cases with traditional full-incision was significantly greater than that of the cases of reverse double eyelid blepharoplasty with the capillary network preserved (45.68 ​± ​5.27 ​min and 31.11 ​± ​5.58 ​min, respectively; t=14.018 9, P=0.000 0). Patient satisfaction was 42% and 78.69%, respectively, at 1 week post-operation (χ2=15.724 8, P=0.000 1), 62% and 90.16% at 4 weeks post-operation (χ2=12.490 2, P=0.000 4), and 90% and 95.08%, at 12 weeks post-operation (χ2=1.061 1, P=0.303 0). Conclusion: Reverse double eyelid blepharoplasty with preserved subcutaneous capillary network effectively decreases the operation time and improves post-operative patient satisfaction. It is a double eyelid blepharoplasty method worthy of popularization.

Improving piezoelectric strain and voltage constant generally compromises piezoelectric performance and mechanical softness. Here, the authors report a bond weakening strategy for organic-inorganic hybrid piezoelectrics and mitigated these issues.

Abstract Background To summarize our clinical experience of cryoablation in renal cell carcinoma (RCC) of Chinese population and to evaluate the long-term outcomes of laparoendoscopic single-site (LESS) cryoablation (LCA) as well as percutaneous CT-guided cryoablation (PCA) for biopsy-proven T1a and T1b RCC. Methods This was a multi-center, retrospective study investigating T1 stage RCC patients from 2011 to 2021. The patients were treated by LCA or PCA according to individual situation. Overall survival (OS), cancer-related survival (CSS), and progression-free survival (PFS) were evaluated for oncological outcomes, and kidney function, complications, and hospital stay were used to estimate technical outcomes. Results A total of 163 consecutive patients were included. Among them, 59 cases were treated by LCA and PCA was performed in 104 cases. All operations were processed successfully. Mean diameter of the mass was (2.9±1.4) cm; median blood volume was 45ml (10~200 ml). The mean operation time was 84.0 ± 24.5 min. The median postoperative hospital stay was 3 days (1~6 days). Compared with LCA, procedure time of PCA was shortened, the volume of bleeding was reduced, and the hospital stay was decreased. The overall adverse events rate was 9.8% (16/163). The mean preoperative and postoperative eGFR of LCA were 77.6±15.3 ml/min and 75.6±17.4 ml/min, respectively. Analogously, the values of PCA were 78.7±12.9 ml/min and 76.7±14.3 ml/min. Mean follow-up time was 64.2 ± 30.2 months (range, 7–127 months). Local recurrence was observed in 13 patients (8.0%), 4 (6.8%) cases of LCA and 9 (8.7%) cases of PCA. PFS at 5 and 10 years were 95.5% and 69.2% for LCA and 96.7% and 62.8% for PCA. In total, 26 patients (16.0%) (11 patients from LCA and 15 from PCA) died throughout the follow-up period. OS at 5 and 10 years were 93.8% and 31.4% for LCA, and 97.4% and 52.7% for PCA. Six patients (3.7%) (3 cases from LCA and 3 from PCA) died of metastatic RCC. CCS for LCA were 98.0% and 82.8% at 5 and 10 years, while the data were 100% and 86.4% for PCA. Conclusion LCA and PCA for T1 stage RCC provides satisfactory long-term oncological and renal function preservation outcomes, with acceptable complication rates.

Abstract Background Methyltransferase-like 3 (METTL3) expression could be found in various normal and cancerous tissues. As of now, the clinical significance of METTL3 expression in human pancreatic cancer (PC) tissues still remains to be understood. Our present study aims to investigate the prognostic value and clinical implications of METTL3 expression in PC tissues. Methods The TCGA, GTEx, and GEO public databases were used to study the mRNA expression level of the m6A family members and its relationship among PC tissues and normal pancreatic tissue. The immunohistochemistry was used to analyze the difference of METTL3 expression between cancer tissues and adjacent normal tissues. The prognostic value was evaluated by using the Log-rank survival analysis and Cox model analysis. PAAD samples from TCGA and GEO databases were used to perform the immune infiltration analysis and gene set enrichment analysis based on the genes that were highly correlated with METTL3. Results Based on the analysis of TCGA, GTEx, and GEO public database, we found that the m6A family members showed a higher correlation in PC tissues compared to normal pancreatic tissues, and the mRNA expression level of the m6A family members showed a significant difference between PC tissues and adjacent normal tissues. Moreover, scRNA-seq data indicated that METTL3 showed a higher expression level in malignant epithelial cells. Our immunohistochemistry results also confirmed that the intensity of METTL3 immunostaining in PC tissues was significantly higher than that in adjacent normal tissues (P = 0.015). The overall survival (OS) of PC patients with high expression of METTL3 protein were significantly poorer than those with low expression of METTL3 protein (HR = 1.788, 95% CI 1.071–2.984, P = 0.026). Further analysis of PC data from the database showed that METTL3 expression was associated with a variety of tumor-infiltrating immune cells and was involved in m6A modification and metabolism in PC tissues. Conclusion Increased METTL3 expression at the protein level could be found in PC tissues, suggesting that the METTL3 expression was involved in the progression of PC and could serve as an important marker for prognostic prediction of this malignancy.

Abstract Wuliangye‐flavor liquor (WLFL), a specific Chinese traditional liquor, one of the major type of global distilled spirits, offers a unique flavor system acquired across thousands of years of development. Free amino acids (FAAs), as major health factors, are considered to be primarily derive from the hydrolysis of protein from the Zaopeis (ZPs) by microbial populations during fermentation. Here, we investigated the changes of microbial communities in ZPs and FAAs in raw liquor (RL) directly related ZPs from different ages of WLFL fermentation pits by phospholipid fatty acid fingerprint (PLFA) and high performance liquid chromatography method. Results indicated that the total PLFAs of 20‐ and 50‐year ZPs were significantly higher (p 1; p

Objectives: The molecular landscape of non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer based on molecular characteristics is essential but poorly understood. In this pilot study we aimed to identify a multi-omics signature that can distinguish MIBC from NMIBC. Such a signature can assist in finding potential mechanistic biomarkers and druggable targets. Methods: Patients diagnosed with NMIBC (n = 15) and MIBC (n = 11) were recruited at a tertiary-care hospital in Nanjing from 1 April 2021, and 31 July 2021. Blood, urine and stool samples per participant were collected, in which the serum metabolome, urine metabolome, gut microbiome, and serum extracellular vesicles (EV) proteome were quantified. The differences of the global profiles and individual omics measure between NMIBC vs. MIBC were assessed by permutational multivariate analysis and the Mann–Whitney test, respectively. Logistic regression analysis was used to assess the association of each identified analyte with NMIBC vs. MIBC, and the Spearman correlation was used to investigate the correlations between identified analytes, where both were adjusted for age, sex and smoking status. Results: Among 3168 multi-omics measures that passed the quality control, 159 were identified to be differentiated in NMIBC vs. MIBC. Of these, 46 analytes were associated with bladder cancer progression. In addition, the global profiles showed significantly different urine metabolome (p = 0.029), gut microbiome (p = 0.036), and serum EV (extracellular vesicles) proteome (p = 0.039) but not serum metabolome (p = 0.059). We also observed 17 (35%) analytes that had been developed as drug targets. Multiple interactions were obtained between the identified analytes, whereas for the majority (61%), the number of interactions was at 11–20. Moreover, unconjugated bilirubin (p = 0.009) and white blood cell count (p = 0.006) were also shown to be different in NMIBC and MIBC, and associated with 11 identified omics analytes. Conclusions: The pilot study has shown promising to monitor the progression of bladder cancer by integrating multi-omics data and deserves further investigations.

Abstract Background Increasing evidence has demonstrated that circular RNAs (circRNAs) are implicated in cancer progression. However, the aberrant expression and biological functions of circRNAs in clear cell renal cell carcinoma (cRCC) remain largely elusive. Method Differentially expressed circRNAs in cRCC were filtered via bioinformatics analysis. Aberrant circPOLR2A expression was validated in cRCC tissues and cell lines via qRT-PCR. Sanger sequencing was used to identify the backsplicing site of circPOLR2A. In vitro and in vivo functional experiments were performed to evaluate the role of circPOLR2A in cRCC malignancy. RNA pull-down, mass spectrometry, RIP, FISH and immunofluorescence assays were used to identify and validate the circPOLR2A-interacting proteins. Ubiquitination modification and interaction between proteins were detected via Co-IP and western blotting. The m6A modification in circPOLR2A was validated by the meRIP assay. Results Bioinformatics analysis revealed that circPOLR2A was highly expressed in cRCC tissues and metastatic cRCC tissues. CircPOLR2A expression was associated with tumor size and TNM stage in cRCC patients. In vitro and in vivo functional assays revealed that circPOLR2A accelerated cRCC cell proliferation, migration, invasion and angiogenesis, while inhibiting apoptosis. Further mechanistic research suggested that circPOLR2A could interact with UBE3C and PEBP1 proteins, and that UBE3C could act as a specific ubiquitin E3 ligase for the PEBP1 protein. The UBE3C/circPOLR2A/PEBP1 protein-RNA ternary complex enhanced the UBE3C-mediated ubiquitination and degradation of the PEBP1 protein which could inactivate the ERK signaling pathway. Rescue experiments revealed that the PEBP1 protein was the functional downstream target of circPOLR2A. Furthermore, m6A modification in circPOLR2A was confirmed, and the m6A reader YTHDF2 could regulate circPOLR2A expression. Conclusion Our study demonstrated that circPOLR2A modulated the UBE3C-mediated ubiquitination and degradation of the PEBP1 protein, and further activated the ERK pathway during cRCC progression and metastasis. The m6A reader, YTHDF2, regulated circPOLR2A expression in cRCC. Hence, circPOLR2A could be a potential target for the diagnosis and treatment of cRCC.

Abstract Background This retrospective study included an alternative treatment for types A2, A3, and B1 distal radius fractures using percutaneous fixation with a cemented K-wire frame. Methods From January 2017 to January 2020, 78 patients with distal radius fractures were treated with percutaneous internal fixation using a cemented K-wire frame. There were 47 male patients and 31 female patients. The fractures were classified into types A2 (n = 10), A3 (n = 46), and B1 (n = 22). X-rays were taken immediately after surgery and after the bone had healed. Wrist function was assessed using the Mayo Wrist Score (90–100, excellent; 80–90, good; 60–80, satisfactory; 0.05). Osteomyelitis was not observed in this series. All patients achieved bone healing after a mean of 4.5 weeks (range, 4 to 8 weeks). Follow-up lasted a mean of 27 months (range, 24 to 33 months). The mean score of wrist function was 97 (range, 91 to 100). Among them, 66 results were excellent and 12 results were good. The mean patient satisfaction was 10 cm (range, 8 to 10 cm). Conclusions Percutaneous fixation with cemented K-wire frame is a safe and preferred choice for the treatment of types A2, A3, and B1 distal radius fractures. The frame provides support to prevent wire migration. The fixation technique is a minimally invasive procedure that is easy to perform. Level of Evidence Therapeutic study, Level IVa.

Abstract Background Percutaneous cement discoplasty (PCD) is a minimally invasive treatment for degenerative lumbar spine disease, but the relationship between decompression effect on the nerve root and different doses of bone cement is uncertain. Purpose To investigate the indirect decompression effect of cement with different doses on nerve roots and the biomechanical changes on the spine during PCD using finite element analysis (FEA). Methods FEA was adapted to analyze the mechanical changes in the lumbar vertebrae before and after the application of PCD.CT scan images of adult males were utilized to establish a finite element model of the lumbar vertebral body using mimics and Pro/E software. The images were divided into four models: the normal model (normal, model N), the disc degeneration model (high, model H), the intervertebral disc injected with 3 mL of bone cement (model H1), and the intervertebral disc injected with 5 mL of bone cement (model H2). All models were analyzed using the ABAQUS6.14.2 software. The normal physiological movements were simulated, and the mechanical changes in the lumbar vertebrae were observed prior to and after the cement filling application. Results The stress of the nerve root in model H was the largest. The nerve root stress in the model H2 was the smallest during flexion, extension, left bending, right bending, left rotation, and right rotation at 90%, 44%, 25%, 56%, 56%, and 51% of the normal benchmark, respectively. After the injection of bone cement, the nerve root stress is reduced. The greater the amount of cement, the lesser the nerve root stress. The motion was reduced in models H, H1, and H2, and there were differences between models H1 and H2. Cartilage endplate stress was less in model H2 than in model H1. Conclusions The nerve root stress increased after degeneration and decreased after intervertebral height recovery through cement injection, resulting in a significant indirect decompression effect.The stress of the nerve root decreased with the increase in the amount of cement injection.

Abstract Background Temperature is involved in the regulation of carotenoid accumulation in many plants. The floral color of sweet osmanthus (Osmanthus fragrans Lour.) which is mainly contributed by carotenoid content, is affected by temperature in autumn. However, the mechanism remains unknown. Here, to reveal how temperature regulates the floral color of sweet osmanthus, potted sweet osmanthus ‘Jinqiu Gui’ were treated by different temperatures (15 °C, 19 °C or 32 °C). The floral color, carotenoid content, and the expression level of carotenoid-related genes in petals of sweet osmanthus ‘Jinqiu Gui’ under different temperature treatments were investigated. Results Compared to the control (19 °C), high temperature (32 °C) changed the floral color from yellow to yellowish-white with higher lightness (L*) value and lower redness (a*) value, while low temperature (15 °C) turned the floral color from yellow to pale orange with decreased L* value and increased a* value. Total carotenoid content and the content of individual carotenoids (α-carotene, β-carotene, α-cryptoxanthin, β-cryptoxanthin, lutein and zeaxanthin) were inhibited by high temperature, but were enhanced by low temperature. Lower carotenoid accumulation under high temperature was probably attributed to transcriptional down-regulation of the biosynthesis gene OfPSY1, OfZ-ISO1 and OfLCYB1, and up-regulation of degradation genes OfNCED3, OfCCD1-1, OfCCD1-2, and OfCCD4-1. Up-regulation of OfLCYB1, and down-regulation of OfNCED3 and OfCCD4-1 were predicted to be involved in low-temperature-regulated carotenoid accumulation. Luciferase assays showed that the promoter activity of OfLCYB1 was activated by low temperature, and repressed by high temperature. However, the promoter activity of OfCCD4-1 was repressed by low temperature, and activated by high temperature. Conclusions Our study revealed that high temperature suppressed the floral coloration by repressing the expression of carotenoid biosynthesis genes, and activating the expression of carotenoid degradation genes. However, the relative low temperature had opposite effects on floral coloration and carotenoid biosynthesis in sweet osmanthus. These results will help reveal the regulatory mechanism of temperature on carotenoid accumulation in the petals of sweet osmanthus.

Abstract Objective Post-hepatectomy liver failure (PHLF) is a severe complication in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. This study aims to develop a nomogram of PHLF grade B–C in patients with huge HCC (diameter ≥ 10 cm). Methods We retrospectively collected clinical information of 514 and 97 patients who underwent hepatectomy for huge HCC at two medical centers between 2016 and 2021. Univariate and multivariate analysis were carried out to screen the independent risk factors of PHLF grade B–C, which were visualized as a nomogram. Results Three Hundred Forty Three Thousand One Hundred Seventy One and 97 HCC patients were included in the training cohort, internal validation cohort, and external validation cohort, with probabilities of PHLF grade B–C of 15.1%, 12.9%, and 22.7%, respectively. Pre-operative modified albumin-bilirubin (mALBI) grade (p

Advances in 3D neuronal cultures have allowed unprecedented access to the mechanisms underlying brain diseases. This work describes the novel Modular Neuronal Network (MoNNet) system, which enables more complex studies of cortical neuronal ensemble dynamics.

A microheater with a small temperature coefficient of resistance (TCR) at liquid hydrogen temperature was designed and fabricated by microfabrication technology. The NiCr heater annealed in N2 at 250 °C achieved the smallest TCR. The crystal structures of the NiCr film annealed in nitrogen were analyzed using a scanning electron microscope (SEM) and by x-ray diffraction (XRD). The crystallization of the NiCr film improved with the increase in annealing temperature. The failure mechanism of the microheater is studied, and it is seen that the central area of the heating film and the joint of the heating film and the electrode are most vulnerable to destruction.

Landscape ecological risk reflects the impact of human activities or natural hazards on landscape patterns, functions, and processes in a region. The scientific assessment of its evolutionary trends can play an essential role in maintaining and improving regional human wellbeing. This study focused on the Fuchunjiang River Basin in the suburbs of Hangzhou, a large city in China with a high degree of landscape heterogeneity and rapid economic growth. Based on land use data from 1990 to 2020, an ecological risk assessment model and geodetector tools were combined to study the spatiotemporal variation characteristics and influencing factors of landscape ecological risk in the basin. The results showed the following: (1) from 1990 to 2020, the landscape pattern of various land use types showed a general trend of an increasing degree of agglomeration and decreasing loss index; (2) the spatial distribution pattern of landscape ecological risk was “high in the northwest and low in the southeast.” From basin to township scales, landscape ecological risk showed a decreasing trend on long time scales, although the changes were relatively drastic in short time periods; (3) GDP, human interference, area of urban and rural residential land, area of arable land transferred in, and area of arable land transferred out were the dominant influencing factors of landscape ecological risk; (4) the coupling between landscape ecological risk and GDP in 2020 exhibited an inverted “U” shaped relationship, indicating that the environmental Kuznets curve (EKC) may have the same applicability in the ecological risk management; (5) according to the main functions of different risk agglomerations, targeted ecological risk management strategies were proposed. In short, this study carried out the landscape ecological risk assessment at the township scale for the first time, quantitatively analyzed the relationship between economic development and ecological risk, and proposed targeted risk prevention strategies, which are instructive for other basin areas that are experiencing rapid urbanization in the world.

PMMA bone cement is commonly used in the field of orthopedics as a filling material. However, due to the lack of biological activity and high elastic modulus, its application scope and efficacy are greatly limited, such as in the treatment of osteoporotic vertebral compression fractures(OVCF). For this reason, new functional bone cement was synthesized and designed to address and improve those shortcomings. In this study, Tetracalcium phosphate (TTCP) and Whitlockite (WH) were incorporated with PMMA cement to prepare a novel bone cement (TTCP/WH) and systemically evaluated its characteristics such as the operational working time and mechanical properties, etc. based on the International Standardization Organization standard (ISO 5833). Also, the biocompatibility and osteogenic activity of TTCP/WH bone cement were analyzed in vitro, and the rabbit ilium bone defect model was also used to evaluate osteoconduction and osseointegration with native bone tissue. Our results showed that TTCP/WH functional bone cement exhibited good osteoconductivity compared with bio-inert PMMA bone cement, facilitated new bone formation, and was histocompatible with surrounding bone tissue while maintaining its original purpose of supporting. So, TTCP/WH functional bone cement may be a promising alternative to overcome PMMA cement’s limitations in treating OVCF.

Abstract Organic single crystals (OSCs) offer a unique combination of both individual and collective properties of the employed molecules, but it remains highly challenging to achieve OSCs with both high mobilities and strong fluorescence emissions for their potential applications in multifunctional optoelectronics. Herein, we demonstrate the design and synthesis of two novel triphenylamine‐functionalized thienoacenes‐based organic semiconductors, 4,8‐distriphenylamineethynylbenzo[1,2‐b:4,5‐b′]dithiophene (4,8‐DTEBDT) and 2,6‐distriphenylamineethynylbenzo[1,2‐b:4,5‐b′]dithiophene (2,6‐DTEBDT), with high‐mobility and strong fluorescence emission. The two compounds show the maximum mobilities up to 0.25 and 0.06 cm2 V−1 s−1, the photoluminescence quantum yields (PLQYs) of 51% and 45%, and the small binding energies down to 55.13 and 58.79 meV. The excellent electrical and optical properties ensured the application of 4,8‐DTEBDT and 2,6‐DTEBDT single crystals in ultrasensitive UV phototransistors, achieving high photoresponsivity of 9.60 × 105 and 6.43 × 104 A W−1, and detectivity exceeding 5.68 × 1017 and 2.99 × 1016 Jones.