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Abstract Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4’s function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

Abstract Eukaryotic initiation translation factor 3 subunit h (EIF3H) plays critical roles in regulating translational initiation and predicts poor cancer prognosis, but the mechanism underlying EIF3H tumorigenesis remains to be further elucidated. Here, we report that EIF3H is overexpressed in colorectal cancer (CRC) and correlates with poor prognosis. Conditional Eif3h deletion suppresses colorectal tumorigenesis in AOM/DSS model. Mechanistically, EIF3H functions as a deubiquitinase for HAX1 and stabilizes HAX1 via antagonizing βTrCP-mediated ubiquitination, which enhances the interaction between RAF1, MEK1 and ERK1, thereby potentiating phosphorylation of ERK1/2. In addition, activation of Wnt/β-catenin signaling induces EIF3H expression. EIF3H/HAX1 axis promotes CRC tumorigenesis and metastasis in mouse orthotopic cancer model. Significantly, combined targeting Wnt and RAF1-ERK1/2 signaling synergistically inhibits tumor growth in EIF3H-high patient-derived xenografts. These results uncover the important roles of EIF3H in mediating CRC progression through regulating HAX1 and RAF1-ERK1/2 signaling. EIF3H represents a promising therapeutic target and prognostic marker in CRC.

Abstract Acne vulgaris is a type of chronic skin disorder caused by Propionibacterium acnes (P. acnes). Neutrophil extrinsic traps (NETs) play key role in many types of inflammatory skin diseases. Adipose-derived stem cells (ADSCs) was reported modulate immune responses and neutrophil activity. Here, we explored the potential role of ADSCs and the potential mechanism associated with neutrophil extracellular traps (NETs) in relieving acne vulgaris. In the P. acnes-infected ear skin model, histological staining was used to evaluate the inflammatory infiltration and NET formation in control, P. acnes, and P. acnes + ADSCs groups. Besides, western blot was used to detect the expression levels of cit-H3, MPO, and Nrf2 in ear tissue. In vitro, the immunofluorescence staining of MPO and cit-H3, and SYTOX green staining were performed to measure the NET formation. CCK-8 assay, EdU staining, and wound healing assay were used to detect the proliferation and migration abilities of keratinocytes. ELISA assay was utilized to detect the secretion of inflammatory cytokines. In P. acnes-infected ear skin, ADSC treatment significantly attenuated inflammation and NET formation via activating Nrf2 signaling pathway. In vitro, the conditioned medium of ADSCs reduced the formation of P. acne-induced NETs. Besides, ADSCs could inhibit that the NETs efficiently promoted the proliferation, migration, and inflammatory cytokine secretion of keratinocytes. Our study suggested that ADSCs could attenuate P. acne-related inflammation by inhibiting NET formation. This study provides a novel therapeutic perspective of ADSCs in combating acne vulgaris.

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.

Background: Acute myeloid leukemia (AML) is the most common form of leukemia among adults and is characterized by uncontrolled proliferation and clonal expansion of hematopoietic cells. There has been a significant improvement in the treatment of younger patients, however, prognosis in the elderly AML patients remains poor.Methods: We used computational methods and machine learning (ML) techniques to identify and explore the differential high-risk genes (DHRGs) in AML. The DHRGs were explored through multiple in silico approaches including genomic and functional analysis, survival analysis, immune infiltration, miRNA co-expression and stemness features analyses to reveal their prognostic importance in AML. Furthermore, using different ML algorithms, prognostic models were constructed and validated using the DHRGs. At the end molecular docking studies were performed to identify potential drug candidates targeting the selected DHRGs.Results: We identified a total of 80 DHRGs by comparing the differentially expressed genes derived between AML patients and normal controls and high-risk AML genes identified by Cox regression. Genetic and epigenetic alteration analyses of the DHRGs revealed a significant association of their copy number variations and methylation status with overall survival (OS) of AML patients. Out of the 137 models constructed using different ML algorithms, the combination of Ridge and plsRcox maintained the highest mean C-index and was used to build the final model. When AML patients were classified into low- and high-risk groups based on DHRGs, the low-risk group had significantly longer OS in the AML training and validation cohorts. Furthermore, immune infiltration, miRNA coexpression, stemness feature and hallmark pathway analyses revealed significant differences in the prognosis of the low- and high-risk AML groups. Drug sensitivity and molecular docking studies revealed top 5 drugs, including carboplatin and austocystin-D that may significantly affect the DHRGs in AML.Conclusion: The findings from the current study identified a set of high-risk genes that may be used as prognostic and therapeutic markers for AML patients. In addition, significant use of the ML algorithms in constructing and validating the prognostic models in AML was demonstrated. Although our study used extensive bioinformatics and machine learning methods to identify the hub genes in AML, their experimental validations using knock-out/-in methods would strengthen our findings.

In order to address the issues of excessive brittle intermetallic compounds (IMC) formation in the TC4 brazed joints, two types of novel Ti-Zr-Cu-Ni-Sn amorphous braze fillers were designed. The microstructure and shear strength of the TC4/Ti-Zr-Ni-Cu-Sn/TC4 brazed joints were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffractometer (XRD) and electronic universal materials testing machine. The results show that the optimized Ti35Zr25Ni15Cu20Sn5 braze filler whose chemical composition is closer to the eutectic point possesses a lower melting point compared with the equiatomic Ti23.75Zr23.75Ni23.75Cu23.75Sn5. This was beneficial to the sufficient diffusion of Cu and Ni elements with the base metal during brazing and reduces the residual (Ti,Zr)2(Ni,Cu) content in the joint, which helps to improve the joint performance. The room-temperature and high-temperature shear strength of the TC4 brazed joints using the near eutectic component Ti35Zr25Ni15Cu20Sn5 filler reached a maximum of 472 MPa and 389 MPa at 970 °C/10 min, which was 66% and 48% higher than that of the TC4 joints brazed with the equiatomic Ti23.75Zr23.75Ni23.75Cu23.75Sn5 braze filler. Microstructural evolution and the corresponding mechanical response were in-depth discussed.

Abstract The medium‐thick plate is an important type of steel product widely used in construction and engineering machinery. The orders are usually characterised by multiple specifications and small quantities. The plate design is an important part in the production process of medium‐thick plate, which includes the combination of sub‐plates and the size design of the motherboard. A multi‐objective model for medium‐thick plate design is proposed based on the 2D bin packing model, comprehensively considering spatial and size constraints of the plate production. A two‐stage genetic algorithm (TSGA) is developed to solve the proposed model. In the first stage, an improved GA is used to optimise the corresponding relationship between the sub‐plates and the slab, as well as the size of the motherboard. In the second stage, an exact algorithm based on the integer programming model is applied to calculate the order layout to minimise the surplus materials. To validate the proposed method, computational experiments are conducted based on actual production data from a steel plant. The experimental results show the effectiveness of the TSGA algorithm in solving the plate design problem.

Among major nondestructive testing technologies (NDT), such as X-ray and ultra-sound, Terahertz (THz) waves present significant transmission rate through most of nonconductive materials without the need of applying couplant while posing zero ionized radiation hazard. In comparison to microwave NDT, terahertz technology boasts a superior spatial resolution and measurement precision due to its shorter wavelength. As such, it is considered to be the most promising technology for industrial NDT applications. To analyze of THz wave transmission characteristics within porcelain insulator and obtain large quantity of testing data with repeatable measurement condition, this paper reports an experimental approach using Kaolin, in powdery form, to emulate the aging behavior of porcelain, and a THz sensor to detect such imperceptible aging process where micrometer-scale cracks slowly develop inside of porcelain insulators. To support the data acquisition from distance, a LORA communication module was integrated in the sensor for using under high-voltage environment. In addition, a dedicated user-interface software has been developed to receive the wireless data as well as conducting data analysis, crack recognition and graphic display. The experiment successfully demonstrated a very feasible solution for online monitoring of the aging process of porcelain insulators by using compact THz sensor buried in the insulator.

Highlights A facile and generalized design strategy of polymer precursor inks was developed for direct ink writing of metal oxide into submicron 3D architectures. The Maillard reaction between polyethyleneimine and glucose endows the 3D-printed precursors with the excellent shape fidelity during high-temperature pyrolysis. As-printed 3D periodic dielectric structure with woodpile geometry shows a significant light-matter effect in mid-infrared region.

Objective There is a new medial malleolar fracture classification based on 3D CT reconstruction. However, there is no study assessing the reliability and accuracy of the new classification system and comparison between the new and the classic classification. This study aimed to compare the reliability and accuracy of the medial malleolar fracture classification based on 3D CT reconstruction and the Herscovici classification system. Methods We retrospectively analyzed the consecutive ankle fractures in our hospital from January 2013 to September 2020. Five inexperienced and five experienced orthopedic surgeons were included as observers to assess 68 cases with medial malleolar fractures. Ten evaluators classified the cases according to the two classification systems. The reference results of each case were made by the consensus of three senior trauma surgeons. The interobserver reliability, intraobserver reliability, and accuracy were evaluated at an interval of 6 weeks using Fleiss's kappa (κ) statistics. Results We found substantial interobserver and intraobserver reliability and 81.4% accuracy for the new classification, which was statistically superior to the Herscovici classification (P

Abstract The Golden2-like (GLK) transcription factors are plant-specific transcription factors (TFs) that perform extensive and significant roles in regulating chloroplast development. Here, genome-wide identification, classification, conserved motifs, cis-elements, chromosomal locations, evolution and expression patterns of the PtGLK genes in the woody model plant Populus trichocarpa were analyzed in detail. In total, 55 putative PtGLKs (PtGLK1-PtGLK55) were identified and divided into 11 distinct subfamilies according to the gene structure, motif composition and phylogenetic analysis. Synteny analysis showed that 22 orthologous pairs and highly conservation between regions of GLK genes across P. trichocarpa and Arabidopsis were identified. Furthermore, analysis of the duplication events and divergence times provided insight into the evolutionary patterns of GLK genes. The previously published transcriptome data indicated that PtGLK genes exhibited distinct expression patterns in various tissues and different stages. Additionally, several PtGLKs were significantly upregulated under the responses of cold stress, osmotic stress, and methyl jasmonate (MeJA) and gibberellic acid (GA) treatments, implying that they might take part in abiotic stress and phytohormone responses. Overall, our results provide comprehensive information on the PtGLK gene family and elucidate the potential functional characterization of PtGLK genes in P. trichocarpa.

Cell dielectric property measurement holds significant potential for application in cell detection and diagnosis due to its label-free and noninvasive nature. In this study, we developed a biosensor designed to measure the permittivity of liquid samples, particularly cell suspensions at the nanoliter scale, utilizing microwave and millimeter wave coplanar waveguides in conjunction with a microchannel. This biosensor facilitates the measurement of scattering parameters within a frequency domain ranging from 1 GHz to 110 GHz. The obtained scattering parameters are then converted into dielectric constants using specific algorithms. A cell capture structure within the microchannel ensures that cell suspensions remain stable within the measurement zone. The feasibility of this biosensor was confirmed by comparison with a commercial Keysight probe. We measured the dielectric constants of three different cell suspensions (HepG2, A549, MCF-7) using our biosensor. We also counted the number of cells captured in multiple measurements for each cell type and compared the corresponding changes in permittivity. The results indicated that the real part of the permittivity of HepG2 cells is 0.2–0.8 lower than that of the other two cell types. The difference between A549 and MCF-7 was relatively minor, only 0.2–0.4. The fluctuations in the dielectric spectrum caused by changes in cell numbers during measurements were smaller than the differences observed between different cell types. Thus, the sensor is suitable for measuring cell suspensions and can be utilized for label-free, noninvasive studies in identifying biological cell suspensions.

Pesticides play a crucial role in agricultural production by preventing diseases and pests and ensuring food yield. However, the irrational use of pesticides can lead to numerous issues that compromise crop quality and counteract the original intentions of their application. Therefore, it is necessary to identify more effective methods to counteract pesticide stress. Here we review the impacts of herbicides, insecticides, and fungicides on plants and the measures taken to reduce pesticide residues on plants. We have found that despite the substantial differences in the mechanisms of action of the aforementioned three types of pesticides, the adverse effects they inflict on plants are similar, and at certain dosages, they can severely constrain plant growth and disrupt physiological functions. Also, most current research on using exogenous growth regulators to alleviate pesticide stress still focuses on photosynthesis, the antioxidant system, three-stage detoxification, and secondary metabolites, neglecting the search for genes that respond to pesticide stress. We believe that by combining biological protection with post-harvest treatment techniques and exploring potential genes that are responsive to pesticide stress, a better strategy for dealing with pesticide stress can be found, thereby promoting sustainable agricultural development.

Remote sensing images are usually obtained from high-altitude observation. The spatial resolution of the images varies greatly and there are scale differences both between and within object classes, resulting in a diversified distribution of object scales. In order to solve these problems, we propose a novel object detection algorithm that maintains adaptability to multi-scale object detection based on feature interaction and Gaussian distribution in remote sensing images. The proposed multi-scale feature interaction model constructs feature interaction modules in the feature layer and spatial domain and combines them to fully utilize the spatial and semantic information of multi-level features. The proposed regression loss algorithm based on Gaussian distribution takes the normalized generalized Jensen–Shannon divergence with Gaussian angle loss as the regression loss function to ensure the scale invariance of the model. The experimental results demonstrate that our method achieves 77.29% mAP on the DOTA-v1.0 dataset and 97.95% mAP on the HRSC2016 dataset, which are, respectively, 1.12% and 1.41% higher than that of the baseline. These experimental results indicate the effectiveness of our method for object detection in remote sensing images.

Abstract Continuous de novo fatty acid synthesis is required for the biosynthetic demands of tumor. FBXW7 is a highly mutated gene in CRC, but its biological functions in cancer are not fully characterized. Here, we report that FBXW7β, a FBXW7 isoform located in the cytoplasm and frequently mutated in CRC, is an E3 ligase of fatty acid synthase (FASN). Cancer-specific FBXW7β mutations that could not degrade FASN can lead to sustained lipogenesis in CRC. COP9 signalosome subunit 6 (CSN6), an oncogenic marker of CRC, increases lipogenesis via interacting with and stabilizing FASN. Mechanistic studies show that CSN6 associates with both FBXW7β and FASN, and antagonizes FBXW7β’s activity by enhancing FBXW7β autoubiquitination and degradation, which in turn prevents FBXW7β-mediated FASN ubiquitination and degradation, thereby regulating lipogenesis positively. Both CSN6 and FASN are positively correlated in CRC, and CSN6-FASN axis, regulated by EGF, is responsible for poor prognosis of CRC. The EGF-CSN6-FASN axis promotes tumor growth and implies a treatment strategy of combination of orlistat and cetuximab. Patient-derived xenograft experiments prove the effectiveness of employing orlistat and cetuximab combination in suppressing tumor growth for CSN6/FASN-high CRC. Thus, CSN6-FASN axis reprograms lipogenesis to promote tumor growth and is a target for cancer intervening strategy in CRC.

Abstract Wound healing is a dynamic and highly sequential process involving a series of overlapping spatial and temporal phases, including hemostasis, inflammation, proliferation, and tissue remodeling. Mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal, multidirectional differentiation potential, and paracrine regulation. Exosomes are subcellular vesicular components 30–150 nm in size and are novel carriers of intercellular communication in regulating the biological behaviors of skin cells. Compared to MSCs, MSC-derived exosomes (MSC-exos) possess lower immunogenicity, easy storage, and highly effective biological activity. MSC-exos, mainly derived from adipose-derived stem cells (ADSCs), bone marrow-derived MSCs (BMSCs), human umbilical cord MSCs (hUC-MSCs), and other stem cell types, play a role in shaping the activity of fibroblasts, keratinocytes, immune cells, and endothelial cells in diabetic wounds, inflammatory wound repair, and even wound-related keloid formation. Therefore, this study focuses on the specific roles and mechanisms of different MSC-exos in wound healing, as well as the current limitations and various perspectives. Deciphering the biological properties of MSC-exos is crucial to providing a promising cell-free therapeutic tool for wound healing and cutaneous regeneration. Graphical Abstract

Abstract Regenerated silk fibroin (RSF) and regenerated sericin (RSS) have attracted much attention for tissue engineering due to excellent biocompatibility and controllable degradation. However, pure RSF films prepared by existing methods are brittle, which limits applications in the field of high-strength and/or flexible tissues (e.g. cornea, periosteum and dura). A series of RSF/RSS composite films were developed from solutions prepared by dissolving silks with different degumming rates. The molecular conformation, crystalline structure and tensile properties of the films and the effect of sericin content on the structure and properties were investigated. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction results revealed more β-sheets in films prepared by boiling water degumming than in Na2CO3-degummed RSFC film. Analysis of mechanical properties showed that the breaking strength (3.56 MPa) and elongation (50.51%) of boiling water-degummed RSF/RSS film were significantly increased compared with RSFC film (2.60 MPa and 32.31%), and the flexibility of films could be further improved by appropriately reducing the degumming rate.

AbstractBackground Orofacial clefts are the most common congenital malformation, but the global burden and trends of orofacial clefts have not been comprehensively analysed. The aim of this study was to assess the global incidence, deaths and disability-adjusted life years (DALYs) of orofacial clefts by countries, regions, sex and sociodemographic index (SDI) from 1990 to 2019.Methods The data on orofacial clefts were obtained from the Global Burden of Disease Study 2019. The incidence, deaths and DALYs were analysed by countries, regions, sex and SDI. Age-standardized rates and estimated annual percentage change (EAPC) were calculated to evaluate the burden and temporal trend of orofacial clefts. The association between EAPC and the human development index was assessed.Results Globally, the incidence, deaths and DALYs of orofacial clefts decreased from 1990 to 2019. The high SDI region showed the biggest downward trend in incidence rate from 1990 to 2019, along with the lowest age-standardized death rate and DALY rate. Some countries, such as Suriname and Zimbabwe, experienced increased death rate and DALY rate over time. The age-standardized death rate and DALY rate were negatively associated with the level of socioeconomic development.Conclusion Global achievement is evident in the control of the burden of orofacial clefts. The future focus of prevention should be on low-income countries, such as South Asia and Africa, by increasing healthcare resources and improving quality.KEY MESSAGESThis is the most recent estimate of the global epidemiology of orofacial clefts, with some countries not previously assessed.The global burden of orofacial clefts showed downward trends from 1990 to 2019; however, some low-income countries are still suffering from increasing burdens.Effective measures should be taken to reduce the burden of orofacial clefts in the uncontrolled regions.

Abstract The Lundberg-Palmgren (L-P) fatigue life formula, as a statistical fatigue theory, has been widely used in the industry. However, its direct applicability is limited to the components treated by surface strengthening technologies. Rolling contact fatigue tests and surface integrity measurements of American Iron and Steel Institute (AISI) 9310 rollers with several surface treatments were performed to address this issue. Based on these results, a modified L-P fatigue model was proposed, enabling the consideration of surface modification including surface roughness, residual stress, and hardening introduced by different surface treatments. Compared with the original L-P fatigue formula, its results are more accurate for surface strengthened specimens. Furthermore, this method can assess the contact fatigue life of gears treated by surface strengthening techniques.

Computer-aided Diagnosis (CADx) based on explainable artificial intelligence (XAI) can gain the trust of radiologists and effectively improve diagnosis accuracy and consultation efficiency. This paper proposes BI-RADS-Net-V2, a novel machine learning approach for fully automatic breast cancer diagnosis in ultrasound images. The BI-RADS-Net-V2 can accurately distinguish malignant tumors from benign ones and provides both semantic and quantitative explanations. The explanations are provided in terms of clinically proven morphological features used by clinicians for diagnosis and reporting mass findings, i.e., Breast Imaging Reporting and Data System (BI-RADS). The experiments on 1,192 Breast Ultrasound (BUS) images indicate that the proposed method improves the diagnosis accuracy by taking full advantage of the medical knowledge in BI-RADS while providing both semantic and quantitative explanations for the decision.

Abstract Background This study investigated the characteristics of humeral geometric and morphological parameters in northern Chinese population by three-dimensional measurements, and compared whether there were differences in humeral morphology among populations from different geographical regions. Methods Computed tomography scans of 80 humerus were obtained, reconstructed and measured. Differences in humeral morphological parameters between genders and sides were compared. Correlation analysis was used to explore possible correlations among the parameters. The differences in humeral geometric morphometric parameters between Western and East Asian populations were compared according to pool results of present and previous studies. Results The average (and standard deviation) of humeral head radius curvature, arc angle, diameter, and thickness was 151.79 ± 6.69°, 23.36 ± 2.08 mm, 44.83 ± 3.92 mm and 17.55 ± 1.84 mm in coronal humeral head plane, and 152.05 ± 8.82°, 21.81 ± 1.88 mm, 41.77 ± 3.44 mm and 16.52 ± 1.92 mm in transversal humeral head plane. The average of the humeral head medial offset and posterior offset was 7.34 ± 2.47 mm and 0.08 ± 1.72 mm. Humeral head inclination angle, arc angle and radius curvature of humeral neck-shaft averaged 137.69 ± 4.92°, 34.7 ± 5.29° and 55.76 ± 13.43 mm. Superior, inferior, anterior, posterior concave angle of humeral anatomical neck averaged 150.41 ± 10.91°, 146.55 ± 10.12°, 146.43 ± 13.53° and 149.33 ± 14.07°. The average of height of the greater tuberosity, height of the lesser tuberosity, depth, concave angle and volume of the intertubercular groove was 14.19 ± 1.7 mm, 8.9 ± 1.54 mm, 0.92 ± 0.31 mm3, 31.28 ± 9.61 mm, 4.98 ± 1.19 mm and 89.35 ± 17.62°. The upper angle of the greater tuberosity averaged 161.04 ± 7.84°, the upper angle of the greater tuberosity was 165.94 ± 3.6°. Differences in parameters of proximal humerus between genders and sides were found. There was no correlation between parameters of proximal humerus and age. Correlations were found among humeral morphological parameters. East Asian populations differed in proximal humeral morphology from Western populations. Conclusions This study will provide references for diagnosing and classifying shoulder disease, designing prosthesis and instrument, enhancing surgical precision and guiding patient recovery.

Abstract Background The treatment of posterior malleolar fractures is changing rapidly, and the evidence base is still catching up. This study aimed to assess the mid-term prognosis of posterior malleolar fractures based on different morphological types and provides evidence for the treatment of posterior malleolar fractures. Methods We retrospectively analyzed the data of inpatients with posterior malleolar fractures from 1 January 2012 to 31 December 2019 at one high-volume tertiary trauma center. Fracture morphology was classified into small-shell fragment, single-fragment (small-fragment and large-fragment) and multifragment (double-fragment and compressive-fragment) by computed tomography according to our previous study. All patients were followed up at an average of 5.06 (range, 2.21–8.70) years. The Olerud-Molander Ankle Score (OMAS), EuroQol-5 Dimensions (EQ-5D) and American Orthopedic Foot and Ankle Society (AOFAS) score were recorded. Results Seventy-nine patients were included, and 7 patients were classified into the small-shell group, 52 patients into the single-fragment group and 20 patients into the multifragment group. Of all the patients, the average OMAS, EQ-5D and AOFAS scores were 85.9, 82.8 and 92.5, respectively. In the single-fragment group, patients who underwent surgical fixation in the posterior malleolus had significantly better scores (P = 0.037, 0.033 and 0.027). Among the patients with small fragments, the surgical fixation group also had higher OMAS (93.1 ± 7.5 vs. 83.5 ± 19.5, P = 0.042) and AOFAS scores (98.1 ± 3.1 vs. 91.0 ± 14.1, P = 0.028). The mean OMAS, EQ-5D and AOFAS scores were 85.5, 85.7 and 91.7, respectively, in patients with multiple fragments who underwent surgical fixation. Conclusion This study shows that in fractures with a single fragment, surgical fixation of the posterior malleolar fragment led to a better prognosis in the midterm. All single fragments should be fixed regardless of size. Fixation of the posterior region in all single- and multi-fragments in posterior malleolar fractures led to satisfactory outcomes. Level of Evidence Level III, follow-up study.

The NH3 sensor is of great significance in preventing NH3 leakage and ensuring life safety. In this work, the Pd-decorated ZnO hexagonal microdiscs are synthesized using hydrothermal and annealing processes, and the gas sensor is fabricated based on Pd-decorated ZnO hexagonal microdiscs. The gas-sensing test results show that the Pd-ZnO gas sensor has a good response to NH3 gas. Specifically, it has a good linear response within 0.5–50 ppm NH3 at the optimal operating temperature of 230 °C. In addition, the Pd-ZnO gas sensor exhibits good repeatability, short response time (23.2 s) and good humidity resistance (10–90% relative humidity). This work provides a useful reference for developing an NH3 sensor.

Timely and accurate acquisition of spatial distribution and changes in cropland is of significant importance for food security and ecological preservation. Most studies that monitor long-term changes in cropland tend to overlook the rationality in the process of cropland evolution, and there are conflicts between the interannual cropland data, so they cannot be used to analyze land use change. This study focuses on the rationality of annual identification results for cropland, considering the long-term evolution and short-term variations influenced by natural environmental changes and human activities. An approach for annual monitoring of cropland based on long time series and deep learning is also proposed. We acquired imagery related to cropland’s vegetation lush period (VLP) and vegetation differential period (VDP) from Landsat images on the Google Earth Engine (GEE) platform and used the ResUNet-a structural model for training. Finally, a long-time-series cropland correction algorithm based on LandTrendr is introduced, and interannual cropland maps of Guangdong Province from 1991 to 2020 were generated. Evaluating the cropland monitoring results in Guangdong Province every five years, we found an overall accuracy of 0.91–0.93 and a kappa coefficient of 0.80–0.83. Our results demonstrate good consistency with agricultural statistical data. Over the past 30 years, the total cropland area in Guangdong Province has undergone three phases: a decrease, significant decrease, and stabilization. Significant regional variations have also been observed. Our approach can be applied to long-time-series interannual cropland monitoring in the southern regions of China, providing valuable data support for the further implementation of cropland protection.

Abstract Numerous studies have demonstrated that individual proteins can moonlight. Eukaryotic Initiation translation factor 3, f subunit (eIF3f) is involved in critical biological functions; however, its role independent of protein translation in regulating colorectal cancer (CRC) is not characterized. Here, it is demonstrated that eIF3f is upregulated in CRC tumor tissues and that both Wnt and EGF signaling pathways are participating in eIF3f's oncogenic impact on targeting phosphoglycerate dehydrogenase (PHGDH) during CRC development. Mechanistically, EGF blocks FBXW7β‐mediated PHGDH ubiquitination through GSK3β deactivation, and eIF3f antagonizes FBXW7β‐mediated PHGDH ubiquitination through its deubiquitinating activity. Additionally, Wnt signals transcriptionally activate the expression of eIF3f, which also exerts its deubiquitinating activity toward MYC, thereby increasing MYC‐mediated PHGDH transcription. Thereby, both impacts allow eIF3f to elevate the expression of PHGDH, enhancing Serine–Glycine–One–Carbon (SGOC) signaling pathway to facilitate CRC development. In summary, the study uncovers the intrinsic role and underlying molecular mechanism of eIF3f in SGOC signaling, providing novel insight into the strategies to target eIF3f‐PHGDH axis in CRC.

AbstractFreshwater lakes are subjected to increasing eutrophication and algal blooms worldwide, which have dramatically impacted the aquatic biodiversity. This situation is especially true in the Yangtze River Floodplain, China. However, few researches have been focused on differences in the spatial and temporal patterns of benthic macroinvertebrates assemblages between the two adjacent lakes in this floodplain. In this study, we conducted seasonal investigations in 2021 to compare the spatial and temporal patterns of macroinvertebrates in Lakes Taihu and Lake Chaohu. Non-metric multidimensional scaling (NMDS) analyses showed Lake Taihu was found to have differences in assemblages within the lake, but Lake Chaohu was found to have uniform assemblage across the entire lake. Macrophyte-dominated lake regions (eastern Lake Taihu) were characterised by the highest species richness and diversity indices than those in other lake regions. The pollution sensitive species (e.g. EPT: Ephemeroptera, Plecoptera and Trichoptera) were only distributed in the macrophytic areas of Lake Taihu. Corbicula fluminea, polychaetes Nephtys oligobranchia and Capitella sp. were dominant in the middle central lake regions in Lake Taihu. Lake Chaohu and the northern Lake Taihu, with turbid algal-dominated state, were characterised by dominance of Oligochaetes and Chironomids. These differences were attributed to varying habitats and environmental parameters among different lake regions. Canonical correspondence analysis (CCA) demonstrated that macrophytes, chemical oxygen demand (CODMn), temperature, ammonium (NH3-N) and electric conductivity (EC) were detected as important factors influencing such macroinvertebrate assemblage patterns between these two lakes. This study contributes to the scientific knowledge of within lake habitats, community assemblages, nutrients and pollution within these lakes.

PurposeThe prevalence of depressive disorder (DD) and subclinical hypothyroidism (SH) was almost twofold higher in women compared with men, both of which are confirmed to be related to cardiovascular disease (CVD) risk. The current study aimed to identify the prevalence of CVD risk factors and evaluate the 10-year CVD risk in female depressed patients with and without comorbid SH.MethodsWe recruited 1744 female inpatients with a diagnosis of DD. Venous blood samples were taken from all patients for lipid and thyroid hormones. Framingham Risk Score (FRS) was used to estimate the 10-year CVD risk.ResultsFemale depressed patients with SH had increased BMI, higher Hamilton Anxiety Scale (HAMA) scores, higher LDL-C, TC, UA, and a higher 10-year CVD risk than euthyroid DD groups. Serum TSH levels and HAMA scores were critical predictive variables for 10-year CVD risk in female depressed patients with comorbid SH.ConclusionOur study suggests that female depressed patients with SH have a high 10-year CVD risk. Serum TSH levels and HAMA scores may be helpful to predict cardiovascular risk in female patients with SH. The increased CVD risk in female depressed patients with comorbid SH requires more attention from researchers and clinicians.

Abstract Chromodomain helicase DNA binding protein (CHD) family plays critical roles in regulating gene transcription. The family is linked to cancer disease, but the family member’s role in tumorigenesis remains largely unknown. Here, we report that CHD6 is highly expressed in colorectal cancer (CRC). CHD6 knockdown inhibited cancer cell proliferation, migration, invasion, and tumorigenesis. Consistently, Villin-specific Chd6 knockout in mice attenuates cancer formation in AOM/DSS model. We found that aberrant EGF signals promoted the stability of CHD6 by diminishing ubiquitin-mediated degradation. EGF signal inhibits GSK3β activity, which in turn prevents phosphodegron formation of CHD6, thereby hindering E3 ligase FBXW7-mediated CHD6 ubiquitination and degradation. CHD6’s chromatin remodeler activity engages in binding Wnt signaling transcription factor TCF4 to facilitate the transcriptional expression of TMEM65, a mitochondrial inner membrane protein involved in ATP production and mitochondrial dynamics. In addition, Wnt signaling is also an upstream regulator of CHD6. CHD6 promoter contains TCF4 and β-catenin binding site, and CHD6 can be transcriptionally activated by Wnt ligand to facilitate TMEM65 transcription. Thus CHD6-TMEM65 axis can be regulated by both EGF and Wnt signaling pathways through two different mechanisms. We further illustrate that CHD6-TMEM65 axis is deregulated in cancer and that co-administration of Wnt inhibitor LGK974 and the anti-EGFR monoclonal antibody cetuximab largely restricted the growth of patient-derived xenografts of CRC. Targeting CHD6-TMEM65 axis may be effective for cancer intervention.

Abstract Background: To evaluate the influence of preoperative optical zone on myopic correction in small incision lenticule extraction. Methods: In this retrospective clinical study, 581 eyes from 316 patients underwent SMILE were selected, including 117 eyes in the small optical zone group (range from 6.0 to 6.4 mm) and 464 eyes in the large optical zone group (range from 6.5 to 6.8 mm). The measurements included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical, and cylinder were measured preoperatively and 3 months postoperatively. Propensity score match (PSM) analysis was performed with age, gender, eye (right/left), keratometry and preoperative spherical equivalent between two different groups. The influence of optical zones on postoperative refractive outcomes were evaluated using univariate regression analysis. Results: In total, 78 pairs of eyes were selected by PSM (match ratio 1:1). There were no differences in the age, gender, eye (right/left), keratometry or preoperative spherical equivalent between the small and large optical zone groups. However, the difference of postoperative spherical equivalent was significantly between groups. Patients with larger optical zones had a trend towards less undercorrection (P = 0.018). Univariate linear regression model analysis found that each millimeter larger optical zone resulted in 8.13% or 0.39D less undercorrection (P

Observation of a Bloch-Siegert shift has remained elusive. Here, Wu et al, reports spin-selective Bloch-Siegert shift in lead halide perovskite quantum dots, and highlights the importance of many-body interactions in correctly modeling the shift.

High-surface-area corundum are used in ceramics and catalyst supports, yet the synthesis is hampered by high energy barrier and aggregation. Here the authors report the ultrafast synthesis of corundum nanoparticles via the resistive hotspot triggered phase transformation in electric heating process.

Unique large-scale cooperation and fairness norms are essential to human society, but the emergence of prosocial behaviors is elusive. The fact that heterogeneous social networks prevail raised a hypothesis that heterogeneous networks facilitate fairness and cooperation. However, the hypothesis has not been validated experimentally, and little is known about the evolutionary psychological basis of cooperation and fairness in human networks. Fortunately, research about oxytocin, a neuropeptide, may provide novel ideas for confirming the hypothesis. Recent oxytocin-modulated network game experiments observed that intranasal administration of oxytocin to a few central individuals significantly increases global fairness and cooperation. Here, based on the experimental phenomena and data, we show a joint effect of social preference and network heterogeneity on promoting prosocial behaviors by building evolutionary game models. In the network ultimatum game and the prisoner’s dilemma game with punishment, inequality aversion can lead to the spread of costly punishment for selfish and unfair behaviors. This effect is initiated by oxytocin, then amplified via influential nodes, and finally promotes global cooperation and fairness. In contrast, in the network trust game, oxytocin increases trust and altruism, but these effects are confined locally. These results uncover general oxytocin-initiated mechanisms underpinning fairness and cooperation in human networks.

In this paper, we study cooperation and coordination in a threshold public goods game with asymmetric players where players have different endowments ei, productivities pi, and rewards ri. In general, this game has a defective Nash equilibrium (NE), in which no one contributes, and multiple cooperative NEs, in which the group’s collective contribution equals the threshold. We then study how multiple dimensions of inequality influence people’s cooperation and coordination. We show that heterogeneity in eipi can promote cooperation in the sense that the existence condition of the defective NE becomes stricter. Furthermore, players with higher eipi are likely to contribute more at a cooperative NE in terms of collective contribution (i.e., absolute contribution multiplied by productivity).

PANoptosis is a newly recognized inflammatory pathway for programmed cell death (PCD). It participates in regulating the internal environment, homeostasis, and disease process in various complex ways and plays a crucial role in tumor development, but its mechanism of action is still unclear. In this study, we comprehensively analyzed the expression of 14 PANoptosis-related genes (PANRGs) in 28 types of tumors. Most PANRGs are upregulated in tumors, including Z-DNA binding protein 1 (ZBP1), nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), caspase (CASP) 1, CASP6, CASP8, PYCARD, FADD, MAP3K7, RNF31, and RBCK1. PANRGs are highly expressed in GBM, LGG, and PAAD, while their levels in ACC are much lower than those in normal tissues. We found that both the CNV and SNV gene sets in BLCA are closely related to survival performance. Subsequently, we conducted clustering and LASSO analysis on each tumor and found that the inhibitory and the stimulating immune checkpoints positively correlate with ZBP1, NLRP3, CASP1, CASP8, and TNFAIP3. The immune infiltration results indicated that KIRC is associated with most infiltrating immune cells. According to the six tumor dryness indicators, PANRGs in LGG show the strongest tumor dryness but have a negative correlation with RNAss. In KIRC, LIHC, and TGCT, most PANRGs play an important role in tumor heterogeneity. Additionally, we analyzed the linear relationship between PANRGs and miRNA and found that MAP3K7 correlates to many miRNAs in most cancers. Finally, we predicted the possible drugs for targeted therapy of the cancers. These data greatly enhance our understanding of the components of cancer and may lead to the discovery of new biomarkers for predicting immunotherapy response and improving the prognosis of cancer patients.

The blast furnace slag was modified with DTAC to prepare a low-cost and environment-friendly adsorbent for the treatment of dye wastewater. The study analyzes theadsorbent dose, adsorption time, initial dye concentration and pH value on the adsorption capacity of KN-R reactive brilliant blue from the modified slag , and the variation rule of characterization of the modified slag was also analyzed. The results show that when the amount of modified slag is 10 g/L, the initial concentration of dye is 60 mg/L, the pH value is 2, and the adsorption time is 120 min, the maximum decolorization rate of the modified slag can reach 96%, and the initial concentration of 150 mg/L is the optimal solubility, the decolorization rate and adsorption capacity are both high at this concentration. Through XRD and FTIR tests, the characterization characteristics of slag and modified slag were compared and analyzed. It was found that DTAC could better modify slag, and the adsorption capacity of modified slag was significantly improved.

PurposeTo establish a fast and accurate detection method for interspecies contaminations in the patient-derived xenograft (PDX) models and cell lines, and to elucidate possible mechanisms if interspecies oncogenic transformation is detected.MethodsA fast and highly sensitive intronic qPCR method detecting Gapdh intronic genomic copies was developed to quantify if cells were human or murine or a mixture. By this method, we documented that murine stromal cells were abundant in the PDXs; we also authenticated our cell lines to be human or murine.ResultsIn one mouse model, GA0825-PDX transformed murine stromal cells into a malignant tumorigenic murine P0825 cell line. We traced the timeline of this transformation and discovered three subpopulations descended from the same GA0825-PDX model: epithelium-like human H0825, fibroblast-like murine M0825, and main passaged murine P0825 displayed differences in tumorigenic capability in vivo. P0825 was the most aggressive and H0825 was weakly tumorigenic. Immunofluorescence (IF) staining revealed that P0825 cells highly expressed several oncogenic and cancer stem cell markers. Whole exosome sequencing (WES) analysis revealed that TP53 mutation in the human ascites IP116-generated GA0825-PDX may have played a role in the human-to-murine oncogenic transformation.ConclusionThis intronic qPCR is able to quantify human/mouse genomic copies with high sensitivity and within a time frame of a few hours. We are the first to use intronic genomic qPCR for authentication and quantification of biosamples. Human ascites transformed murine stroma into malignancy in a PDX model.

Soft pneumatic actuators (SPAs) have attracted enormous attention in the growing field of robotics. Among different SPAs, composite reinforced actuators (CRAs) are widely used because of their simple structure and high controllability. However, multistep molding, a time-consuming method, is still the predominant fabrication method. Here, we propose a multimaterial embedded printing method (ME3P) to fabricate CRAs. In comparison with other 3-dimensional printing methods, our method improves fabrication flexibility greatly. Via the design and fabrication of the reinforced composites’ patterns and different geometries of the soft body, we demonstrate actuators with programmable responses (elongation, contraction, twisting, bending, and helical and omnidirectional bending). Finite element analysis is employed for the prediction of pneumatic responses and the inverse design of actuators based on specific actuation needs. Lastly, we use tube-crawling robots as a model system to demonstrate our ability to fabricate complex soft robots for practical applications. This work demonstrates the versatility of ME3P for the future manufacturing of CRA-based soft robots.

Accurate prediction of physical properties is critical for discovering and designing novel materials. Machine learning technologies have attracted significant attention in the materials science community for their potential for large-scale screening. Graph Convolution Neural Network (GCNN) is one of the most successful machine learning methods because of its flexibility and effectiveness in describing 3D structural data. Most existing GCNN models focus on the topological structure but overly simplify the three-dimensional geometric structure. However, in materials science, the 3D-spatial distribution of atoms is crucial for determining the atomic states and interatomic forces. This paper proposes an adaptive GCNN with a novel convolution mechanism that simultaneously models atomic interactions among all neighboring atoms in three-dimensional space. We apply the proposed model to two distinctly challenging materials properties prediction problems. The first is Henry’s constant for gas adsorption in Metal-Organic Frameworks (MOFs), which is notoriously difficult because of its high sensitivity to atomic configurations. The second is the ion conductivity in solid-state crystal materials, which is difficult because of the few labeled data available for training. The new model outperforms existing graph-based models on both data sets, suggesting that the critical three-dimensional geometric information is indeed captured.

Abstract Background Liposuction is one of the most commonly performed aesthetic procedures. Toxic shock syndrome(TSS) is a rare, life-threatening complication. The incidence rate of TSS is very low in the plastic surgery field, especially after liposuction and fat transfer. Case presentation A 23-year-old female patient was transferred to our emergency department from an aesthetic clinic with sepsis shock features after received liposuction and fat transfer. The patient underwent TSS, disseminated intravascular coagulation(DIC), multiple organ dysfunction syndrome (MODS), symmetrical peripheral gangrene (SPG), and necrotizing soft tissue infection of the buttocks in the next 10 days. Authors used a series of debridement and reconstructive surgery including vacuum sealing drainage (VSD) treatment, artificial dermis grafts,split-thickness skin grafts, amputation surgeries when her vital signs were stable. The patient experienced desquamation of the hand on the 26th day. The skin grafts survived and the function of both fingers and toes recovered. She was discharged 2 months after admission and was in good health. Conclusion TSS is extremely rare in the field of liposuction and autologous fat transfer. The mortality rate of TSS is very high. Early diagnosis and operative treatment, as well as correction of systemic abnormalities, are the important keys to save a patient's life.

Guillain–Barré syndrome (GBS) is a potentially life-threatening post-infectious autoimmune disease characterized by rapidly progressive symmetrical weakness of the extremities. Herein, we report a case of GBS associated with drug poisoning complicated by Klebsiella pneumoniae infection. A 38-year-old woman was admitted to the intensive care unit after taking an overdose of amitriptyline and was later diagnosed with coma, Klebsiella pneumoniae infection, and septic shock. Thirteen days after admission, she was diagnosed with GBS based on acute muscle pain, flaccid paralysis, hyporeflexia, reduced amplitude of compound muscle action potential, and albuminocytologic dissociation in the cerebrospinal fluid. GBS rarely occurs after a drug overdose and septic shock, and this is the first report of a rapidly progressive GBS following amitriptyline overdose and severe Klebsiella pneumoniae infection.

Abstract Background The purpose of this study was to evaluate and compare the long-term clinical outcomes between the total patellectomy and osteosynthesis with tension band wiring in patients with highly comminuted patella fractures. Methods Between January 1987 and December 2003, this retrospective study included a total of 35 patients (mean age, 51.4±16.8 years) with a minimum of 10 years follow-up period, comprising 29 males and 6 females, who were divided into the total patellectomy group (17 patients) or the open reduction and internal fixation (ORIF) group (18 patients) in the Third Affiliated Hospital of Hebei Medical University. We retrospectively collected patient demographics and data on the type of trauma, fracture type, and postoperative complications. Clinical outcomes including knee range of motion (ROM), 36-Item Short-Form Health Survey (SF-36) score [including physical component score (PCS) and mental component score (MCS)], Knee Injury and Osteoarthritis Outcome Score (KOOS), and Kujala score were evaluated and compared between the two groups. Biodex System dynamometer was used to quantitatively evaluate quadriceps femoris muscle power following measurement of peak torque. Results The mean follow-up periods of the total patellectomy group and the ORIF group were 17.2±5.6 and 16.8±4.9 years, respectively. There were no significant differences between the two groups of patient demographics in terms of the number of patients, age, sex, injury side, time to surgery, type of trauma, and fracture classification (p>0.05). Total patellectomy was comparable to osteosynthesis with tension band wiring in terms of ROM [injured knee: 120.4±3.1° vs 118.6±3.3°; uninjured knee: 126.5±2.8° vs 127.3±1.7°; both p>0.05], peak torque [Injured knee: 96.2±2.3 vs 97.3±2.6, N· m; Uninjured knee: 107.6±2.1 vs 106.3±1.8, N· m; both p>0.05], SF-36 score [PCS: 64.1±18.0 vs 61.5±17.9; MCS: 55.1±13.8 vs 54.3±12.4; both p>0.05], KOOS score [76.3±12.1 vs 73.4±11.7; p>0.05], and Kujala score [67.6±11.8 vs 70.8±11.9; p>0.05] at the final follow-up, while total patellectomy had significantly shorter operation time than ORIF group (47.5±12.1 vs 68.8±22.3, min, p

Accumulating evidence suggests that dysregulation of the intestinal flora potentially contributes to the occurrence and development of nonalcoholic fatty liver disease (NAFLD). Phyllanthus emblica (PE), an edible and medicinal natural resource, exerts excellent effects on ameliorating NAFLD, but the potential mechanism remains unclear. In the present study, a mouse NAFLD model was established by administering a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). The protective effects of the aqueous extract of PE (AEPE) on the gut microbiota and fecal metabolites in NAFLD mice were detected by performing 16S rRNA gene sequencing and untargeted metabolomics. The administration of middle- and high-dose AEPE decreased the levels of ALT, AST, LDL-C, TG, and Hyp and increased HDL-C levels in CDAHFD-fed mice. Hematoxylin–eosin (H&E), Oil Red O, and Masson’s trichrome staining indicated that AEPE treatment attenuated hepatic steatosis and fibrotic lesions. Moreover, the disordered intestinal microflora was remodeled by AEPE, including decreases in the abundance of Peptostreptococcaceae, Faecalibaculum, and Romboutsia. The untargeted metabolomics analysis showed that AEPE restored the disturbed glutathione metabolism, tryptophan metabolism, taurine and hypotaurine metabolism, and primary bile acid biosynthesis of the gut bacterial community in NAFLD mice, which strongly correlated with hepatic steatosis and fibrosis. Collectively, AEPE potentially ameliorates NAFLD induced by a CDAHFD through a mechanism associated with its modulatory effects on the gut microbiota and microbial metabolism.

In this study, we develop a data-driven heuristic method to solve the irregular flight recovery problem. Based on operational data from China South Airlines, Beijing, China, we evaluate the importance of a flight in the flight network and the influence of a delay on a flight and its subsequent flights. Then, we classify historical states into three scenarios according to their delay reasons and investigate the recovery patterns for each scenario. Inspired by the results of the data analysis, we develop a heuristic algorithm that imitates dispatcher actions. The algorithm is based on two basic operations: swapping the tail numbers of two flights and resetting their flight departure times. The algorithm can provide multiple recovery plans in real time for different scenarios, and we continue to refine and validate the algorithm for more robust and general solutions through a cost analysis. Finally, we test the efficiency and effectiveness of the recovery method based on the flight schedule, with real and simulated delays, and compare it with two other methods and the recovery actions of dispatchers.

As a template-free, data-driven methodology, the molecular transformer model provides an alternative by which to predict the outcome of chemical reactions and design the route of the retrosynthetic plane in the field of organic synthesis and polymer chemistry. However, in consideration of the small datasets of chemical reactions, the data-driven model suffers from the difficulty of low accuracy in the prediction tasks of chemical reactions. In this contribution, we integrate the molecular transformer model with the strategies of data augmentation and normalization preprocessing to accomplish the three tasks of chemical reactions, including the forward predictions of chemical reactions, and single-step retrosynthetic predictions with and without the reaction classes. It is clearly demonstrated that the prediction accuracy of the molecular transformer model can be significantly raised by the use of proposed strategies for the three tasks of chemical reactions. Notably, after the introduction of the 40-level data augmentation and normalization preprocessing, the top-1 accuracy of the forward prediction increases markedly from 71.6% to 84.2% and the top-1 accuracy of the single-step retrosynthetic prediction with additional reaction class increases from 53.2% to 63.4%. Furthermore, it is found that the superior performance of the data-driven model originates from the correction of the grammatical errors of the SMILES strings, especially for the case of the reaction classes with small datasets.

The accurate extraction of cropland distribution is an important issue for precision agriculture and food security worldwide. The complex characteristics in southern China pose great challenges to the extraction. In this study, for the objective of accurate extraction and mapping of cropland parcels in multiple crop growth stages in southern China, we explored a method based on unmanned aerial vehicle (UAV) data and deep learning algorithms. Our method considered cropland size, cultivation patterns, spectral characteristics, and the terrain of the study area. From two aspects—model architecture of deep learning and the data form of UAV—four groups of experiments are performed to explore the optimal method for the extraction of cropland parcels in southern China. The optimal result obtained in October 2021 demonstrated an overall accuracy (OA) of 95.9%, a Kappa coefficient of 89.2%, and an Intersection-over-Union (IoU) of 95.7%. The optimal method also showed remarkable results in the maps of cropland distribution in multiple crop growth stages, with an average OA of 96.9%, an average Kappa coefficient of 89.5%, and an average IoU of 96.7% in August, November, and December of the same year. This study provides a valuable reference for the extraction of cropland parcels in multiple crop growth stages in southern China or regions with similar characteristics.

Abstract Background Lateral tibial plateau fractures (TPFs) are often treated with conventional open reduction and internal fixation (ORIF) through standard anterolateral sub-meniscal arthrotomy. There has been increasing support for “bidirectional rapid redactor” device-assisted closed reduction and internal fixation (CRIF) for treating TPFs. The aim of the present study is to compare the clinical and radiological outcomes between CRIF and ORIF procedures. Methods We performed a retrospective cohort study of 55 lateral TPF patients (Schatzker types I–III) who accepted surgical treatment at our trauma level 1 center between January 2016 and January 2018. They were divided into the CRIF group (32 patients) and the ORIF group (23 patients) based upon the different surgical protocols. The patients’ clinical outcome analysis was evaluated by using the Knee Society Score (KSS) and Rasmussen’s clinical score. For radiological assessment, changes in tibial plateau width (TPW), articular depression depth (ADD), medial proximal tibial angle (MPTA), and posterior tibial slope angle (PTSA) were evaluated using radiographs and computed tomography (CT) scan. Results The CRIF group had a mean follow-up of 28.9 months, and the ORIF group had a mean follow-up of 30.7 months (p>0.05). Furthermore, there was no statistically significant difference in terms of age, gender, injury mechanism, follow-up time, time interval from injury to surgery, and Schatzker classification in the two groups. With respect to the clinical outcomes including the KSS score and Rasmussen’s clinical score, there was also no significant difference (p>0.05). Nevertheless, the CRIF group had lower intra-operative blood loss, shorter hospitalization days, and better range of movement of the knee joint than the ORIF group (p0.05). Conclusion The present study showed that CRIF could achieve comparable clinical outcomes and better radiological results for treating lateral TPFs as compared with conventional ORIF.

Hemostasis is achieved through the comprehensive effect of multiple pathways. A composite porous material was designed consisting of silk fibroin (SF), gelatin (GA) and calcium alginate (CA), integrating the good biocompatibility of SF, swelling property of GA and hemostatic factor Ca2+ of CA. Water absorption, platelet adhesion, fibrinogen adsorption, blood coagulation activity, and cytotoxicity were investigated. Pore size in SF/GA porous materials increased with increasing content of GA in SF but decreased significantly in SF/CA porous materials after incorporating CA in SF. Based on the water binding capacity of materials and capillary effect of pores, the binary composites SF/GA1:1 and SF/CA3:1 displayed the best water absorption. Although GA and CA were more favorable for fibrinogen adsorption, SF/GA1:1 and SF/CA1:1 exhibited greater numbers of adhered platelets, shorter clotting times, and greater whole blood coagulation ability. Human skin fibroblasts spread well on the pure SF and GA and all the composites of SF/GA and SF/CA, and they showed high proliferative activity. Pure CA inhibited cell proliferation. For ternary composite materials, the comprehensive hemostatic ability of SF/GA/CA1:1:1 was greater than that of SF/GA/CA1:1:3.

Summary: Bioinformatic analysis of 94 patient-derived xenografts (PDXs), cell lines, and organoids (PCOs) identifies three intrinsic transcriptional subtypes of metastatic castration-resistant prostate cancer: androgen receptor (AR) pathway + prostate cancer (PC) (ARPC), mesenchymal and stem-like PC (MSPC), and neuroendocrine PC (NEPC). A sizable proportion of castration-resistant and metastatic stage PC (M-CRPC) cases are admixtures of ARPC and MSPC. Analysis of clinical datasets and mechanistic studies indicates that MSPC arises from ARPC as a consequence of therapy-induced lineage plasticity. AR blockade with enzalutamide induces (1) transcriptional silencing of TP53 and hence dedifferentiation to a hybrid epithelial and mesenchymal and stem-like state and (2) inhibition of BMP signaling, which promotes resistance to AR inhibition. Enzalutamide-tolerant LNCaP cells re-enter the cell cycle in response to neuregulin and generate metastasis in mice. Combined inhibition of HER2/3 and AR or mTORC1 exhibits efficacy in models of ARPC and MSPC or MSPC, respectively. These results define MSPC, trace its origin to therapy-induced lineage plasticity, and reveal its sensitivity to HER2/3 inhibition.

Abstract This study was designed to investigate the prognostic value of the number and sites of extracranial metastasis (ECM) in NSCLC patients with BM. NSCLC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were enrolled in analysis. Patients from 2010 to 2013 were included in the training set and those from 2014 to 2015 in the validation set. ECM sites among different subtypes of NSCLC were compared by Chi‐square tests. Kaplan–Meier methods and Cox regression models were performed to analyze survival data. Competing‐risks analysis was used to predict cumulative incidence rates for CSS and non‐CSS cause. We included 5974 patients in the training cohort and 3561 patients in the validation cohort. Most (nearly 80%) NSCLC patients with BM showed 0–1 involved extracranial organ, with the most and least common ECM organ being bone and distant lymph nodes (DLNs) among all subtypes of NSCLC, respectively. The number of involved extracranial organs was an independent prognostic factor for patients with BM from NSCLC (p

Aims: In this study, we aimed to identify cuproptosis-associated ferroptosis genes in the atherosclerosis microarray of the Gene Expression Omnibus (GEO) database and to explore hub gene-mediated immune infiltration in atherosclerosis. Background: Immune infiltration plays a crucial role in atherosclerosis development. Ferroptosis is a mode of cell death caused by the iron-dependent accumulation of lipid peroxides. Cuproptosis is a recently discovered type of programmed cell death. No previous studies have examined the mechanism of cuproptosis-associated ferroptosis gene regulation in immune infiltration in atherosclerosis. Methods: We searched the qualified atherosclerosis gene microarray in the GEO database, integrated it with ferroptosis and cuproptosis genes, and calculated the correlation coefficients. We then obtained the cuproptosis-associated ferroptosis gene matrix and screened differentially expressed genes. Subsequently, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and protein–protein interaction network analysis of differentially expressed genes. We also screened hub genes according to the Matthews correlation coefficient (MCC) algorithm. We conducted enrichment analysis of hub genes to explore their functions and predict related microRNAs (P