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Abstract Background Restoring the function of the ovary is important for chemotherapy-induced ovarian failure (COF) patients. Stem cell and extracellular vesicles (EVs) therapy show promise but need further improvement. Methods Human umbilical cord mesenchymal stem cells (hUC-MSCs) were primarily cultured and further three-dimensional (3D) cultured using an ultra-low attachment surface method. The expression levels of nutritional cytokines and immunomodulatory and stemness-related genes of 3D-cultured hUC-MSCs were analyzed. EVs were isolated by ultracentrifugation and characterized. Ovaries were decellularized with sodium dodecyl sulfate to obtain extracellular matrix (ECM). Lyophilized EVs from three-dimensional (2D) or 3D hUC-MSCs were mixed with ECM to prepare the 2D/3D-MSC-EVs-ECM gels. The therapeutic effect of the MSC-EVs-ECM gel on cyclophosphamide (CTX) -treated rats was analyzed through various tests. RNA sequencing was used to analyze the expression changes of genes before and after treatment. Results After culturing in ultra-low attachment dishes, hUC-MSCs aggregated into spheroids and significantly upregulated the expression levels of immunomodulatory and stemness-related genes. The total EVs yield was also upregulated (5.6-fold) after 3D culture. The cell viability of CTX-treated ovarian granulosa cells (OGCs) was significantly rescued by coculture with the 3D-MSC-EVs-ECM gel. Hormones indicative of ovarian function, AMH, E2, and FSH, were recovered in both the CTX + 2D-MSC-EVs-ECM gel group and the CTX + 3D-MSC-EVs-ECM gel group, while the apoptosis-related protein Bax was significantly downregulated. The 3D-MSC-EVs-ECM gel was more effective than the 2D-MSC-EVs-ECM gel. Significantly differentially expressed genes, such as Hbb-b1, Gpd1, and Sirpa, were detected by RNA sequencing. Hbb-b1 was increased in the ovaries of CTX-treated rats, and this increase was attenuated by injecting the 2D/3D-MSC-EVs-ECM gel. Gpd1 was increased after CTX treatment, and this increase was reversed by the 3D-MSC-EVs-ECM gel. Sirpa was decreased in the ovaries of CTX-treated rats, and this decrease was attenuated by injecting the 3D-MSC-EVs-ECM gel. Conclusions Our study demonstrated that the 3D-MSC-EVs-ECM gel is an efficient strategy for the recovery of ovarian function in CTX-induced ovarian failure.

Abstract Resection of thoracic wall tumors results in significant defects in the chest wall, leading to various complications. In recent years, the use of three-dimensional (3D) printed titanium alloy prostheses in clinical practice has demonstrated enhanced outcomes in chest wall reconstruction surgery. A cohort of seven patients with sternal tumors was identified for this study. Following a helical CT scan, a digital model was generated for the design of the prosthesis. Subsequently, the tumors were then removed together with the affected sternum and ribs. The chest wall was then reconstructed using 3D-printed titanium alloy prosthesis for bone reconstruction, mesh for pleural reconstruction, and flap for soft tissue reconstruction. Patients were monitored for a period of one year post-surgery. In the seven cases examined, the tumors were found in various locations with varying degrees of invasion. Based on the scope of surgical resection and the size of the defect, 3D-printed titanium alloy prosthesis was custom-designed for chest wall reconstruction. Prior to bone reconstruction, pleural reconstruction was achieved with Bard Composix E/X Mesh, while soft tissue repair involved muscle flap and musculocutaneous flap procedures. A one-year follow-up assessment revealed that the utilization of the 3D-printed titanium alloy prosthesis led to secure fixation, favorable histocompatibility, and enhanced lung function. The findings demonstrate that the utilization of 3D printed titanium alloy prostheses represents a significant advancement in the field of chest wall reconstruction and thoracic surgical procedures.

Abstract Fungal natural products from various species often feature hydroxamic acid motifs that have the ability to chelate iron. These compounds have an array of medicinally and ecologically relevant activities. Through genome mining, gene deletion in the host Aspergillus terreus, and heterologous expression experiments, this study has revealed that a nonribosomal peptide synthetase (NRPS) TamA and a specialized cytochrome P450 monooxygenase TamB catalyze the sequential biosynthetic reactions in the formation of terramides A-C, a series of diketopiperazines (DKPs) with hydroxamic acid motifs. Feeding experiments showed that TamB catalyzes an unprecedented di-hydroxylation of the amide nitrogens in the diketopiperazine core. This tailoring reaction led to the formation of two bidentate iron-binding sites per molecule with an unusual iron-binding stoichiometry. The structure of the terramide A-Fe complex was characterized by liquid chromatography-mass spectrometry (LC-MS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy and electron paramagnetic resonance spectroscopy (EPR). Antimicrobial assays showed that the iron-binding motifs are crucial for the activity against bacteria and fungi. Murine infection experiments indicated that terramide production is crucial for the virulence of A. terreus and could be a potential antifungal drug target.

Abstract Background Sepsis-induced cardiomyopathy (SICM) is a common and life-threatening complication of sepsis, significantly contributing to elevated mortality. This study aimed to identify crucial indicators for the prompt and early assessment of SICM. Methods Patients diagnosed with sepsis or SICM within 24 h of intensive care unit (ICU) admission were enrolled in this prospective observational study. Patients were assigned to the training set, validation set and external test set. The primary endpoint was 7-day ICU mortality, and the secondary endpoint was 28-day ICU mortality. Three machine learning algorithms were utilized to identify relevant indicators for diagnosing SICM, incorporating 64 indicators including serum biomarkers associated with cardiac, renal, and liver function, lipid metabolism, coagulation, and inflammation. Internal and external validations were performed on the screening results. Patients were then stratified based on the cut-off value of the most diagnostically effective biomarker identified, and their prognostic outcomes were observed and analyzed. Results A total of 270 patients were included in the training and validation set, and 52 patients were included in the external test set. Age, sex, and comorbidities did not significantly differ between the sepsis and SICM groups (P > 0.05). The support vector machine (SVM) algorithm identified six indicators with an accuracy of 84.5%, the random forest (RF) algorithm identified six indicators with an accuracy of 81.9%, and the logistic regression (LR) algorithm screened out seven indicators. Following rigorous selection, a diagnostic model for sepsis-induced cardiomyopathy was established based on heart-type fatty acid binding protein (H-FABP) (OR 1.308, 95% CI 1.170–1.462, P

Although rare earth zirconates (RE2Zr2O7) have garnered attention as viable candidates for thermal barrier coatings (TBCs), they suffer from low fracture toughness and accelerated calcium–magnesium–alumina–silicate (CMAS) melt corrosion at high service temperatures, which impedes their practical application. In this work, we developed a series of REAlO3/RE2Zr2O7 (RE = La, Nd, Sm, Eu, Gd, and Dy) composites with a eutectic composition that not only significantly enhanced the fracture toughness by more than 40% relative to that of RE2Zr2O7 but also exhibited improved resistance to CMAS corrosion. The increase in toughness arises from multiple mechanisms, such as ferroelastic toughening, fine-grain strengthening, and residual stress toughening, all of which trigger more crack defects and energy consumption. Additionally, the CMAS penetration depth of the REAlO3/RE2Zr2O7 composites is approximately 36% lower than that of RE2Zr2O7. Al–O constituents in composites can capture CaO, SiO2, and MgO in CMAS melts and increase their viscosity, resulting in enhanced CMAS corrosion resistance. The thermophysical properties of the REAlO3/RE2Zr2O7 composites were also investigated, and their coefficient of thermal expansion and thermal conductivity are comparable to those of 7–8 wt %Y2O3 partially stabilized ZrO2 (YSZ), indicating their potential as TBC materials.

Abstract CD8+ T-cell exhaustion is a promising prognostic indicator of sepsis-induced acute respiratory distress syndrome (ARDS). Patients with sepsis-related ARDS had reduced levels of HSP90AA1. However, whether the changes in CD8+ T cells were related to HSP90α, encoded by the HSP90AA1 gene, was unclear. This study aimed to examine the regulatory mechanism of HSP90α and its impact on CD8+ T-cell exhaustion in lipopolysaccharide (LPS)-induced acute lung injury (ALI). In this study, by conducting a mouse model of ALI, we found that one week after LPS-induced ALI, CD8+ T cells showed exhaustion characteristics. At this time, proliferation and cytokine release in CD8+ T cells were reduced. The inhibitory costimulatory factors PD-1 and Tim-3, on the other hand, were enhanced. Meanwhile, the expression of HSP90α and STAT1 decreased significantly. The in vitro studies showed that HSP90α stimulation or inhibition affected the CD8+ T-cell exhaustion phenotype. Interference with STAT1 reduced the expression of HSP90α and impaired its regulation of CD8+ T cells. The Co-Immunoprecipitation results indicated that HSP90α can directly or indirectly bind to TOX to regulate TOX expression and downstream signal transduction. In summary, by inhibiting TOX-mediated exhaustion signaling pathways, HSP90α inhibited CD8+ T-cell exhaustion in ALI. The participation of STAT1 in the regulation of HSP90α was required.

Abstract The potential brain mechanism underlying resilience to socially transferred allodynia remains unknown. Here, we utilize a well-established socially transferred allodynia paradigm to segregate male mice into pain-susceptible and pain-resilient subgroups. Brain screening results show that ventral tegmental area glutamatergic neurons are selectively activated in pain-resilient mice as compared to control and pain-susceptible mice. Chemogenetic manipulations demonstrate that activation and inhibition of ventral tegmental area glutamatergic neurons bi-directionally regulate resilience to socially transferred allodynia. Moreover, ventral tegmental area glutamatergic neurons that project specifically to the nucleus accumbens shell and lateral habenula regulate the development and maintenance of the pain-resilient phenotype, respectively. Together, we establish an approach to explore individual variations in pain response and identify ventral tegmental area glutamatergic neurons and related downstream circuits as critical targets for resilience to socially transferred allodynia and the development of conceptually innovative analgesics.

With the rapid increase in urban gas consumption, the frequency of maintenance and repair of gas pipelines has escalated, leading to a rise in safety accidents during these processes. The traditional manual supervision model presents challenges such as inaccurate monitoring results, incomplete risk factor analysis, and a lack of quantitative risk assessment. This research focuses on developing a dynamic risk assessment technology for gas emergency repair operations by integrating the monitoring outcomes of artificial olfactory for gas leakage information and video object recognition for visual safety factor monitoring data. To quantitatively evaluate the risk of the operation process, a three-dimensional risk assessment model combining gas leakage with risk-correlated sensitivity was established as well as a separate three-dimensional risk assessment model integrating visual risk factors with predictable risk disposition. Furthermore, a visual risk quantification expression mode based on the risk matrix-radar map method was introduced. Additionally, a risk quantification model based on the fusion of visual and olfactory results was formulated. The verification results of simulation scenarios based on field data indicate that the visual-olfactory fusion risk assessment method can more accurately reflect the dynamic risk level of the operation process compared to simple visual safety factor monitoring. The outcomes of this research can contribute to the identification of safety status and early warning of risks related to personnel, equipment, and environmental factors in emergency repair operations. Moreover, these results can be extended to other operational scenarios, such as oil and gas production stations and long-distance pipeline operations.

Summary: Motor neurons are highly polarized, and their axons extend over great distances to form connections with myofibers via neuromuscular junctions (NMJs). Local translation at the NMJs in vivo has not been identified. Here, we utilized motor neuron-labeled RiboTag mice and the TRAP (translating ribosome affinity purification) technique to spatiotemporally profile the translatome at NMJs. We found that mRNAs associated with glucose catabolism, synaptic connection, and protein homeostasis are enriched at presynapses. Local translation at the synapse shifts from the assembly of cytoskeletal components during early developmental stages to energy production in adulthood. The mRNA of neuronal Agrin (Agrn), the key molecule for NMJ assembly, is present at motor axon terminals and locally translated. Disrupting the axonal location of Agrn mRNA causes impairment of synaptic transmission and motor functions in adult mice. Our findings indicate that spatiotemporal regulation of mRNA local translation at NMJs plays critical roles in synaptic transmission and motor functions in vivo.

BackgroundInflammaging, an immune status characterized by a sustained increase in pro-inflammatory markers and a decline in anti-inflammatory mechanisms, is a critical risk factor in the development of sarcopenia. Landscapes of the causal relationships between immunity and sarcopenia are needed to understand the mechanism of sarcopenia and provide novel treatments comprehensively.MethodsWe used Mendelian Randomization (MR) as the basic method in this study. By setting immune proteins, immune cells, and sarcopenia as exposures and outcomes alternatively, and then combining them in different directions, we potentially estimated their causal relationships and directions and subsequently mapped the comprehensive causal landscape based on this information efficiently. To further understand the network, we developed a method based on rank-sums to integrate multiple algorithms and identify the key immune cells and proteins.ResultsMore than 1,000 causal relationships were identified between immune cell phenotypes, proteins, and sarcopenia traits (p < 0.05), and the causal maps of these linkages were established. In the threshold of FDR < 0.05, hundreds of causal linkages were still significant. The final comprehensive map included 13 immune cell phenotypes and 8 immune proteins. The star factors in the final map included EM CD8br %CD8br, EM DN (CD4- CD8-) %DN, SIRT2, and so on.ConclusionBy reading the landscapes in this study, we may not only find the factors and the pathways that have been reported and proven but also identify multiple novel immunity cell phenotypes and proteins with enriched upstream and downstream pathways.

Abstract Esophageal adenocarcinoma is the most common histological subtype of esophageal cancer in Western countries and shows poor prognosis with rapid growth. EAC is characterized by a strong male predominance and racial disparity. EAC is up to fivefold more common among Whites than Blacks, yet Black patients with EAC have poorer survival rates. The racial disparity remains largely unknown, and there is limited knowledge of mutations in EAC regarding racial disparities. We used whole-exome sequencing to show somatic mutation profiles derived from tumor samples from 18 EAC male patients. We identified three molecular subgroups based on the pre-defined esophageal cancer-specific mutational signatures. Group 1 is associated with age and NTHL1 deficiency-related signatures. Group 2 occurs primarily in Black patients and is associated with signatures related to DNA damage from oxidative stress and NTHL1 deficiency-related signatures. Group 3 is associated with defective homologous recombination-based DNA often caused by BRCA mutation in White patients. We observed significantly mutated race related genes (LCE2B in Black, SDR39U1 in White) were (q-value

Abstract Background/Purpose Risk factors for re-bleeding and death after acute variceal bleeding (AVB) in cirrhotic HCC patients are not fully understood.We aimed to (1) explore how the combination of high-risk esophageal varices, HCC status, and portal vein tumor thrombus (i.e., HCC Portal Hypertension Imaging Score [HCCPHTIS]) helps predict increased risk of variceal re-bleeding and mortality; (2) assess predictability and reproducibility of the identified variceal re-bleeding rules. Methods This prospective study included 195 HCC patients with first-time AVB and liver cirrhosis, and conducted multivariable Cox regression analysis and Kaplan-Meier analysis. Receiver operating characteristic curve analysis was calculated to find the optimal sensitivity, specificity, and cutoff values of the variables. The reproducibility of the results obtained was verified in a different but related group of patients. Results 56 patients (28.7%) had re-bleeding within 6 weeks; HCCPHTIS was an independent risk factor for variceal re-bleeding after AVB (Odd ratio, 2.330; 95% confidence interval: 1.728–3.142, p 3 was 66.2%, sensitivity 83.9%, and specificity 82.3%. HCCPHTIS area under the curve was higher than Child-Pugh score (89% vs. 75%, p 4 was associated with increased risk of death within 6 weeks after AVB (p 3 is a strong predictor of variceal re-bleeding within the first 6 weeks. However, patients with HCCPHTIS > 4 were at increased risk of death within 6 weeks.

Abstract Plants are capable of altering root growth direction to curtail exposure to a saline environment (termed halotropism). The root cap that surrounds root tip meristematic stem cells plays crucial roles in perceiving and responding to environmental stimuli. However, how the root cap mediates root halotropism remains undetermined. Here, we identified a root cap-localized NAC transcription factor, SOMBRERO (SMB), that is required for root halotropism. Its effect on root halotropism is attributable to the establishment of asymmetric auxin distribution in the lateral root cap (LRC) rather than to the alteration of cellular sodium equilibrium or amyloplast statoliths. Furthermore, SMB is essential for basal expression of the auxin influx carrier gene AUX1 in LRC and for auxin redistribution in a spatiotemporally-regulated manner, thereby leading to directional bending of roots away from higher salinity. Our findings uncover an SMB-AUX1-auxin module linking the role of the root cap to the activation of root halotropism.

With the background of carbon neutrality, the resource and energy utilization of excess sludge (ES) have become the focus of future research. The pyrolysis of ES can produce biochar and enrich phosphorus (P). In this paper, the existing forms and recovery efficiencies of P in biochar from ES (BCES) were investigated. The results showed that the total phosphorus (TP) content of BCES at 850 °C was 65.1 mg/g, and the inorganic phosphorus (IP) content was 64.2 mg/g. The TP content of BCES was two times heavier than that of ES. The main ingredient of ES was quartz (SiO2), while the main phases of BCES were quartz (SiO2) and aluminum phosphate (AlPO4) at 650 –850 °C, and P mainly existed in the form of AlPO4. When the pyrolysis temperature was 800 and 850 °C, two new minerals appeared: Ca5(PO4)3OH and CaZn2(PO4)2·2H2O. Based on the conditions of a leaching time of 150 min, a H2SO4 concentration of 0.2 mol/L, a stirring rate of 220 rpm and a liquid–solid ratio of 50 mL/g, the leaching efficiency of P in BCES was found to be 100%. The pyrolysis temperature had no effect on leaching efficiencies of P; however, a higher pyrolysis temperature promoted metal leaching content. ;

Abstract Background RNA secondary structure (RSS) can influence the regulation of transcription, RNA processing, and protein synthesis, among other processes. 3′ untranslated regions (3′ UTRs) of mRNA also hold the key for many aspects of gene regulation. However, there are often contradictory results regarding the roles of RSS in 3′ UTRs in gene expression in different organisms and/or contexts. Results Here, we incidentally observe that the primary substrate of miR159a (pri-miR159a), when embedded in a 3′ UTR, could promote mRNA accumulation. The enhanced expression is attributed to the earlier polyadenylation of the transcript within the hybrid pri-miR159a-3′ UTR and, resultantly, a poorly structured 3′ UTR. RNA decay assays indicate that poorly structured 3′ UTRs could promote mRNA stability, whereas highly structured 3′ UTRs destabilize mRNA in vivo. Genome-wide DMS-MaPseq also reveals the prevailing inverse relationship between 3′ UTRs’ RSS and transcript accumulation in the transcriptomes of Arabidopsis, rice, and even human. Mechanistically, transcripts with highly structured 3′ UTRs are preferentially degraded by 3′–5′ exoribonuclease SOV and 5′–3′ exoribonuclease XRN4, leading to decreased expression in Arabidopsis. Finally, we engineer different structured 3′ UTRs to an endogenous FT gene and alter the FT-regulated flowering time in Arabidopsis. Conclusions We conclude that highly structured 3′ UTRs typically cause reduced accumulation of the harbored transcripts in Arabidopsis. This pattern extends to rice and even mammals. Furthermore, our study provides a new strategy of engineering the 3′ UTRs’ RSS to modify plant traits in agricultural production and mRNA stability in biotechnology.

Abstract Abnormal inflammatory states in the brain are associated with a variety of brain diseases. The dynamic changes in the number and function of immune cells in cerebrospinal fluid (CSF) are advantageous for the early prediction and diagnosis of immune diseases affecting the brain. The aggregated factors and cells in inflamed CSF may represent candidate targets for therapy. The physiological barriers in the brain, such as the blood‒brain barrier (BBB), establish a stable environment for the distribution of resident immune cells. However, the underlying mechanism by which peripheral immune cells migrate into the brain and their role in maintaining immune homeostasis in CSF are still unclear. To advance our understanding of the causal link between brain diseases and immune cell status, we investigated the characteristics of immune cell changes in CSF and the molecular mechanisms involved in common brain diseases. Furthermore, we summarized the diagnostic and treatment methods for brain diseases in which immune cells and related cytokines in CSF are used as targets. Further investigations of the new immune cell subtypes and their contributions to the development of brain diseases are needed to improve diagnostic specificity and therapy.

ABSTRACTObjectives: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress.Methods: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo.Results: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models.Discussion: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.

Abstract Pooling operations, essential for neural networks, reduce feature map dimensions while preserving key features and enhancing spatial invariance. Traditional pooling methods often miss the feature maps' alternating currentcomponents. This study introduces a novel global pooling technique utilizing spectral self‐attention, leveraging the discrete cosine transform for spectral analysis and a self‐attention mechanism for assessing frequency component significance. This approach allows for efficient feature synthesis through weighted averaging, significantly boosting TOP‐1 accuracy with minimal parameter increase, outperforming existing models.

Hydrogel presents a three-dimensional polymer network with high water content. Over the past decade, hydrogel has developed from static material to intelligent material with controllable response. Various stimuli are involved in the formation of hydrogel network, among which photo-stimulation has attracted wide attention due to the advantages of controllable conditions, which has a good application prospect in the treatment of ophthalmic diseases. This paper reviews the application of photo-crosslink hydrogels in ophthalmology, focusing on the types of photo-crosslink hydrogels and their applications in ophthalmology, including drug delivery, tissue engineering and 3D printing. In addition, the limitations and future prospects of photo-crosslink hydrogels are also provided.

The Blasingame method is a valuable tool for analysing the diminishing production challenge in the presence of variable bottomhole pressure and diverse production conditions. It is essential to highlight that the Blasingame method views the closed reservoir as the outer boundary condition for its model. This paper introduces the concept of the equivalent well control radius and formulates the Blasingame method based on the fluid flow characteristics inherent in twin-well production, taking into account the influence of inter-well interference. This study provides an in-depth analysis of production variations in reservoirs with inter-well interference by examining Blasingame type-curve definitions of the dimensionless parameters. Additionally, it investigates key factors impacting production, including neighbouring wells’ production, distance, and opening time: variations in all three parameters lead to different levels of interference between wells, which manifests itself in the regularised production integral derivative curve with different lengths and heights of convexity. Numerical simulations employing orthogonality are conducted to validate the reliability of this method. The results of these simulations offer theoretical support for the precise evaluation of reservoirs facing similar challenges.

Abstract Background The growing demand for electrophysiology (EP) treatment in China presents a challenge for current EP care delivery systems. This study constructed a discrete event simulation (DES) model of an inpatient EP care delivery process, simulating a generalized inpatient journey of EP patients from admission to discharge in the cardiology department of a tertiary hospital in China. The model shows how many more patients the system can serve under different resource constraints by optimizing various phases of the care delivery process. Methods Model inputs were based on and validated using real-world data, simulating the scheduling of limited resources among competing demands from different patient types. The patient stay consists of three stages, namely: the pre-operative stay, the EP procedure, and the post-operative stay. The model outcome was the total number of discharges during the simulation period. The scenario analysis presented in this paper covers two capacity-limiting scenarios (CLS): (1) fully occupied ward beds and (2) fully occupied electrophysiology laboratories (EP labs). Within each CLS, we investigated potential throughput when the length of stay or operative time was reduced by 10%, 20%, and 30%. The reductions were applied to patients with atrial fibrillation, the most common indication accounting for almost 30% of patients. Results Model validation showed simulation results approximated actual data (137.2 discharges calculated vs. 137 observed). With fully occupied wards, reducing pre- and/or post-operative stay time resulted in a 1–7% increased throughput. With fully occupied EP labs, reduced operative time increased throughput by 3–12%. Conclusions Model validation and scenario analyses demonstrated that the DES model reliably reflects the EP care delivery process. Simulations identified which phases of the process should be optimized under different resource constraints, and the expected increases in patients served.

Automatic registration of unordered point clouds is the prerequisite for urban reconstruction. However, most of the existing technologies still suffer from some limitations. On one hand, most of them are sensitive to noise and repetitive structures, which makes them infeasible for the registration of large-scale point clouds. On the other hand, most of them dealing with point clouds with limited overlaps and unpredictable location. All these problems make it difficult for registration technology to obtain qualified results in outdoor point cloud. To overcome these limitations, this paper presents a grid graph-based point cloud registration (GGR) algorithm to align pairwise scans. First, point cloud is divided into a set of 3D grids. We propose a voting strategy to measure the similarity between two grids based on feature descriptor, transforming the superficial correspondence into 3D grid expression. Next, a graph matching is proposed to capture the spatial consistency from putative correspondences, and graph matching hierarchically refines the corresponding grids until obtaining point-to-point correspondences. Comprehensive experiments demonstrated that the proposed algorithm obtains good performance in terms of successful registration rate, rotation error, translation error, and outperformed the state-of-the-art approaches.

Abstract Background and objectives This study focused on changes in intestinal motility during different sleep stages based on long-term bowel sounds. Methods A modified higher order statistics algorithm was devised to identify the effective bowel sound segments. Next, characteristic values (CVs) were extracted from each bowel sound segment, which included 4 time-domain, 4 frequency-domain and 2 nonlinear CVs. The statistical analysis of these CVs corresponding to the different sleep stages could be used to evaluate the changes in intestinal motility during sleep. Results A total of 6865.81 min of data were recorded from 14 participants, including both polysomnographic data and bowel sound data which were recorded simultaneously from each participant. The average accuracy, sensitivity and specificity of the modified higher order statistics detector were 96.46 ± 2.60%, 97.24 ± 2.99% and 94.13 ± 4.37%. In addition, 217088 segments of effective bowel sound corresponding to different sleep stages were identified using the modified detector. Most of the CVs were statistically different during different sleep stages ( $$p

Coastal areas face severe corrosion issues, posing significant risks and economic losses to equipment, personnel, and the environment. YOLO v5, known for its speed, accuracy, and ease of deployment, has been employed for the rapid detection and identification of marine corrosion. However, corrosion images often feature complex characteristics and high variability in detection targets, presenting significant challenges for YOLO v5 in recognizing and extracting corrosion features. To improve the detection performance of YOLO v5 for corrosion image features, this study investigates two enhanced models: EfficientViT-NWD-YOLO v5 and Gold-NWD-YOLO v5. These models specifically target improvements to the backbone and neck structures of YOLO v5, respectively. The performance of these models for corrosion detection is analyzed in comparison with both YOLO v5 and NWD-YOLO v5. The evaluation metrics including precision, recall, F1-score, Frames Per Second (FPS), pre-processing time, inference time, non-maximum suppression time (NMS), and confusion matrix were used to evaluate the detection performance. The results indicate that the Gold-NWD-YOLO v5 model shows significant improvements in precision, recall, F1-score, and accurate prediction probability. However, it also increases inference time and NMS time, and decreases FPS. This suggests that while the modified neck structure significantly enhances detection performance in corrosion images, it also increases computational overhead. On the other hand, the EfficientViT-NWD-YOLO v5 model shows slight improvements in precision, recall, F1-score, and accurate prediction probability. Notably, it significantly reduces inference and NMS time, and greatly improves FPS. This indicates that modifications to the backbone structure do not notably enhance corrosion detection performance but significantly improve detection speed. From the application perspective, YOLO v5 and NWD-YOLO v5 are suitable for routine corrosion detection applications. Gold-NWD-YOLO v5 is better suited for scenarios requiring high precision in corrosion detection, while EfficientViT-NWD-YOLO v5 is ideal for applications needing a balance between speed and accuracy. The findings can guide decision making for corrosion health monitoring for critical infrastructure in coastal areas.

The prediction of fuel consumption and Carbon Intensity Index (CII) of ships is crucial for optimizing decarbonization strategies in the maritime industry. This study proposes a ship fuel consumption prediction model based on the Long Short-Term Memory with Self-Attention Mechanism (SA-LSTM). The model is applied to a container ship of 2400 TEU to predict its hourly fuel consumption, hourly CII, and annual CII rating. Four different feature sets are selected from these data sources and are used as inputs for SA-LSTM and another ten models. The results demonstrate that the SA-LSTM model outperforms the other models in prediction accuracy. Specifically, the Mean Absolute Percentage Error (MAPE) for fuel consumption predictions using the SA-LSTM model is reduced by up to 20% compared to the XGBoost and by up to 12% compared to the LSTM model. Additionally, the SA-LSTM model achieves the highest accuracy in annual CII predictions.

Transgenic technology is a potent tool for verifying gene functions, and poplar serves as a model system for genetically transforming perennial woody plants. However, the current poplar genetic transformation system is limited to a few genotypes. In this study, we developed an efficient transformation system based on the Agrobacterium-mediated transformation of Populus wulianensis, a rare and endangered tree species endemic to Shandong Province. Aseptic seedlings of P. wulianensis were used as experimental materials, and the optimal medium for inducing adventitious buds was explored as 1/2(NH4NO3) MS + 0.05 mg/L naphthalene acetic acid (NAA) + 0.5 mg/L 6-benzylaminopurine (6-BA), resulting in up to 35 adventitious buds. The selection resistance critical pressure of 300 mg/L for timentin can effectively inhibit the growth of Agrobacterium while promoting the induction of adventitious buds in leaves. The critical screening pressure for kanamycin for producing resistant adventitious buds and inducing resistant rooting seedlings was 100 mg/L. We optimized several independent factors, which significantly enhanced the efficiency of genetic transformation. The leaves were infected with Agrobacterium suspension diluted twice by adding 100 μmol/L acetylsyringone (β-AS) (OD600 = 0.6) for 15 min, followed by co-culture in the dark for 3 d. Using this improved transformation system, we obtained transgenic P. wulianensis clones overexpressing the enhanced green fluorescent protein (EGFP) gene through direct organogenesis. Among the 112 resistant buds obtained, 17 developed resistant rooting in seedlings. Eight positive plants were identified through DNA, RNA, and protein level analyses, with a positivity rate of 47.06%. This study provides a foundation for developing and utilizing P. wulianensis germplasm resources and lays the groundwork for resource improvement.

Nitric oxide (NO) has been firmly established as a key signaling molecule in plants, playing a significant role in regulating growth, development and stress responses. Given the imperative of sustainable agriculture and the urgent need to meet the escalating global demand for food, it is imperative to safeguard crop plants from the effects of climate fluctuations. Plants respond to environmental challenges by producing redox molecules, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), which regulate cellular, physiological, and molecular processes. Nitric oxide (NO) plays a crucial role in plant stress tolerance, acting as a signaling molecule or free radical. NO is involved in various developmental processes in plants through diverse mechanisms. Exogenous NO supplementation can alleviate the toxicity of abiotic stresses and enhance plant resistance. In this review we summarize the studies regarding the production of NO in peroxisomes, and how its molecule and its derived products, (ONOO−) and S-nitrosoglutathione (GSNO) affect ROS metabolism in peroxisomes. Peroxisomal antioxidant enzymes including catalase (CAT), are key targets of NO-mediated post-translational modification (PTM) highlighting the dynamic metabolism of ROS and RNS in peroxisomes.

Phosphogypsum-based cementitious material (PBC) is acknowledged as a low-carbon green composite material. The addition of lime to modify PBC has been found to significantly enhance PBC utilization rate. This study investigates the effects of varying lime contents in PBC on mechanical properties, volume expansion, hydration products, micromorphology, and pore structure of modified Phosphogypsum (PS). The results demonstrate that lime effectively counteracts the retarding effect of water-soluble impurities in PS, thereby reducing setting time. Additionally, the 7 days and 28 days strength of PBC initially increases and then decreases with increasing lime content, with the 28 days compressive strength of B0 (0.5%) reaching 48 MPa. A 0.5% lime-modified PS proves beneficial in promoting PBC hydration, reducing pore size, densifying the microstructure, and enhancing mechanical properties. Moreover, the volume expansion results highlight the significant influence of the alkaline environment on both the generation and distribution of ettringite, consequently impacting PBC expansion.

This study investigates the shale oil drainage characteristics from the Gulong Sag, The objective is to clarify the development method for effective recovery enhancement of terrestrial shale oil. The investigation employs elastic depletion, CO2 displacement, and CO2 huff and puff coupled with nuclear magnetic resonance (NMR) measurements and numerical simulation methods. The study found that the elastic depletion, CO2 displacement, and CO2 huff and puff utilization efficiencies were 17.4%, 18.87%, and 21%, respectively. The study evaluated the oil drainage efficiency of different pore sizes in elastic depletion and CO2 huff and puff modes. The results demonstrated a clear trend in the order of micropore, mesoporous and macropore, with micropores exhibiting the highest oil drainage efficiency due to gas channeling during CO2 displacement. The use of CO2 huff and puff has been shown to improve oil drainage efficiency by 6.02%∼9.2% for different pore sizes. The numerical simulation optimization results suggest an injection volume of 3,000 t per round per well, an injection rate of 100 t/d, and a soaking time of 20 d for optimal CO2 huff and puff injection. This will increase oil production by 65,000 m³, resulting in an overall improvement of 24%. The study results provide a strong theoretical foundation for improving the recovery rates of terrestrial shale oil and gas through injection.

Discogenic low back pain (DLBP) is a multifactorial disease and associated with intervertebral disc degeneration. Calcitonin gene-related protein (CGRP) plays a critical role in pain processing, while the role in DLBP remains unclear. This study aims to investigate the anti-nociceptive role and related mechanisms of CGRP in DLBP. Here we established the DLBP rat and validated the model using histology and radiography. Minocycline, a microglial inhibitor, and CGRP were intrathecally injected and the behavioral test was performed to determine hyperalgesia. Further, BV2 microglial cells and microglial activation agent lipopolysaccharide (LPS) were employed for the in vitro experiment. We observed obvious lumbar intervertebral disc degeneration and hyperalgesia at 12 weeks postoperation in DLBP group, with significantly activated microglia in the spinal cord. CGRP treatment significantly inhibited the upregulation of proinflammatory cytokines and NLRP3/caspase-1 expression induced by LPS in BV2 cells, whereas treatment with CGRP alone had little effect on BV2 cells. The intrathecal injection of CGRP into DLBP rats relieved mechanical and thermal hyperalgesia, reverted the microglial activation and decreased the expression of NLRP3/caspase-1, similar to the effects produced by minocycline. Our results provide evidence that microglial activation in the spinal cord play a key role in hyperalgesia in DLBP rats. CGRP alleviates DLBP induced hyperalgesia and inhibits microglial activation in the spinal cord. Regulation of CGRP and microglial activation may provide a new strategy for ameliorating DLBP.

The prevention and control measures adopted by various countries have different effects in the face of COVID-19. The performance in some socialist countries and capitalist countries were compared from three aspects, including the proportion of confirmed cases and deaths to the national population, economic recovery and production and living, social satisfaction and international evaluation. The overall performance of listed socialist countries was better than that of capitalist countries. China's performance, forming a unique Chinese model of the epidemic prevention and control, was better than that of other socialist countries. The successful experience of Chinese model can be mainly reflected in four aspects, including resource allocation, social participation, speed and quality, system and mechanism optimization. The successful experience roots in the four institutional advantages of the leadership of the Communist Party of China (CPC), coordinated national response, basic economic system and traditional Chinese culture. In the future, Chinese government should adhere to the socialist system with Chinese characteristics and improve the public health and emergency management system. Chinese government should accelerate the construction of a community with a shared future for mankind and promote the modernization of the national governance system and governance capacity. These findings are of great significance in understanding China's prevention and control measures, the institutional advantages and subsequent optimization.

Abstract Introduction The aim of this work is to determine the interocular differences in peripapillary retinal nerve fiber layer (p-RNFL) thickness and its associations among school children in Hong Kong. Methods We conducted a population-based study including 4034 children aged 6–8 years from the Hong Kong Children Eye Study (HKCES). All participants received comprehensive ocular examinations where p-RNFL thickness was measured using spectral-domain optical coherence tomography (SD-OCT). The degree of symmetry between both eyes was analyzed and represented by intraclass correlation coefficient (ICC) values. Multivariable linear regression analysis was used to investigate the associations between ocular and systemic factors with p-RNFL thickness difference. Results The study included 4034 children with a mean age of 7.61 ± 0.98 years. The mean global p-RNFL thickness was 106.60 ± 9.41 μm in right eyes and 105.99 ± 9.30 μm in left eyes. The ICC for global p-RNFL difference was 0.866 (95% CI 0.858–0.873, p

Abstract Colorectal cancer (CRC) patients with liver metastases usually obtain less benefit from immunotherapy, and the underlying mechanisms remain understudied. Here, we identify that fibrinogen-like protein 1 (FGL1), secreted from cancer cells and hepatocytes, facilitates the progression of CRC in an intraportal injection model by reducing the infiltration of T cells. Mechanistically, tumor-associated macrophages (TAMs) activate NF-ĸB by secreting TNFα/IL-1β in the liver microenvironment and transcriptionally upregulate OTU deubiquitinase 1 (OTUD1) expression, which enhances FGL1 stability via deubiquitination. Disrupting the TAM-OTUD1-FGL1 axis inhibits metastatic tumor progression and synergizes with immune checkpoint blockade (ICB) therapy. Clinically, high plasma FGL1 levels predict poor outcomes and reduced ICB therapy benefits. Benzethonium chloride, an FDA-approved antiseptics, curbs FGL1 secretion, thereby inhibiting liver metastatic tumor growth. Overall, this study uncovers the critical roles and posttranslational regulatory mechanism of FGL1 in promoting metastatic tumor progression, highlighting the TAM-OTUD1-FGL1 axis as a potential target for cancer immunotherapy.

Abstract Linear ubiquitination is a specific post-translational modification in which ubiquitin is linked through M1 residue to form multiple types of polyubiquitin chains on substrates in order to regulate cellular processes. LUBAC comprised by HOIP, HOIL-1L, and SHARPIN as a sole E3 ligase catalyzes the generation of linear ubiquitin chains, and it is simultaneously adjusted by deubiquitinases such as OTULIN and CYLD. Several studies have shown that gene mutation of linear ubiquitination in mice accompanied by different modalities of cell death would develop relative diseases. Cell death is a fundamental physiological process and responsible for embryonic development, organ maintenance, and immunity response. Therefore, it is worth speculating that linear ubiquitin mediated signaling pathway would participate in different diseases. The relative literature search was done from core collection of electronic databases such as Web of Science, PubMed, and Google Scholar using keywords about main regulators of linear ubiquitination pathway. Here, we summarize the regulatory mechanism of linear ubiquitination on cellular signaling pathway in cells with apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Intervening generation of linear ubiquitin chains in relative signaling pathway to regulate cell death might provide novel therapeutic insights for various human diseases.

To explore the effects of crushing processes on the rheological properties and edible quality of minced meat, blunt cutting tool and sharp cutting tool on two devices of beating machine and chopping machine were used to prepare minced meat. The pH value, salt soluble protein content, protein secondary structure, particle size distribution, color, stability and cooking loss, water holding capacity, texture characteristics and microstructure of minced meat gel were investigated. The results showed that the four crushing processes had different degrees of muscle fiber fragmentation, resulting in different properties of the low-fat minced meat and the resulting gel. Compared with the beater, the low-fat minced meat treated by the chopper had a higher G′ value in the temperature scanning. The low-fat minced meat beaten with blunt knife had the lowest viscosity and showed poor stability in frequency scanning. The high intensity cutting action of the chopper resulted in a lower end temperature and smaller particle size of the broken low-fat minced meat, and higher water holding capacity of the low-fat minced meat gel. Compared with the other three processes, the blunt knife chopped low-fat minced meat had the highest redness value (15.95), pH value (6.66), salt-soluble protein content (77.05 mg/mL), relative content of β-fold (43.71%), and the low-fat minced meat gel had the lowest cooking loss (17.48%), the highest hardness (4147.72 g), gumminess (2883.72), chewiness (2496.02 g), sensory scores, which may be attributed to the tighter microstructure of low-fat minced meat gel formed by this treatment with moderate muscle fragmentation. Therefore, the blunt chopping is suitable for the crushing production of low-fat minced meat, which can improve its salt-soluble protein content, relative content of β-sheet, redness, water holding capacity and texture properties.

Abstract Traditional ecological restoration technology has many challenges in dealing with the greening of steep rock slopes, especially in the case of serious soil erosion. In order to overcome these problems, this study aims to organically combine the traditional protection and reinforcement technology with the new vegetation restoration technology, and put forward a new ecological protection technology of composite vegetation concrete to realize the comprehensive protection and ecological restoration of rocky slopes. In this paper, by analyzing the mechanism and existing problems of ecological protection of rocky slopes, the design requirements of composite vegetation concrete are studied in detail, and the related construction technology is expounded. In the experiment, the vegetation coverage and incidence were systematically analyzed, and the results showed that some samples showed high vegetation coverage and low incidence. Comprehensive consideration shows that the average vegetation coverage rate is 93.7%, and the average incidence rate is only 5.21%, which all meet the corresponding standards. The composite vegetation concrete technology has a wide application prospect in stone slope protection, which significantly improves the slope vegetation coverage and compressive strength, and effectively promotes the slope greening and ecological sustainable development. Through this study, we aim to convey to readers that the comprehensive method of combining traditional and innovative technologies can achieve encouraging results in solving the problem of ecological restoration of steep rock slopes, and provide useful reference for engineering practice in similar environments.

To study the effect of dry ice on the performance of alkali-activated binders, we added dry ice to an alkali-activated slag (AAS). The addition amount was set to 5%, 10%, and 15% of the slag mass, depending on the amount of CO2 emitted by the material used in the preparation process. Microscopic experiments were performed to analyze the effect of dry ice on the hydration products of the AAS paste; transmission electron microscopy and scanning electron microscopy were used to observe the morphology of the hydration products. Furthermore, experimental tests for the compressive strength, ultrasonic pulse velocity, and electrical resistivity were performed. The results showed that compared with the content of the overall reaction products, the effect of dry ice on the reaction rate was more evident. The addition of dry ice slowed the hydration of the AAS, and the production of the hydration products, such as calcium aluminum silicate hydrate (C-A-S-H) gels, was significantly reduced in the early stage (1 d). Experiments on the strength showed that adding more than 5% dry ice degraded the early mechanical properties of the AAS. However, the mechanical properties of the AAS with dry ice added in the middle (3 and 7 d) and late (28 d) stages rapidly improved because the dry ice was added to the AAS to form potassium and calcium carbonate. In the middle (3 and 7 d) and late (28 d) stages, CO32− underwent a carbonation reaction to form carbonate compounds, enhancing the mechanical properties of the AAS.

Abstract Telomerase reverse transcriptase (TERT/hTERT) serves as the pivotal catalytic subunit of telomerase, a crucial enzyme responsible for telomere maintenance and human genome stability. The high activation of hTERT, observed in over 90% of tumors, plays a significant role in tumor initiation and progression. An in-depth exploration of hTERT activation mechanisms in cancer holds promise for advancing our understanding of the disease and developing more effective treatment strategies. In breast cancer, the expression of hTERT is regulated by epigenetic, transcriptional, post-translational modification mechanisms and DNA variation. Besides its canonical function in telomere maintenance, hTERT exerts non-canonical roles that contribute to disease progression through telomerase-independent mechanisms. This comprehensive review summarizes the regulatory mechanisms governing hTERT in breast cancer and elucidates the functional implications of its activation. Given the overexpression of hTERT in most breast cancer cells, the detection of hTERT and its associated molecules are potential for enhancing early screening and prognostic evaluation of breast cancer. Although still in its early stages, therapeutic approaches targeting hTERT and its regulatory molecules show promise as viable strategies for breast cancer treatment. These methods are also discussed in this paper. Video Abstract

Abstract Background Obesity increases breast cancer risk and breast cancer-specific mortality, particularly for people with estrogen receptor (ER)-positive tumors. Body mass index (BMI) is used to define obesity, but it may not be the best predictor of breast cancer risk or prognosis on an individual level. Adult weight gain is an independent indicator of breast cancer risk. Our previous work described a murine model of obesity, ER-positive breast cancer, and weight gain and identified fibroblast growth factor receptor (FGFR) as a potential driver of tumor progression. During adipose tissue expansion, the FGF1 ligand is produced by hypertrophic adipocytes as a stimulus to stromal preadipocytes that proliferate and differentiate to provide additional lipid storage capacity. In breast adipose tissue, FGF1 production may stimulate cancer cell proliferation and tumor progression. Methods We explored the effects of FGF1 on ER-positive endocrine-sensitive and resistant breast cancer and compared that to the effects of the canonical ER ligand, estradiol. We used untargeted proteomics, specific immunoblot assays, gene expression profiling, and functional metabolic assessments of breast cancer cells. The results were validated in tumors from obese mice and breast cancer datasets from women with obesity. Results FGF1 stimulated ER phosphorylation independently of estradiol in cells that grow in obese female mice after estrogen deprivation treatment. Phospho- and total proteomic, genomic, and functional analyses of endocrine-sensitive and resistant breast cancer cells show that FGF1 promoted a cellular phenotype characterized by glycolytic metabolism. In endocrine-sensitive but not endocrine-resistant breast cancer cells, mitochondrial metabolism was also regulated by FGF1. Comparison of gene expression profiles indicated that tumors from women with obesity shared hallmarks with endocrine-resistant breast cancer cells. Conclusions Collectively, our data suggest that one mechanism by which obesity and weight gain promote breast cancer progression is through estrogen-independent ER activation and cancer cell metabolic reprogramming, partly driven by FGF/FGFR. The first-line treatment for many patients with ER-positive breast cancer is inhibition of estrogen synthesis using aromatase inhibitors. In women with obesity who are experiencing weight gain, locally produced FGF1 may activate ER to promote cancer cell metabolic reprogramming and tumor progression independently of estrogen.

With the development of globalization and artificial intelligence, as well as the outbreak of COVID-19, unmanned vehicles have played an important role in cargo distribution. In order to better analyze the research directions of unmanned vehicle distribution, this paper summarizes the models and algorithms of unmanned vehicle distribution optimization. The research results show that most of the studies have established the goal of optimizing the total costs or travel time. Many researchers have begun to study multi-objective optimization problems, but there are certain limitations, so some studies convert these problems into single-objective optimization for solving, such as converting time and energy consumption into cost, waiting time into distance, and time delay into penalty cost. With the development of unmanned vehicle distribution technology, in future research, a multi-objective model with the lowest cost, the shortest distance and the best security should be established and solved. Most studies have proposed heuristic algorithms for solving the unmanned vehicle distribution problem, and improved optimization solutions have been obtained. In order to ensure the diversity of solution methods, and give consideration to solution time and solution quality, hybrid methods with other algorithms will be a future research direction, for example, the combination of heuristic algorithm and exact algorithm. With the gradual deepening of research, integrated distribution of multiple types of unmanned equipment will become the focus of future research.

High temperature represents a critical constraint in the development of gas sensors. Therefore, investigating gas sensors operating at room temperature holds significant practical importance. In this study, coal-based porous carbon (C-700) and coal-based C/MoO2 nanohybrid materials were synthesized using a simple one-step vapor deposition and sintering method, and their gas-sensing performance was investigated. The gas-sensing performance for several VOC gases (phenol, ethyl acetate, ethanol, acetone, triethylamine, and toluene) and a 95% RH high-humidity environment were tested. The results indicated that the C/MoO2-450 sample sintered at 450 °C exhibited excellent specific selectivity towards acetone at room temperature, with a response value of 4153.09% and response/recovery times of 10.8 s and 2.9 s, respectively. Furthermore, the C/MoO2-450 sample also demonstrated good repeatability and long-term stability. The sensing mechanism of the synthesized materials was also explored. The superior gas-sensing performance can be attributed to the synergistic effect between the porous carbon and MoO2 nanoparticles. Given the importance of enhancing the high-tech and high-value-added utilization of coal, this study provides a viable approach for utilizing coal-based carbon materials in detecting volatile organic compounds at room temperature.

Abstract Objectives Pulmonary sarcomatoid carcinoma (PSC) is a rare histological type of non-small cell lung cancer (NSCLC). There are no specific treatment guidelines for PSC. For advanced PSC (stage II-IV), the role of chemotherapy is still controversial. The purpose of this study was to investigate the effect of chemotherapy on the prognosis of advanced PSC. Methods A total of 960 patients with advanced PSC from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2019 were enrolled in this study. To investigate the prognostic factors, the Cox proportional hazard regression model was conducted. A total of 642 cases were obtained after propensity score matching (PSM). The Kaplan‒Meier method was applied to compare overall survival (OS) and cancer-specific survival (CSS). Results For all 960 cases included in this study, the Cox proportional hazard model was applied for prognostic analysis. Univariate and multivariate analyses showed that stage, T stage, N stage, M stage, surgery, and chemotherapy were prognostic factors for OS and CSS (P

Abstract Background Esophageal cancer is one of the most common malignant tumors in the world, which is characterized by poor prognosis, aggressiveness, and poor survival. Mucin 13 (MUC13) is a member of the membrane-bound mucin and located on chromosome 3q21.2 and consists of α and β subunits. It has been found that MUC13 is overexpressed in a variety of tumor cells and acts a vital role in the invasiveness and malignant progression of several types of tumors. However, the role and regulatory mechanism of MUC13 in the progression of esophageal cancer remain unclear. Methods The expression level of MUC13 was detected in 15 esophageal cancer tissues and 15 pairs of adjacent nontumor tissues by immunohistochemistry (IHC). In addition, the expression of MUC13 mRNA level in human esophageal cancer cell lines (EC9706 and ECA109 and TE-1) was measured by qRT-PCR. In vitro, after silencing MUC13 with lentiviral interference technology, CCK8 assay, clone formation assay, and flow cytometry were applied to investigate the proliferation activity, clone formation ability and anti-apoptosis ability of EC9706 and ECA109 cells. The tumor xenograft growth assay was used to confirm the influence of MUC13 knockdown on the growth of esophageal tumors in vivo. The qRT-PCR assay and western blot experiments were taken to study the mechanism of MUC13 regulating the proproliferation and antiapoptotic of esophageal cancer. Results The results showed that MUC13 was overexpressed in esophageal cancer tissues and cell lines (EC9706 and ECA109 and TE-1), especially in EC9706 and ECA109 cells, but low expressed in human esophageal epithelial cell line (HEEC). Next, silencing MUC13 inhibits proliferation, blocks cell cycle progression, and promotes cell apoptosis in vitro, and restrains the growth of esophageal cancer tissues in vivo. Finally, MUC13 affects the proproliferation and antiapoptotic by regulating the expression of GLANT14, MUC3A, MUC1, MUC12, and MUC4 that closely related to O-glycan process. Conclusions This study proved that MUC13 is an important molecule that regulates the O-glycan process and then affects the progress of esophageal cancer. MUC13 may be a novel therapeutic target for patients with esophageal cancer.

Abstract With the rapid development of electronic equipment and communication technology, the demand for polymer composites with high thermal conductivity and mechanical properties has increased significantly. However, its nondegradable polymer matrix will inevitably bring more and more serious environmental pollution. Therefore, it is urgent to develop biodegradable thermally conductive polymer composites. In this work, biodegradable poly(butylene adipate‐co‐terephthalate) (PBAT) is used as the matrix material, and vacuum‐assisted filtration technology is employed to prepare carbon nanotube (CNT) and cellulose nanocrystal (CNC) networks with high thermal conductivity. Then CNT–CNC/PBAT composites with high thermal conductivity and excellent mechanical properties are prepared by the ultrasonic‐assisted forced infiltration method. Both experiment and simulation methods are used to systematically investigate the thermally conductive and dissipation performances of the CNT–CNC/PBAT composites. Above all, a simple alcoholysis reaction is applied to realize the separation of the PBAT matrix and functional fillers without destroying the conductive network skeleton, which makes it possible for the recycling of thermally conductive polymer composites.

Abstract Background Tianhuang formula (THF) is a Chinese medicine prescription that is patented and clinically approved, and has been shown to improve energy metabolism, but the underlying mechanism remains poorly understood. The purpose of this study is to clarify the potential mechanisms of THF in the treatment of type 2 diabetes mellitus (T2DM). Methods A murine model of T2DM was induced by high-fat diet (HFD) feeding combined with low-dose streptozocin (STZ) injections, and the diabetic mice were treated with THF by gavaging for consecutive 10 weeks. Fasting blood glucose (FBG), serum insulin, blood lipid, mitochondrial Ca2+ (mCa2+) levels and mitochondrial membrane potential (MMP), as well as ATP production were analyzed. The target genes and proteins expression of visceral adipose tissue (Vat) was tested by RT-PCR and western blot, respectively. The underlying mechanism of the regulating energy metabolism effect of THF was further explored in the insulin resistance model of 3T3-L1 adipocytes cultured with dexamethasone (DXM). Results THF restored impaired glucose tolerance and insulin resistance in diabetic mice. Serum levels of lipids were significantly decreased, as well as fasting blood glucose and insulin in THF-treated mice. THF regulated mCa2+ uptake, increased MMP and ATP content in VAT. THF increased the mRNA and protein expression of AMPK, phosphorylated AMPK (p-AMPK), MICU1, sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). THF could increase the mCa2+ level of 3T3-L1 adipocytes and regulate mitochondrial function. The protein expression of AMPK, p-AMPK, mCa2+ uniporter (MCU) and MICU1 decreased upon adding AMPK inhibitor compound C to 3T3-L1 adipocytes and the protein expression of MCU and MICU1 decreased upon adding the MCU inhibitor ruthenium red. Conclusions These results demonstrated that THF ameliorated glucose and lipid metabolism disorders in T2DM mice through the improvement of AMPK/MICU1 pathway-dependent mitochondrial function in adipose tissue.

Fhb7 is a major gene that was transferred from Thinopyrum ponticum to chromosome 7D of wheat (Triticum aestivum) and confers resistance to both Fusarium head blight (FHB) and Fusarium crown rot (FCR). However, Fhb7 is tightly linked to the PSY-E2 gene, which causes yellow flour, limiting its application in breeding. To break this linkage, marker K-PSY was developed for tagging PSY-E2 and used with Fhb7 markers to identify recombination between the two genes. Screening 21,000 BC1F2 backcross progeny (Chinese Spring ph1bph1b*2/SDAU 2028) revealed two Fhb7+ wheat-Tp7el2L lines, Shannong 2–16 and Shannong 16–1, that carry a desired truncated Fhb7+ translocation segment without PSY-E2. The two lines show levels of resistance to FHB and FCR similar to those of the original translocation line SDAU 2028, but have white flour. To facilitate Fhb7 use in wheat breeding, STS markers were developed and used to isolate Fhb7 on a truncated Tp7el2 translocation segment. Near-isogenic lines carrying the Fhb7+ segment were generated in the backgrounds of three commercial cultivars, and Fhb7+ lines showed increased FHB and FCR resistance without yield penalty. The breakage of the tight linkage between Fhb7 and PSY-E2 via homoeologous recombination provides genetic resources for improvement of wheat resistance to FHB and FCR and permit the large-scale deployment of Fhb7 in breeding using marker-assisted selection.

Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action.

Despite women representing most of those affected by major depression, preclinical studies have focused almost exclusively on male subjects, partially due to a lack of ideal animal paradigms. As the persistent need regarding the sex balance of neuroscience research and female-specific pathology of mental disorders surges, the establishment of natural etiology-based and systematically validated animal paradigms for depression with female subjects becomes an urgent scientific problem. This study aims to establish, characterize, and validate a “Multiple Integrated Social Stress (MISS)” model of depression in female C57BL/6J mice by manipulating and integrating daily social stressors that females are experiencing. Female C57BL/6J mice randomly experienced social competition failure in tube test, modified vicarious social defeat stress, unescapable overcrowding stress followed by social isolation on each day, for ten consecutive days. Compared with their controls, female MISS mice exhibited a relatively decreased preference for social interaction and sucrose, along with increased immobility in the tail suspension test, which could last for at least one month. These MISS mice also exhibited increased levels of blood serum corticosterone, interleukin-6 L and 1β. In the pharmacological experiment, MISS-induced dysfunctions in social interaction, sucrose preference, and tail suspension tests were amended by systematically administrating a single dose of sub-anesthetic ketamine, a rapid-onset antidepressant. Compared with controls, MISS females exhibited decreased c-Fos activation in their anterior cingulate cortex, prefrontal cortex, nucleus accumbens and some other depression-related brain regions. Furthermore, 24 h after the last exposure to the paradigm, MISS mice demonstrated a decreased center zone time in the open field test and decreased open arm time in the elevated plus-maze test, indicating anxiety-like behavioral phenotypes. Interestingly, MISS mice developed an excessive nesting ability, suggesting a likely behavioral phenotype of obsessive-compulsive disorder. These data showed that the MISS paradigm was sufficient to generate pathological profiles in female mice to mimic core symptoms, serum biochemistry and neural adaptations of depression in clinical patients. The present study offers a multiple integrated natural etiology-based animal model tool for studying female stress susceptibility.