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Abstract Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.

Abstract The primary cilium behaves as a platform for sensing and integrating extracellular cues to control a plethora of cellular activities. However, the functional interaction of this sensory organelle with epithelial-mesenchymal transition (EMT) during pulmonary fibrosis remains unclear. Here, we reveal a critical role for cylindromatosis (CYLD) in reciprocally linking the EMT program and ciliary homeostasis during pulmonary fibrosis. A close correlation between the EMT program and primary cilia is observed in bleomycin-induced pulmonary fibrosis as well as TGF-β-induced EMT model. Mechanistic study reveals that downregulation of CYLD underlies the crosstalk between EMT and ciliary homeostasis by inactivating histone deacetylase 6 (HDAC6) during pulmonary fibrosis. Moreover, manipulation of primary cilia is an effective means to modulate the EMT program. Collectively, these results identify a pivotal role for the CYLD/HDAC6 signaling in regulating the reciprocal interplay between the EMT program and ciliary homeostasis during pulmonary fibrosis.

Abstract Lead-barium silicate system products, represented by barium copper silicate and lead-barium glass, epitomize a unique artistic craftsmanship of ancient China. Specifically, barium copper silicate products were the only known artificially synthesized blue-purple inorganic pigments in ancient China. Painted pottery decorated with barium copper silicate pigment, predominantly found in elite tombs after 2nd century B.C., is exceedingly rare and holds immense archaeological significance. This case employed multi micro-scale analytical techniques, such as ultra-depth-of-field microscopy, Raman spectroscopy, µ X-ray Diffraction, and electron probe microanalysis, for comprehensive microscopic examination of a rare Chinese Purple (CP, BaCuSi2O6) pigments on painted pottery. The analytical results confirm that the purple pigment is BaCuSi2O6, accompanied by cinnabar for the red and bone white for the white sections, suggesting the probable use of organic residues as an adhesive. Additionally, the study reveals microstructural characteristics in CP faience and CP pigments, notably the encapsulation of CP particles by quartz particles. Therefore, it can be hypothesized that the process of manufacturing purple pigment was achieved by grinding faience into fine particles and then using an organic-based adhesive to adhere these particles to the pottery. This implies that the evolutions in CP products circa the 2nd century B.C. were driven not by technological advances from lead-barium glass, but rather by shifts in application methods, reflecting an adaptation process among different cultures. This study provides new perspectives and significant insights for comprehending the interplay between barium copper silicate and lead-barium glass, reconstructing ancient pottery painting techniques, and exploring the era’s technological and cultural interactions.

Abstract Background The burden and characteristics of respiratory viral infections in children hospitalized for acute respiratory tract infections (ARTIs) during the post-COVID-19 pandemic era are unclear. We analyzed the epidemiological and clinical characteristics of pediatric patients hospitalized with common respiratory virus infections before and after relaxation of non-pharmaceutical interventions in Hangzhou, China and evaluated the diagnostic value of the six-panel respiratory pathogen detection system. Methods Six types of respiratory viruses were detected in respiratory samples from children with suspected ARTIs by multiplex real-time quantitative polymerase chain reaction (RT-qPCR). Changes in virus detection rates and epidemiological and clinical characteristics, obtained from electronic health records, were analyzed. Binary logistic regression was used to identify respiratory tract infections risk factors. Multiplex RT-qPCR and targeted next-generation sequencing results were compared in random samples. Results Among the 11,056 pediatric samples, 3228 tested positive for one or more of six common respiratory pathogens. RSV and PIV-3 detection rates differed significantly across age groups (both P

Abstract Although circular RNAs (circRNA) have been demonstrated to modulate tumor initiation and progression, their roles in the proliferation of hepatocellular carcinoma (HCC) are still poorly understood. Based on the analysis of GEO data (GSE12174), hsa-circRNA-0015004 (circ-0015004) was screened and validated in 80 sets of HCC specimens. Subcellular fractionation analysis was designed to determine the cellular location of circ-0015004. Colony formation and cell counting kit-8 were performed to investigate the role of circ-0015004 in HCC. Dual-luciferase reporter gene assays, RNA immunoprecipitation and chromatin immunoprecipitation were employed to verify the interaction among circ-0015004, miR-330-3p and regulator of chromatin condensation 2 (RCC2). The expression level of circ-0015004 was significantly upregulated in HCC cell lines and HCC tissues. HCC patients with higher circ-0015004 levels displayed shorter overall survival, and higher tumor size and TNM stage. Moreover, knockdown of circ-0015004 significantly reduced HCC cell proliferation in vitro and inhibited the growth of HCC in nude mice. Mechanistic studies revealed that circ-0015004 could upregulate the expression of RCC2 by sponging miR-330-3p, thereby promoting HCC cell proliferation. Furthermore, we identified that Ying Yang 1 (YY1) could function as an important regulator of circ-0015004 transcription. This study systematically demonstrated the novel regulatory signaling of circ-0015004/miR-330-3p/RCC2 axis in promoting HCC progression, providing insight into HCC diagnosis and treatment from bench to clinic.

Abstract. Background:. Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC. Methods:. We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results:. The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion:. The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Abstract Background In this study, we investigated the relationship between the risk of postoperative progressive disease (PD) in breast cancer and depression and sleep disorders in order to develop and validate a suitable risk prevention model. Methods A total of 750 postoperative patients with breast cancer were selected from the First People’s Hospital of LianYunGang, and the indices of two groups (an event group and a non-event group) were compared to develop and validate a risk prediction model. The relationship between depression, sleep disorders, and PD events was investigated using the follow-up data of the 750 patients. Results SAS, SDS, and AIS scores differed in the group of patients who experienced postoperative disease progression versus those who did not; the differences were statistically significant and the ability to differentiate prognosis was high. The area under the receiver operating characteristic (ROC) curves (AUC) were: 0.8049 (0.7685–0.8613), 0.768 (0.727–0.809), and 0.7661 (0.724-–0.808), with cut-off values of 43.5, 48.5, and 4.5, respectively. Significant variables were screened by single-factor analysis and multi-factor analysis to create model 1, by lasso regression and cross-lasso regression analysis to create model 2, by random forest calculation method to create model 3, by stepwise regression method (backward method) to create model 4, and by including all variables for Cox regression to include significant variables to create model 5. The AUC of model 2 was 0.883 (0.848–0.918) and 0.937 (0.893–0.981) in the training set and validation set, respectively. The clinical efficacy of the model was evaluated using decision curve analysis and clinical impact curve, and then the model 2 variables were transformed into scores, which were validated in two datasets, the training and validation sets, with AUCs of 0.884 (0.848–0.919) and 0.885 (0.818–0.951), respectively. Conclusion We established and verified a model including SAS, SDS and AIS to predict the prognosis of breast cancer patients, and simplified it by scoring, making it convenient for clinical use, providing a theoretical basis for precise intervention in these patients. However, further research is needed to verify the generalization ability of our model.

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.

In recent years, the mining state of mineral resources has changed from open air to underground and from shallow to deep. In the drilling and blasting construction of deep rock masses, in-situ stress has a significant impact on the blasting effect. An improved continuum-discontinuum element method (CDEM) considering energy dissipation in the crushing zone under blasting load is used to study the stress evolution process and rupture damage characteristics of ordinary straight hole cut blasting and large empty hole cut blasting under different in-situ stress conditions based on a two-dimensional plane strain model. The numerical results show that the existence of the large empty hole enhances the reflection and stretching effect of the explosion stress wave, weakens the inhibitory effect of the ground stress on the explosion crack expansion, promotes the expansion of the main explosion crack, increases the fractal damage and damage area of the trough blast, and improves the crushing degree of the rock mass of the trough blasting. The bi-directional isobaric in-situ stress has an inhibitory effect on the propagation of blast-induced cracks, especially on the propagation of radial cracks. The larger in-situ stress weakens the interaction of blasting stress waves between holes, and the guiding effect of adjacent holes on the propagation of the main crack is weakened. With the increase of in-situ stress, the fractal dimension and fractal damage of explosion crack decrease gradually on the whole, but the fissure differentiated damage and damage area of large empty hole blasting are significantly greater than the fissure differentiated damage and damage area of ordinary straight hole blasting. It shows that in the high in-situ stress environment, the large empty hole cut blasting can still significantly increase the rock crushing degree and crushing range and improve the blasting effect and crushing efficiency.

Abstract Cancer, a prevalent and complex disease, presents a significant challenge to the medical community. It is characterized by irregular cell differentiation, excessive proliferation, uncontrolled growth, invasion of nearby tissues, and spread to distant organs. Its progression involves a complex interplay of several elements and processes. Extracellular vesicles (EVs) serve as critical intermediaries in intercellular communication, transporting critical molecules such as lipids, RNA, membrane, and cytoplasmic proteins between cells. They significantly contribute to the progression, development, and dissemination of primary tumors by facilitating the exchange of information and transmitting signals that regulate tumor growth and metastasis. However, EVs do not have a singular impact on cancer; instead, they play a multifaceted dual role. Under specific circumstances, they can impede tumor growth and influence cancer by delivering oncogenic factors or triggering an immune response. Furthermore, EVs from different sources demonstrate distinct advantages in inhibiting cancer. This research examines the biological characteristics of EVs and their involvement in cancer development to establish a theoretical foundation for better understanding the connection between EVs and cancer. Here, we discuss the potential of EVs from various sources in cancer therapy, as well as the current status and future prospects of engineered EVs in developing more effective cancer treatments.

Abstract Soils are a principal global reservoir of mercury (Hg), a neurotoxic pollutant that is accumulating through anthropogenic emissions to the atmosphere and subsequent deposition to terrestrial ecosystems. The fate of Hg in global soils remains uncertain, however, particularly to what degree Hg is re-emitted back to the atmosphere as gaseous elemental mercury (GEM). Here we use fallout radionuclide (FRN) chronometry to directly measure Hg accumulation rates in soils. By comparing these rates with measured atmospheric fluxes in a mass balance approach, we show that representative Arctic, boreal, temperate, and tropical soils are quantitatively efficient at retaining anthropogenic Hg. Potential for significant GEM re-emission appears limited to a minority of coniferous soils, calling into question global models that assume strong re-emission of legacy Hg from soils. FRN chronometry poses a powerful tool to reconstruct terrestrial Hg accumulation across larger spatial scales than previously possible, while offering insights into the susceptibility of Hg mobilization from different soil environments.

Abstract Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delineate an important layer of UBE3B regulation by VHL.

Abstract Background Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named “IEsohunter”) for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. Methods Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. Results We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880–0.927) and 0.727 (95% CI 0.653–0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1–85.6), 87.3% (95% CI 79.4–92.4), 92.5% (95% CI 85.9–96.2), and 96.9% (95% CI 84.3–99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4–90.6) and specificity of 93.3% (95% CI 91.2–94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. Conclusions The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.

Abstract Metabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3′−5′ RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3β complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits oxidative phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC.

Abstract This article reports a case of a female patient admitted with swelling and subcutaneous mass in the right forearm, initially suspected to be multiple nerve fibroma. However, through preoperative imaging and surgery, the final diagnosis confirmed superficial thrombophlebitis. This condition resulted in entrapment of the radial nerve branch, leading to noticeable nerve entrapment and radiating pain. The surgery involved the excision of inflammatory tissue and thrombus, ligation of the cephalic vein, and complete release of the radial nerve branch. Postoperative pathology confirmed the presence of Superficial Thrombophlebitis. Through this case, we emphasize the importance of comprehensive utilization of clinical, imaging, and surgical interventions for more accurate diagnosis and treatment. This is the first clinical report of radial nerve branch entrapment due to superficial thrombophlebitis.

Fueled by substantial advancements in deep learning, the domain of autonomous driving is swiftly advancing towards more robust and effective intelligent systems. One of the critical challenges in this field is achieving accurate 3D object detection, which is often hindered by data sparsity and occlusion. To address these issues, we propose a method centered around a multi-modal fusion strategy that leverages vehicle-road cooperation to enhance perception capabilities. Our approach integrates label information from roadside perception point clouds to harmonize and enrich the representation of image and LiDAR data. This comprehensive integration significantly improves detection accuracy by providing a fuller understanding of the surrounding environment. Rigorous evaluations of our proposed method on two benchmark datasets, KITTI and Waymo Open, demonstrate its superior performance, with our model achieving 87.52% 3D Average Precision (3D AP) and 93.71% Bird’s Eye View Average Precision (BEV AP) on the KITTI val set. These results highlight the effectiveness of our method in detecting sparse and distant objects, contributing to the development of safer and more efficient autonomous driving solutions.

Background: The breeding of high-quality, high-yield, and disease-resistant varieties is closely related to food security. The investigation of breeding results relies on the evaluation of seed phenotype, which is a key step in the process of breeding. In the global digitalization trend, digital technology based on optical sensors can perform the digitization of seed phenotype in a non-contact, high throughput way, thus significantly improving breeding efficiency. Aim of review: This paper provides a comprehensive overview of the principles, characteristics, data processing methods, and bottlenecks associated with three digital technique types based on optical sensors: spectroscopy, digital imaging, and three-dimensional (3D) reconstruction techniques. In addition, the applicability and adaptability of digital techniques based on the optical sensors of maize seed phenotype traits, namely external visible phenotype (EVP) and internal invisible phenotype (IIP), are investigated. Furthermore, trends in future equipment, platform, phenotype data, and processing algorithms are discussed. This review offers conceptual and practical support for seed phenotype digitization based on optical sensors, which will provide reference and guidance for future research. Key scientific concepts of review: The digital techniques based on optical sensors can perform non-contact and high-throughput seed phenotype evaluation. Due to the distinct characteristics of optical sensors, matching suitable digital techniques according to seed phenotype traits can greatly reduce resource loss, and promote the efficiency of seed evaluation as well as breeding decision-making. Future research in phenotype equipment and platform, phenotype data, and processing algorithms will make digital techniques better meet the demands of seed phenotype evaluation, and promote automatic, integrated, and intelligent evaluation of seed phenotype, further helping to lessen the gap between digital techniques and seed phenotyping.

Abstract Background Acute pulmonary thromboembolism (PTE) is a common cardiovascular disease and recognizing low prognosis risk patients with PTE accurately is significant for clinical treatment. This study evaluated the value of federated learning (FL) technology in PTE prognosis risk assessment while ensuring the security of clinical data. Methods A retrospective dataset consisted of PTE patients from 12 hospitals were collected, and 19 physical indicators of patients were included to train the FL-based prognosis assessment model to predict the 30-day death event. Firstly, multiple machine learning methods based on FL were compared to choose the superior model. And then performance of models trained on the independent (IID) and non-independent identical distributed(Non-IID) datasets was calculated and they were tested further on Real-world data. Besides, the optimal model was compared with pulmonary embolism severity index (PESI), simplified PESI (sPESI), Peking Union Medical College Hospital (PUMCH). Results The area under the receiver operating characteristic curve (AUC) of logistic regression(0.842) outperformed convolutional neural network (0.819) and multi layer perceptron (0.784). Under IID, AUC of model trained using FL(Fed) on the training, validation and test sets was 0.852 ± 0.002, 0.867 ± 0.012 and 0.829 ± 0.004. Under Real-world, AUC of Fed was 0.855 ± 0.005, 0.882 ± 0.003 and 0.835 ± 0.005. Under IID and Real-world, AUC of Fed surpassed centralization model(NonFed) (0.847 ± 0.001, 0.841 ± 0.001 and 0.811 ± 0.001). Under Non-IID, although AUC of Fed (0.846 ± 0.047) outperformed NonFed (0.841 ± 0.001) on validation set, it (0.821 ± 0.016 and 0.799 ± 0.031) slightly lagged behind NonFed (0.847 ± 0.001 and 0.811 ± 0.001) on the training and test sets. In practice, AUC of Fed (0.853, 0.884 and 0.842) outshone PESI (0.812, 0.789 and 0.791), sPESI (0.817, 0.770 and 0.786) and PUMCH(0.848, 0.814 and 0.832) on the training, validation and test sets. Additionally, Fed (0.842) exhibited higher AUC values across test sets compared to those trained directly on the clients (0.758, 0.801, 0.783, 0.741, 0.788). Conclusions In this study, the FL based machine learning model demonstrated commendable efficacy on PTE prognostic risk prediction, rendering it well-suited for deployment in hospitals.

Abstract Background Childbirth is a long-lasting physiological stress. As one of the main stressors, labor pain exists throughout the whole process. Childbirth self-efficacy is the confidence, or belief that they can manage pain during childbirth. This sense of self-efficacy determines how pregnant women deal with labor pain and enables them to regulate their behavior and actively deal with childbirth. However, the difference in pain sensitivity between single births (primiparas) and multiple births (multiparas) has rarely been investigated. Objectives This study is aimed at investigating self-efficacy, fear of childbirth, labor pain of primiparas and multiparas and exploring factors related to the perceived labor pain intensity of pregnant women. Design Prospective cross-sectional study. Setting(s) Labour and delivery in a large academic specialized hospital in Guangzhou, China. Participants A total of 347 women, (182 primiparas and 165 multiparas) were enrolled in the data analysis. Pain was assessed before cervical dilatation (cervical dilatation ≤ 3 cm for the first delivery and ≤ 2 cm for the second delivery). Method The general information of participants was obtained by questionnaire and obstetrical records of the subjects were obtained from the electronic medical records extracted from the electronic medical record system (EMRS). Childbirth self-efficacy, fear of childbirth (FOC) and labor pain were compared between primiparas and multiparas. Paired t-test, chi-square test, Mann–Whitney test, univariate and multivariate regression analysis were used to analyze labor pain between the two groups and investigate factors related perceived labor pain intensity. Results The total scores related to fear of childbirth, fetal health, self-control, and labor pain injury of multiparas were notably reduced compared with primiparas (all P

Three-cycle minimum surface structures show excellent lightweight and energy absorption capabilities, and additive manufacturing techniques provide a unique degree of freedom for lattice structure design. Therefore, in this study, three-period minimum surface (TPMS) structures of Schwarz-P boron steel alloys were prepared by Selective Laser Melting (SLM) technique. By investigating the effect of lattice structure design, we have analyzed the deformation behavior, mechanical properties and energy absorption capacity under compression. In addition, tensile properties and fracture morphology were analyzed to gain insight into the performance characteristics of these structures, and the effect of structural design on hardness was explored. The results of the study show that the structural design has a small effect on the microstructure and hardness. Under compressive loading, the P (0.5 1) structure exhibits a uniform deformation behavior, while the other four structures show a crushing deformation pattern. In particular, the P (0.5 1) structure exhibits excellent compressive performance, with an energy absorption work per unit mass as high as 296.2 J/mm^3, and its stiffness reaches 1627 MPa. Meanwhile, the P (0.35 1) structure exhibits excellent tensile performance with the tensile strength of 687 MPa. The morphological analysis of the tensile fracture reveals that the fracture mainly occurs in the strut nodes, and it mainly exhibits ductile tensile fracture.

Abstract Magnetic Resonance Imaging (MRI) is increasingly being used in treatment planning due to its superior soft tissue contrast, which is useful for tumor and soft tissue delineation compared to computed tomography (CT). However, MRI cannot directly provide mass density or relative stopping power (RSP) maps, which are required for calculating proton radiotherapy doses. Therefore, the integration of artificial intelligence (AI) into MRI-based treatment planning to estimate mass density and RSP directly from MRI has generated significant interest. A deep learning (DL) based framework was developed to establish a voxel-wise correlation between MR images and mass density as well as RSP. To facilitate the study, five tissue substitute phantoms were created, representing different tissues such as skin, muscle, adipose tissue, 45% hydroxyapatite (HA), and spongiosa bone. The composition of these phantoms was based on information from ICRP reports. Additionally, two animal tissue phantoms, simulating pig brain and liver, were prepared for DL training purposes. The phantom study involved the development of two DL models. The first model utilized clinical T1 and T2 MRI scans as input, while the second model incorporated zero echo time (ZTE) MRI scans. In the patient application study, two more DL models were trained: one using T1 and T2 MRI scans as input, and another model incorporating synthetic dual-energy computed tomography (sDECT) images to provide accurate bone tissue information. The DECT empirical model was used as a reference to evaluate the proposed models in both phantom and patient application studies. The DECT empirical model was selected as the reference for evaluating the proposed models in both phantom and patient application studies. In the phantom study, the DL model based on T1, and T2 MRI scans demonstrated higher accuracy in estimating mass density and RSP for skin, muscle, adipose tissue, brain, and liver. The mean absolute percentage errors (MAPE) were 0.42%, 0.14%, 0.19%, 0.78%, and 0.26% for mass density, and 0.30%, 0.11%, 0.16%, 0.61%, and 0.23% for RSP, respectively. The DL model incorporating ZTE MRI further improved the accuracy of mass density and RSP estimation for 45% HA and spongiosa bone, with MAPE values of 0.23% and 0.09% for mass density, and 0.19% and 0.07% for RSP, respectively. These results demonstrate the feasibility of using an MRI-only approach combined with DL methods for mass density and RSP estimation in proton therapy treatment planning. By employing this approach, it is possible to obtain the necessary information for proton radiotherapy directly from MRI scans, eliminating the need for additional imaging modalities.

Inertia friction welding (IFW) is a robust joining technique, particularly for hybrid structures composed of similar or dissimilar alloys. The highly transient thermal responses during friction heating produce variations in heat generation and temperature distribution, which are crucial for designing and controlling the IFW process. This study establishes a finite element (FE) model of the IFW process for dissimilar superalloys and investigates the transition of the interfacial friction regime and its impact on the transient thermal responses. The in-process state variables, including the frictional stress and heat flux, along with their spatial distributions at the welding interface, are obtained through FE simulations. The predicted results indicate that the transient transition of the friction regime produces two Coulomb friction zones accompanied by a shear friction zone. To capture the transient evolution of the friction regime, a novel phenomenological formula is developed. This model accurately predicts the shrinkage and disappearance of the two Coulomb friction zones and the enhancement of the shear friction zone from the initial 0.42 R0–0.87 R0 (where R0 is the workpiece radius) to the entire interface during the IFW process. The variations in interfacial heat flux, frictional stress, and temperature caused by the transition of the friction regime are comprehensively analyzed. Our results reveal that the transition from the Coulomb friction regime to shear friction regime at the interface is beneficial for temperature homogenization at the welding interface. The FE simulation results are validated against published experimental measurements, which confirms the accuracy and reliability of the FE model.

Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a ''cold tumor''-like immune silent microenvironment, allowing the persistence of IRIs. To address this challenge, an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum (CFCP) was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response. Specifically, enhanced sonodynamic therapy (SDT) from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA (dsDNA). Immunogenic dsDNA promoted dendritic cell (DC) maturation through activation of the stimulator of interferon gene (STING) and amplified the immune stimulation of neutrophils via interferon-β (IFN-β). At the same time, enhanced BAA presentation aroused humoral immunity in B and T cells, creating long-term resistance to repetitive infections. Encouragingly, CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.

For the collaborative treatment and resource utilization of an industrial coke oven on municipal solid waste (MSW), this study used MSW to prepare refuse-derived fuel (RDF). The influence of different mix ratio between RDF and coal on coking products was considered, and technical and economic analyses were conducted. The results showed that under the low mixture ratio (3%), the pyrolytic carbon obtained basically met the class III standard of metallurgical carbon. In the experiment of medium mixture ratio (25%, 30%, 35%), the product contained a certain amount of calorific value, lower than that of the metallurgical coke. It might be that the ash content increased, and such product can be used for civil coke or chemical coke. When the mixture ratio was 100%, the calorific value of pyrolysis carbon was 7.53 MJ/kg, representing 25.7% of the calorific value of ordinary coke. The gas production rate of the discharged gas was 0.35, and the calorific value is 14.0 MJ/kg, reaching 73.6% of the coke oven gas. Under the condition of no coal input, the MSW was converted into usable energy. The results demonstrated that coke oven pyrolysis with 100% RDF addition is the most feasible way to recycle resources and energy.

Abstract The miniaturised wideband filter with good frequency selectivity and wide stopband is proposed, which is based on three‐dimensional (3D) heterogeneous integrated passive device technology. The proposed sixth‐order wideband bandpass filter is based on the magnetic‐coupling‐loaded highpass‐lowpass lumped topology and implemented by the 3D heterogeneous integration process, integrating GaAs‐based and Glass‐based micro‐nano‐scale processes together. Then, lumped inductors are designed in the Glass substrate with low dielectric loss tangent and realised by a three‐dimensional spiral structure. Therefore, the inductors have high quality factors and small sizes. The lumped capacitors are designed using the GaAs thin film process. Finally, a prototype with a 3‐dB fractional bandwidth of 42% is designed and fabricated at 3.875 GHz (f0). The upper‐stopband attenuation higher than 30 dB is extended to more than 5.15f0. It occupies only 0.014 × 0.018 λ02 (1.1 × 1.42 mm2), where λ0 is the free‐space wavelength at f0.

Abstract A miniaturised high‐isolation K‐/Ka‐band diplexer with exceeding adjacent channels using 3D antarafacial channel integration and vertical‐quasi‐coaxial‐based matching network is proposed. For smaller size, lower loss and lower channel interference, the high‐order low‐pass filter for the K‐band channel and the four‐line‐interdigital‐coupled wideband bandpass filter for the Ka‐band channel are respectively designed on two low‐loss glass‐based substrates, and these two substrates are integrated on the two antarafacial surface of the mounting board. The vertical‐quasi‐coaxial (VQC) embedded in the mounting board is not only used as three‐dimensional (3D) interconnection of the two antarafacial channels but also designed as the constituent part of the matching/isolation network, and this can effectively decrease the impedance traction caused by the Ka‐band filter for the K‐band channel of the diplexer. In addition, four transmission zeros of the K‐band filter are designed at the whole passband of the Ka‐band channel to improve the isolation to the K‐band channel for guaranteeing the performance of the diplexer at the Ka‐band channel. Furthermore, working principle, design method and test solution of this proposed K‐/Ka‐band diplexer are well illustrated, and the high‐isolation (>40 dB) in very adjacent wideband channels at K‐band (18–23.5 GHz) and Ka‐band (25.8–31.6 GHz) is achieved within a tiny size of 9 × 4 × 0.87 mm.

Abstract Soft-tissue sarcomas (STS) emerges as formidable challenges in clinics due to the complex genetic heterogeneity, high rates of local recurrence and metastasis. Exploring specific targets and biomarkers would benefit the prognosis and treatment of STS. Here, we identified RCC1, a guanine-nucleotide exchange factor for Ran, as an oncogene and a potential intervention target in STS. Bioinformatics analysis indicated that RCC1 is highly expressed and correlated with poor prognosis in STS. Functional studies showed that RCC1 knockdown significantly inhibited the cell cycle transition, proliferation and migration of STS cells in vitro, and the growth of STS xenografts in mice. Mechanistically, we identified Skp2 as a downstream target of RCC1 in STS. Loss of RCC1 substantially diminished Skp2 abundance by compromising its protein stability, resulting in the upregulation of p27Kip1 and G1/S transition arrest. Specifically, RCC1 might facilitate the nucleo-cytoplasmic trafficking of Skp2 via direct interaction. As a result, the cytoplasmic retention of Skp2 would further protect it from ubiquitination and degradation. Notably, recovery of Skp2 expression largely reversed the phenotypes induced by RCC1 knockdown in STS cells. Collectively, this study unveils a novel RCC1-Skp2-p27Kip1 axis in STS oncogenesis, which holds promise for improving prognosis and treatment of this formidable malignancy.

Objective:. Real-world diagnostic and treatment data for pancreatic cancer in China are lacking. As such, the present study investigated the clinical characteristics, diagnosis, and treatment of advanced pancreatic cancer (including locally advanced and metastatic disease) in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database. Methods:. A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database. The entire course of real-world pancreatic cancer management was analyzed. Results:. The proportion of patients with advanced pancreatic cancer was higher among males than females (62.4% vs 37.6%, respectively). Patients typically had a history of hypertension (30.8%), diabetes (21.6%), and cholangitis (20.2%). Abdominal pain (51.6%), abdominal distension (27.1%), jaundice (20.1%), and weight loss (16.3%) were the main symptoms observed in patients with advanced pancreatic cancer in this cohort. Serum carbohydrate antigen (CA)19-9 is one of the most common tumor markers. In the present study, 2562 patients underwent first-line therapy. The median progression-free survival (PFS) for patients undergoing first-line therapy was 4.1 months. The major options for first-line therapy included gemcitabine (GEM) plus S-1 (GS/X) (23.4%), nab-paclitaxel plus GEM (AG) (18.1%), oxaliplatin, irinotecan, and leucovorin-modulated fluorouracil (FOLFIRINOX; 11.9%), nab-paclitaxel plus S-1 (AS) (8.9%), and GEM combined with oxaliplatin/cisplatin (GEMOX/GP) (7.6%). The AS and GS/X regimens were associated with the highest PFS rates. Conclusion:. This is the first study to report multicenter, real-world data regarding advanced pancreatic cancer in China. Results revealed that real-world treatment options differed from guideline recommendations, and PFS was shorter than that in previously reported data. Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

Abstract A new CTOD calculation method is investigated in this study, considering the FPZ and the effective Young’s modulus. The calculated CTOD values from four theoretical models are compared with the measured CTOD values from the three-point beam experiments, and the differences between them are analyzed. The measured CTOD consists of two parts: (1) the displacement generated by the elastic–plastic deformation in the crack tip region, and (2) the displacement generated by micro-damage in the FPZ. CTOD value caused by micro-damage in the FPZ accounts for 81–92% of the overall CTOD. Thus, the FPZ and the effective Young’s modulus are introduced to modify the models for calculating CTOD. The result indicates that the modified plastic zone model is better than the strip-yield model, the plastic zone model and the modified strip-yield model in calculating CTOD, and CTOD error is reduced from 81 to 90% between the plastic zone model and the experiment to 4–34% between the modified plastic zone model and the experiment, with nearly half of the specimens having an error of less than 10%.

The catalytic performance of different acidic catalysts for diethyl oxalate synthesis from the one-step transesterification of dimethyl oxalate and ethanol was evaluated. The effects of different factors (e.g., acidity, electron accepting capacity, cations type and crystalline water) on the catalytic activity of acidic catalysts were investigated respectively. It was proposed and confirmed that the transesterification reaction catalyzed by a Lewis acid (FeCl3) and a Bronsted acid (H2SO4) follows a first-order kinetic reaction process. In addition, the Lewis acid-catalyzed transesterification processes with different ester structures were used to further explore and understand the speculated reaction mechanism. This work enriches the theoretical understanding of acid-catalyzed transesterification reactions and is of great significance for the development of highly active catalysts for diethyl oxalate synthesis, diminishing the industrial production cost of diethyl oxalate, and developing downstream bulk or high-value-added industrial products.

IntroductionPre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients.MethodsThis retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival.ResultsThere were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002).ConclusionImplementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments.

BackgroundIn recent years, the decline in sperm quality in men has become a global trend. There is a close relationship between sperm quality and pregnancy outcome. There is a large body of literature supporting the role of plasma lipidome in male infertility, while the complex mechanisms between them and male infertility are still less clear. Systematic study of the causal relationship between plasma lipidome and MI can help to provide new therapeutic ideas and targets for male infertility.MethodsIn this study, we used a two-sample Mendelian randomization analysis based on Genome-wide association studies pooled data of 179 causal relationships between plasma lipidome and male infertility. We used employed the inverse variance weighted method as the main analysis to assess causality between exposure and outcome, in addition to MR-Egger, Weighted median as complementary methods, and tests for multiplicity and heterogeneity.ResultsWe identified 13 plasma lipidome comprising 4 types of plasma lipidome that were associated with male infertility. Among these, 9 plasma lipidome were found to be protective factors, while 4 were risk factors. Notably, the largest proportion of these plasma lipidome were triglyceride types, with Sphingomyelin (d40:1) exhibiting the strongest association with male infertility.ConclusionThese findings contribute to the current better understanding of male infertility and provide new perspectives on the underlying etiology of male infertility as well as prevention and treatment strategies. In addition, clinical trial validation is needed to assess the potential of these plasma lipidome as biomarkers.

Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria in the pathogenesis and progression of neurological diseases has become increasingly prominent. Mitochondria serve not only as a source of energy, but also as regulators of cellular growth and death. Both oxidative stress and mitophagy are intimately associated with mitochondria, and there is mounting evidence that mitophagy and oxidative stress exert a pivotal regulatory influence on the pathogenesis of neurological diseases. In recent years, there has been a notable rise in the prevalence of cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), and Alzheimer’s disease (AD), which collectively represent a significant public health concern. Reduced levels of mitophagy have been observed in CI/RI, VaD and AD. The improvement of associated pathology has been demonstrated through the increase of mitophagy levels. CI/RI results in cerebral tissue ischemia and hypoxia, which causes oxidative stress, disruption of the blood–brain barrier (BBB) and damage to the cerebral vasculature. The BBB disruption and cerebral vascular injury may induce or exacerbate VaD to some extent. In addition, inadequate cerebral perfusion due to vascular injury or altered function may exacerbate the accumulation of amyloid β (Aβ) thereby contributing to or exacerbating AD pathology. Intravenous tissue plasminogen activator (tPA; alteplase) and endovascular thrombectomy are effective treatments for stroke. However, there is a narrow window of opportunity for the administration of tPA and thrombectomy, which results in a markedly elevated incidence of disability among patients with CI/RI. It is regrettable that there are currently no there are still no specific drugs for VaD and AD. Despite the availability of the U.S. Food and Drug Administration (FDA)-approved clinical first-line drugs for AD, including memantine, donepezil hydrochloride, and galantamine, these agents do not fundamentally block the pathological process of AD. In this paper, we undertake a review of the mechanisms of mitophagy and oxidative stress in neurological disorders, a summary of the clinical trials conducted in recent years, and a proposal for a new strategy for targeted treatment of neurological disorders based on both mitophagy and oxidative stress.

Fatty acid desaturases (FADs) are rate-limiting enzymes for the biosynthesis of highly unsaturated fatty acids (HUFAs). As a new member of the FAD family, Fad6 and its roles remain unclear in various teleost fishes. In this study, we identified a fad6 gene from yellow catfish (ycfad6) and determined its spatiotemporal expression patterns and responses to different initial diets and nutritional status in yellow catfish. Our results showed that the open reading frame (ORF) of ycfad6 was 1,080 bp in length, encoding a protein of 359 amino acids. Multiple protein sequences alignment proved that fad6 is highly conserved among diverse vertebrates. Meanwhile, phylogenetic analysis revealed that Southern catfish and yellow catfish were clustered into one branch, supporting evolutionary consistence between the fad6 gene and fish morphology. Moreover, comparisons of genomic synteny and gene structure revealed functional and evolutionary conservation of the fad6 gene in various teleost fishes. Tissue distribution analysis by quantitative RT-PCR demonstrated that the ycfad6 gene was extensively expressed in examined tissues, with higher transcription levels in the heart and liver. Meanwhile, ycfad6 gene was widely expressed in various developmental stages, indicating Fad6 may play important roles in HUFA biosynthesis at early developmental stages in yellow catfish. Functional experiments verified that the transcription of ycfad6 decreased significantly with the extension of feeding time (with egg yolk or Artemia nauplii) at the early developmental stages, indicating that a diet rich in HUFA can remarkably inhibit the transcription of ycfad6 in yellow catfish. In addition, ycfad6 transcription was significantly reduced after a short-term (24-h) or long-term food deprivation (1-week) and then continued to decrease during refeeding, suggesting that nutritional states can affect the transcription of ycfad6, which further regulates the metabolism of HUFAs. Anyway, these fundamental findings provide basic references for further investigating evolutionary and physiological functions of the fad6 gene in yellow catfish as well as in other teleost fishes.

Cervical cancer ranks fourth in women in terms of incidence and mortality. The RNA-binding protein YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2) contributes to cancer progression by incompletely understood mechanisms. We show how YTHDF2 controls the fate of cervical cancer cells and whether YTHDF2 could be a valid target for the therapy of cervical cancer. Sphere formation and alkaline phosphatase staining assays were performed to evaluate tumor stemness of cervical cancer cells following YTHDF2 knockdown. Apoptosis was detected by flow cytometry and TUNEL assay. The compounds 4PBA and SP600125 were used to investigate the correlation between JNK, endoplasmic reticulum stress, tumor stemness, and apoptosis. Data from The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) revealed that GLI family zinc finger 2 (GLI2) might be the target of YTHDF2. The transcription inhibitor actinomycin D and dual-luciferase reporter gene assays were employed to investigate the association between the GLI2 mRNA and YTHDF2. Nude mouse xenografts were generated to assess the effects of YTHDF2 knockdown on cervical cancer growth in vivo. Knockdown of YTHDF2 up-regulated the expression of GLI2, leading to JNK phosphorylation and endoplasmic reticulum stress. These processes inhibited the proliferation of cervical cancer cells and their tumor cell stemness and promotion of apoptosis. In conclusion, the knockdown of YTHDF2 significantly affects the progression of cervical cancer cells, making it a potential target for treating cervical cancer.

IntroductionPseudomonas aeruginosa is present throughout nature and is a common opportunistic pathogen in the human body. Carbapenem antibiotics are typically utilized as a last resort in the clinical treatment of multidrug-resistant infections caused by P. aeruginosa. The increase in carbapenem-resistant P. aeruginosa poses an immense challenge for the treatment of these infections. Bacteriophages have the potential to be used as antimicrobial agents for treating antibiotic-resistant bacteria.Methods and ResultsIn this study, a new virulent P. aeruginosa phage, Phage_Pae01, was isolated from hospital sewage and shown to have broad-spectrum antibacterial activity against clinical P. aeruginosa isolates (83.6%). These clinical strains included multidrug-resistant P. aeruginosa and carbapenem-resistant P. aeruginosa. Transmission electron microscopy revealed that the phage possessed an icosahedral head of approximately 80 nm and a long tail about 110 m, indicating that it belongs to the Myoviridae family of the order Caudovirales. Biological characteristic analysis revealed that Phage_Pae01 could maintain stable activity in the temperature range of 4~ 60°C and pH range of 4 ~ 10. According to the in vitro lysis kinetics of the phage, Phage_Pae01 demonstrated strong antibacterial activity. The optimal multiplicity of infection was 0.01. The genome of Phage_Pae01 has a total length of 93,182 bp and contains 176 open reading frames (ORFs). The phage genome does not contain genes related to virulence or antibiotic resistance. In addition, Phage_Pae01 effectively prevented the formation of biofilms and eliminated established biofilms. When Phage_Pae01 was combined with gentamicin, it significantly disrupted established P. aeruginosa biofilms.ConclusionWe identified a novel P. aeruginosa phage and demonstrated its effective antimicrobial properties against P. aeruginosa in both the floating and biofilm states. These findings offer a promising approach for the treatment of drug-resistant bacterial infections in clinical settings.

Abstract The photoreceptor cilium is vital for maintaining the structure and function of the retina. However, the molecular mechanisms underlying the photoreceptor cilium integrity and retinal homeostasis are largely unknown. Herein, it is shown that kinesin family member 11 (KIF11) localizes at the transition zone (connecting cilium) of the photoreceptor and plays a crucial role in orchestrating the cilium integrity. KIF11 depletion causes malformations of both the photoreceptor ciliary axoneme and membranous discs, resulting in photoreceptor degeneration and the accumulation of drusen‐like deposits throughout the retina. Mechanistic studies show that the stability of KIF11 is regulated by an interplay between its UFMylation and ubiquitination; UFMylation of KIF11 at lysine 953 inhibits its ubiquitination by synoviolin 1 and thereby prevents its proteasomal degradation. The lysine 953‐to‐arginine mutant of KIF11 is more stable than wild‐type KIF11 and also more effective in reversing the ciliary and retinal defects induced by KIF11 depletion. These findings identify a critical role for KIF11 UFMylation in the maintenance of photoreceptor cilium integrity and retinal homeostasis.

Scrophularia ningpoensis Hemsl. (SN) is an herbal medicine used as a functional food in China. SN has traditionally been used to treat diabetes mellitus (DM), but its mechanism of action is not well understood. Our previous study indicated that the aqueous extract of SN can reduce hepatic insulin resistance and correct the irregular shape of pancreatic islets in diabetic mice. This study aims to investigate whether the aqueous extract of SN can regulate pyroptosis in pancreatic β-cells and explore its underlying mechanisms. Db/db mice were orally given an aqueous extract of SN for eight weeks. Subsequently, their pancreatic tissues were collected for histopathological analysis and immunoblotting. Rat insulinoma (INS-1) cells were cultured either alone or with the aqueous extract of SN and evaluated for cell viability, pyroptotic body formation, AMP-activated protein kinase (AMPK) activity, the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome and gasdermin D (GSDMD) activation, and reactive oxygen species (ROS) production under high glucose (HG) exposure conditions. The aqueous extract of SN reduced insulitis and pancreatic β-cell death in db/db mice. Increased AMPK phosphorylation and decreased NLRP3 inflammasome and GSDMD activation were observed in pancreatic tissues after administration of the aqueous extract of SN. In vitro, the aqueous extract of SN increased cell viability and AMPK phosphorylation in a concentration-dependent manner. Additionally, the aqueous extract of SN corrected excessive ROS generation, NLRP3 inflammasome and GSDMD activation, and pyroptotic body formation. Inhibition of AMPK negated these beneficial effects of the aqueous extract of SN on INS-1 cells. The study concluded that the aqueous extract of SN alleviates β-cell pyroptosis by inhibiting NLRP3/GSDMD activation in an AMPK-dependent manner.

Abstract Introduction Fatigue is a common symptom that negatively affects the outcomes and functions of rheumatoid arthritis (RA) patients. This study aimed to assess the fatigue by two scales and validate their consistency, also to comprehensively evaluate fatigue‐related risk factors in RA patients. Methods In this case–control study, the fatigue of 160 RA patients and 60 healthy controls was evaluated by the Bristol Rheumatoid Arthritis Fatigue Multi‐Dimensional Questionnaire (BRAF‐MDQ) and the Chinese version of the Brief Fatigue Inventory (BFI‐C). The 28‐joint disease activity score using erythrocyte sedimentation rate of RA patients was assessed. Results The BRAF‐MDQ and BFI‐C scores were elevated in RA patients versus healthy controls (all p

Abstract Objective To investigate the prognostic factors of patients with anti‐melanoma differentiation‐associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and interstitial lung disease (ILD). Methods A retrospective analysis was conducted on clinical data of 125 patients with anti‐MDA5 + CADM‐ILD collected from 10 branches in eastern China between December 2014 and December 2022. Prognostic factors were analyzed using χ2 test, Log‐rank test, COX and logistic regression analysis. Results In this cohort, 125 anti‐MDA5 + CADM‐ILD patients exhibited a rapidly progressive interstitial lung disease (RPILD) incidence of 37.6%, and an overall mortality rate of 24.8%. One patient was lost to follow‐up. After diagnosis of RPILD, a mortality rate of 53.2% occurred in patients died within 3 months, and that of 5.6% appeared in those who survived for more than 3 months. Multiple factor analysis revealed that C‐reactive protein (CRP) ≥ 10 mg/L (p = 0.01) and recombinant human tripartite motif containing 21 (Ro52) (+) (p = 0.003) were associated with a higher risk of RPILD in anti‐MDA5 + CADM‐ILD patients; CRP ≥ 10 mg/L (p = 0.018) and the presence of RPILD (p = 0.003) were identified as the factors influencing survival time in these patients, while arthritis was the protective factor (p = 0.016). Conclusion Patients with anti‐MDA5 + CADM‐ILD will have a higher mortality rate, and the initial 3 months after diagnosis of RPILD is considered the risk window for the dismal prognosis. Patients with CRP ≥ 10 mg/L, Ro52 (+) and RPILD may be related to a shorter survival time, while patients complicated with arthritis may present with relatively mild conditions.

BackgroundOsteoking has been extensively used for the treatment of knee osteoarthritis (KOA). However, it is lack of high-quality evidence on the clinical efficacy of Osteoking against KOA and the comparison with that of nonsteroidal anti-inflammatory drugs (NSAIDs).AimsTo evaluate the efficacy and safety of Osteoking in treating KOA.MethodsIn the current study, a total of 501 subjects were recruited from 20 medical centers, and were divided into the Osteoking treatment group (n = 428) and the NSAIDs treatment group (n = 73). The Propensity Score Matching method was used to balance baseline data of different groups. Then, the therapeutic effects of Osteoking and NSAIDs against KOA were evaluated using VAS score, WOMAC score, EQ-5D-3L and EQ-VAS, while the safety of the two treatment were both assessed based on dry mouth, dizziness, diarrhea, etc.ResultsAfter 8 weeks of treatment, the Osteoking group was compared with the NSAIDs group, the VAS score [2.00 (1.00, 3.00) vs. 3.00 (2.00, 4.00)], WOMAC pain score [10.00 (8.00, 13.00) vs. 11.00 (8.00, 16.00) ], WOMAC physical function score [32.00 (23.00, 39.00) vs. 39.07 ± 16.45], WOMAC total score [44.00 (31.00, 55.00) vs. 53.31 ± 22.47) ], EQ-5D-3L score [0.91 (0.73, 0.91) vs. 0.73 (0.63, 0.83) ] and EQ-VAS score [80.00 (79.00, 90.00) vs. 80.00 (70.00, 84.00) ] were improved by the treatment of Osteoking for 8 weeks more effectively than that by the treatment of NSAIDs. After 8 weeks of treatment with Osteoking, the VAS scores of KOA patients with the treatment of Osteoking for 8 weeks were reduced from 6.00 (5.00, 7.00) to 2.00 (1.00, 3.00) (p < 0.05), which was better than those with the treatment of NSAIDs starting from 2 weeks during this clinical observation. Importantly, further subgroup analysis revealed that the treatment of Osteoking was more suitable for alleviating various clinical symptoms of KOA patients over 65 years old, with female, KL II-III grade and VAS 4-7 scores, while the clinical efficacy of NSAIDs was better in KOA patients under 65 years old and with VAS 8–10 scores. Of note, there were no differences in adverse events and adverse reactions between the treatment groups of the two drugs.ConclusionOsteoking may exert a satisfying efficacy in relieving joint pain and improving life quality of KOA patients without any adverse reactions, especially for patients with KL II-III grades and VAS 4–7 scores.Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=55387, Identifier ChiCTR2000034475

This study assesses the morphological effectiveness of benign prostatic hyperplasia (BPH) surgery using multislice spiral computed tomography three-dimensional imaging (CT3D) with urethral contrast. Twenty-five male patients with BPH and bladder outlet obstruction (BOO) who underwent bipolar transurethral resection of the prostate were selected. Preoperative and postoperative CT3D indicators of retrograde and voiding cystourethrography, including bladder neck diameter, length of the posterior urethra, and degree of prostate protrusion into the bladder and upper and lower diameter of the prostate were used to assess bladder neck and posterior urethra morphology and BOO severity. In addition, preoperative and postoperative International Prostate Symptom Scores and maximum urine flow rates were compared. Postoperative CT3D was used to evaluate changes following obstruction relief postsurgery. Preoperative CT3D indicated significant BOO, whereas postoperative imaging showed improved patency but with irregular posterior urethral lumens and varying degrees of residual glandular tissue. Comparative analysis of preoperative and postoperative bladder outlet metrics revealed significant changes ( p < 0.05). Urethral contrast CT3D effectively visualizes the prostate, bladder neck, and prostatic urethra. It quantifies changes in the urethral lumen postsurgery, correlating the extent of posterior urethral lumen spaciousness with urinary flow rates.

The exponential growth of China’s economy, coupled with the surge in online commerce, has led to a significant expansion of the logistics industry. In 2022, China’s express delivery industry generated approximately 9 million tons of waste paper and 1.8 million tons of plastic. This study analyzed the current composition and utilization of logistics waste in China, with suggestions for recycling. Logistics waste can be defined as the packaging waste generated in the logistics industry. Corrugated paper and plastic waste were chosen as the objects for utilization. Due to its high cellulose content, corrugated paper can be utilized along with other paper waste for biomass resourcing. Biodegradable plastics can also be converted into biomass resources through the action of specific microorganisms. These polymers can be enzymatically depolymerized by certain bacteria and fungi, yielding valuable organic products. In general, logistics wastes all have potential for biomass resource recovery. By adopting appropriate recovery and conversion technologies, these waste streams can be transformed into high-value bio-based products, such as biofuels, biochemicals, and biopolymers, thus contributing to the development of a circular and sustainable economy.

Abstract Multiple structural phases of tellurium (Te) have opened up various opportunities for the development of two-dimensional (2D) electronics and optoelectronics. However, the phase-engineered synthesis of 2D Te at the atomic level remains a substantial challenge. Herein, we design an atomic cluster density and interface-guided multiple control strategy for phase- and thickness-controlled synthesis of α-Te nanosheets and β-Te nanoribbons (from monolayer to tens of μm) on WS2 substrates. As the thickness decreases, the α-Te nanosheets exhibit a transition from metallic to n-type semiconducting properties. On the other hand, the β-Te nanoribbons remain p-type semiconductors with an ON-state current density (ION) up to ~ 1527 μA μm−1 and a mobility as high as ~ 690.7 cm2 V−1 s−1 at room temperature. Both Te phases exhibit good air stability after several months. Furthermore, short-channel (down to 46 nm) β-Te nanoribbon transistors exhibit remarkable electrical properties (ION = ~ 1270 μA μm−1 and ON-state resistance down to 0.63 kΩ μm) at Vds = 1 V.

Abstract Memory CD8+ T cell generation is crucial for pathogen elimination and effective vaccination against infection. The cellular and molecular circuitry that underlies the generation of memory CD8+ T cells remains elusive. Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense. Here we report that eosinophils are required for the generation of memory CD8+ T cells by inhibiting CD8+ T cell apoptosis. Eosinophil-deficient mice display significantly impaired memory CD8+ T cell response and weakened resistance against Listeria monocytogenes (L.m.) infection. Mechanistically, eosinophils secrete interleukin-4 (IL-4) to inhibit JNK/Caspase-3 dependent apoptosis of CD8+ T cells upon L.m. infection in vitro. Furthermore, active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+ T cell apoptosis during early stage of L.m. infection in vivo. Adoptive transfer of wild-type (WT) eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+ T cell memory responses. Together, our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+ T cell memory and enhances immune defense against L.m. infection. Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

Abstract Tamoxifen (TAM) is the frontline therapy for estrogen receptor-positive (ER+) breast cancer in premenopausal women that interrupts ER signaling. As tumors with elevated heterogeneity, amounts of ER-negative (ER−) cells are present in ER+ breast cancer that cannot be directly killed by TAM. Despite complete remissions have been achieved in clinical practice, the mechanism underlying the elimination of ER− cells during TAM treatment remains an open issue. Herein, we deciphered the elimination of ER− cells in TAM treatment from the perspective of the bystander effect. Markable reductions were observed in tumorigenesis of ER− breast cancer cells by applying both supernatants from TAM-treated ER+ cells and a transwell co-culture system, validating the presence of a TAM-induced bystander effect. The major antitumor protein derived from ER+ cells, peptidyl-prolyl cis-trans isomerase B (PPIB), is the mediator of the TAM-induced bystander effect identified by quantitative proteomics. The attenuation of ER− cells was attributed to activated BiP/eIF2α/CHOP axis and promoted endoplasmic reticulum stress (ERS)-induced apoptosis, which can also be triggered by PPIB independently. Altogether, our study revealed a novel TAM-induced bystander effect in TAM treatment of ER+ breast cancer, raising the possibility of developing PPIB as a synergistic antitumor agent or even substitute endocrine therapy.

Abstract Tuberous sclerosis complex 1 (TSC1) plays important roles in regulating innate immunity. However, the precise role of TSC1 in macrophages in the regulation of oxidative stress response and hepatic inflammation in liver ischemia/reperfusion injury (I/R) remains unknown. In a mouse model of liver I/R injury, deletion of myeloid-specific TSC1 inhibited AKT and MST1 phosphorylation, and decreased NRF2 accumulation, whereas activated TLR4/NF-κB pathway, leading to increased hepatic inflammation. Adoptive transfer of AKT- or MST1-overexpressing macrophages, or Keap1 disruption in myeloid-specific TSC1-knockout mice promoted NRF2 activation but reduced TLR4 activity and mitigated I/R-induced liver inflammation. Mechanistically, TSC1 in macrophages promoted AKT and MST1 phosphorylation, and protected NRF2 from Keap1-mediated ubiquitination. Furthermore, overexpression AKT or MST1 in TSC1-knockout macrophages upregulated NRF2 expression, downregulated TLR4/NF-κB, resulting in reduced inflammatory factors, ROS and inflammatory cytokine-mediated hepatocyte apoptosis. Strikingly, TSC1 induction in NRF2-deficient macrophages failed to reverse the TLR4/NF-κB activity and production of pro-inflammatory factors. Conclusions: Macrophage TSC1 promoted the activation of the AKT/MST1 signaling pathway, increased NRF2 levels via reducing Keap1-mediated ubiquitination, and modulated oxidative stress-driven inflammatory responses in liver I/R injury. Our findings underscore the critical role of macrophage TSC1 as a novel regulator of innate immunity and imply the therapeutic potential for the treatment of sterile liver inflammation in transplant recipients. Schematic illustration of macrophage TSC1-mediated AKT/MST1/NRF2 signaling pathway in I/R-triggered liver inflammation. Macrophage TSC1 can be activated in I/R-stressed livers. TSC1 activation promotes phosphorylation of AKT and MST1, which in turn increases NRF2 expression and inhibits ROS production and TLR4/NF-κB activation, resulting in reduced hepatocellular apoptosis in I/R-triggered liver injury.

Genomic selection (GS) has been widely used in livestock, which greatly accelerated the genetic progress of complex traits. The population size was one of the significant factors affecting the prediction accuracy, while it was limited by the purebred population. Compared to directly combining two uncorrelated purebred populations to extend the reference population size, it might be more meaningful to incorporate the correlated crossbreds into reference population for genomic prediction. In this study, we simulated purebred offspring (PAS and PBS) and crossbred offspring (CAB) base on real genotype data of two base purebred populations (PA and PB), to evaluate the performance of genomic selection on purebred while incorporating crossbred information. The results showed that selecting key crossbred individuals via maximizing the expected genetic relationship (REL) was better than the other methods (individuals closet or farthest to the purebred population, CP/FP) in term of the prediction accuracy. Furthermore, the prediction accuracy of reference populations combining PA and CAB was significantly better only based on PA, which was similar to combine PA and PAS. Moreover, the rank correlation between the multiple of the increased relationship (MIR) and reliability improvement was 0.60–0.70. But for individuals with low correlation (Cor(Pi, PA or B), the reliability improvement was significantly lower than other individuals. Our findings suggested that incorporating crossbred into purebred population could improve the performance of genetic prediction compared with using the purebred population only. The genetic relationship between purebred and crossbred population is a key factor determining the increased reliability while incorporating crossbred population in the genomic prediction on pure bred individuals.

Abstract Morphing attacks (MAs) pose a substantial security threat to the Automatic Border Control (ABC) system. While a few morphing attack detection (MAD) methods have been proposed, the face morphing accomplice's facial restoration has not received sufficient attention. Due to the inability to foresee the morphing factor used for a particular morphed image, selecting the appropriate de‐morphing factor becomes a challenging problem in the restoration of the accomplice's facial image. If the morphing factor cannot be chosen reasonably, achieving the desired restoration effect is difficult. Therefore, this paper presents an adaptive de‐morphing factor framework (ADFF) architecture for restoring the accomplice's facial image. By exploiting the morphed images stored in the electronic passport system and the real‐time captured criminal's images, ADFF can effectively restore the accomplice's facial image. Experimental results and analysis show that ADFF can significantly reduce the security threats of MAs on ABC.