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Abstract Objective The early differentiation of adrenal lipid-poor adenomas from non-adenomas is a crucial step in reducing excessive examinations and treatments. This study seeks to construct an eXtreme Gradient Boosting (XGBoost) predictive model utilizing the minimum attenuation values (minAVs) from non-contrast CT (NCCT) scans to identify lipid-poor adenomas. Materials and methods Retrospective analysis encompassed clinical data, minAVs, CT histogram (CTh), mean attenuation values (meanAVs), and lesion diameter from patients with pathologically or clinically confirmed adrenal lipid-poor adenomas across two medical institutions, juxtaposed with non-adenomas. Variable selection transpired in Institution A (training set), with XGBoost models established based on minAVs and CTh separately. Institution B (validation set) corroborated the diagnostic efficacy of the two models. Receiver operator characteristic (ROC) curve analysis, calibration curves, and Brier scores assessed the diagnostic performance and calibration of the models, with the Delong test gauging differences in the area under the curve (AUC) between models. SHapley Additive exPlanations (SHAP) values elucidated and visualized the models. Results The training set comprised 136 adrenal lipid-poor adenomas and 126 non-adenomas, while the validation set included 46 and 40 instances, respectively. In the training set, there were substantial inter-group differences in minAVs, CTh, meanAVs, diameter, and body mass index (BMI) (p 0.05 for both). SHAP value analysis for the minAV model suggested that minAVs had the highest absolute weight (AW) and negative contribution. Conclusion The XGBoost predictive model based on minAVs demonstrates effective discrimination between adrenal lipid-poor adenomas and non-adenomas. The minAV variable is easily obtainable, and its diagnostic performance is comparable to that of the CTh model. This provides a basis for patient diagnosis and treatment plan selection.

Abstract Background β-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the β-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation. Results In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of β-catenin. Our analysis showed that a truncated β-catenin lacking both N- and C-terminal domains (ΔN148C) could robustly rescue the DE formation, whereas hyperactive β-catenin mutants with S33Y mutation or N-terminal deletion (ΔN90) had limited ability to induce DE lineage. Notably, the ΔN148C mutant exhibited significant nuclear translocation that was positively correlated with successful DE rescue. Transcriptomic analysis further uncovered that two weak β-catenin mutants lacking the C-terminal transactivation domain (CTD) activated primitive streak (PS) genes, whereas the hyperactive β-catenin mutants activated mesoderm genes. Conclusion Our study uncovered an unconventional regulatory function of β-catenin through weak transactivation, indicating that the levels of β-catenin activity determine the lineage bifurcation from mesendoderm into endoderm and mesoderm.

Abstract We generalize Integration-By-Parts (IBP) and differential equations methods to de Sitter correlators related to inflation. While massive correlators in de Sitter spacetime are usually regarded as highly intricate, we find they have remarkably hidden concise structures from the perspective of IBP. We find the factorization of the IBP relations of each vertex integral family corresponding to dτ i integration. Furthermore, with a smart construction of master integrals, the universal formulas for iterative reduction and d log-form differential equations of arbitrary vertex integral family are presented and proved. These formulas dominate all tree-level de Sitter correlators and play a kernel role at the loop-level as well.

Abstract Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic synapses in medial prefrontal cortic (mFPC) neurons. Ketamine induced profound changes in a number of molecular pathways in a mouse model for chronic stress. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling was decreased after chronic administration of corticosterone but increased following ketamine administration in most of the excitatory neurons. Similar decrease of PCP signaling in excitatory neurons was predicted in dorsolateral prefrontal cortical (dl-PFC) neurons of patients with major depressive disorder (MDD). We showed that the basolateral amygdala (BLA)-projecting infralimbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Conditionally knocking out Celsr2 and Celsr3 or Prickle2 in the BLA-projecting IL PFC neurons abolished ketamine-induced synapse restoration and behavioral remission. Therefore, PCP proteins in IL PFC-BLA neurons mediate synapse restoration induced by of low-dose ketamine.

Abstract Nuclear factor erythroid 2-related factor 2 (NRF2) hyperactivation has been established as an oncogenic driver in a variety of human cancers, including non-small cell lung cancer (NSCLC). However, despite massive efforts, no specific therapy is currently available to target NRF2 hyperactivation. Here, we identify peptidylprolyl isomerase A (PPIA) is required for NRF2 protein stability. Ablation of PPIA promotes NRF2 protein degradation and blocks NRF2-driven growth in NSCLC cells. Mechanistically, PPIA physically binds to NRF2 and blocks the access of ubiquitin/Kelch Like ECH Associated Protein 1 (KEAP1) to NRF2, thus preventing ubiquitin-mediated degradation. Our X-ray co-crystal structure reveals that PPIA directly interacts with a NRF2 interdomain linker via a trans-proline 174-harboring hydrophobic sequence. We further demonstrate that an FDA-approved drug, cyclosporin A (CsA), impairs the interaction of NRF2 with PPIA, inducing NRF2 ubiquitination and degradation. Interestingly, CsA interrupts glutamine metabolism mediated by the NRF2/KLF5/SLC1A5 pathway, consequently suppressing the growth of NRF2-hyperactivated NSCLC cells. CsA and a glutaminase inhibitor combination therapy significantly retard tumor progression in NSCLC patient-derived xenograft (PDX) models with NRF2 hyperactivation. Our study demonstrates that targeting NRF2 protein stability is an actionable therapeutic approach to treat NRF2-hyperactivated NSCLC.

Objective In well-trapped hydrothermal geothermal reservoirs, the research on injecting CO2 into reservoirs simultaneously with recharge water is carried out, which has both economic and environmental benefits for carbon sequestration. Methods A 3D reservoir model was established to study the CO2 breakthrough time and the migration of CO2-rich brine in a reservoir under different well spacings, formation inclination angles, sieve tube positions and exploitation and reinjection rates. Results The results show that (1) when the exploitation and reinjection rate is 20 kg/s and the well spacing is 1 200 m within 20 years of operation, there is no CO2 breakthrough. (2) In inclined formations, when the recharge well is located downstream of the production well, as the formation inclination angle increases, the CO2 breakthrough time increases, and the migration distance of carbonated water increases along the downdip direction of the formation. (3) Considering the impact of the screen position on the breakthrough time and CO2 mass fraction in the production well after breakthrough, it is beneficial to ensure the safety and effectiveness of CO2 geological storage when the recharge well sieve tube is located 30 m above the reservoir and the production well sieve is located 30 m below the reservoir. (4) The exploitation and reinjection rates have greater impacts on the CO2 breakthrough time. When the exploitation and reinjection rate is 12 kg/s, there is no CO2 breakthrough. When the exploitation and reinjection rate increases to 28 kg/s, the breakthrough time decreases to 11.8 years. Conclusion Therefore, in practical engineering applications, the CO2 breakthrough time can be delayed, and the safety of CO2 geological storage can be improved through the study of operating parameters and the inherent characteristics of the formation.

Abstract Background Mechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces hepatocyte pyroptosis by regulating mitochondrial dysfunction in AH. Results Liver damage in AH mice was assessed by HE staining, serum levels of AST, ALT, TC, and TG. The levels of IL-1β, IL-18, LDH, inflammasome-associated proteins and hepatocyte death were assessed to determine pyroptosis. Mitochondrial dysfunction was assessed through various parameters including mitochondrial DNA (mtDNA) levels, ROS generation, mitochondrial membrane potential, ATP contents, levels of mitochondrial function-related proteins and morphological changes of mitochondria. AH induced gasdermin D (GSDMD) activation, leading to increased protein expression of N-terminal GSDMD (GSDMD-N), NLRP3, and Caspase 11 in liver tissues. Downregulation of GSDMD alleviated alcohol-induced hepatocyte pyroptosis. Alcohol also causes mitochondrial dysfunction in hepatocytes in AH, which was improved by inhibiting GSDMD. Furthermore, enhancing mitochondrial function suppressed alcohol-induced hepatocyte pyroptosis. Further, knockdown of GSDMD or dynamin-related protein 1 (Drp1) improved AH-induced liver injury, accompanied by a decrease in hepatocyte pyroptosis. Conclusion GSDMD induces hepatocyte pyroptosis by modulating mitochondrial dysfunction during AH-induced inflammation and liver injury. These findings may pave the way to develop new therapeutic treatments for AH.

Abstract Reducing the silver film to 10 nm theoretically allows higher transparency but in practice leads to degraded transparency and electrical conductivity because the ultrathin film tends to be discontinuous. Herein, we developed a thinning-back process to address this dilemma, in which silver film is first deposited to a larger thickness with high continuity and then thinned back to a reduced thickness with an ultrasmooth surface, both implemented by a flood ion beam. Contributed by the shallow implantation of silver atoms into the substrate during deposition, the thinness of silver films down to 4.5 nm can be obtained, thinner than ever before. The atomic-level surface smooth permits excellent visible transparency, electrical conductivity, and the lowest haze among all existing transparent conductors. Moreover, the ultrathin silver film exhibits the unique robustness of mechanical flexibility. Therefore, the ion-beam thinning-back process presents a promising solution towards the excellent transparent conductor for flexible optoelectronic devices.

The preparation of Al/Mg/Al laminated metal composites (LMCs) by lamination technique can well combine the good corrosion resistance of Al alloy and the lightweight characteristics of Mg alloy. In this paper, the atmospheric corrosion behavior and underlying mechanism of 6082/AZ31/6082 LMCs with and without side exposure for one year of filed exposure to the tropical marine atmospheric environment were investigated. The results showed that the corrosion rates of AZ31 and 6082 and LMC-C were 55.967, 1.167, and 0.925 g m−2·a−1, respectively. The microstructure of the Al layer on the surface of LMCs underwent a significant transformation, characterized by a noticeable grain refinement and a concomitant increase in dislocation density. Moreover, the potential disparity between the second phase (AlMnFeSi and Mg2Si) and the matrix was diminished. These findings collectively contribute to the enhanced resistance of 6082/AZ31/6082 LMCs to intergranular corrosion and pitting corrosion. However, the accelerated dissolution of the intermediate Mg layer, facilitated by the galvanic corrosion effect during field exposure of the LMCs, resulted in a 4.5-fold increase in corrosion-induced mass loss. Notably, the ultimate tensile strength of the LMCs exhibited insensitivity to field exposure duration, while their plasticity underwent a gradual decline. This comprehensive study elucidates the corrosion behavior and underlying mechanisms of 6082/AZ31/6082 LMCs subjected to a tropical marine atmospheric environment, providing valuable insights for the rational design and development of LMCs with enhanced comprehensive performance.

In order to develop a method that apply sampling survey data randomly obtained at fishing ports to fish stock assessments, based on fish landing surveys conducted at fishing ports in the northern South China Sea (SCS), 19 Threadfin porgy (Evynnis cardinalis) catch per unit effort (CPUE) datasets were collected for fishing vessels with different gear types and engine powers and incorporated into surplus production models. Considering only the fitting performance, the Schaefer model had the best overall goodness of fit, followed by the Fox, CYP, W–H, and Schnute models. Among fishing vessels with different gears and engine powers, the data were best fitted for single-trawl vessels powered by 301–400-kW engines and for gillnet vessels powered by > 200-kW engines. Eight model expressions were superior and selected for subsequent analyses based on their goodness of fit and relative residuals. The Kobe plot analysis results showed an optimistic fish stock status when using the four model expressions, required more caution when using three model expressions and output pessimistic estimations using one model expression. Considering the incomplete information acquired, a compromising decision-making method was used to derive a 2017 northern SCS E. cardinalis total allowed catch (TAC) of 44,691.21 t. The different conclusions drawn from estimations using CPUEs reflect variable exploitation and utilization fish stock statuses among fishing vessels with different gears and engine powers. Hence, the fishing operations were grouped according to their CPUE relationship, and recommendations regarding optimum fishing efforts were assigned to the groups following a fundamental principle: to improve fishery TAC management, fishing efforts should be reduced if the fish stock assessment is pessimistic and maintained if the assessment is optimistic. This study providing a feasible technical method for the TAC management of China's offshore fisheries.

The study utilizes a multi-directional compression (MDC) process on a basal-textured ZK60 alloy with the aim of inducing extensive twinning, which is followed by an aging treatment on the pre-deformed sample. The mechanical response and corrosion behavior of the deformed and aged samples are systematically investigated. The MDC process effectively generates numerous {10 1‾ 2} twins with increased compression passes, resulting in the enhanced grain refinement. The interplay between twins and numerous dislocations formed during pre-deformation plays a crucial role in altering both the distribution and morphology of the second phase precipitated during aging. During the aging process, the alloy exhibits a higher concentration of dense rod-like β′ phase and disk-like β″ phase. Remarkably, the compressive yield strength and ultimate strength of aged ZK60 alloy along the rolling direction are significantly improved without obvious compromise of ductility by pre-compression. Notably, the yield strength of the sample after 12-passes compression and aging (APD-12) is approximately 45 % higher than that of the sample without pre-compression (APD-0). Furthermore, the corrosion resistance of ZK60 alloy displays notable improvement upon pre-compression treatment. Specifically, the hydrogen evolution in the APD-12 sample is halved compared to the APD-0 sample. Electrochemical assessments were conducted on both pre-compressed and non-pre-compressed samples, revealing their distinct behaviors. Furthermore, an in-depth exploration has also been undertaken into the underlying mechanisms contributing to the enhancement of mechanical properties and corrosion resistance resulting from the pre-compression.

Objectives: Sarcopenia has a detrimental impact on the prognosis of individuals with liver cirrhosis, however, the clinical significance of alterations in muscle mass remains uncertain. This study aims to investigate the influence of loss of skeletal muscle mass (LSMM) on the prognostic outcomes among patients diagnosed with cirrhosis. Methods: In this retrospective analysis, a total of 158 individuals with cirrhosis who visited our hospital during the period from January 2018 to August 2023 were included. Computed tomography was utilized to measure the cross-sectional area of the skeletal muscles at the level of the third lumbar vertebra. This measurement enabled the determination of the skeletal muscle index for the purpose of diagnosing sarcopenia. The annual relative change in skeletal muscle area (ΔSMA/y) was calculated for each patient, and LSMM was defined as ΔSMA/y

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is an important manifestation and mechanism of pulmonary vascular remodeling. Resolvin D1 (RvD1) is an endogenous lipid mediator promoting the resolution of inflammation. However, the role of RvD1 on EndMT in PH remains unknown. Here, we aimed to investigate the effect and mechanisms of RvD1 on the treatment of PH. We showed that RvD1 and its receptor FPR2 expression were markedly decreased in PH patients and both chronic hypoxia-induced PH (CH-PH) and sugen 5416/hypoxia-induced PH (SuHx-PH) mice models. RvD1 treatment decreased right ventricular systolic pressure (RVSP) and alleviated right ventricular function, and reduced pulmonary vascular remodeling and collagen deposition in the perivascular of both two PH mice models. Then, RvD1 inhibited EndMT in both the lungs of PH mice models and primary cultured human umbilical vein endothelial cells (HUVECs) treated with TGF-β and IL-1β. Moreover, RvD1 inhibited EndMT by downregulating Smad2/3 phosphorylation in vivo and in vitro via FPR2. In conclusion, our date suggest that RvD1/FPR2 axis prevent experimental PH by inhibiting endothelial-mensenchymal-transition and may be a therapeutic target for PH.

With a growing focus on the environment, the power system is evolving into a cleaner and more efficient energy supply infrastructure. Photovoltaic (PV) and storage are key assets for the power industry’s shift to sustainable energy. PV generation has zero carbon emission, and the integration of a substantial number of PV units is fundamentally important to decarbonize the power system. However, it also poses challenges in terms of voltage stability and uncertainty. Besides, the daily load and real-time price are also uncertain. As a prosumer, energy storage demonstrates the capacity to enhance accommodation and stability. The adoption of Virtual Power Plants (VPPs) emerges as a promising strategy to address these challenges, which allows the coordinated orchestration of PV systems and storage to participate power dispatch as a virtual unit. It further augments the flexibility of the power distribution system (PDS). To maximize the profit of VPP, a data-driven price forecasting method is proposed to extract useful information from historical datasets based on a novel LSTM-Transformer-combined neural network. Then, an improved sparrow searching algorithm (SSA) is proposed to schedule VPPs by combining the secant line search strategy. The numerical results, obtained from testing the model on IEEE 13-node and 141-node distribution systems, demonstrate the effectiveness and efficiency of the proposed model and methodology.

To understand how many kinds of mRNAs in female adults can be transferred into the eggs and the molecular basis of embryonic axis specification in Sogatella furcifera, we performed de novo transcriptome sequencing of six cDNA libraries of female adults and unfertilized eggs. Total 60,306 unigenes were obtained, with an average length of 1114.51 bp and N50 length of 2112 bp. Total 2900 differentially expressed genes with 496 upregulated and 2404 downregulated were found in unfertilized egg compared to female adult. Most of mRNAs in female adult could be passed into its eggs. Total 65 maternal effect genes were identified, including many homologous genes involved in embryonic axis specialization of D. melanogaster. This study provide transcriptome resources to elucidate the functions of maternal effect genes and the molecular basis of embryonic axis specification in S. furcifera in the future.

Abstract The thermal properties of major minerals play a key role in understanding the internal dynamic mechanism and thermal evolution of the Earth and rocky planets. In this study, we first investigated the effect of Fe on the thermal conductivity (κ) and the thermal diffusivity (D) of orthopyroxene at 1–3 GPa and 293–873 K by the transient plane source method. The κ and D both decrease with increasing temperature and decreasing pressure. With increasing Fe content, the two parameters both quickly decrease from the beginning and then slack off. We further modeled the thermal evolution of S‐type asteroids, which strongly depends on the composition model and the dimension of the planet. Combining the present data with surface heat flow and heat production, the lunar's geotherm until 1,400 km is constructed. The core‐mantle boundary temperature of the Moon is refined from 1,883 to 1,754 K.

Abstract Background/aims Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. Methods PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. Results Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P

Abstract Aims Selective lateral pelvic lymph node (LPN) dissection (LPND) following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer is widely recognized. This study aimed to determine the effects of nCRT before LPND on local control and prognosis of rectal cancer patients. Materials and methods Data were retrieved from a prospective database for rectal cancer patients with clinical LPN metastasis receiving total mesorectal excision and LPND at three institutions between January 2012 and December 2019. Selection bias was minimized using propensity score matching (PSM) and short-term and clinical outcomes were compared. Results Patients (n = 213) were enrolled and grouped as either nCRT (n = 97) or non-nCRT (n = 116). PSM was used to identify 83 matched pairs. In the matched cohort, nCRT patients had a longer operation duration (310.6 vs. 265.0 min, P = 0.001), lower pathological LPN metastasis rate (32.5% vs. 48.2%, P = 0.040), and fewer harvested lymph nodes (22 vs. 25, P = 0.018) compared to the non-nCRT group. However, after PSM, the two groups had similar estimated overall 3-year survival (79.5% vs. 80.7%, P = 0.922), 3-year disease-free survival (66.1% vs. 65.5, P = 0.820), and 3-year local recurrence-free survival (88.6% vs. 89.7%, P = 0.927). Distant metastasis was the predominant recurrence pattern in the overall (45/58, 77.6%) and matched (33/44, 75.0%) cohorts. Conclusions LPND without nCRT is effective and sufficient in preventing local recurrence in patients with LPN metastases. Future prospective randomized controlled studies are warranted to confirm these findings. Since systemic metastasis is the predominant recurrence pattern in patients with LPN metastasis post-LPND, improved perioperative systemic chemotherapy is needed to prevent micrometastasis.

Predicting outage areas for affected customers in a disaster requires real-time meteorological data, which can be challenging to obtain and process with high quality. In particular, missing or inaccurate data can occur in certain regions or during extreme weather events. Therefore, a Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) based algorithm is proposed to improve the accuracy and reduce the prediction time in the outage region. Ground-based automated weather observatories are used to obtain real-time weather data, including extreme weather data. These data are pre-processed to enhance data quality and accuracy by removing duplicates, filling in missing values, handling anomalies, normalizing input variables, and reducing dimensionality. Based on the results of the data pre-processing, the outage rate was calculated for different types of meteorological disasters and the geographical characteristics of the outages were analyzed. This analysis provides insights into the impact of different types of meteorological disasters on power outages and helps improve the accuracy of predictive models. The proposed algorithm employs a CNN neural network to capture spatial and temporal information from raw meteorological data by stacking convolution and pooling layers. The extracted features are then organized and output by fully connected layers, laying the foundation for subsequent time series modeling. An LSTM network is further utilized to construct a prediction model for the outage area, which takes as input the feature extraction results of the meteorological data. By integrating the temporal dimension information of meteorological data, the model outputs accurate predictions for the outage area. The experimental results demonstrate a consistent outcome with the actual test results, achieving high prediction accuracy with a short prediction time of 4.3 s and a maximum non-outage detection rate of 2%. Therefore, the proposed algorithm proves to be significant for accurate and fast prediction of outage areas for affected customers in real world applications.

Grain weight is one of the key components of wheat (Triticum aestivum L.) yield. Genetic manipulation of grain weight is an efficient approach for improving yield potential in breeding programs. A recombinant inbred line (RIL) population derived from a cross between W7268 and Chuanyu 12 (CY12) was employed to detect quantitative trait loci (QTLs) for thousand-grain weight (TGW), grain length (GL), grain width (GW), and the ratio of grain length to width (GLW) in six environments. Seven major QTLs, QGl.cib-2D, QGw.cib-2D, QGw.cib-3B, QGw.cib-4B.1, QGlw.cib-2D.1, QTgw.cib-2D.1 and QTgw.cib-3B.1, were consistently identified in at least four environments and the best linear unbiased estimation (BLUE) datasets, and they explained 2.61 to 34.85% of the phenotypic variance. Significant interactions were detected between the two major TGW QTLs and three major GW loci. In addition, QTgw.cib-3B.1 and QGw.cib-3B were co-located, and the improved TGW at this locus was contributed by GW. Unlike other loci, QTgw.cib-3B.1/QGw.cib-3B had no effect on grain number per spike (GNS). They were further validated in advanced lines using Kompetitive Allele Specific PCR (KASP) markers, and a comparison analysis indicated that QTgw.cib-3B.1/QGw.cib-3B is likely a novel locus. Six haplotypes were identified in the region of this QTL and their distribution frequencies varied between the landraces and cultivars. According to gene annotation, spatial expression patterns, ortholog analysis and sequence variation, the candidate gene of QTgw.cib-3B.1/QGw.cib-3B was predicted. Collectively, the major QTLs and KASP markers reported here provide valuable information for elucidating the genetic architecture of grain weight and for molecular marker-assisted breeding in grain yield improvement.

Abstract Collagen-based biomaterials (CBB) are highly esteemed by researchers in materials science and biomedicine due to their extensive applications across various biomedical disciplines. In recent years, owing to advancements in developmental biology techniques, this superior biomaterial has seen increasing utilization in 3D in vitro tissue culture. Three-dimensional cell cultures, often referred to as organoids, have emerged in response to technological advancements in biomaterials and the growing need in the field of medical research. They serve as important models for simulating normal physiological activities in vivo, addressing limitations in experimental material sources, and resolving ethical issues. In this review, we discuss the material characteristics of CBBs commonly used for organoid culture, integrating aspects such as Matrigel and decellularized ECM as culture matrices. We also analyzed the development prospects and directions of various materials in the context of biology, clinical medicine, and particularly reproductive medicine. Currently, despite the FDA approval and clinical research incorporating numerous CBBs, existing challenges in multiple studies indicate a significant unmet need in the development of key tissue models for both medical research and clinical applications. In summary, CBBs are swiftly broadening their applicability in the realms of organoid nature and medical research, serving as a versatile and high-performing material for 3D in vitro tissue culture. Graphical abstract

Abstract Human norovirus is a leading cause of foodborne illness worldwide, and its detection in foods remains a challenge due to the difficulty of eluting and enriching trace amounts of viral particles. In this study, we developed porcine gastric mucin–labeled magnetic capture probes and optimized the conditions for their binding with norovirus, elution of viral particles, and RNA isolation based on the previous research. We evaluated the magnetic capture‐based pretreatment method in artificially contaminated strawberry samples and compared it with the conventional polyethylene glycol precipitation–based method using reverse transcriptional‐quantitative PCR (RT‐qPCR). The results revealed that Tris·HCl (pH 9.5) was the optimal buffer for the binding of magnetic probes with viral particles, and RNA recovery rate obtained by heating‐based release was significantly higher than that obtained by a commercial kit, with only active virus being captured. This buffer was similar to the RT‐qPCR buffer, which facilitated the sensitivity of RT‐qPCR. Furthermore, the buffer was an effective solution for eluting viral particles from foods in previous research and was optimized to ensure maximum elution and no inhibitory effect on viral capture. We explored multiple factors or steps to ensure that the sensitivity of our method was three orders of magnitude higher than that of the conventional method. Our findings suggest that magnetic capture‐based detection has great potential for the sensitive detection of human norovirus.

Abstract Background The purpose of this study is to use three-dimensional finite-element analysis to better understand the biomechanical features of various internal fixators for ankle arthrodesis. Methods We used finite-element analysis to compare four different types of internal fixations in ankle arthrodesis: Group A had three crossed screws (Ø6.5 mm); Group B had two crossed screws (Ø6.5 mm) and an anterior plate (Ø2.7 mm); Group C only had an anterior anatomical plate (Ø3.5 mm); Group D had one anterior anatomical plate (Ø3.5 mm) and one posterior–lateral screw (Ø6.5 mm). We adopted Ansys 21.0 software to analyze and compare the four types in terms of the displacement of the arthrodesis surface and the stress peak and stress distribution of these models under intorsion, extorsion, dorsiflexion torque, and neutral vertical load. Results ① Displacement of the arthrodesis surface: In Group A, the maximum displacement was larger than Group D under neutral vertical load and dorsiflexion torque but less than it under intorsion and extorsion torque. In Group B, the maximum displacement against dorsiflexion, neutral vertical load, intorsion, and extorsion was less than that in the other three fixation models. In Group C, the maximum displacement against the above four loading patterns were significantly higher than that in another three fixation models. ② Stress peak and stress distribution: based on the stress distribution of the four models, the peak von Mises stress was concentrated in the central sections of the compression screws, plate joints, and bending parts of the plates. Conclusions The fixation model consisting of two crossed screws and an anterior outperformed the other three fixation models in terms of biomedical advantages; thus, this model can be deemed a safe and reliable internal fixation approach for ankle arthrodesis.

ABSTRACTControlling grain temperatures is the main approach employed in large commercial warehouses to maintain quality and prevent infestation by insects and fungi. Large commercial warehouses in northeast China have been utilizing inner cyclic cooling aeration (ICCA), a newly developed method for managing summertime temperatures, haphazardly and without tight standards. We utilized a homemade detector to track the temperature, humidity, and CO2 concentrations of maize that was held for four years under ICCA treatment. The monitoring occurred every week, specifically from July 1st to September 30th. In addition, we conducted weekly tests to determine the moisture content (MC) and free fatty acids (FFA) of the stored maize samples. Without the use of ICCA, the average temperature of the stored maize above a depth of 3.5 m ranged from 20°C to 28°C, and the relative humidity (RH) in the headspace was typically higher than 75%. However, when ICCA was applied, the average temperature could be maintained at 22°C, and the RH was below 65% for most of the time. In the first year, the MC of the stored maize at a depth of 1.0 m experienced a loss of approximately 0.5%. However, for one year, there was no significant loss in the MC of the maize stored at the same depth. Furthermore, the FFA in the stored maize at a depth of 1 m increased by 1–5 mg KOH/100 g. The use of ICCA effectively controls the temperature and RH in the stored maize, reducing the risk of insect and fungal reproduction.

IntroductionInfection with SARS-CoV-2 begins in the upper respiratory tract and can trigger the production of mucosal spike-specific secretory IgA (sIgA), which provides protection against reinfection. It has been recognized that individuals with high level of nasal spike-specific IgA have a lower risk of reinfection. However, mucosal spike-specific sIgA wanes over time, and different individuals may have various level of spike-specific sIgA and descending kinetics, leading to individual differences in susceptibility to reinfection. A method for detecting spike-specific sIgA in the nasal passage would be valuable for predicting the risk of reinfection so that people at risk can have better preparedness.MethodsIn this study, we describe the development of a colloidal gold-based immunochromatographic (ICT) strip for detecting SARS-CoV-2 Omicron spike-specific sIgA in nasal mucosal lining fluids (NMLFs).ResultsThe ICT strip was designed to detect 0.125 μg or more spike-specific sIgA in 80 μL of NMLFs collected using a nasal swab. Purified nasal sIgA samples from individuals who recently recovered from an Omicron BA.5 infection were used to demonstrate that this ICT strip can specifically detect spike-specific sIgA. The signal levels positively correlated with neutralizing activities against XBB. Subsequent analysis revealed that people with low or undetectable levels of spike-specific sIgA in the nasal passage were more susceptible to SARS-CoV-2 reinfection.ConclusionsThis nasal spike-specific sIgA ICT strip provides a non-invasive, rapid, and convenient method to assess the risk of reinfection for achieving precision preparedness.

In2O3 based materials are one of the most promising high-temperature thermoelectric materials for application. Herein, Sm doped In2O3 samples were prepared by mechanical alloying, high-temperature calcination, and discharge plasma sintering, and the influence mechanism of rare earth element doping on the thermoelectric properties of In2O3 based semiconductors was studied. The results indicate that the electrical conductivity increased significantly. Due to the introduction of Sm impurity levels, the density of states near the Fermi level significantly increases. The bandgap widens, and the mobility first decreases and then increases. Due to the increase in carrier concentration, the absolute value of the Seebeck coefficient decreases, but the gain effect caused by the increase in conductivity is greater than the debuff caused by the decrease in the absolute value of the Seebeck coefficient. The power factor increases after Sm doping.The thermal conductivity decreases due to the decrease in Young's modulus, enhanced heterogeneous scattering, and enhanced heavy element scattering. The ZT value was raised to ∼0.327 at 973 K, obtained by Sm doped In2O3 sample with x = 0.060, which is ∼6 times as that of the pristine In2O3 sample.

Study region: As part of the active Xianshuihe Fault system, the Kangding geothermal field is a representative high-temperature hydrothermal system in the southeastern Tibetan Plateau, China. The strong tectonic and hydrothermal activity serves as a unique location to study the interaction between earthquakes and geothermal fluids. Study focus: We have collected water samples taken from thermal springs and boreholes in the geothermal field to identify fluid composition and reservoir temperature of the deep granite and shallow metamorphic rock using geochemical analysis and the Integrated Multicomponent Geothermometry (IMG) method. Two typical thermal springs that offer long-term hydrochemical data were selected to investigate the effect of earthquakes on the shallow and deep reservoir temperatures. New hydrological insights for the region: The deep reservoir temperature in the Kangding geothermal field is in the range 222 ℃ to 256 ℃, while the shallow reservoir temperature ranges from 128 ℃ to 171 ℃. Both thermal springs show changes in reservoir temperature following the 2008 Wenchuan, the 2013 Lushan, and the 2014 Kangding earthquakes. The temperature changes are similar in the deep reservoir of the two springs but different in the case of the shallow reservoir. We propose that the changes in reservoir temperature, steam fraction, and dilution factor indicate that the deep reservoir is more sensitive to earthquake-induced permeability changes than the shallow reservoir.

Abstract Background Previous studies have indicated that HBV pregenome RNA (HBV pgRNA) could predict HBeAg seroconversion among the chronic hapatitis B (CHB) patients treated with pegylated interferon (Peg-IFN) or nucleos(t)ide analogues (NAs). However, the data about the prediction of HBV pgRNA for spontaneous HBeAg seroconversion is limited. Methods One hundred thirteen CHB patients with HBeAg-positive in the immune active phase were followed up for 76 weeks without antiviral treatment. Based on the laboratory test results of liver function, HBeAg, anti-HBe, and HBV DNA at week 76, patients were assigned to two groups: spontaneous HBeAg seroconversion (group A, n = 18) and non-spontaneous HBeAg seroconversion group. Among the latter group, 36 patients were selected as controls (group B, n = 36). Results At week 12, between group A and group B, there was a significant difference in the level of HBV pgRNA (group A 6.35 ± 1.24 log10 copies/ml and group B 7.52 ± 0.79 log10 copies/ml, P = 0.001), and the difference enlarged at week 28. The receiver operating characteristic curves (AUROCs) of the HBV pgRNA level and the ∆HBV pgRNA at week 28 were 0.912 (P = 0.001, 95% CI: 0.830–0.994), and 0.934 (P = 0.001, 95% CI: 0.872–0.996), respectively. The optimal cutoffs of HBV pgRNA and the reduction from baseline (∆HBV pgRNA) at week 28 for spontaneous HBeAg seroconversion prediction were 5.63 log10 copies/ml and 1.85 log10 copies/ml, respectively. The positive predictive value and negative predictive value of HBV pgRNA and ∆HBV pgRNA at week 28 were 86.7% and 87.2%, 87.5% and 89.5%, respectively. And the combination of the HBV pgRNA level and the HBV pgRNA decreased could provide better prediction. Conclusions HBV pgRNA is a sound predictor for spontaneous HBeAg seroconversion among the CHB patients in immune active phase. Dynamic monitoring of HBV pgRNA is helpful for clinical treatment decision.

It is a great challenge to simultaneously improve the strength and ductility of magnesium matrix composites (MMCs). In this work, AZ91 alloys reinforced with 1 wt%, 2 wt%, and 3 wt% Ti particles were produced using stir casting combined with ball milling process. The microstructure of the extruded composite sheets was analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM), electron backscatter diffraction (EBSD). Transmission electron microscopy (TEM) was utilized to observe the structure of the Ti/Mg interface. The mechanical properties of the composite sheets were also investigated. The results show that the adding Ti particles, the texture strength decreased, and the growth of recrystallization grains was also restrained. Due to the interfacial reaction between Ti and Al, the formation of β-phase (Mg17Al12) was inhibited. The tensile test demonstrated that the Ti particles could significantly improve the mechanical properties of the AZ91 alloy sheets. Compared to AZ91 sheet, 2Ti/AZ91 composite sheet along extrusion direction (ED) showed the best comprehensive mechanical properties. The improvement in mechanical properties was mainly attributed to grain refinement, texture weakening, mismatched coefficient of thermal expansion (CTE), and work hardening.

Abstract In the real world, road networks with weight and label on edges can be applied in several application domains. The shortest path query with label restrictions has been receiving increasing attention recently. To efficiently answer such kind of queries, a novel index, namely Contraction Hierarchies with Label Restrictions (CHLR), is proposed in the literature. However, existing studies mainly focus on the static road networks and do not support the CHLR maintenance when the road networks are dynamically changed. Motivated by this, in this paper, we investigate the CHLR maintenance problem in dynamic road networks. We first devise a baseline approach to update CHLR by recomputing the potential affected shortcuts. However, many shortcuts recomputed in baseline do not change in fact, which leads to unnecessary overhead of the baseline. To overcome the drawbacks of baseline, we further propose a novel CHLR maintenance algorithm which can only travel little shortcuts through an update propagate chain with accuracy guarantee. Moreover, an optimization strategy is presented to further improve the efficiency of index maintenance. Considering the frequency of edge changes, we also propose a batch index maintenance algorithm to handle batch edge changes which can process a large number of edge changes at once. Furthermore, a parallel method is proposed to further accelerate calculations. Extensive and comprehensive experiments are conducted on real road networks. The experimental results demonstrate the efficiency and effectiveness of our proposed algorithms.

Abstract Background Lumbar disk herniation (LDH) is one of the most common diseases of the spine, especially occurring in L4-5 and L5-S1 intervertebral disks, and surgery is a choice when conservative treatment is ineffective. The purpose of this study is to investigate the clinical efficacy and radiologic outcomes of one-hole split endoscopy (OSE) technique versus unilateral biportal endoscopy (UBE) technique in the treatment of L5-S1 lumbar disk herniation (LDH). Methods A total of 133 patients of a single center surgically treated for L5-S1 LDH between 2019 and 2021 were retrospectively included in this study, of which 70 were treated by UBE technique and the rest were treated by OSE technique. Hospitalization time, operative time, intraoperative blood loss, fluoroscopy times, incision length and related complications were recorded. Bone resection area (BRA), articular process resection rate, range of motion (ROM), sagittal translation (ST), disk height (DH), Visual Analog Score (VAS), Oswestry Disability Index (ODI) and Macnab criteria were used to evaluated the clinical efficacy. Results There was no statistically significant difference in hospitalization time or fluoroscopy times between the two groups. The operation time was shorter in the UBE group than that in the OSE group; however, the incision length was longer. Intraoperative blood loss and BRA were larger in the UBE group than in the OSE group. There was no significant difference in ROM, ST, DH, or postoperative facet resection rate between the two groups. There was no significant difference in ROM, ST, or postoperative facet resection rate compared with preoperative indicators in each group, but there was a significant difference in DH among distinct groups. At any time point, the lower back and leg VAS and ODI in each group were significantly improved compared to those before the operation, with no significant difference between the two groups. There was one case of dural tear in the UBE group. One case of transient hypoesthesia occurred in each of the two groups. The excellent–good rates of the UBE group and the OSE group were 88.6% and 90.5%, respectively. Conclusion The OSE technique is an effective minimally invasive surgical option as well as the UBE technique in the treatment of L5-S1 LDH.

To study the mechanical properties of the membrane bag sand cofferdam under the action of geotextile hoop during the construction, the theoretical derivation of the film-bag sand enhancement mechanism was carried out firstly. A finite element model of sand blowing cofferdam with measured material parameters was established based on the ANSYS platform, and then different pipes were used to calculate the bag height under self-weight and external load, and the variation law of self-weight and external load, as well as the sand blowing cofferdam under different concrete slab thickness was analyzed. The main conclusions include: (1) The relationship between the height of the membrane sandbag and the tensile force of the soil sandbag is proposed, the relationship between the shape of the sandbag and the external load is further deduced. (2) The axial tension of the type bag is proportional to the quadratic of the height of the type bag sand without considering the friction condition. (3) As the concrete slab thickness increases, the vertical settlement of the blown sand cofferdam gradually decreases under the action of the cast-in-place bracket, and the reduction of the uneven settlement in the cross-bridge direction is greater than that of the vertical settlement.

During electromagnetic ultrasonic testing, it is difficult to recognize small-size bottom cracks by time of flight (ToF), and the lift-off fluctuation of the probe affects the accuracy and consistency of the inspection results. In order to overcome the difficulty, a novel composite sensor of an electromagnetic acoustic transducer (EMAT) and pulse eddy current (PEC) is designed. We use the amplitude of a bottom echo recorded by EMAT to identify the tiny bottom crack as well as the amplitude of PEC signals picked up by the integrated symmetric coils to measure the average lift-off of the probe in real time. Firstly, the effects of lift-off and bottom cracks on the amplitude of bottom echo are distinguished by combining the theoretical analysis and finite element method (FEM). And then an amplitude correction method based on the fusion of EMAT and PEC signals is proposed to reduce the impact of lift-off on the defect signal. The experimental results demonstrate that the designed composite sensor can effectively detect a bottom crack as small as 0.1 mm × 0.3 mm. The signal fusion method can accurately correct the amplitude of defect signals and the relative error is less than ±8%.

Immune checkpoint proteins have become recent research hotspots for their vital role in maintaining peripheral immune tolerance and suppressing immune response function in a wide range of tumors. Therefore, investigating the immunomodulatory functions of immune checkpoints and their therapeutic potential for clinical use is of paramount importance. The immune checkpoint blockade (ICB) is an important component of cancer immunotherapy, as it targets inhibitory immune signaling transduction with antagonistic antibodies to restore the host immune response. Anti-programmed cell death-1 (PD-1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies are two main types of widely used ICBs that drastically improve the survival and prognosis of many patients with cancer. Nevertheless, the response rate of most cancer types remains relatively low due to the drug resistance of ICBs, which calls for an in-depth exploration to improve their efficacy. Accumulating evidence suggests that immune checkpoint proteins are glycosylated in forms of N-glycosylation, core fucosylation, or sialylation, which affect multiple biological functions of proteins such as protein biosynthesis, stability, and interaction. In this review, we give a brief introduction to several immune checkpoints and summarize primary molecular mechanisms that modulate protein stability and immunosuppressive function. In addition, newly developed methods targeting glycosylation on immune checkpoints for detection used to stratify patients, as well as small-molecule agents disrupting receptor–ligand interactions to circumvent drug resistance of traditional ICBs, in order to increase the clinical efficacy of immunotherapy strategies of patients with cancer, are also included to provide new insights into scientific research and clinical treatments.

BackgroundThis study examined national similarities and differences in people's engagement in health preventive behaviors during a public health crisis, as well as investigated the underlying individual-level psychological mechanisms. A conceptual distinction was made between self-focused and other-involved preventive behaviors in response to public health crises.MethodTwo cross-sectional surveys were conducted in the United States (N = 888) and China (N = 844) during the early stage of the COVID-19 pandemic. Hayes' PROCESS was utilized to assess national differences in seven preventive behaviors, along with the mediating effects of self-construal and health locus of control.ResultsThe results showed that American participants reported greater engagement in self-focused preventive behaviors than Chinese, whereas Chinese participants reported greater engagement in other-involved preventive behaviors than Americans. Chinese participants also engaged more in other-involved than self-focused preventive behaviors. Self-construal and health locus of control partially explained the observed differences in engagement in preventive behaviors.DiscussionThis study introduces a culture-sensitive approach to provide insights for crafting communication interventions that can enhance the effectiveness of health campaigns in the context of a public health crisis.

IntroductionThe etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions.MethodsThis retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions.ResultsAmong the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04).ConclusionsChinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

Grain hardness (Gh) is important for wheat processing and end-product quality. Puroindolines polymorphism explains over 60% of Gh variation and the novel genetic factors remain to be exploited. In this study, a total of 153 quantitative trait loci (QTLs), clustered into 12 genomic intervals (C1-C12), for 13 quality-related traits were identified using a recombinant inbred line population derived from the cross of Zhongkemai138 (ZKM138) and Chuanmai44 (CM44). Among them, C7 (harboring eight QTLs for different quality-related traits) and C8 (mainly harboring QGh.cib-5D.1 for Gh) were attributed to the famous genes, Rht-D1 and Pina, respectively, indicating that the correlation of involved traits was supported by the pleotropic or linked genes. Notably, a novel major stable QTL for Gh was detected in the C12, QGh.cib-7D, with ZKM138-derived allele increasing grain hardness, which was simultaneously mapped by the BSE-Seq method. The geographic pattern and transmissibility of this locus revealed that the increasing-Gh allele is highly frequently present in 85.79% of 373 worldwide wheat varieties and presented 99.31% transmissibility in 144 ZKM138-derivatives, indicating the non-negative effect on yield performance and that its indirect passive selection has happened during the actual breeding process. Thus, the contribution of this new Gh-related locus was highlighted in consideration of improving the efficiency and accuracy of the soft/hard material selection in the molecular marker-assisted process. Further, TraesCS7D02G099400, TraesCS7D02G098000, and TraesCS7D02G099500 were initially deduced to be the most potential candidate genes of QGh.cib-7D. Collectively, this study provided valuable information of elucidating the genetic architecture of Gh for wheat quality improvement.

Grain number per spike (GNS) is a crucial component of grain yield and plays a significant role in improving wheat yield. To identify quantitative trait loci (QTL) associated with GNS, a recombinant inbred line (RIL) population derived from the cross of Zhongkemai 13F10 and Chuanmai 42 was employed to conduct QTL mapping across eight environments. Based on the bulked segregant exome sequencing (BSE-Seq), genomic regions associated with GNS were detected on chromosomes 5A and 6A. According to the constructed genetic maps, two major QTL QGns.cib-5A (LOD = 4.35–8.16, PVE = 8.46–14.43%) and QGns.cib-6A (LOD = 3.82–30.80, PVE = 5.44–12.38%) were detected in five and four environments, respectively. QGns.cib-6A is a QTL cluster for other seven yield-related traits. QGns.cib-5A and QGns.cib-6A were further validated using linked Kompetitive Allele Specific PCR (KASP) markers in different genetic backgrounds. QGns.cib-5A exhibited pleiotropic effects on productive tiller number (PTN), spike length (SL), fertile spikelet number per spike (FSN), and ratio of grain length to grain width (GL/GW) but did not significantly affect thousand grain weight (TGW). Haplotype analysis revealed that QGns.cib-5A and QGns.cib-6A were the targets of artificial selection during wheat improvement. Candidate genes for QGns.cib-5A and QGns.cib-6A were predicted by analyzing gene annotation, spatiotemporal expression patterns, and orthologous and sequence differences. These findings will be valuable for fine mapping and map-based cloning of genes underlying QGns.cib-5A and QGns.cib-6A.

In the field of youth mentoring, mentor support, as an important scaffold for youth development, is linked to match relationship quality between mentors and mentees. This study examined associations between the support provided by different categories of mentors and internal match quality among 240 mentors in youth mentoring programs. Four clusters of mentors emerged, representing different combinations of purposes for mentor-mentee interactions. Mentors who focused less on the character development of their mentees showed reduced benefits in other forms of interactions, such as fun, sharing, future outlook, or academics in promoting high overall mentor-mentee internal match quality, including relational quality and instrumental quality. While mentors who focused less on future outlook in their mentoring interactions showed reduced benefits for other purposes in promoting internal instrumental quality. These findings were not influenced by mentors’ demographic differences such as gender, age, race, and educational background. The significance of the findings for future research and practice is discussed.

Ultrasonic peen forming (UPF) is an emerging technology that exhibits great superiority in both its flexible operating modes and the deep residual stress that it produces compared with conventional plastic forming methods. Although ultrasonic transducers with longitudinal vibration have been widely studied, they have seldom been incorporated into UPF devices for machining in confined spaces. To meet the requirements of this type of machining, a sandwich-type piezoelectric transducer with coupled longitudinal–flexural vibrational modes is proposed. The basic structure of the transducer is designed to obtain large vibrational amplitudes in both modes. Experimental results obtained with a prototype device demonstrate the feasibility of the proposed transducer. The measured vibrational amplitude for the working face in the longitudinal vibrational mode is 1.0 μm, and electrical matching increases this amplitude by 40%. The flexural vibration characteristics of the same prototype transducer are also tested and are found to be slightly smaller than those of longitudinal mode. The resultant working strokes of the UPF impact pins reach 1.7 mm and 1.2 mm in the longitudinal and flexural modes, respectively. The forming capability of the prototype has been evaluated via 15-min machining on standard 2024-T351 aluminum plates. After UPF, an improved surface morphology with lower surface roughness is obtained. The aluminum plate test piece has an apparent upper deformation with an arc height of 0.64 mm. The measured peak value of the compressive residual stress is around 250 MPa, appearing at a depth of 100 μm. The proposed longitudinal–flexural hybrid transducer thus provides a high-performance tool for plate peen forming in confined spaces.

Complex-amplitude holographic metasurfaces (CAHMs) with the flexibility in modulating phase and amplitude profiles have been used to manipulate the propagation of wavefront with an unprecedented level, leading to higher image-reconstruction quality compared with their natural counterparts. However, prevailing design methods of CAHMs are based on Huygens-Fresnel theory, meta-atom optimization, numerical simulation and experimental verification, which results in a consumption of computing resources. Here, we applied residual encoder-decoder convolutional neural network to directly map the electric field distributions and input images for monolithic metasurface design. A pretrained network is firstly trained by the electric field distributions calculated by diffraction theory, which is subsequently migrated as transfer learning framework to map the simulated electric field distributions and input images. The training results show that the normalized mean pixel error is about 3% on dataset. As verification, the metasurface prototypes are fabricated, simulated and measured. The reconstructed electric field of reverse-engineered metasurface exhibits high similarity to the target electric field, which demonstrates the effectiveness of our design. Encouragingly, this work provides a monolithic field-to-pattern design method for CAHMs, which paves a new route for the direct reconstruction of metasurfaces.

Copper (Cu)-containing single-source precursors (SSPs) for the preparation of SiCuCN-based ceramic nanocomposites were successfully synthesized for the first time using polysilazane (PSZ), copper(II) acetate monohydrate (CuAc), and 2-aminoethanol via nucleophilic substitution reactions at silicon (Si) centers of PSZ. The synthesis process, polymer-to-ceramic transformation, and high-temperature microstructural evolution of the prepared ceramics were characterized. Dielectric properties and electromagnetic wave (EMW) absorbing performance of the ceramics were investigated as well. The results show that the polymer-to-ceramic transformation finishes at ca. 900 ℃, and Cu nanoparticles are homogeneously distributed in a SiCN matrix, forming a SiCN/Cu nanocomposite. After annealing at 1200 ℃, the Cu nanoparticles completely transform into copper silicide (Cu3Si). Interestingly, the thermal stability of the Cu nanoparticles can be strongly improved by increasing the free carbon content, so that a part of metallic Cu nanoparticles can be detected in the ceramics annealed even at 1300 ℃, forming a SiCN/Cu/Cu3Si/C nanocomposite. Compared with SiCN, the SiCuCN-based nanocomposites exhibit strongly enhanced dielectric properties, which results in outstanding EMW absorbing performance. The minimum reflection coefficient (RCmin) of the SiCN/Cu/Cu3Si/C nanocomposites annealed at 1300 ℃ achieves −59.85 dB with a sample thickness of 1.55 mm, and the effective absorption bandwidth (EAB) broadens to 5.55 GHz at 1.45 mm. The enhanced EMW absorbing performance can be attributed to an in situ formed unique network, which was constructed with Cu and Cu3Si nanoparticles connected by ring-like carbon ribbons within the SiCN matrix.

Abstract Background Lumbar disc herniation (LDH) is one of the most common diseases of the spine, and migrated LDH is a more serious type, associated with nerve root function injury or abnormality. Regarding the increasing surgery adoption of treating migrated LDH, we aimed to investigate the clinical efficacy and safety of discectomy with a novel technique–one-hole split endoscope (OSE) technique. Methods This was a retrospective analysis of migrated LDH treated between December 2020 and September 2021. Hospitalization time, operative duration, intraoperative blood loss, number of fluoroscopy exposures, incision length, postoperative facet preservation rate, number of excellent–good cases, lower back and leg visual analogue score (VAS), Oswestry Disability Index (ODI) and surgical complications were compared between high-grade migration group (82 cases) and low-grade migration group (148 cases). The Macnab criteria was used to evaluate the clinical outcome. The Shapiro‒Wilk test was used to test measurement data, and the χ 2 test was used to test counting data. Results There was no significant difference in hospitalization time, operative duration, intraoperative blood loss, number of fluoroscopy exposures, incision length or postoperative facet preservation rate between the two groups by independent sample t test or nonparametric test. At any time point, the lower back and leg VAS and ODI of the two groups were significantly improved compared to those before the operation, but there was no significant difference between the two groups at the same time point by two-way repeated measures ANOVA. There were two cases of postoperative nerve root stimulation symptoms in the high-grade migration group and three cases in the low-grade migration group. There was one patient reoperated in the high-grade migration group. There was no significant difference in number of excellent–good cases between the two groups. The overall excellent–good rate was 89.6%. Conclusion The OSE technique has the advantages of less trauma, faster recovery, complete removal of the nucleus pulposus and a satisfactory early clinical efficacy in the treatment of migrated LDH.

For magnesium matrix composites (MMCs), it is crucial to enhance their strength while maintaining plasticity. In this work, Ti particle (TiP) reinforced VW94 composites (TiP/VW94 composites) with varying amounts of Ti particles were prepared using a semi-solid stirring-assisted ultrasonic vibration method followed by homogenizing treatment. Microstructural analysis revealed that the addition of Ti particles resulted in grain refinement and facilitated the formation of lamellar long period stacking ordered structure (LPSO) during homogenizing treatment due to the increasing dislocation density. In addition, the jagged interfacial product of MnTi phase was generated at the interface between Ti particles and Mg matrix, and a strong interfacial bonding was formed at the Mg/Ti interface. The tensile test results show that the strength and elongation of TiP/VW94 composites all improved than VW94 matrix alloy and the 5%TiP/VW94 composite presents the best tensile properties with yield strength (YS), ultimate tensile strength (UTS), and elongation of 173 MPa, 256 MPa and 5.9%, respectively. The improved tensile properties of TiP/VW94 composites can be attributed to grain refinement, load transfer, dispersion strengthening, dislocation strengthening, and an increase in lamellar LPSO.

Neuroblastoma (NB) is a common solid tumor in children and infants, the formation and regression of which is closely linked to the tumor-host immune relationship. Stimulator of interferon genes (STING) agonists, particularly cyclic dinucleotide (CDN), have promising potential in NB therapy by generating innate and adaptive immune stimulation, thus leading to tumor control. CDN delivery in vivo is challenging due to the negative charge, hydrophilicity, and susceptibility to degradation by phosphodiesterase, which hinders the effectiveness of CDN. Thus, our study proposed four methods to load CDN into liposomes, using 2′,3′-cGAMP as the model drug. Lipid nanoparticles were prepared, followed by physicochemical characterization. Subsequently, cellular inhibition and immune stimulation were investigated. As a result, lipid calcium phosphate nanoparticles (LCP-NPs) possessed the highest encapsulation efficiency among the four preparation methods, with a diameter of 82.57±3.72 nm. LCP-NPs maintained size stability under refrigeration conditions at 4°C within 48 h. The surface of the liposome was positively charged. Compared to free cGAMP, LCP-NPs resulted in a slower release, enhanced cytotoxicity against tumor cells, greater activation of the cGAS-STING pathway, and increased expression of the immune factors. Taken together, these findings clearly demonstrated the effectiveness of the liposomal delivery system for cGAMP and provided a promising strategy for the treatment of NB.

Abstract Background Since hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analog (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that some patients remain virologically responsive even after NA cessation. However, there is still controversy surrounding whether NA discontinuation increases the HBsAg loss rate. Therefore, this study aimed to assess the cumulative rate of HBsAg loss and identify the predictors of HBsAg loss after NA discontinuation. Methods This multicenter prospective study included HBV e antigen (HBeAg)-positive patients without cirrhosis from 12 hospitals in China who met the inclusion criteria. The enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occurred. Results Overall, 158 patients were classified into two groups. Group A included patients with HBsAg positivity at NA cessation (n = 139), and Group B included patients with HBsAg negativity at NA cessation (n = 19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were4.3%and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P

Cervical cancer, as the fourth most common cancer in women, poses a significant threat to women’s health. Vaginal colposcopy examination, as the most cost-effective step in cervical cancer screening, can effectively detect precancerous lesions and prevent their progression into cancer. The size of the lesion areas in the colposcopic images varies, and the characteristics of the lesions are complex and difficult to discern, thus heavily relying on the expertise of the medical professionals. To address these issues, this paper constructs a vaginal colposcopy image dataset, ACIN-3, and proposes a Fusion Multi-scale Attention Network for the detection of cervical precancerous lesions. First, we propose a heterogeneous receptive field convolution module to construct the backbone network, which utilizes combinations of convolutions with different structures to extract multi-scale features from multiple receptive fields and capture features from different-sized regions of the cervix at different levels. Second, we propose an attention fusion module to construct a branch network, which integrates multi-scale features and establishes connections in both the spatial and channel dimensions. Finally, we design a dual-threshold loss function and introduce positive and negative thresholds to improve sample weights and address the issue of data imbalance in the dataset. Multiple experiments are conducted on the ACIN-3 dataset to demonstrate the superior performance of our approach compared to some classical and recent advanced methods. Our method achieves an accuracy of 92.2% in grading and 94.7% in detection, with average AUCs of 0.9862 and 0.9878. Our heatmap illustrates the accuracy of our approach in focusing on the locations of lesions.

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L−1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L−1), phycoerythrin (102.95 mg L−1), and polysaccharide (1.42 g L−1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.