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Summary Nannochloropsis oceanica is an industrially relevant marine microalga rich in eicosapentaenoic acid (EPA, a valuable ω‐3 polyunsaturated fatty acid), yet the algal production potential remains to be unlocked. Here we engineered N. oceanica to synthesize the high‐value carotenoid astaxanthin independent of high‐light (HL) induction for achieving multifaceted benefits. By screening β‐carotenoid ketolases and hydroxylases of various origins, and strategically manipulating compartmentalization, fusion patterns, and linkers of the enzyme pair, a remarkable 133‐fold increase in astaxanthin content was achieved in N. oceanica. Iterative metabolic engineering efforts led to further increases in astaxanthin synthesis up to 7.3 mg g−1, the highest reported for microalgae under nonstress conditions. Astaxanthin was found in the photosystem components and allowed the alga HL resistance and augmented EPA production. Besides, we achieved co‐production of astaxanthin and EPA by the engineered alga through a fed‐batch cultivation approach. Our findings unveil the untapped potential of N. oceanica as a robust, light‐driven chassis for constitutive astaxanthin synthesis and provide feasible strategies for the concurrent production of multiple high‐value biochemicals from CO2, thereby paving the way for sustainable biotechnological applications of this alga. [ABSTRACT FROM AUTHOR]

The forming interface is the weak link of thermoplastic composite complex structures. To explore the effect of polymer crosslinking on the failure behavior of thermoplastic composite remelting interface using "Preforming + Remelting bonding" process, the all‐atom models of different types of interfaces were established, and a molecular dynamics (MD) simulation was conducted on the uniaxial tensile failure process of the remelting interface. The failure behavior of the remelting interface with different preforming processes was tested to verify the correctness of MD simulation, and the influencing mechanism of polymer crosslinking reactions in the preforming stage to the remelting interface properties was clarified. The results showed that the yield stress of the uncrosslinked interface reaches 283.2 MPa and 16.0% and 50.6% higher than that of the unilateral and bilateral crosslinked interfaces respectively. The polymer crosslinking reaction during the preforming stage will reduce the interlaminar bonding performance. The interlaminar shear strength (ILSS) of the uncrosslinked interface is 87.46 MPa and 7.21% and 27.36% higher than that of the unilateral and bilateral crosslinked interface respectively, and only 3.95% lower than that of the non‐remelting sample formed by standard process. This research provides a new approach for predicting and analyzing the effect of polymer crosslinking on remelting interface properties of thermoplastic composite using "Preforming + Remelting bonding" process. Highlights: The failure behavior of different thermoplastic composite remelting interfaces was studied.MD simulation was conducted on the uniaxial tensile failure process of the remelting interface.The influencing mechanism of polymer crosslinking reactions in the preforming stage to the remelting interface properties was clarified.It is effective to explore the failure mechanism of thermoplastic remelting interface by MD simulation. [ABSTRACT FROM AUTHOR]

It is of great significance to explore the causality between regional integration (RI) and PM2.5 pollution within urban agglomerations in the current pursuit of ecological civilization construction and high‐quality development. Using panel data of 285 prefecture‐level cities in China from 2003 to 2016, this study considers the expansion of the city economic coordination committee in Yangtze River Delta (YRDECC) as a quasi‐natural experiment of RI, and use a difference‐in difference method to explore the effect and inner mechanisms of RI on PM2.5 concentration. After a descriptive analysis of the spatial‐temporal variation trend of the PM2.5 concentration in the Yangtze River Delta urban agglomeration, the empirical results show that RI helps to alleviate 4.8% of the PM2.5 concentration overall. For the original cities, the reduction effect on the PM2.5 concentration is 5.2%, for the new cities, however, RI exacerbates 2.1% of the local PM2.5 concentration. A series of robustness tests confirm the validity of the baseline results, and further indicate that the effect of RI remains significant in the long term and starts to increase from the third year. Furthermore, the reduction effect of RI on PM2.5 concentration is more pronounced in cities with larger scales, more developed economies, and higher degrees of marketization. The mechanism analysis shows that industrial transfer, population migration and technological innovation are significant channels of RI that affect PM2.5 concentrations. The conclusions of this paper provide a new path to alleviate PM2.5 pollution and achieve ecological conservation and high‐quality development in the city cluster area. [ABSTRACT FROM AUTHOR]

Summary: This article addresses the position control issue of multi‐quadrotor unmanned aerial vehicle (QUAV) formation. Concerning the translational dynamic of a multi‐QUAV system, on the one hand, it is an under‐actuation dynamic; on the other hand, it does not satisfy the matching condition. These features will cause inevitable thorny in the formation position control design. Furthermore, because of the state coupling problem, the formation control of multi‐QUAV system is more challenging and knotty than the control of single QUAV system. To achieve this control, both backstepping technique and neural network (NN) approximation strategy are combined by introducing an intermediary control, where NN is employed to compensate the system uncertainty. However, since the traditional adaptive NN control methods need to train a large number of adaptive parameters for the high approximation accuracy, it will cause the heavy computing burden if traditional adaptive method is used for the QUAV formation control. The proposed adaptive NN strategy in this paper only requires training a scalar adaptive parameter, which is generated from the norm of NN weight vector or matrix, thereby significantly reducing computational burden. Finally, according to Lyapunov stability proof and computer simulation, it is demonstrated that the control tasks can be successfully accomplished. [ABSTRACT FROM AUTHOR]

Background and purpose: Human motor planning and control depend highly on optimal feedback control systems, such as the neocortex–cerebellum circuit. Here, diffusion tensor imaging was used to verify the disruption of the neocortex–cerebellum circuit in spinocerebellar ataxia type 3 (SCA3), and the circuit's disruption correlation with SCA3 motor dysfunction was investigated. Methods: This study included 45 patients with familial SCA3, aged 17–67 years, and 49 age‐ and sex‐matched healthy controls, aged 21–64 years. Tract‐based spatial statistics and probabilistic tractography was conducted using magnetic resonance images of the patients and controls. The correlation between the local probability of probabilistic tractography traced from the cerebellum and clinical symptoms measured using specified symptom scales was also calculated. Results: The cerebellum‐originated probabilistic tractography analysis showed that structural connectivity, mainly in the subcortical cerebellar–thalamo–cortical tract, was significantly reduced and the cortico–ponto–cerebellar tract was significantly stronger in the SCA3 group than in the control group. The enhanced tract was extended to the right lateral parietal region and the right primary motor cortex. The enhanced neocortex–cerebellum connections were highly associated with disease progression, including duration and symptomatic deterioration. Tractography probabilities from the cerebellar to parietal and sensorimotor areas were significantly negatively correlated with motor abilities in patients with SCA3. Conclusion: To our knowledge, this study is the first to reveal that disrupting the neocortex–cerebellum loop can cause SCA3‐induced motor dysfunctions. The specific interaction between the cerebellar–thalamo–cortical and cortico–ponto–cerebellar pathways in patients with SCA3 and its relationship with ataxia symptoms provides a new direction for future research. [ABSTRACT FROM AUTHOR]

Background: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP‐ALL prognosis has not been determined. Method s : A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP‐ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. Results: The BCP‐ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3‐year DFS: 88.7% [95% CI: 83.4%–94.0%] vs. 93.5% [95% CI: 92.0%–94.9%], P =.021; 3‐year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P =.003]), with a concurrent increase in 3‐year TRM (6.4% [95% CI: 2.3%–10.5%] vs. 2.9% [95% CI: 1.9%–3.8%], P =.025). However, the 3‐year CIR was comparable between the two groups (5.7% [95% CI: 1.8%–9.5%] vs. 3.7% [95% CI: 2.6%–4.7%], P =.138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P =.084). Particularly in BCR::ABL positive subgroup, the 3‐year DFS was remarkably improved from 53.6% ± 20.1% with non‐intensive chemotherapy to 100% with intensive chemotherapy (P =.026). Conclusions: Pediatric BCP‐ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive. [ABSTRACT FROM AUTHOR]

To gain a holistic understanding of how science teachers dealt with STEM education, this study explored two science teachers’ perceptions and practices at primary schools via the lens of curriculum ideology. By examining their perceptions and practices from six essential aspects (i.e., aim, content, student, teaching, learning, and assessment), we aim to provide deeper insights into what STEM education visions they have, why they promote it, and how they enact it in primary school settings. Combining deductive and inductive approaches, we analyzed data collected from multiple sources, including two rounds of semi‐structured interviews, field notes of school visits, artifact like students’ works, and documents like lesson plans and classroom videotapes. Results showed that the two teachers dealt with STEM education differently: one focused on teaching how to think and work as scientists or engineers with a scholar‐academic orientation, whereas the other was devoted to laying a foundation for students’ development and future lives with a learner‐centered orientation. Based on different value stances and aims, two teachers conceptualize STEM education and translate it into school courses and instructional activities differently, leading to varying degrees of curriculum integration, distinct cognitions of worthwhile content, and different teaching orientations. These findings have implications for researchers and practitioners to comprehend and reflect on how teachers deal with the issues involved in STEM education in school settings. The identified tensions and harmonies between different orientations provide insights into coordinating different values and interests to promote STEM education. [ABSTRACT FROM AUTHOR]

In the rapidly evolving Metaverse, enhancing user immersion through clear, lifelike, and ergonomic near‐eye displays is crucial. However, existing rigid near‐eye displays encounter challenges such as insufficient resolution, limited adaptability, and suboptimal visual experiences. To address these issues, a strategic shift is proposed to flexible ultrahigh‐resolution (FUR) displays, which combine ultrahigh resolution with the ability to conform to individual eye curvature for a more realistic field of view. FUR quantum dot light‐emitting diodes (FUR‐QLEDs) featuring 9072 pixels per inch (PPI), a maximum external quantum efficiency (EQE) of 15.7%, and peak brightness of 15 163 cd m−2 are achieved through the integration of nanoimprinting and surface modification technologies. The degradation mechanism of FUR‐QLEDs under bending fatigue tests is investigated, identifying the high elastic modulus of the insulating patterned film as the primary cause through theoretical analysis, simulation, and experimental characterizations. Optimizing the elastic modulus of the patterned film enabled to maintain 91% of its initial brightness after 400 bending cycles, demonstrating exceptional bending stability and durability of FUR‐QLEDs. [ABSTRACT FROM AUTHOR]

Real‐time detection of different physiological characteristics is crucial for human physical and mental health. A detection system with multimodal sensing capability, high sensitivity, excellent mechanical properties, and environmental stability is highly desirable, but it is still a great challenge. Inspired by the structural gradient of biological tissues, a multifunctional sensor based on carboxylic styrene butadiene rubber (XSBR) and sodium polyacrylate (PAANa) non‐covalently modified MXenes is prepared in this study, in which the MXenes exhibit a gradient distribution and simultaneously formed an orientation arrangement at the bottom of the matrix through the formation of hydrogen bonding interactions with PAANa. The material shows a considerable stretchability of 244% and strength of 7.67 MPa, high electrical conductivity of 55.40 S m‒1, low percolation threshold of 2.48 wt%, and excellent response to strain (gauge factor of 906.7 within 98% strain) and humidity (relative resistance change of 530% within 11–93% relative humidity). Based on the superior performances of the XSBR/PAANa/MXene composite, an integrated detection system is designed to accurately detect respiration and body movements at various scales. This work provides a new perspective for the development of a novel biomimetic functional material for sensor applications. [ABSTRACT FROM AUTHOR]

In this study, imidazolium‐based multifunctional ionic polymer (IP 1–IP 3) series, co‐incorporated with phenolic hydroxyl groups as hydrogen bond donors (HBDs) and Cl− as nucleophiles, are synthesized by a facile quaternization method. The physicochemical characterizations of these IPs are systematically examined by using FTIR, XPS, BET, TGA, CO2‐TPD, SEM with elemental mapping and TEM methods. Their catalytic activities are evaluated toward the conversion of carbon dioxide (CO2) and epoxides into cyclic carbonates under solvent‐ and additive‐free environments. Apart from the synergy effect between HBDs and Cl−, it is found that the types of the spacer linking the two imidazole units in the diimidazole precursors (L1–L3) also play an important role in the catalytic activity. And IP 2, with a pyridine spacer as a Lewis base site, exhibits the best catalytic performance under solvent‐free mild conditions i. e., atmospheric pressure CO2, 80 °C, and 5 h. Notably, the catalyst demonstrates a good substrate applicability. Furthermore, IP 2 exhibited good reusability, stability, and it can be recycled for ten successive runs with stable and potential catalytic activity. This study provides an alternative route to construct IPs with efficient activity for CO2 catalytic conversion and fixation under mild‐conditions. [ABSTRACT FROM AUTHOR]

Electrochemical reduction of N2 to NH3 provides an alternative to the Haber‐Bosch process for sustainable NH3 production driven by renewable electricity. Here, we reported carbon nanotubes (CNTs) covalently modified with boron carbide (B4C) as a nonmetallic catalyst for efficient electrochemical nitrogen reduction reaction (NRR) under ambient conditions. The structure of the catalyst was characterized by transmission electron microscopy (TEM), X‐ray diffraction (XRD), elemental mapping, X‐ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The catalyst held a superior selectivity for NRR with high Faraday efficiency of 78.2 % accompanying with NH3 yield rate of 14.0 μg mg−1cat. h−1 under the condition of 0.1 M Na2SO4 and −0.6 V vs. RHE. Electrochemical experiments including cyclic voltammetry, electrochemical impedance spectroscopy and Tafel polarization curves were performed to explain the best electrochemical properties of B4C/CNTs among the samples. This work demonstrates that the strategy of covalent modification plays an important role to improve the selectivity of electrochemical NRR catalyst, thus allowing the reactions to proceed more efficiently. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel form of programmed cell death and is considered to be a druggable target for colorectal cancer (CRC) therapy. However, the role of ferroptosis in CRC and its underlying mechanism are not fully understood. In the present study we found that a protein enriched in the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3), was overexpressed in human CRC tissue and in several CRC cell lines. The expression of GOLPH3 was significantly correlated with the expression of ferroptosis‐related genes in CRC. The overexpression of GOLPH3 in Erastin‐induced Caco‐2 CRC cells reduced ferroptotic phenotypes, whereas the knockdown of GOLPH3 potentiated ferroptosis in HT‐29 CRC cells. GOLPH3 induced the expression of prohibitin‐1 (PHB1) and prohibitin‐2 (PHB2), which also inhibited ferroptosis in Erastin‐treated CRC cells. Moreover, GOLPH3 interacted with PHB2 and nuclear factor erythroid 2‐related factor 2 (NRF2) in Caco‐2 cells. These observations indicate that GOLPH3 is a negative regulator of ferroptosis in CRC cells. GOLPH3 protects these cells from ferroptosis by inducing the expression of PHB1 and PHB2, and by interacting with PHB2 and NRF2. [ABSTRACT FROM AUTHOR]

Background: Gestational Diabetes Mellitus (GDM) poses significant risks to maternal and fetal health. Current diagnostic methods based on glucose tolerance tests have limitations for early detection. tRNA‐derived small RNAs (tsRNAs) have emerged as potential molecular regulators in various diseases, including metabolic disorders. However, the diagnostic value of tsRNAs in plasma for early GDM or postpartum remains unclear. Methods: This longitudinal study profiled the expression of tsRNAs across different gestational stages and postpartum in women with GDM (n = 40) and healthy control gestational women (HCs, n = 40). High‐throughput small RNA sequencing identified candidate tsRNAs, which were then validated and correlated with clinical biochemical markers such as fasting blood glucose (FBG), HOMA‐IR, and GHbA1c. Results: tRF‐1:32‐Val‐AAC‐1‐M6, tRF‐1:31‐Glu‐CTC‐1‐M2, and tRF‐1:30‐Gly‐CCC‐1‐M4 were consistently upregulated in the GDM group compared to HCs during the second trimester (p < 0.05). Only tRF‐1:31‐Glu‐CTC‐1‐M2 was highly expressed during the first trimester, and tRF‐1:30‐Gly‐CCC‐1‐M4 increased during postpartum. tRF‐1:31‐Glu‐CTC‐1‐M2 showed a significant correlation with FBG levels in the first trimester (R = 0.317, p = 0.047). The expression of tRF‐1:30‐Gly‐CCC‐1‐M4 was significantly correlated with HOMA‐IR (r = 0.65, p < 0.001) and GHBA1c (r = 0.33, p = 0.037) during postpartum. A joint diagnostic model incorporating tsRNAs expression and clinical markers demonstrated enhanced predictive power for GDM (ROC AUC = 0.768). Conclusion: Our results revealed distinct expression patterns of specific tsRNAs in GDM, showcasing their correlation with key metabolic parameters. This underscores their promising role as biomarkers for early prediction and diagnosis of GDM. The integration of tRFs into a composite biomarker panel holds the potential to improve clinical outcomes by enabling personalized risk assessment and targeted interventions. [ABSTRACT FROM AUTHOR]

Histone phosphorylation is instrumental in regulating diverse cellular processes across eukaryotes. Unraveling the kinases that target specific histone sites is key to deciphering the underlying mechanisms. Among the various sites on histone tails that can undergo phosphorylation, the kinase responsible for H3.3S31 phosphorylation remained elusive. Since both H3.3S31ph and H3T3ph occur specifically during mitosis, and Haspin is the known kinase for H3T3 phosphorylation, we investigated its potential role in H3.3S31 phosphorylation. We employed CRISPR/Cas9, RNA interference, and specific small molecule inhibitors to eliminate Haspin function in various cell types. Our data consistently revealed a link between Haspin and H3.3S31ph. Furthermore, in vitro kinase assays provided evidence supporting Haspin's contribution to H3.3S31ph. Loss‐ and gain‐of‐function experiments targeting Haspin and Aurora B further suggested a hierarchical relationship. Haspin acts as a downstream kinase of Aurora B, specifically orchestrating H3.3S31 phosphorylation in mESCs. This study unveils a novel role for Haspin as a kinase in regulating H3.3S31 phosphorylation during mitosis. This discovery holds promise for expanding our understanding of the functional significance of Haspin and H3.3S31ph in mammals. [ABSTRACT FROM AUTHOR]

This study aimed to establish a novel noninvasive model based on the serum N‐glycan spectrum for providing an objective value for determining the stage of liver necroinflammation related to chronic hepatitis B (CHB) patients. N‐glycan profiles of the sera of 295 treatment‐naïve CHB patients were analyzed. N‐glycan profiles were tested for different liver necroinflammation stages using DNA sequence‐assisted fluorophore‐assisted carbohydrate electrophoresis. A serum N‐glycan model named N‐glycan‐LI (NGLI) using support vector machine was selected to evaluate the classification of liver necroinflammation (G < 2 and G ≥ 2). The area under the receiver operating characteristic curves (AUROCs) was 0.898 (training set, n = 236) and 0.911 (validation set, n = 59) regardless of the stage of liver fibrosis (AUROC = 0.886 and 0.926, respectively, in S < 2 and S ≥ 2 group). The NGLI correspondingly had the highest specificity (SP) of 90.79% and negative predictive value of 92.00% in an inactive stage (including immune‐tolerant [IT] and inactive‐carrier [IC] stage), had the highest positive predictive value of 95.18% in stage immune‐active, and had the highest SP of 93.94% in grey zone IT + IC. N‐glycan profiles appear to correlate well with hepatic necroinflammation in CHB when compared with liver biopsy. The newly developed model appears to reliably predict liver damage in naïve‐treatment patients with CHB. [ABSTRACT FROM AUTHOR]

DNA nanostructures, known for their programmability, ease of modification, and favourable biocompatibility, have gained widespread application in the biomedical field. Among them, Tetrahedral DNA Origami (TDOs), as a novel DNA nanostructure, possesses well‐defined structures, multiple modification sites, and large cavities, making it a promising drug carrier. However, current understanding of TDOs' interactions with biological systems, particularly with target cells and organs, remains unexplored, limiting its further applications in biomedicine. In this work, we prepared TDOs with an average particle size of 40 nm and labelled them with Cy5 fluorescent molecules. Following intravenous injection in mice, the uptake of TDOs by different types of liver and kidney cells was observed. Results indicated that TDOs accumulate in renal tubules and are metabolized by Kupffer cells, epithelial cells, and hepatocytes in the liver. Additionally, in a tumour‐bearing mouse model, TDOs passively targeted tumour tissues and exhibited excellent tumour penetration and retention after rapid metabolism in hepatocytes. Our findings provide crucial insights for the development of TDO‐based drug delivery systems. [ABSTRACT FROM AUTHOR]

For any finite group G, the Terwilliger algebra T(G) of the group association scheme satisfies the following inclusions: T0(G)⊆T(G)⊆T˜(G), where T0(G) is a specific vector space and T˜(G) is the centralizer algebra of the permutation representation of G induced by the action of conjugation. The group G is said to be triply transitive if T0(G)=T˜(G). In this paper, we determine the dimensions of T0(G) and T˜(G) for G being Tn,k=〈a,b∣a2n=1,an=b2,bab−1=ak〉, Cn⋊Cp and Cp⋊Cn, and show that Tn,k,Cn⋊C2 and C3⋊C2n are triply transitive. Additionally, we give a complete characterization of the Wedderburn components of the Terwilliger algebras of Tn,k, Cn⋊Cp and Cp⋊Cn when they are triply transitive. [ABSTRACT FROM AUTHOR]

Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi‐omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population‐specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon‐stimulated genes (ISGs). Validation through multi‐immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune‐negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi‐omics analysis integrating bulk transcriptomic, single‐cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs. Highlights: This study integrates liver bulk transcriptomic data, single‐cell sequencing data, and clinical data to analyze the factors inducing hepatic inflammation in chronic hepatitis B from a multi‐omics perspective by Bayesian regression.Macrophages secrete chemokines like CCL20 and CXCL8 to recruit immune‐exhausted T lymphocytes (CTLA4, TIGIT) into liver tissue.Innate immunity within hepatocytes is suppressed, impeding interferon‐stimulated genes from initiating antiviral effects.Activation of innate immune pathways in infiltrating T cells and macrophages further exacerbates inflammation formation. [ABSTRACT FROM AUTHOR]

Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products. [ABSTRACT FROM AUTHOR]

Objectives: High‐grade gliomas (HGGs) are highly malignant, aggressive, and have a high incidence and mortality rate. The aim of this study was to investigate survival outcomes and prognostic factors in patients with HGGs. Methods: In this retrospective study, a total of 159 patients with histologically confirmed HGGs were included. The recruitment period was from January 2011 to December 2019. We evaluated patient demographic data, tumor characteristics, treatment methods, immunocytochemistry results, overall survival (OS) time, and progression‐free survival (PFS) time using Kaplan–<>Meier survival analysis with log‐rank testing. Additionally, we employed Cox regression analysis to identify independent factors associated with survival outcomes. Results: Kaplan–Meier survival analysis revealed that the 1‐, 2‐, and 5‐years OS rates were 81.8%, 50.3%, and 12.6%, respectively. Similarly, the 1‐, 2‐, and 5‐years PFS rates were 50.9%, 22.4%, and 3.1%, respectively. The median OS duration was 35.0 months. The univariate analysis indicated that postoperative pathological classification, grade, and age were significantly associated with patient outcomes (p < 0.01). Among the patients, 147 received concurrent chemoradiotherapy, while 12 did not. The immunohistochemical markers of ki‐67, MGMT, IDH1R132H, and p53 demonstrated statistically significant differences in their prognostic impact (p = 0.001, p = 0.020, p = 0.003, and p = 0.021, respectively). In conclusion, we found that grades, age, pathological classification, ki‐67, MGMT, and IDH1R132H expression were statistically significantly associated with PFS (p < 0.01, p = 0.004, p = 0.003, p = 0.001, p = 0.036, and p = 0.028). Additionally, immunohistochemical expressions of TRIB3 and AURKA were significantly higher in patients with shorter survival (p = 0.015 and p = 0.023). Conclusions: Tumor grade and the use of concurrent chemoradiotherapy after surgery were independent prognostic factors that significantly influenced patient survival. Additionally, tumor grade and MGMT expression were found to be independent factors affecting progression‐free survival (PFS). Notably, the expression of TRIB3 and AURKA was higher in patients with poor survival outcomes. [ABSTRACT FROM AUTHOR]

Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional profiling to systematically analyze natural killer (NK) cell surface receptors, we identify leukocyte immunoglobulin like receptor B1 (LILRB1) as a critical checkpoint receptor that defines a TB-associated cell subset (LILRB1+ NK cells) and drives NK cell exhaustion in TB. Mechanistically, Mtb-infected macrophages display high expression of human leukocyte antigen-G (HLA-G), which upregulates and activates LILRB1 on NK cells to impair their functions by inhibiting mitogen-activated protein kinase (MAPK) signaling via tyrosine phosphatases SHP1/2. Furthermore, LILRB1 blockade restores NK cell-dependent anti-Mtb immunity in immuno-humanized mice. Thus, LILRB1-HLA-G axis constitutes a NK cell immune checkpoint in TB and serves as a promising immunotherapy target. Synopsis: The immune inhibitory receptor leukocyte immunoglobulin like receptor B1 (LILRB1), which is upregulated and activated by human leukocyte antigen-G (HLA-G), drives natural killer (NK) cell exhaustion in tuberculosis (TB) patients, thus serving as a promising target for TB immunotherapy. The inhibitory receptor LILRB1 defines a TB-associated NK cell subset and drives NK cell exhaustion in TB patients. Mtb-infected macrophages display high expression of HLA-G, which upregulates and activates LILRB1 on NK cells in TB patients. LILRB1-HLA-G interaction drives NK cell exhaustion by inhibiting mitogen-activated protein kinase (MAPK) signaling via tyrosine phosphatases SHP1/2. LILRB1 checkpoint blockade unleashes host NK cell-dependent anti-TB immunity. The immune inhibitory receptor leukocyte immunoglobulin like receptor B1 (LILRB1), which is upregulated and activated by human leukocyte antigen-G (HLA-G), drives natural killer (NK) cell exhaustion in tuberculosis (TB) patients, thus serving as a promising target for TB immunotherapy. [ABSTRACT FROM AUTHOR]

This article studies the model‐free learning‐based distributed cooperative tracking control of human‐in‐the‐loop multi‐agent systems in the presence of an active leader. The core role of human‐in‐the‐loop is to use the ground station to send control commands to the non‐zero control input of the leader, and then directly or indirectly control a group of agents to complete complex tasks. Meanwhile, three essential demands including the completely unknown system model, the control objective obtained optimally, as well as no initial admissible control strategy requirement, are satisfied simultaneously. It is worth emphasizing that the relevant results only satisfy one or two demands at most, which are essentially not applicable to this problem. In this article, a model‐based human‐in‐the‐loop learning algorithm is first presented to achieve the optimal tracking control, as well as the convergence of the proposed learning algorithm is proved. Then, a bias‐based data‐driven learning algorithm is proposed, which provides the potential opportunities to overcome the difficulties caused by the above‐mentioned three demands. Finally, the validity of theoretical results is testified by a numerical example. [ABSTRACT FROM AUTHOR]

The viscoelastic dampers (VEDs), which can provide both stiffness and damping, have been recently introduced into the field of structural vibration control for seismic enhancement of civil engineering structures. In this study, a kind of high damping acrylic polymer matrix VEDs (HDPVED) is developed independently, and this innovative HDPVED can solve the significant problem of service performance under medium‐high temperature environments, as well as low‐frequency vibration control under earthquake actions for civil engineering structures. To systematically investigate the influencing rules of frequency, temperature, and displacement amplitude on the mechanical properties and damping dissipation performance of HDPVEDs, a series of dynamic mechanical performance tests of the developed HDPVEDs are carried out at different frequencies, temperatures, and displacement amplitudes. The research results show that HDPVED exhibits excellent damping dissipation capability and adaptability under medium‐high temperature environments and low‐frequency excitations. The mechanical properties and energy dissipation performance present a strong correlation with frequency, temperature and displacement amplitude, and there is an obvious coupling effect between the three influencing factors. Based on the macroscopic mechanical property research of HDPVED, the microscopic damping mechanism and microscopic mechanical properties of HDPVED are then investigated. High‐order fractional derivative fraction Voigt and Maxwell model in parallel (FVMP) models are preferred to characterize the combined hyper‐elasticity and viscoelasticity owned by networked molecular chains and free molecular chains. The breaking and reconstruction theory of microphysical bonds is used to assess the effect of packing particles, and the time‐temperature equivalence principle is introduced to assess the effect of temperature. The multi‐scale refinement model is proposed, and the validity and accuracy of this model are verified by testing data of HDPVED. The study results show that the proposed model can accurately describe the effects of frequency, temperature, displacement amplitude, and microstructure on the multi‐scale mechanical properties of HDPVED. It provides a theoretical basis for the multi‐scale design and development of high damping VEDs. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the synovial joints and the dysfunction of regulatory T cells (Tregs) in the peripheral blood. Therefore, an optimal treatment strategy should aim to eliminate the inflammatory response in the joints and simultaneously restore the immune tolerance of Tregs in peripheral blood. Accordingly, we developed an efferocytosis‐mimicking nanovesicle that contains three functional factors for immunomodulating of efferocytosis, including "find me" and "eat me" signals for professional (macrophage) or non‐professional phagocytes (T lymphocyte), and "apoptotic metabolite" for metabolite digestion. We showed that efferocytosis‐mimicking nanovesicles targeted the inflamed joints and spleen of mice with collagen‐induced arthritis, further recruiting and selectively binding to macrophages and T lymphocytes to induce M2 macrophage polarization and Treg differentiation and T helper cell 17 (Th17) recession. Under systemic administration, the efferocytosis‐mimicking nanovesicles effectively maintained the pro‐inflammatory M1/anti‐inflammatory M2 macrophage balance in joints and the Treg/Th17 imbalance in peripheral blood to prevent RA progression. This study demonstrates the potential of efferocytosis‐mimicking nanovesicles for RA immunotherapy. [ABSTRACT FROM AUTHOR]

Targeting "undruggable" targets with intrinsically disordered structures is of great significance for the treatment of disease. The transcription factor c‐Myc controls global gene expression and is an attractive therapeutic target for multiple types of cancers. However, due to the lack of defined ligand binding pockets, targeted c‐Myc have thus far been unsuccessful. Herein, to address the dilemma of lacking ligands, an efficient and high throughput aptamer screening strategy is established, named polystyrene microwell plate‐based systematic evolution of ligands by exponential enrichment (microwell‐SELEX), and identify the specific aptamer (MA9C1) against c‐Myc. The multifunctional aptamer‐based Proteolysis Targeting Chimeras (PROTAC) for proteolysis of the c‐Myc (ProMyc) is developed using the aptamer MA9C1 as the ligand. ProMyc not only significantly degrades c‐Myc by the ubiquitin‐proteasome system, but also reduces the Max protein, synergistically inhibiting c‐Myc transcriptional activity. Combination of the artificial cyclization and anti‐PD‐L1 aptamer (PA1)‐based delivery system, circular PA1‐ProMyc chimeras achieve tumor regression in the xenograft tumor model, laying a solid foundation for the development of efficacious c‐Myc degrader for the clinic. Therefore, this aptamer‐based degrader provides an invaluable potential degrader in drug discovery and anti‐tumor therapy, offering a promising degrader to overcome the challenge of targeting intractable targets. [ABSTRACT FROM AUTHOR]

Layered oxides of sodium‐ion batteries suffer from severe side reactions on the electrode/electrolyte interface, leading to fast capacity degradation. Although surface reconstruction strategies are widely used to solve the above issues, the utilization of the low‐cost wet chemical method is extremely challenging for moisture‐sensitive Na‐based oxide materials. Here, the solvation tuning strategy is proposed to overcome the deterioration of NaNi1/3Mn1/3Fe1/3O2 in water‐based solution and conduct the surface reconstruction. When capturing the water molecules by the solvation structure of cations, here is Li+, the structural collapse and degradation of layered oxides in water‐based solvents are greatly mitigated. Furthermore, Li(H2O)3EA+ promotes the profitable Li+/Na+ exchange to build a robust surface, which hampers the decomposition of electrolytes and the structural evolution upon cycling. Accordingly, the lifespan of Li‐reinforced materials is prolonged to three times that of the pristine one. This work represents a step forward in understanding the surface reconstruction operated in a water‐based solution for high‐performance sodium layered oxide cathodes. [ABSTRACT FROM AUTHOR]

Layered design is an important method for improving the loss factor of damping materials. However, the composite loss factor does not increase with the increase of the number of layers of the damping material. In response to this issue, this paper investigates the mechanism by combining experimental and simulation analyses. First, for the damping material itself, the relationship between the material loss factor and the number of damping layers was studied based on dynamic mechanical analysis. Second, for the composite structure of damping material and substrate, the relationship between the composite loss factor and the number of damping layers of the free damping structure was obtained by the cantilever resonance method, and the influence of material and structure parameters on the composite loss factor was clarified by finite element analysis. Finally, for aiming at the composite structure of damping material with constraint layer and substrate, the mechanism of the influence of the number of layers of layered damping material on the uncertainty of the composite loss factor was further investigated and discussed. The results indicated that for free damping structures, the composite loss factor increases with the increase of the number of damping layers only when the elastic modulus of the damping layer is similar to that of the substrate. For constrained damping structures, only when the constraint layer is relatively thin and has a certain amount of density and modulus, the composite loss factor of the constrained damping structure increases as the number of damping layers increases. Highlights: The mechanism by which the number of layers of damping material affects the composite loss factor has been clarified.The composite loss factor does not necessarily increase as the number of layers of damping material increases.The composite loss factor of a free damping structure is mainly influenced by the Young's modulus of the damping layer.The composite loss factor of constrained damping structures is mainly influenced by the thickness, density, and modulus of the constrained layer. [ABSTRACT FROM AUTHOR]

Catalyst deactivation by sintering and coking is a long‐standing issue in metal‐catalyzed harsh high‐temperature hydrocarbon reactions. Ultrathin oxide coatings of metal nanocatalysts have recently appeared attractive to address this issue, while the porosity of the overlayer is difficult to control to preserve the accessibility of embedded metal nanoparticles, thus often leading to a large decrease in activity. Here, we report that a nanometer‐thick alumina coating of MgAl2O4‐supported metal catalysts followed by high‐temperature reduction can transform a nonporous amorphous alumina overlayer into a porous Mg1‐xAl2Oy crystalline spinel structure with a pore size of 2–3 nm and weakened acidity. The high porosity stems from the restrained Mg migration from the MgAl2O4 support to the alumina overlayer through solid‐state reactions at high temperatures. The resulting Ni/MgAl2O4 and Pt/MgAl2O4 catalysts with a porous crystalline Mg1‐xAl2Oy overlayer achieved remarkably high stability while preserving much higher activity than the corresponding alumina‐coated Ni and Pt catalysts on MgO and Al2O3 supports in the reactions of dry reforming of methane and propane dehydrogenation, respectively. [ABSTRACT FROM AUTHOR]

Despite plenty of static and dynamic mechanical measurements and modeling for bulk polydimethylsiloxane (PDMS) specimens, a notable gap exists in comprehensively understanding the dynamic mechanics under large cycle, low strain conditions, especially for microscale samples. This study integrates tensile testing and nanoindentation techniques to compare dynamic mechanical response for bulk PDMS samples and μ-pillars. The results from cyclic tensile testing, which involved up to 10,000 cycles at a strain range of 10%–20%, indicate a stabilization of energy dissipation rate after the initial 25 cycles. This attributes to stress relaxation and strain hardening, validating by rapid dual-phase exponential decay in maximum stress, coupled with an incremental increase in elastic modulus. In comparison to tensile testing, μ-pillars exhibited a 0.82% reduction in stiffness, stabilizing ~600th cycle. Concurrently, there was an approximately twofold increase in approaching distance during the initial 120 cycles, and an approximately fourfold increase in dissipated energy over the first 80 cycles, before reaching a plateau. This lagging hysteresis effect attributes to the distribution of the resultant force, including top tension, bottom compression, and base tilt. Overall, this study illuminates temporal mechanical deformations in PDMS under two application scenarios, enhancing our understanding of PDMS mechanical behavior. [ABSTRACT FROM AUTHOR]

Background: Most studies have focused on comparing blood lipid biomarkers between Parkinson's disease (PD) and normal controls (NC). However, further research is necessary to explore the impact of blood lipid levels on motor and cognitive function, as well as the progression of motor dysfunction and cognitive decline over time. Thus, the aim of this study is to investigate the relationship between blood lipid biomarkers and these indicators in individuals with PD. Methods: The cohort study enrolled 157 PD patients and 146 NC from the Tianjin Huanhu Hospital from September 2017 to September 2019. Serum lipid fractions were detected in fasting serum samples. PD patients were followed up at 2 ± 0.6 years for clinical assessment. Results: PD patients exhibited lower serum triglyceride (TG) levels as compared to NC (P = 0.008). PD male patients exhibited lower serum lipoprotein cholesterol(LDL‐C) and total cholesterol (TC) levels than female patients (LDL‐C: P = 0.034; TC: P = 0.019). Serum TG levels correlated significantly with Unified PD Rating Scale III, Hoehn and Yahr stage and Montreal Cognitive Assessment scores in PD patients. Additionally, serum TG levels were associated with follow‐up motor function decline and cognitive decline in adjusted regression models in PD patients. Conclusions: To summarise, the study findings suggest that decreased serum TG levels are significantly associated with greater motor dysfunction, cognitive dysfunction and the greater deterioration of the two indicators. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore gestational weight gain (GWG) trajectories and their associations with adverse pregnancy outcomes. A retrospective cohort study including 11,064 women with gestational diabetes mellitus (GDM) was conducted between 2015 and 2019 in China. The latent class trajectory model was used to identify GWG trajectories, and logistic regression was performed to examine odds ratio (OR) of pregnancy outcomes. Three trajectories of GWG were identified in these 11,604 women with GDM. Trajectory 1: 64.02% of women had sustained moderate GWG throughout pregnancy; Trajectory 2: 17.75% of women showed a high initial GWG but followed by a low GWG from the third trimester until delivery; Trajectory 3: 18.23% had low initial GWG but followed by drastic GWG from the second trimester until delivery. Compared with pregnant women with Trajectory 1, women with Trajectory 2 had a higher risk of large for gestational age (adjusted odds ratio [AOR]: 1.29, 95% confidence interval [CI]: 1.12–1.48) but at a lower risk of having hypertensive disorders of pregnancy (AOR: 0.76, 95% CI: 0.57–0.96). Women in Trajectory 3 were more likely to develop small for gestational age (AOR: 2.12, 95% CI: 1.62–2.78), low birthweight (AOR: 1.49, 95% CI: 1.07–2.08), preterm birth (AOR: 1.28, 95% CI: 1.05–1.63), caesarean section (AOR: 1.26, 95% CI: 1.112–1.42) and hypertensive disorders of pregnancy (AOR: 2.24, 95% CI: 1.82–2.76). The association of GWG trajectory with adverse pregnancy outcomes differs across prepregnancy body mass index and GWG categories. Women with a slow initial GWG but followed by drastic GWG had higher risks of adverse pregnancy outcomes. Early clinical recognition of poor GWG trajectory will contribute to early intervention in high‐risk groups to minimise adverse outcomes. Key messages: Gestational weight gain (GWG) is a controllable factor and is strongly associated with maternal and fetal outcomes, especially among gestational diabetes mellitus.The same total GWG may present different trajectories, and the trajectory patterns of GWG vary with women in different body mass index categories.Clarifying the relationship between GWG trajectory and adverse pregnancy outcomes may contribute to the clear goal of lifestyle interventions based on weight control.Early recognition of an unhealthy GWG trajectory may contribute to early intervention in high‐risk groups to minimise adverse outcomes. [ABSTRACT FROM AUTHOR]

Xinhui Chenpi (XHCP) is a well‐known type of Chenpi (CP) widely used as both a Chinese herb and a food ingredient. While previous studies have explored how the quality of CP changes over time, there has been limited research specifically on XHCP. This study aims to assess the chemical components and quality of XHCP based on total flavonoid content (TF), antioxidant activity (AA), and color value (CV) at two stages: freshly harvested (XHCP‐0Y) and after 3 years of storage (XHCP‐3Y). Thirty‐eight common volatile compounds were identified, and the content of 17 compounds among them, nine nonvolatile compounds, which included one alkaloid (synephrine), three phenolic acids (PA, protocatechuic acid, vanillic acid, and ferulic acid), and five flavonoids (narirutin, hesperidin, sinensetin, nobiletin, and tangeretin), were firstly detected by the newly developed gas chromatograph–mass spectrometer (GC–MS) and ultra‐performance liquid chromatography (UPLC) methods. Compared to XHCP‐0Y, the content of 17 volatile compounds and synephrine decreased in XHCP‐3Y to varying degrees, while the content of PA, five flavonoids, TF, AA, and CV increased. The reduction of dryness caused by volatile compounds and the enhancement of efficacy related to PA, flavonoids, and AA suggested improved quality of XHCP after 3 years of storage. The methods developed in this study show promise for evaluating the quality of XHCP during the aging process. [ABSTRACT FROM AUTHOR]

Aim: Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high‐risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. Methods: We enrolled 53 individuals with CHR who completed a 5‐year follow‐up with a confirmed conversion to psychosis. Granulocyte macrophage‐colony stimulating factor (GM‐CSF), interleukin (IL)‐1β, 2, 6, 8, 10, tumor necrosis factor‐α (TNF‐α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1‐year. Correlation and quantile regression analyses were performed. Results: The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF‐α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF‐α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM‐CSF levels below the 0.5 quantile, IL‐10 levels below the 0.3 quantile, IL‐2 levels below the 0.25 quantile, IL‐6 levels between the 0.65 and 0.75 quantiles, TNF‐α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL‐10 and IL‐2, and significant group effects for changes in IL‐2 and TNF‐α. Conclusions: Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles. [ABSTRACT FROM AUTHOR]

Aim: Climate is widely understood to determine elevational patterns of soil microbial communities, whereas the effects of parental material are uncertain. Changes in the composition of parental materials along elevational transects could also affect soil microbial communities by influencing soil pH and nutrient availability. Here, we aim to illustrate the combined effects of climate and parental material on the biomass and composition of soil microbial communities along an elevational transect. Location: A subtropical forest on a karst mountain (Mt. Jinfo), China. Taxon: Bacteria and Fungi. Methods: We use phospholipid fatty acid analysis (PLFA) and DNA amplicon high‐throughput sequencing to determine biomass and diversity patterns of soil microbial communities along a subtropical elevational gradient with contrasting parental materials (limestone and clasolite). Results: We observed that the microbial communities were more diverse (α‐diversity) and productive (biomass) on limestone than on clasolite. Additionally, we found that parental material played a role in shaping the composition (β‐diversity) of soil microbial communities along the elevational gradient. The impact of climate on soil microbial communities was found to be significant, albeit relatively weak. Structural equation models provided evidence for both direct and indirect effects of climate and parental material on microbial biomass and α‐diversity along the elevational gradient. Notably, the changes in soil pH, influenced by both parental material and climate, were identified as a key factor driving these effects. Main Conclusions: Our results underline the importance of both climate and parental material variations in space‐for‐time studies investigating soil microbial communities along elevational gradients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Postmenopausal osteoporosis (PMO) is associated with dysregulation of bone metabolism and gut microbiota. Quinoa is a grain with high nutritional value, and its effects and potential mechanisms on PMO have not been reported yet. Therefore, the purpose of this study is to investigate the bone protective effect of quinoa on ovariectomy (OVX) rats by regulating bone metabolism and gut microbiota. Results: Quinoa significantly improved osteoporosis‐related biochemical parameters of OVX rats and ameliorated ovariectomy‐induced bone density reduction and trabecular structure damage. Quinoa intervention may repair the intestinal barrier by upregulating the expression of tight junction proteins in the duodenum. In addition, quinoa increased the levels of Firmicutes, and decreased the levels of Bacteroidetes and Prevotella, reversing the dysregulation of the gut microbiota. This may be related to estrogen signaling pathway, secondary and primary bile acid biosynthesis, benzoate degradation, synthesis and degradation of ketone bodies, NOD‐like receptor signaling pathway and biosynthesis of tropane, piperidine and pyridine alkaloids. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and parameters related to osteoporosis. Conclusion: Quinoa could significantly reverse the high intestinal permeability and change the composition of gut microbiota in OVX rats, thereby improving bone microstructure deterioration and bone metabolism disorder, and ultimately protecting the bone loss of OVX rats. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aims: Spinocerebellar Ataxia Type 3 (SCA3) is a rare genetic ataxia that impacts the entire brain and is characterized as a neurodegenerative disorder affecting the neural network. This study explores how alterations in the functional hierarchy, connectivity, and structural changes within specific brain regions significantly contribute to the heterogeneity of symptom manifestations in patients with SCA3. Methods: We prospectively recruited 51 patients with SCA3 and 59 age‐and sex‐matched healthy controls. All participants underwent comprehensive multimodal neuroimaging and clinical assessments. In SCA3 patients, an innovative approach utilizing gradients in resting‐state functional connectivity (FC) was employed to examine atypical patterns of hierarchical processing topology from sensorimotor to supramodal regions in the cerebellum and cerebrum. Coupling analyses of abnormal FC and structural connectivity among regions of interest (ROIs) in the brain were also performed to characterize connectivity alterations. Additionally, relationships between quantitative ROI values and clinical variables were explored. Results: Patients with SCA3 exhibited either compression or expansion within the primary sensorimotor‐to‐supramodal gradient through four distinct calculation methods, along with disruptions in FC and structural connectivity coupling. A comprehensive correlation was identified between the altered gradients and the clinical manifestations observed in patients. Notably, altered fractional anisotropy values were not significantly correlated with clinical variables. Conclusion: Abnormal gradients and connectivity in the cerebellar and cerebral cortices in SCA3 patients may contribute to disrupted motor‐to‐supramodal functions. Moreover, these findings support the potential utility of FCG analysis as a biomarker for diagnosing SCA3 and assessing treatment efficacy. [ABSTRACT FROM AUTHOR]

Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case–control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan–Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan–Meier analyses showed different time‐to‐SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012–1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094–3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193–4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01–1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036–10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001–1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Protein‐protein interactions (PPIs) play a crucial role in drug discovery and disease treatment. However, the development of effective drugs targeting PPIs remains challenging due to limited methodologies for probing their spatiotemporal anisotropy. Here, we propose a single‐molecule approach using a unique force circuit to investigate PPI dynamics and anisotropy under mechanical forces. Unlike conventional techniques, this approach enables the manipulation and real‐time monitoring of individual proteins at specific amino acids with defined geometry, offering insights into molecular mechanisms at the single‐molecule level. The DNA force circuit was constructed using click chemistry conjugation methods and genetic code expansion techniques, facilitating orthogonal conjugation between proteins and nucleic acids. The SET domain of the MLL1 protein and the tail of histone H3 were used as a model system to demonstrate the application of the DNA force circuit. With the use of atomic force microscopy and magnetic tweezers, optimized assembly procedures were developed. The DNA force circuit provides an exceptional platform for studying the anisotropy of PPIs and holds promise for advancing drug discovery research targeted at PPIs. [ABSTRACT FROM AUTHOR]

Fluid diapirs are widespread in the northern South China Sea (SCS), are significant indicators of the existence and distribution of hydrocarbons and natural gas hydrates and are of great petroleum geological significance. Based on high‐precision 3D seismic and drilling data, this paper analyses the tectonic features and genetic mechanism of a fluid diapir zone in the northern SCS and a development model of fluid diapirs is proposed herein. Studies have revealed that the northern SCS large‐scale fluid diapir zone is located within a concealed structural transition zone, which is consistent with the spatial distribution location and direction of a concealed structural transition zone and that the formation of a fluid diapir zone is strongly influenced by the structural transition zone. Fluid diapirs are large continuously spreading bright reflection zones in shallow surface layers and are downwards converging high‐variance ribbons in middle and shallow layers, all of which are spreading in a NW–NNW orientation on the plane. The profile shows a conical or mushroom‐shaped shape that converges from shallow to deep, with a height of approximately 7 km and is characterized by a compound gas chimney fuzzy zone. The main body of the concealed structural transition zone is a slope structure and is flanked by large‐scale NW–NNW‐oriented fault systems. Minor en echelon spreading NW–NNW‐oriented faults and fractures are developed within the structural transition zone and are soft linkages that match well with the distribution direction and location of the fluid diapirs. On the profile, the overall display is a composite flower‐like structure dispersed from deep to shallow, which belongs to a large strike‐slip fault zone with a tectonic transformation effect. A comprehensive analysis suggests that the formation and development of the structural transition zone are mainly controlled by pre‐existing structures in the basement and that minor faults, fractures and slope zones within the structural transition zone serve as dominant pathways for the migration of deep overpressure fluids and gas hydrates. Consequently, the concealed structural transition zone provides favourable conditions for fluid diapirs to develop. Moreover, the stratigraphic overpressure systems mainly caused by gas generation provided the main driving force for the formation of fluid diapirs. Obviously, the development location, distribution direction, formation and evolution of the northern SCS fluid diapirs are jointly controlled by internal minor faults and fractures of the Eocene‐Miocene structural transition zone and the overpressure of the rifting period after the Pliocene. The main development period of the northern SCS large‐scale fluid diapirs was the second phase of the Dongsha Movement. During the exploration of gas hydrates and hydrocarbons in the Pearl River Mouth Basin, it is essential to consider the mutually restricting relationships between fluid diapir structures and gas hydrates and hydrocarbons. [ABSTRACT FROM AUTHOR]

This article examines the use of axicabtagene ciloleucel (axi-cel), a CAR T-cell therapy, as a second-line treatment for large B-cell lymphoma (LBCL) in a real-world setting. The study analyzes data from patients who received axi-cel at a single center and evaluates various outcomes such as survival rates, response rates, and side effects. The results indicate that axi-cel is effective and well-tolerated, providing valuable insights for its use in clinical practice. However, larger studies with longer follow-up are needed to further validate its efficacy and practicality. [Extracted from the article]

Diffuse large B‐cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism‐ and immune‐related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune‐related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions. [ABSTRACT FROM AUTHOR]

Currently, the concentration of carbon dioxide (CO2) has exceeded 400 ppm in the atmosphere. Thus, there is an urgent need to explore CO2 reduction and utilization technologies. Photocatalytic technology can convert CO2 to valuable hydrocarbons (CH4, CH3OH, and C2H5OH, etc.), realizing the conversion of solar energy to chemical energy as well as solving the problems of fossil fuel shortage and global warming. Graphitic carbon nitride (g‐C3N4), as a two‐dimensional nonmetallic semiconductor material, shows great potential in the field of CO2 photoreduction due to its moderate bandgap, easy synthesis method, low cost, and visible light response properties. This review elaborates the research progress of g‐C3N4‐based photocatalysts for photocatalytic CO2 reduction. The modification strategies (e.g., morphology engineering, elemental doping, crystallinity modulation, cocatalyst modification, and constructing heterojunction) of g‐C3N4‐based photocatalysts for CO2 reduction application have been discussed in detail. Finally, the challenges and development prospects of g‐C3N4‐based photocatalytic materials for CO2 reduction are presented. [ABSTRACT FROM AUTHOR]

Background: Accurate, noninvasive, and reliable assessment of epidermal growth factor receptor (EGFR) mutation status and EGFR molecular subtypes is essential for treatment plan selection and individualized therapy in lung adenocarcinoma (LUAD). Radiomics models based on 18F‐FDG PET/CT have great potential in identifying EGFR mutation status and EGFR subtypes in patients with LUAD. The validation of multi‐center data, model visualization, and interpretation are significantly important for the management, application and trust of machine learning predictive models. However, few EGFR‐related research involved model visualization and interpretation, and multi‐center trial. Purpose: To develop explainable optimal predictive models based on handcrafted radiomics features (HRFs) extracted from multi‐center 18F‐FDG PET/CT to predict EGFR mutation status and molecular subtypes in LUAD. Methods: Baseline 18F‐FDG PET/CT images of 383 LUAD patients from three hospitals and one public data set were collected. Further, 1808 HRFs were extracted from the primary tumor regions using Pyradiomics. Predictive models were built based on cross‐combination of seven feature selection methods and seven machine learning algorithms. Yellowbrick and explainable artificial intelligence technology were used for model visualization and interpretation. Receiver operating characteristic curve, classification report and confusion matrix were used for model performance evaluation. Clinical applicability of the optimal models was assessed by decision curve analysis. Results: STACK feature selection method combined with light gradient boosting machine (LGBM) reached optimal performance in identifying EGFR mutation status ([area under the curve] AUC = 0.81 in the internal test cohort; AUC = 0.62 in the external test cohort). Random forest feature selection method combined with LGBM reached optimal performance in predicting EGFR mutation molecular subtypes (AUC = 0.89 in the internal test cohort; AUC = 0.61 in the external test cohort). Conclusions: Explainable machine learning models combined with radiomics features extracted from multi‐center/scanner 18F‐FDG PET/CT have certain potential to identify EGFR mutation status and subtypes in LUAD, which might be helpful to the treatment of LUAD. [ABSTRACT FROM AUTHOR]

One of the key goals of ecology is to understand how communities are assembled. The species co‐existence theory suggests that community β‐diversity is influenced by species pool and community assembly processes, such as environmental filtering, dispersal events, ecological drift and biotic interactions. However, it remains unclear whether there are similar β‐diversity patterns among different soil microbial groups and whether all these mechanisms play significant roles in mediating β‐diversity patterns. By conducting a broad survey across Chinese deserts, we aimed to address these questions by investing biological soil crusts (biocrusts). Through amplicon‐sequencing, we acquired β‐diversity data for multiple microbial groups, that is, soil total bacteria, diazotrophs, phoD‐harbouring taxa, and fungi. Our results have shown varying distance decay rates of β‐diversity across microbial groups, with soil total bacteria showing a weaker distance‐decay relationship than other groups. The impact of the species pool on community β‐diversity varied across microbial groups, with soil total bacteria and diazotrophs being significantly influenced. While the contributions of specific assembly processes to community β‐diversity patterns varied among different microbial groups, significant effects of local community assembly processes on β‐diversity patterns were consistently observed across all groups. Homogenous selection and dispersal limitation emerged as crucial processes for all groups. Precipitation and soil C:P were the key factors mediating β‐diversity for all groups. This study has substantially advanced our understanding of how the communities of multiple microbial groups are structured in desert biocrust systems. [ABSTRACT FROM AUTHOR]