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Autoimmune diseases, allergies, transplant rejections, generation of antidrug antibodies, and chronic inflammatory diseases have impacted a large group of people across the globe. Conventional treatments and therapies often use systemic or broad immunosuppression with serious efficacy and safety issues. Tolerogenic vaccines represent a concept that has been extended from their traditional immune-modulating function to induction of antigen-specific tolerance through the generation of regulatory T cells. Without impairing immune homeostasis, tolerogenic vaccines dampen inflammation and induce tolerogenic regulation. However, achieving the desired potency of tolerogenic vaccines as preventive and therapeutic modalities calls for precise manipulation of the immune microenvironment and control over the tolerogenic responses against the autoantigens, allergens, and/or alloantigens. Engineered nano-/microparticles possess desirable design features that can bolster targeted immune regulation and enhance the induction of antigen-specific tolerance. Thus, particle-based tolerogenic vaccines hold great promise in clinical translation for future treatment of aforementioned immune disorders. In this review, we highlight the main strategies to employ particles as exciting tolerogenic vaccines, with a focus on the particles' role in facilitating the induction of antigen-specific tolerance. We describe the particle design features that facilitate their usage and discuss the challenges and opportunities for designing next-generation particle-based tolerogenic vaccines with robust efficacy to promote antigen-specific tolerance for immunotherapy.

Falls are the important causes of morbidity and mortality in older adults. Although clinical staff have paid attention to the management of falls, adherence to fall interventions is not satisfactory, resulting in the high incidence of fall. Understanding the older adults' own perception of fall risk from their perspective may be the key to fall prevention, especially active fall prevention. In this paper, we reviewed the concept of fall risk perception, behavioral consequences and influencing factors of fall risk perception in older adults from the perspective of "the first person responsible for health", and found that there are fewer studies on fall risk perception in older adults at home and abroad, the conceptual connotation still needs to be further explored. Subjective perceptions of fall risk in older adults can lead to different patterns of fall risk coping behaviors that influence fall risk. The influencing factors of fall risk perception mainly focus on the emotional psychology, physiological conditions, social culture, and physical environment, with the influencing process through subjective cognition. Empirical studies can be used to further validate the psychological cognitive mechanisms of fall risk perception in conjunction with the risk perception formation process in the future, in order to provide empirical evidence for proactive fall prevention.

Abstract In this paper, we consider a coupling mechanism between the kinetic term and the gravity, in which a coupling function F (R) is introduced into the kinetic term of the five-dimensional scalar field. Based on this scenario, we investigate the localization of scalar fields in three specific braneworld models: the Minkowski brane, the de Sitter brane, and the Anti-de Sitter brane. The brane models considered here are regular with no singularity for scalar curvature. For the Minkowshi brane case, the zero mode can always be localized on the brane, and the massive modes can be localized or quasi-localized on the brane. For the dS4 brane case, two forms of factor F (R) is considered. The zero mode can always be localized, and the massive modes could be quasi-localized on the brane. Besides, with the second coupling factor, the scalar zero mode could be localized on the both sides of the origin of extra dimension, while the massive modes could be quasi-localized on the origin. Lastly, for the AdS4 brane case, the localization of the scalar zero mode requires the consideration of a coupling potential V (Φ, φ), while the massive modes can still be localized on the brane with an infinite number.

Abstract Culture-dependent and metagenomic binning techniques were employed to gain an insight into the diversification of gut bacteria in Rhinopithecius bieti, a highly endangered primate endemic to China. Our analyses revealed that Bacillota_A and Bacteroidota were the dominant phyla. These two phyla species are rich in carbohydrate active enzymes, which could provide nutrients and energy for their own or hosts’ survival under different circumstances. Among the culturable bacteria, one novel bacterium, designated as WQ 2009T, formed a distinct branch that had a low similarity to the known species in the family Sphingobacteriaceae, based on the phylogenetic analysis of its 16S rRNA gene sequence or phylogenomic analysis. The ANI, dDDH and AAI values between WQ 2009T and its most closely related strains S. kitahiroshimense 10CT, S. pakistanense NCCP-246T and S. faecium DSM 11690T were significantly lower than the accepted cut-off values for microbial species delineation. All results demonstrated that WQ 2009T represent a novel genus, for which names Rhinopithecimicrobium gen. nov. and Rhinopithecimicrobium faecis sp. nov. (Type strain WQ 2009T = CCTCC AA 2021153T = KCTC 82941T) are proposed.

Abstract Background Hypertension (HTN) involves genetic variability in the renin‐angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen (AGT) messenger RNA (mRNA) is endogenously bound by miR‐122‐5p and rs699 A > G decreases reporter mRNA in the microRNA functional‐assay PASSPORT‐seq. The AGT promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases AGT transcription. The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C > T counterbalances AGT decreased by rs699 A > G, and when these variants occur independently, it translates to HTN‐related phenotypes. Methods We used in silico, in vitro, in vivo, and retrospective models to test this hypothesis. Results In silico, rs699 A > G is predicted to increase miR‐122‐5p binding affinity by 3%. Mir‐eCLIP results show rs699 is 40–45 nucleotides from the strongest microRNA‐binding site in the AGT mRNA. Unexpectedly, rs699 A > G increases AGT mRNA in an AGT‐plasmid‐cDNA HepG2 expression model. Genotype‐Tissue Expression (GTEx) and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A > G occurs independently from rs5051 C > T. However, GTEx and the in vitro experiments suggest rs699 A > G confers cell‐type‐specific effects on AGT mRNA abundance, and suggest paracrine renal renin‐angiotensin‐system perturbations could mediate the rs699 A > G associations with HTN. Conclusions We found that rs5051 C > T and rs699 A > G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a fourfold larger effect than in White participants. Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C > T or rs699 A > G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

Abstract Training large neural networks on big datasets requires significant computational resources and time. Transfer learning reduces training time by pre-training a base model on one dataset and transferring the knowledge to a new model for another dataset. However, current choices of transfer learning algorithms are limited because the transferred models always have to adhere to the dimensions of the base model and can not easily modify the neural architecture to solve other datasets. On the other hand, biological neural networks (BNNs) are adept at rearranging themselves to tackle completely different problems using transfer learning. Taking advantage of BNNs, we design a dynamic neural network that is transferable to any other network architecture and can accommodate many datasets. Our approach uses raytracing to connect neurons in a three-dimensional space, allowing the network to grow into any shape or size. In the Alcala dataset, our transfer learning algorithm trains the fastest across changing environments and input sizes. In addition, we show that our algorithm also outperformance the state of the art in EEG dataset. In the future, this network may be considered for implementation on real biological neural networks to decrease power consumption.

Abstract The development of cost-effective and eco-friendly fertilizers is crucial for enhancing iron (Fe) uptake in crops and can help alleviate dietary Fe deficiencies, especially in populations with limited access to meat. This study focused on the application of MgFe-layered double hydroxide nanoparticles (MgFe-LDHs) as a potential solution. We successfully synthesized and characterized MgFe-LDHs and observed that 1–10 mg/L MgFe-LDHs improved cucumber seed germination and water uptake. Notably, the application of 10 mg/L MgFe-LDHs to roots significantly increased the seedling emergence rate and growth under low-temperature stress. The application of 10 mg/L MgFe-LDHs during sowing increased the root length, lateral root number, root fresh weight, aboveground fresh weight, and hypocotyl length under low-temperature stress. A comprehensive analysis integrating plant physiology, nutrition, and transcriptomics suggested that MgFe-LDHs improve cold tolerance by upregulating SA to stimulate CsFAD3 expression, elevating GA3 levels for enhanced nitrogen metabolism and protein synthesis, and reducing levels of ABA and JA to support seedling emergence rate and growth, along with increasing the expression and activity of peroxidase genes. SEM and FTIR further confirmed the adsorption of MgFe-LDHs onto the root hairs in the mature zone of the root apex. Remarkably, MgFe-LDHs application led to a 46% increase (p

Abstract Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour’s metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H2O2-dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal——iron overload——through WNT/MYC signalling, as well as the subsequent elevated polyamine synthesis, thus forming a ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H2O2 positive feedback loop that amplifies ferroptosis. Meanwhile, we notice that ferroptotic cells release enhanced polyamine-containing extracellular vesicles into the microenvironment, thereby further sensitizing neighbouring cells to ferroptosis and accelerating the “spread” of ferroptosis in the tumour region. Besides, polyamine supplementation also sensitizes cancer cells or xenograft tumours to radiotherapy or chemotherapy through inducing ferroptosis. Considering that cancer cells are often characterized by elevated intracellular polyamine pools, our results indicate that polyamine metabolism exposes a targetable vulnerability to ferroptosis and represents an exciting opportunity for therapeutic strategies for cancer.

Abstract Background The underrepresentation of human genomic resources from Southern Chinese populations limited their health equality in the precision medicine era and complete understanding of their genetic formation, admixture, and adaptive features. Besides, linguistical and genetic evidence supported the controversial hypothesis of their origin processes. One hotspot case was from the Chinese Guangxi Pinghua Han people (GPH), whose language was significantly similar to Southern Chinese dialects but whose uniparental gene pool was phylogenetically associated with the indigenous Tai-Kadai (TK) people. Here, we analyzed genome-wide SNP data in 619 people from four language families and 56 geographically different populations, in which 261 people from 21 geographically distinct populations were first reported here. Results We identified significant population stratification among ethnolinguistically diverse Guangxi populations, suggesting their differentiated genetic origin and admixture processes. GPH shared more alleles related to Zhuang than Southern Han Chinese but received more northern ancestry relative to Zhuang. Admixture models and estimates of genetic distances showed that GPH had a close genetic relationship with geographically close TK compared to Northern Han Chinese, supporting their admixture origin hypothesis. Further admixture time and demographic history reconstruction supported GPH was formed via admixture between Northern Han Chinese and Southern TK people. We identified robust signatures associated with lipid metabolisms, such as fatty acid desaturases (FADS) and medically relevant loci associated with Mendelian disorder (GJB2) and complex diseases. We also explored the shared and unique selection signatures of ethnically different but linguistically related Guangxi lineages and found some shared signals related to immune and malaria resistance. Conclusions Our genetic analysis illuminated the language-related fine-scale genetic structure and provided robust genetic evidence to support the admixture hypothesis that can explain the pattern of observed genetic diversity and formation of GPH. This work presented one comprehensive analysis focused on the population history and demographical adaptative process, which provided genetic evidence for personal health management and disease risk prediction models from Guangxi people. Further large-scale whole-genome sequencing projects would provide the entire landscape of southern Chinese genomic diversity and their contributions to human health and disease traits.

Abstract Background Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis. This research aimed to determine the PKM2 role in lymphatic metastasis in HPC and the underlying molecular mechanism contributing to this phenomenon. Methods PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. In vitro and in vivo studies also confirmed lymphatic metastasis’s mechanism. Results Prominent PKM2 overexpression was seen in patients with lymphatic metastasis of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition, but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and lymphatic metastasis. Conclusions Our findings suggest that PKM2 may be a tumor’s promoter gene of lymphatic metastasis, which may promote lymphatic metastasis of HPC by regulating epithelial-mesenchymal transition. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.

Abstract Objective To investigate whether T2-weighted imaging (T2WI)-based intratumoral and peritumoral radiomics can predict extranodal extension (ENE) and prognosis in patients with resectable rectal cancer. Methods One hundred sixty-seven patients with resectable rectal cancer including T3T4N + cases were prospectively included. Radiomics features were extracted from intratumoral, peritumoral 3 mm, and peritumoral-mesorectal fat on T2WI images. Least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature score (Radscore) was built with logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each Radscore. A clinical-radiomics nomogram was constructed by the most predictive radiomics signature and clinical risk factors. A prognostic model was constructed by Cox regression analysis to identify 3-year recurrence-free survival (RFS). Results Age, cT stage, and lymph node-irregular border and/or adjacent fat invasion were identified as independent clinical risk factors to construct a clinical model. The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and independent clinical risk factors achieved a better AUC than the clinical model in the training (0.799 vs. 0.736) and validation cohorts (0.723 vs. 0.667). Nomogram-based ENE (hazard ratio [HR] = 2.625, 95% CI = 1.233–5.586, p = 0.012) and extramural vascular invasion (EMVI) (HR = 2.523, 95% CI = 1.247–5.106, p = 0.010) were independent risk factors for predicting 3-year RFS. The prognostic model constructed by these two indicators showed good performance for predicting 3-year RFS in the training (AUC = 0.761) and validation cohorts (AUC = 0.710). Conclusion The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and clinical risk factors could predict preoperative ENE. Combining nomogram-based ENE and MRI-reported EMVI may be useful in predicting 3-year RFS. Critical relevance statement A clinical-radiomics nomogram could help preoperative predict ENE, and a prognostic model constructed by the nomogram-based ENE and MRI-reported EMVI could predict 3-year RFS in patients with resectable rectal cancer. Key points • Intratumoral and peritumoral 3 mm Radscore showed the most capability for predicting ENE. • Clinical-radiomics nomogram achieved the best predictive performance for predicting ENE. • Combining clinical-radiomics based-ENE and EMVI showed good performance for 3-year RFS. Graphical Abstract

Abstract Background Lung cancer is one of the most common tumors in the world, and metastasis is one of the major causes of tumor-related death in lung cancer patients. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and are frequently associated with tumor metastasis in human cancers. However, the regulatory mechanisms of TAMs in lung cancer metastasis remain unclear. Methods Single-cell sequencing analysis of lung cancer and normal tissues from public databases and from 14 patients who underwent surgery at Zhongshan Hospital was performed. In vitro co-culture experiments were performed to evaluate the effects of TAMs on lung cancer migration and invasion. Changes in the expression of IL-6, STAT3, C/EBPΒ, and EMT pathway were verified using RT-qPCR, western blotting, and immunofluorescence. Dual luciferase reporter assays and ChIP were used to reveal potential regulatory sites on the transcription factor sets. In addition, the effects of TAMs on lung cancer progression and metastasis were confirmed by in vivo models. Results TAM infiltration is associated with tumor progression and poor prognosis. IL-6 secreted by TAMs can activate the JAK2/STAT3 pathway through autocrine secretion, and STAT3 acts as a transcription factor to activate the expression of C/EBPβ, which further promotes the transcription and expression of IL-6, forming positive feedback loops for IL6-STAT3-C/EBPβ-IL6 in TAMs. IL-6 secreted by TAMs promotes lung cancer progression and metastasis in vivo and in vitro by activating the EMT pathway, which can be attenuated by the use of JAK2/STAT3 pathway inhibitors or IL-6 monoclonal antibodies. Conclusions Our data suggest that TAMs promote IL-6 expression by forming an IL6-STAT3-C/EBPβ-IL6 positive feedback loop. Released IL-6 can induce the EMT pathway in lung cancer to enhance migration, invasion, and metastasis. The use of IL-6-neutralizing antibody can partially counteract the promotion of LUAD by TAMs. A novel mechanism of macrophage-promoted tumor progression was revealed, and the IL6-STAT3-C/EBPβ-IL6 signaling cascade may be a potential therapeutic target against lung cancer. Graphical Abstract IL-6 secreted by TAM acts on itself to promote STAT3 phosphorylation, and pSTAT3 transfers into the nucleus, promotes the expression of C/EBPβ. C/EBPβ is able to further promote IL-6 expression, which forms positive feedback for IL-6 secretion. IL-6 secreted by TAMs acts on lung cancer to promote their metastasis through activation of EMT.

PurposeLymph node-based staging protocols are frequently employed to evaluate the prognosis of esophageal cancer, yet their accuracy remains contentious. The present study was conducted to assess the prognostic significance of three lymph node staging systems, namely N stage, lymph node rate (LNR), and log odds of positive lymph nodes (LODDS), in patients diagnosed with advanced (T2-T4) esophageal squamous cell carcinoma (ESCC).MethodsThis cohort comprised 319 eligible patients, with an additional 409 individuals retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, forming the validation cohort. Differences in overall survival (OS) of patients between groups were assessed using the log-rank test. Prognostic independent risk variables were identified, and lymph nodes (LN) prognostic models were built using multivariate Cox regression analysis. Besides, the predictive accuracy of each model was evaluated utilizing the (-2) log-likelihood ratio (-2LLR), the likelihood ratio χ2 score (LRχ2), the Akaike information criterion (AIC), and Harrell’s concordance index (C-index). To further evaluate the potential superiority of the model, a nomogram was constructed for comparison with the conventional Tumor Node Metastasis (TNM) staging approach.ResultsIndependent prognostic factors for advanced ESCC include the N stage, LNR, and LODDS. Herein, LODDS presented higher values for C-index and LRχ2, and lower values for AIC and -2LLR in OS compared to the others. Consequently, a nomogram was constructed based on LODDS. Calibration curves exhibited strong agreement, and assessment through C-index, receiver operating characteristic (ROC) curves, and clinical decision curve analysis (DCA) demonstrated promising clinical applicability.ConclusionLODDS emerges as a promising future prognostic indicator. After surgery, the proposed model holds the potential to provide valuable treatment recommendations for patients with advanced ESCC.

Necroptosis is implicated in the pathogenesis of ischemic stroke. However, the mechanism underlying the sequential recruitment of receptor-interacting protein kinase 1 (RIPK1) and N-ethylmaleimide-sensitive fusion ATPase (NSF) in initiating necroptosis remains poorly understood, and the role of NSF in ischemic stroke is a subject of controversy. Here, we utilized a recently emerging RNA-targeting CRISPR system known as CasRx, delivered by AAVs, to knockdown Ripk1 mRNA and Nsf mRNA around the ischemic brain tissue. This approach resulted in a reduction in infarct and edema volume, as well as an improvement in neurological deficits assessed by Bederson score, RotaRod test, and Adhesive removal test, which were achieved by RIPK1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein signaling pathway involved in neuronal necroptosis. In conclusion, the downregulation of Ripk1 mRNA and Nsf mRNA mediated by CRISPR-CasRx holds promise for future therapeutic applications aimed at ameliorating cerebral lesions and neurological deficits following the ischemic stroke.

BackgroundPsoriasis is a chronic dermatological condition characterized by a complex pathogenesis that impacts approximately 3% of adults in the United States and brings enormous social burdens. For many diseases, the systemic immune-inflammatory index (SII), defined as neutrophils × platelets/lymphocytes, has been recognized as a prognostic indicator. Therefore, we conducted a cross-sectional study to assess the association between SII and psoriasis among outpatient US adults.MethodsIn this cross-sectional study, we used data on the US adults 20 to 59 years of age from the National Health and Nutrition Examination Survey (NHANES) spanning 2003–2006 and 2009–2014. Sample-weighted logistic regression and stratified analysis of subgroups were used.ResultsAmong the 16,831 adults, there were 8,801 women and 8,030 men, with a psoriasis prevalence rate of 3.0%. A fully adjusted model revealed a positive association between a SII higher than 479.15 × 109/L and a high risk of psoriasis. According to subgroup analysis and interaction testing (p for interaction > 0.05), age, sex, alcohol drinking status, marital status, and body mass index (BMI) were not significantly correlated with this positive association.ConclusionOur findings suggested that SII higher than 479.15 × 109/L was positively associated with a high risk of psoriasis among outpatient US adults. To the best of our knowledge, this is the first cross-sectional study using NHANES data focused on the risk of higher SII on psoriasis among outpatient US adults. The outcomes of this cross-sectional serve to supplement previous research, indicating a need for larger-scale prospective cohorts for further validation.

Against the backdrop of the unexpected COVID-19 epidemic, governments are facing significant challenges in mobilizing food resources, particularly fresh products. It is inevitable that there will be intermittent shortages of food during the pandemic. As a result, home food gardening has gained considerable attention from city residents and policymakers in modern cities. This is due to its potential to provide food during humanitarian emergencies and lockdown. Moreover, home food gardening is increasingly becoming a popular recreational activity in many countries, offering therapeutic benefits such as fostering social bonds through knowledge-sharing and fruit-sharing, improving mental and psychological well-being, promoting outdoor physical exercise, and strengthening the connection between humans and nature. This review provides a comprehensive summary of the latest advancements in home food gardening, including cultivated species, devices, technologies, and current issues. It also proposes perspectives based on current researches to serve as a reference for future research and development.

IntroductionIn recent years, the perceptual capabilities of robots have been significantly enhanced. However, the task execution of the robots still lacks adaptive capabilities in unstructured and dynamic environments.MethodsIn this paper, we propose an ontology based autonomous robot task processing framework (ARTProF), to improve the robot's adaptability within unstructured and dynamic environments. ARTProF unifies ontological knowledge representation, reasoning, and autonomous task planning and execution into a single framework. The interface between the knowledge base and neural network-based object detection is first introduced in ARTProF to improve the robot's perception capabilities. A knowledge-driven manipulation operator based on Robot Operating System (ROS) is then designed to facilitate the interaction between the knowledge base and the robot's primitive actions. Additionally, an operation similarity model is proposed to endow the robot with the ability to generalize to novel objects. Finally, a dynamic task planning algorithm, leveraging ontological knowledge, equips the robot with adaptability to execute tasks in unstructured and dynamic environments.ResultsExperimental results on real-world scenarios and simulations demonstrate the effectiveness and efficiency of the proposed ARTProF framework.DiscussionIn future work, we will focus on refining the ARTProF framework by integrating neurosymbolic inference.

Summary: The USP7 deubiquitinase regulates proteins involved in the cell cycle, DNA repair, and epigenetics and has been implicated in cancer progression. USP7 inhibition has been pursued for the development of anti-cancer therapies. Here, we describe the discovery of potent and specific USP7 inhibitors exemplified by FX1-5303. FX1-5303 was used as a chemical probe to study the USP7-mediated regulation of p53 signaling in cells. It demonstrates mechanistic differences compared to MDM2 antagonists, a related class of anti-tumor agents that act along the same pathway. FX1-5303 synergizes with the clinically approved BCL2 inhibitor venetoclax in acute myeloid leukemia (AML) cell lines and ex vivo patient samples and leads to strong tumor growth inhibition in in vivo mouse xenograft models of multiple myeloma and AML. This work introduces new USP7 inhibitors, differentiates their mechanism of action from MDM2 inhibition, and identifies specific opportunities for their use in the treatment of AML.

Abstract Loess-paleosol sequences have been used in Asia to study climate and environmental changes during the Quaternary. The scarcity of age control datasets and proxy indices analysis data for Asian loess has limited our understanding of loess depositional processes and the reconstruction of paleoclimatic changes from loess-paleosol records. In this study, we present a dataset that includes 1785 quartz optically stimulated luminescence ages and 1038 K-feldspar post-infrared infrared stimulated luminescence ages from 128 loess-paleosol sequences located in different regions of Asia. We generate 38 high-resolution age-depth models of loess records based on the provided datasets. We provide data on 12,365 grain size records, 14,964 magnetic susceptibility records, 2204 CaCO3 content records, and 3326 color reflection records. This dataset contains the most detailed and accurate chronologies and proxy index data for loess records in Asia yet published. It provides fundamental data for understanding the spatial-temporal variations in loess depositional processes and climatic changes across the continent during the mid-late Quaternary.

Abstract Background The hydrolysis and transphosphatidylation of phospholipase D (PLD) play important roles in the interconversion of phospholipids (PLs), which has been shown to profoundly impact lipid metabolism in plants. In this study, the effect of the PLD1 gene of Schizochytrium limacinum SR21 (S. limacinum SR21) on lipid metabolism was investigated. Results PLD1 knockout had little impact on cell growth and lipid production, but it significantly improved the percentage of polyunsaturated fatty acids in lipids, of which docosahexaenoic acid (DHA) content increased by 13.3% compared to the wild-type strain. Phospholipomics and real-time quantitative PCR analysis revealed the knockout of PLD1 reduced the interexchange and increased de novo synthesis of PLs, which altered the composition of PLs, accompanied by a final decrease in phosphatidylcholine (PC) and an increase in phosphatidylinositol, lysophosphatidylcholine, and phosphatidic acid levels. PLD1 knockout also increased DHA content in triglycerides (TAGs) and decreased it in PLs. Conclusions These results indicate that PLD1 mainly performs the transphosphatidylation activity in S. limacinum SR21, and its knockout promotes the migration of DHA from PLs to TAGs, which is conducive to DHA accumulation and storage in TAGs via an acyl CoA-independent pathway. This study provides a novel approach for identifying the mechanism of DHA accumulation and metabolic regulation strategies for DHA production in S. limacinum SR21.

Abstract The biochar amendment plays a vital role in maintaining soil health largely due to its effects on soil microbial communities. However, individual cases and the variability in biochar properties are not sufficient to draw universal conclusions. The present study aimed to reveal how the biochar application affects soil microbial communities. Metadata of 525 ITS and 1288 16S rRNA sequencing samples from previous studies were reanalyzed and machine learning models were applied to explore the dynamics of soil microbial communities under biochar amendment. The results showed that biochar considerably changed the soil bacterial and fungal community composition and enhanced the relative abundances of Acidobacteriota, Firmicutes, Basidiomycota, and Mortierellomycota. Biochar enhanced the robustness of the soil microbial community but decreased the interactions between fungi and bacteria. The random forest model combined with tenfold cross-validation were used to predict biomarkers of biochar response, indicating that potentially beneficial microbes, such as Gemmatimonadetes, Microtrichales, Candidatus_Kaiserbacteria, and Pyrinomonadales, were enriched in the soil with biochar amendment, which promoted plant growth and soil nutrient cycling. In addition, the biochar amendment enhanced the ability of bacteria to biosynthesize and led to an increase in fungal nutrient patterns, resulting in an increase in the abundance and diversity of saprophytic fungi that enhance soil nutrient cycling. The machine learning model more accurately revealed how biochar affected soil microbial community than previous independent studies. Our study provides a basis for guiding the reasonable use of biochar in agricultural soil and minimizing its negative effects on soil microecosystem. Graphical Abstract

Abstract Plastid ribosomal proteins play a crucial role in the growth and development of plants, mainly in the gene expression and translation of key genes in chloroplasts. While some information is known about the regulatory processes of plastid ribosomal proteins in various plant species, there is limited knowledge about the underlying mechanisms in rice. In this study, ethyl methanesulfonate (EMS) mutagenesis was used to generate a new mutant called wlp3 (white leaf and panicle3), characterized by white or albino leaves and panicles, which exhibited this phenotype from the second leaf stage until tillering. Furthermore, after a certain period, the newly emerging leaves developed the same phenotype as the rice variety ZH11, while the albino leaves of wlp3 showed an incomplete chloroplast structure and significantly low chlorophyll content. A transition mutation (T to C) at position 380 was identified in the coding region of the LOC_Os03g61260 gene, resulting in the substitution of isoleucine by threonine during translation. WLP3 encodes the ribosomal L18 subunit, which is localized in the chloroplast. Complementation experiments confirmed that LOC_Os03g61260 was responsible for the albino phenotype in rice. WLP3 has high expression in the coleoptile, leaves at the three-leaf stage, and panicles at the heading stage. Compared to the wild-type (WT), wlp3 exhibited reduced chlorophyll synthesis and significantly decreased expression levels of genes associated with plastid development. Yeast two-hybrid (Y2H) analysis revealed that WLP3 interacts with other ribosomal subunits, to influence chloroplast development. These results contribute to a better understanding of the underlying molecular mechanisms of chloroplast development and plastid gene translation.

Remote sensing images exhibit rich texture features and strong autocorrelation. Although the super-resolution (SR) method of remote sensing images based on convolutional neural networks (CNN) can capture rich local information, the limited perceptual field prevents it from establishing long-distance dependence on global information, leading to the low accuracy of remote sensing image reconstruction. Furthermore, it is difficult for existing SR methods to be deployed in mobile devices due to their large network parameters and high computational demand. In this study, we propose a lightweight distillation CNN-Transformer SR architecture, named DCTA, for remote sensing SR, addressing the aforementioned issues. Specifically, the proposed DCTA first extracts the coarse features through the coarse feature extraction layer and then learns the deep features of remote sensing at different scales by fusing the feature distillation extraction module of CNN and Transformer. In addition, we introduce the feature fusion module at the end of the feature distillation extraction module to control the information propagation, aiming to select the informative components for better feature fusion. The extracted low-resolution (LR) feature maps are reorganized through the up-sampling module to obtain high-resolution (HR) feature maps with high accuracy to generate high-quality HR remote sensing images. The experiments comparing different methods demonstrate that the proposed approach performs well on multiple datasets, including NWPU-RESISC45, Draper, and UC Merced. This is achieved by balancing reconstruction performance and network complexity, resulting in both competitive subjective and objective results.

Abstract Layered double hydroxides (LDHs) have been widely used in the field of plant engineering, such as DNA/RNA transformation and enhancing plant disease resistance. However, few studies have examined the direct effects of LDHs on plants and their potential utility as nanofertilizers. In this study, the retention capacity of Cu/Fe-layered double hydroxide nanoparticles (CuFe-LDHs) was assessed by comparative experiments on vegetables. The results showed that the retention of CuFe-LDHs in leafy vegetables was high, such as lettuce. Phenotypic analysis revealed that the fresh and dry weights of lettuce leaves were both increased by spraying 10–100 μg/mL CuFe-LDHs. Using the optimal concentration of 10 μg/mL, we conducted further experiments to elucidate the mechanism of CuFe-LDHs promoting lettuce growth. It was found that the application of CuFe-LDHs had a significant effect on growth and induced physiological, transcriptomic, and metabolomic changes, including an increase in the chlorophyll b content, net photosynthetic rate, and intercellular carbon dioxide concentration, as well as modifications in gene expression patterns and metabolite profiles. This work provides compelling evidence that CuFe-LDHs can efficiently adsorb on the surface of lettuce leaves through hydrogen bonding, promote lettuce growth, mitigate the toxicity of heavy metal ions compared to their raw materials at the same concentration and offer a molecular-scale insight into the response of leafy vegetables to CuFe-LDHs. Graphical Abstract

The rhizosphere is one of the key determinants of plant health and productivity. Mixtures of pesticides are commonly used in intensified agriculture. However, the combined mechanisms underlying their impacts on soil microbiota remain unknown. The present study revealed that the rhizosphere microbiota was more sensitive to azoxystrobin and oxytetracycline, two commonly used pesticides, than was the microbiota present in bulk soil. Moreover, the rhizosphere microbiota enhanced network complexity and stability and increased carbohydrate metabolism and xenobiotic biodegradation as well as the expression of metabolic genes involved in defence against pesticide stress. Co-exposure to azoxystrobin and oxytetracycline had antagonistic effects on Arabidopsis thaliana growth and soil microbial variation by recruiting organic-degrading bacteria and regulating ABC transporters to reduce pesticide uptake. Our study explored the composition and function of soil microorganisms through amplicon sequencing and metagenomic approaches, providing comprehensive insights into the synergistic effect of plants and rhizosphere microbiota on pesticides and contributing to our understanding of the ecological risks associated with pesticide use.

Abstract Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3–10 measurable advanced lung adenocarcinoma lesions who underwent first‐line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4–6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression‐free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

Introduction:Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery.Methods:Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).Results:Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target.Conclusion:Unraveling DDIT4’s involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Background Previous studies have shown that self-rated health would be used as a simple assessment indicator for frailty, and individuals with poor self-rated health status are at higher risk of frailty. However, the association between self-rated health and frailty may be different and the effectiveness of self-rated health in frailty assessment may vary in apathetic older adults. Objective To explore the moderating role of apathy in the association between self-rated health and frailty among community-dwelling older adults, so as to provide theoretical guidance for the application of the self-rated health in the assessment of frailty in apathetic older adults. Methods From November 2021 to March 2022, a total of 384 community-dwelling older adults were selected as respondents by convenience sampling method, including 179 cases in Nanjing Dongshan Community and 205 cases in Lianyungang Qinghu Community. Questionnaire surveys were conducted using the General Information Questionnaire, Fried Frailty Phenotyp (FFP) , Geriatric Depression Scale (GDS-3) , and the self-reported health (SRH) . Generalized linear model was used to analyze the association between self-rated health and frailty of community-dwelling older adults. The model 1 of the SPSS macro program process compiled by Hayes was used to analyze the moderating role of apathy on the association between the self-rated health and frailty, with simple slope analyze performed and simple slope graphs plotted. Results The median FFP and SRH item scores of 384 community-dwelling older adults were 1.00 (2.00) and 4.00 (1.00) , respectively, with the detection rate of apathy of 55.5% (213/384) . The results of the generalized linear model showed that the relationship between the self-rated health and frailty of community-dwelling older adults was significant (b=0.310, P

Abstract Background This study’s objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis. Methods A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020. Results Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia, and severe thrombocytopenia, respectively. Baseline hemoglobin level 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were shown to be independent risk factors associated with the development of severe leukopenia. Platelet level