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BACKGROUND/OBJECTIVES: The objective of this study was to determine the postprandial change in free fatty acid (FFA) profiles in subjects with impaired fasting glucose (IFG), and to evaluate the effect of low glycemic index (GI) load on postprandial FFA profiles and inflammation. SUBJECTS/METHODS: First, 50 IFG and 50 healthy subjects were recruited; and 2 -h postprandial changes in FFA profiles were determined. Second, the 50 IFG subjects then received three different loads: glucose load (GL), high glycemic index (HGI) load and low glycemic index (LGI) load, respectively. FFA profile, glucose, insulin, glucagon-like peptide 1 (GLP-1) and inflammatory biomarkers were assayed at 0, 30, 60, 90 and 120 min. RESULTS: Postprandial stearic acid (C18:0) increased compared with baseline in all subjects, whereas the change in postprandial C18:0 was more marked in IFG subjects than in healthy subjects. Compared with subjects who received the GL and HGI load, the area under the curve for insulin, GLP-1, C18:0 and tumor necrosis factor-alpha significantly decreased and adiponectin increased in subjects who received the LGI load. CONCLUSIONS: The rise in postprandial C18:0 in IFG subjects was inhibited by LGI load. European Journal of Clinical Nutrition (2016) 70, 795-801; doi: 10.1038/ejcn.2015.208; published online 6 January 2016, INTRODUCTION Much attention has recently been paid to the metabolic changes in the postprandial state, and postprandial metabolic responses are of great importance in human health. The important change in [...]

Atmospheric methane is the second most important greenhouse gas after carbon dioxide, and is responsible for about 20% of the global warming effect since pre-industrial times (1,2). Rice paddies are the largest anthropogenic methane source and produce 7-17% of atmospheric methane (2,3). Warm waterlogged soil and exuded nutrients from rice roots provide ideal conditions for methanogenesis in paddies with annual methane emissions of 25-100-million tonnes (3,4). This scenario will be exacerbated by an expansion in rice cultivation needed to meet the escalating demand for food in the coming decades (4). There is an urgent need to establish sustainable technologies for increasing rice production while reducing methane fluxes from rice paddies. However, ongoing efforts for methane mitigation in rice paddies are mainly based on farming practices and measures that are difficult to implement (5). Despite proposed strategies to increase rice productivity and reduce methane emissions (4,6), no high-starch low-methane-emission rice has been developed. Here we show that the addition of a single transcription factor gene, barley SUSIBA2 (refs 7, 8), conferred a shift of carbon flux to SUSIBA2 rice, favouring the allocation of photosynthates to aboveground biomass over allocation to roots. The altered allocation resulted in an increased biomass and starch content in the seeds and stems, and suppressed methanogenesis, possibly through a reduction in root exudates. Three-year field trials in China demonstrated that the cultivation of SUSIBA2 rice was associated with a significant reduction in methane emissions and a decrease in rhizospheric methanogen levels. SUSIBA2 rice offers a sustainable means of providing increased starch content for food production while reducing greenhouse gas emissions from rice cultivation. Approaches to increase rice productivity and reduce methane emissions as seen in SUSIBA2 rice may be particularly beneficial in a future climate with rising temperatures resulting in increased methane emissions from paddies (9,10)., High-starch content and low-methane emissions are two important traits in rice breeding that are difficult to achieve simultaneously. In 2002, high-yielding rice cultivars with improved productivity were proposed as a [...]

α-FA 1-x Cs x PbI 3 is a promising absorber material for efficient and stable perovskite solar cells (PSCs) 1,2 . However, the most efficient α-FA 1-x Cs x PbI 3 PSCs require the inclusion of methylammonium chloride (MACl) additive 3,4 , which generates volatile organic residues (i.e., MA) that limit device stability at elevated temperatures 5 . To date, the highest certified power-conversion efficiency (PCE) of α-FA 1-x Cs x PbI 3 PSCs without MACl was only ~24% (ref. 6,7 ), and has yet to exhibit any stability advantages. Here, we identify interfacial contact loss caused by the Cs + accumulation for the conventional α-FA 1-x Cs x PbI 3 PSCs, which deteriorates the device performance and stability. Through in-situ GIWAXS analysis and DFT calculations, we demonstrate an intermediate phase-assisted crystallization pathway enabled by acetate surface coordination to fabricate high-quality α-FA 1-x Cs x PbI 3 film, without using MA-additive. We herein report a certified stabilized power output (SPO) efficiency of 25.94% and a reverse-scanning PCE of 26.64% for α-FA 1-x Cs x PbI 3 PSCs, exhibiting negligible contact losses and enhanced operational stability. The devices retain >95% of their initial PCEs after over 2,000 hours operating at maximum power point under 1 sun, 85 °C, and 60% relative humidity (ISOS-L-3)., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Antioxidant capacity is an important indicator for evaluating the growth and developmental quality of rice. This study has guiding significance for the cultivation of high-nutrient-value varieties. To investigate the molecular mechanisms underlying the antioxidant characteristics of rice grains after the filling stage, Yangzinuo 1 (YZN1) was used as the experimental material, and grains collected at five different time points (7 days apart) after the filling stage were used for transcriptome sequencing. Through weighted gene coexpression network analysis (WGCNA), a coexpression network of gene weights related to antioxidant characteristics was constructed. LOC_Os10g39140, LOC_Os10g38276, and LOC_Os05g45740 were identified from the 2 modules showing the highest correlations with the target traits. GO functional annotation showed that target modules were enriched in pathways related to phenylalanine, flavonoids, and other related pathways, such as GO:0006558, GO:0006559, GO:0009812, and GO:0009813. Correlation analysis with metabolites revealed that differentially expressed genes were significantly enriched in pathways related to antioxidant characteristics and energy metabolism processes, such as glycolysis/gluconeogenesis and flavonoid biosynthesis. The core genes identified in this study were found to be highly correlated with antioxidant characteristics and enriched in pathways related to metabolic and energy pathways and molecular activities. These results provide an effective dataset supporting breeding targeting functional rice characteristics., (© 2024. The Author(s).)

With generative artificial intelligence (GenAI), particularly large language models (LLMs), continuing to make inroads in healthcare, assessing LLMs with human evaluations is essential to assuring safety and effectiveness. This study reviews existing literature on human evaluation methodologies for LLMs in healthcare across various medical specialties and addresses factors such as evaluation dimensions, sample types and sizes, selection, and recruitment of evaluators, frameworks and metrics, evaluation process, and statistical analysis type. Our literature review of 142 studies shows gaps in reliability, generalizability, and applicability of current human evaluation practices. To overcome such significant obstacles to healthcare LLM developments and deployments, we propose QUEST, a comprehensive and practical framework for human evaluation of LLMs covering three phases of workflow: Planning, Implementation and Adjudication, and Scoring and Review. QUEST is designed with five proposed evaluation principles: Quality of Information, Understanding and Reasoning, Expression Style and Persona, Safety and Harm, and Trust and Confidence., (© 2024. The Author(s).)

Two novel 16-membered macrolides, named aldgamycin Q 1 (1) and Q 2 (2), were isolated from the culture broth of the rare actinomycete Saccharothrix sp. 16Sb2-4. The structures of 1 and 2 were elucidated as new aldgamycin analogs with a demethylated mycinose residue by spectroscopic analyses and comparison with data of aldgamycin K. Compounds 1 and 2 showed moderate to weak antibacterial activities against Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus and Acinetobacter baumannii, with MIC values ranging from 16 to 64 μg mL -1 ., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

The first-order antisymmetric (A1) mode lamb wave resonator (LWR) based on Z-cut LiNbO 3 thin films has attracted significant attention and is widely believed to be a candidate for next-generation reconfigurable filters with high frequency and large bandwidth (BW). However, it is challenging for traditional interdigitated electrodes (IDTs) based LWR filters to meet the requirement of a clean frequency spectrum response and enough out-of-band (OoB) rejection. To solve the problem, we propose LWRs with checker-shaped IDTs for the design of filters that meet the Wi-Fi 6E standard. By taking advantage of checker-shaped IDTs with unparalleled boundaries, the fabricated 6-GHz resonators successfully suppress higher-order A1 spurious modes, demonstrating a spurious-free impedance response and a high figure-of-merit (FOM) up to 104. Based on the demonstrated checker-shaped electrode design, the filter features a center frequency (f 0 ) of more than 6 GHz, a 3 dB BW exceeding 620 MHz, and an excellent OoB rejection >25 dB, consistent with the acoustic-electric-electromagnetic (EM) multi-physics simulations. Furthermore, through the capacitance-inductance matching network technology, the filter's voltage standing wave ratio (VSWR) is successfully reduced below 2, showing an excellent 50 Ω impedance matching. This study lays a foundation for ultra-high-frequency and ultra-wideband filters for the Wi-Fi 6/6E application., (© 2024. The Author(s).)

Bruton tyrosine kinase inhibitor (BTKi) combined with rituximab-based chemotherapy benefits diffuse large B-cell lymphoma (DLBCL) patients. However, drug resistance is the major cause of relapse and death of DLBCL. In this study, we conducted a comprehensive analysis BTKi-resistance related genes (BRRGs) and established a 10-gene (CARD16, TRIP13, PSRC1, CASP1, PLBD1, CARD6, CAPG, CACNA1A, CDH15, and NDUFA4) signature for early identifying high-risk DLBCL patients. The resistance scores based on the BRRGs signature were associated with prognosis. Furthermore, we developed a nomogram incorporating the BRRGs signature, which demonstrated excellent performance in predicting the prognosis of DLBCL patients. Notably, tumor immune microenvironment, biological pathways, and chemotherapy sensitivity were different between high- and low-resistance score groups. Additionally, we identified TRIP13 as a key gene in our model. TRIP13 was found to be overexpressed in DLBCL and BTKi-resistant DLBCL cell lines, knocking down TRIP13 suppresses cell proliferation, promotes cell apoptosis, and enhances the apoptosis effect of BTKi on DLBCL cells by regulating the Wnt/β-catenin pathway. In conclusion, our study presents a novel BRRGs signature that could serve as a promising prognostic marker in DLBCL, and TRIP13 might be a potential therapeutic target for resistant DLBCL., (© 2024. The Author(s).)

Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson's disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with TET2 mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11-2.77, p = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, p = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with TET2 mutations, suggesting immune dysregulation in PD pathophysiology., (© 2024. The Author(s).)

Lettuce (Lactuca sativa L., Asteraceae) is one of the most important vegetable crops, known for its various horticultural types and significant morphological variation. The first reference genome of lettuce, a crisphead type (L. sativa var. capitata cv. Salinas), was previously released. Here, we reported a near-complete chromosome-level reference genome for looseleaf lettuce (L. sativa var. crispa). PacBio high-fidelity sequencing, Oxford Nanopore, and Hi-C technologies were employed to produce genome assembly. The final assembly is 2.59 Gb in length with a contig N50 of 205.47 Mb, anchored onto nine chromosomes, containing 14 recognizable telomeres and only 11 gaps. Repetitive sequences account for 77.11% of the genome, and 41,375 protein-coding genes were predicted, with 99.10% of these assigned functional annotations. This chromosome-level genome enriched genomic resources for various horticultural types of lettuce and will facilitate the characterization of morphological variation and genetic improvement in lettuce., (© 2024. The Author(s).)

Materials with electromechanical coupling are essential for transducers and acoustic devices as reversible converters between mechanical and electrical energy 1-6 . High electromechanical responses are typically found in materials with strong structural instabilities, conventionally achieved by two strategies-morphotropic phase boundaries 7 and nanoscale structural heterogeneity 8 . Here we demonstrate a different strategy to accomplish ultrahigh electromechanical response by inducing extreme structural instability from competing antiferroelectric and ferroelectric orders. Guided by the phase diagram and theoretical calculations, we designed the coexistence of antiferroelectric orthorhombic and ferroelectric rhombohedral phases in sodium niobate thin films. These films show effective piezoelectric coefficients above 5,000 pm V -1 because of electric-field-induced antiferroelectric-ferroelectric phase transitions. Our results provide a general approach to design and exploit antiferroelectric materials for electromechanical devices., (© 2024. The Author(s).)

Exploring new strategies to manipulate the order parameter of magnetic materials by electrical means is of great importance not only for advancing our understanding of fundamental magnetism but also for unlocking potential applications. A well-established concept uses gate voltages to control magnetic properties by modulating the carrier population in a capacitor structure 1-5 . Here we show that, in Pt/Al/Fe/GaAs(001) multilayers, the application of an in-plane charge current in Pt leads to a shift in the ferromagnetic resonance field depending on the microwave frequency when the Fe film is sufficiently thin. The experimental observation is interpreted as a current-induced modification of the magnetocrystalline anisotropy ΔH A of Fe. We show that (1) ΔH A decreases with increasing Fe film thickness and is connected to the damping-like torque; and (2) ΔH A depends not only on the polarity of charge current but also on the magnetization direction, that is, ΔH A has an opposite sign when the magnetization direction is reversed. The symmetry of the modification is consistent with a current-induced spin 6-8 and/or orbit 9-13 accumulation, which, respectively, act on the spin and/or orbit component of the magnetization. In this study, as Pt is regarded as a typical spin current source 6,14 , the spin current can play a dominant part. The control of magnetism by a spin current results from the modified exchange splitting of the majority and minority spin bands, providing functionality that was previously unknown and could be useful in advanced spintronic devices., (© 2024. The Author(s).)

In today's globalized agricultural system, information leakage of agricultural biological risk factors can lead to business risks and public panic, jeopardizing corporate reputation. To solve the above problems, this study constructs a blockchain network for agricultural product biological risk traceability based on agricultural product biological risk factor data to achieve traceability of biological risk traceability data of agricultural product supply chain to meet the sustainability challenges. To guarantee the secure and flexible sharing of agricultural product biological risk privacy information and limit the scope of privacy information dissemination, the blockchain-based proxy re-encryption access control method (BBPR-AC) is designed. Aiming at the problems of proxy re-encryption technology, such as the third-party agent being prone to evil, the authorization judgment being cumbersome, and the authorization process not automated, we design the proxy re-encryption access control mechanism based on the traceability of agricultural products' biological risk factors. Designing an attribute-based access control (ABAC) mechanism based on the traceability blockchain for agricultural products involves defining the attributes of each link in the agricultural supply chain, formulating policies, and evaluating and executing these policies, deployed in the blockchain system in the form of smart contracts. This approach achieves decentralization of authorization and automation of authority judgment. By analyzing the data characteristics within the agricultural product supply chain to avoid the malicious behavior of third-party agents, the decentralized blockchain system acts as a trusted third-party agent, and the proxy re-encryption is combined with symmetric encryption to improve the encryption efficiency. This ensures a efficient encryption process, making the system safe, transparent, and efficient. Finally, a prototype blockchain system for traceability of agricultural biological risk factors is built based on Hyperledger Fabric to verify this research method's reliability, security, and efficiency. The experimental results show that this research scheme's initial encryption, re-encryption, and decryption sessions exhibit lower computational overheads than traditional encryption methods. When the number of policies and the number of requests in the access control session is 100, the policy query latency is less than 400 ms, the request-response latency is slightly more than 360ms, and the data uploading throughput is 48.7 tx/s. The data query throughput is 81.8 tx/s, the system performance consumption is low and can meet the biological risk privacy protection needs of the agricultural supply chain. The BBPR-AC method proposed in this study provides ideas for achieving refined traceability management in the agricultural supply chain and promoting digital transformation in the agricultural industry., (© 2024. The Author(s).)

A 28 days pesticide degradation experiment was conducted for broccoli (Brassica oleracea L. var. italica Planch) and pakchoi (Brassica chinensis L.) with three pesticides (chlorantraniliprole (CAP), haloxyfop-etotyl (HPM), and indoxacarb (IXB)) to explore the effects of biochar on pesticide environmental fate and rhizosphere soil diversity. Rice straw biochar (RB) was applied to soil at a 25.00 t ha -1 dosage under greenhouse conditions, and its effects on the degradation of three pesticides in vegetables and in soil were investigated individually. Overall, RB application effectively facilitated CAP and HPM degradation in broccoli by 13.51-39.42% and in broccoli soil by 23.80-74.10%, respectively. RB application slowed the degradation of CAP, HPM and IXB in pakchoi by 0.00-57.17% and slowed the degradation of CAP in pakchoi by 37.32-43.40%. The results showed that the effect of RB application on pesticide degradation in crops and soil was related to biochar properties, pesticide solubility, plant growth status, and soil characteristics. Rhizosphere soil microorganisms were also investigated, and the results showed that biochar application may be valuable for altering bacterial richness and diversity. The effect of biochar application on pesticide residues in crops and soil was influenced by the vegetable variety first, and the second was pesticide characteristics. RB applied to soil at a 25.00 t ha -1 dosage under greenhouse conditions is recommended for broccoli production to ensure food safety. Our results suggested that biochar application in soil could reduce pesticide non-point source pollution, especially for highly soluble pesticides, and could affect soil microorganisms., (© 2024. The Author(s).)

Hydrogen sulfide (H 2 S), methanethiol (MeSH) and dimethylsulfide (DMS) are abundant sulfur gases with roles in biogeochemical cycling, chemotaxis and/or climate regulation. Catabolism of the marine osmolyte dimethylsulfoniopropionate (DMSP) is a major source of DMS and MeSH, but both also result from S-methylation of H 2 S via MddA, an H 2 S and MeSH S-methyltransferase whose gene is abundant in soil but scarce in marine environments. Here we identify the S-adenosine methionine (SAM)-dependent MeSH and H 2 S S-methyltransferase 'MddH', which is widespread in diverse marine bacteria and some freshwater and soil bacteria. mddH is predicted in up to ~5% and ~15% of seawater and coastal sediment bacteria, respectively, which is considerably higher than mddA. Furthermore, marine mddH transcript levels are similar to those for the most abundant DMSP lyase gene dddP. This study implies that the importance of H 2 S and MeSH S-methylation pathways in marine environments is significantly underestimated., (© 2024. The Author(s).)

In unmanned retail store, providing smart customer service requires two stages: understanding customer needs, and guiding the customer to the product. In this paper, we propose an end-to-end (Customer-to-Shelf) software service framework for unmanned retail. The framework integrates visual recognition technology to detect retail objects, large language models to analyze customer shopping needs and make proper recommendations. First, deep neural network based image recognition models are studied for implementing effective stock keeping units (SKUs) object recognition on the shelf. Second, a novel method is proposed to fine-tune large language models (LLMs) with limited training dataset. Metaheuristic approaches are used to optimize the mask locations in a low dimensional parameter space, resulting a more efficient parameter updating method for limited downstream data. Third, by facilitating an automatic analysis of customer preferences powered by large language models, we present a smart recommender system based on domain-specific knowledge, which completes the Customer-to-Shelf software service framework. Experimental results show that our proposed fine-tuning method, is more efficient than other state-of-the-art training methods for limited downstream domain dataset. Using fine-tuned large models, we can successfully create a seamless shopping experience for customers by understanding personalized needs and providing shopping advice in the unmanned retail store., (© 2024. The Author(s).)

Substance Use Disorders (SUDs) present a significant challenge to global public health, with prolonged drug use not only impairing individual health but also hindering social development. Despite various interventions aimed at addressing drug abuse and dependence, a high relapse rate remains a prominent issue. In light of this, this study aims to explore the impact of perceived stress on the relapse of individuals with SUDs, as well as the mediating role of self-control and the moderating role of social support, in hopes of providing new perspectives for interventions to reduce the risk of relapse among individuals with SUDs. By utilizing a convenience sampling method, 420 male individuals with SUDs were recruited from detoxification centers in Guangxi, China. They completed questionnaires on perceived stress, self-control, social support, and tendencies towards relapse. A total of 401 valid datasets were obtained and analyzed using the SPSS Process plugin to conduct a moderated mediation model analysis. Results: (1) Perceived stress had a positive impact on the relapse of individuals with SUDs, (2) Self-control played a partial mediating role between perceived stress and the relapse, (3) The direct effect of perceived stress on the relapse and its first half of the indirect effect were moderated by social support. The research emphasize the critical importance of learning stress management strategies, enhancing self-control, and receiving comprehensive social support in the prevention and treatment of substance dependence. By strengthening self-control and social support as both internal and external resources, the likelihood of relapse among individuals with SUDs can be reduced, contributing to more effective and comprehensive drug rehabilitation strategies., (© 2024. The Author(s).)

Accurate, fast and lightweight dense target detection methods are highly important for precision agriculture. To detect dense apricot flowers using drones, we propose an improved dense target detection method based on YOLOv8, named D-YOLOv8. First, we introduce the Dense Feature Pyramid Networks (D-FPN) to enhance the model's ability to extract dense features and Dense Attention Layer (DAL) to focus on dense target areas, which enhances the feature extraction ability of dense areas, suppresses features in irrelevant areas, and improves dense target detection accuracy. Finally, RAW data are used to enhance the dataset, which introduces additional original data into RAW images, further enriching the feature input of dense objects. We perform validation on the CARPK challenge dataset and constructed a dataset. The experimental results show that our proposed D-YOLOv8m achieved 98.37% AP, while the model parameters were only 13.2 million. The improved network can effectively support any task of dense target detection., (© 2024. The Author(s).)

The precise extraction of winter wheat planting structure holds significant importance for food security risk assessment, agricultural resource management, and governmental decision-making. This study proposed a method for extracting the winter wheat planting structure by taking into account the growth phenology of winter wheat. Utilizing the fitting effect index, the optimal Savitzky-Golay (S-G) filtering parameter combination was determined automatically to achieve automated filtering and reconstruction of NDVI time series data. The phenological phases of winter wheat growth was identified automatically using a threshold method, and subsequently, a model for extracting the winter wheat planting structure was constructed based on three key phenological stages, including seeding, heading, and harvesting, with the combination of hierarchical classification principles. A priori sample library was constructed using historical data on winter wheat distribution to verify the accuracy of the extracted results. The validation of fitting effect on different surfaces demonstrated that the optimal filtering parameters for S-G filtering could be obtained automatically by using the fitting effect index. The extracted winter wheat phenological phases showed good consistency with ground-based observational results and MOD12Q2 phenological products. Validation against statistical yearbook data and the proposed priori knowledge base exhibited high statistical accuracy and spatial precision, with an extracting accuracy of 94.92%, a spatial positioning accuracy of 93.26%, and a kappa coefficient of 0.9228. The results indicated that the proposed method for winter wheat planting structure extracting can identify winter wheat areas rapidly and significantly. Furthermore, this method does not require training samples or manual experience, and exhibits strong transferability., (© 2024. The Author(s).)

Glioblastoma (GBM) is the most common and aggressive primary brain cancer; angiogenesis and immunosuppression exacerbate GBM progression. COUP-TFII demonstrates pro-angiogenesis activity; however, its role in glioma progression remains unclear. This study revealed that COUP-TFII promotes angiogenesis in gliomas by inducing transdifferentiation of glioma cells into endothelial-like cells. Mechanistic investigation suggested that COUP-TFII as a transcription factor exerts its function via binding to the promoter of TXNIP. Interestingly, COUP-TFII knockdown attenuated tumorigenesis and tumor progression in an immunocompetent mouse model but promoted tumor progression in an immuno-deficient mouse model. As an explanation, repression of COUP-TFII induces cellular senescence and activates immune surveillance in glioma cells in vitro and in vivo. In addition, we used heparin-polyethyleneimine (HPEI) nanoparticles to deliver COUP-TFII shRNA, which regulated tumor angiogenesis and immunosuppression in an in situ GBM mouse model. This study provides a novel strategy and potential therapeutic targets to treat GBM., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease. Currently, no oral therapeutics selectively target this pathway. JNJ-77242113 is a peptide targeting the IL-23 receptor with high affinity (K D : 7.1 pM). In human cells, JNJ-77242113 potently and selectively inhibited proximal IL-23 signaling (IC 50 : 5.6 pM) without impacting IL-12 signaling. JNJ-77242113 inhibited IL-23-induced interferon (IFN)γ production in NK cells, and in blood from healthy donors and psoriasis patients (IC 50 : 18.4, 11 and 9 pM, respectively). In a rat trinitrobenzene sulfonic acid-induced colitis model, oral JNJ-77242113 attenuated disease parameters at doses ≥ 0.3 mg/kg/day. Pharmacologic activity beyond the gastrointestinal tract was also demonstrated. In blood from rats receiving oral JNJ-77242113, dose-dependent inhibition of ex vivo IL-23-stimulated IL-17A production was observed. In an IL-23-induced rat skin inflammation model, JNJ-77242113 inhibited IL-23-induced skin thickening and IL-17A, -17F and -22 gene induction. Oral dosing of JNJ-77242113 in healthy human volunteers inhibited ex vivo IL-23-stimulated IFNγ production in whole blood. Thus, JNJ-77242113 provided selective, systemic IL-23 pathway inhibition in preclinical models which translated to pharmacodynamic activity in healthy human volunteers, supporting the potential for JNJ-77242113 as a selective oral therapy for IL-23-driven immune-mediated diseases., (© 2024. The Author(s).)

The endothelial glycocalyx is damaged in postcardiac arrest syndrome (PCAS), but the prognostic value is unknown. We aimed to observe the expression and prognostic value of glycocalyx shedding products, including syndecan-1 (SDC-1), hyaluronan (HA), and heparan sulfate (HS) in PCAS. Data on clinical and 28-day outcomes of seventy-one consecutive patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC) were collected. SDC-1, HA, and HS were measured on days 0, 1, and 3 after ROSC. Thirty healthy individuals were controls. Glycocalyx shedding was observed in human umbilical vein endothelial cells (HUVECs) stimulated during hypoxia and reoxygenation in vitro. Within 4 h of ROSC, SDC-1 and HA levels, significantly increased. In the 28-day non-survivors, HA levels showed a gradual upward trend, SDC-1 remained at a high level, and HS levels first increased, then decreased. Kaplan-Meier curves and binary logistic regression analysis showed the prognostic value of SDC-1 levels on days 0, 1, and 3, HA levels on days 1 and 3, and HS levels on day 1. Only HS levels on day 1 showed a prognostic value for 28-day neurological outcomes. SDC-1 and HA levels were positively correlated with the no-flow time. In vitro, HUVECs showed shedding of SDC-1 and HS during a prolonged duration of hypoxia. After ROSC, SDC-1, HA, and HS levels may predict the 28-day survival after PCAS, and HS levels are associated with functional outcomes., (© 2024. The Author(s).)

Circulating cell-free DNA (cfDNA) in the peripheral blood is a promising biomarker for cancer diagnosis and prognosis. Somatic mutations identified in cancers have been used to detect therapeutic targets for clinical transformation and individualize drug selection, while germline variants can predict a patient's risk of developing cancer and drug sensitivity. However, no platform has been developed to analyze, calculate, integrate, and friendly visualize these pan-cancer cfDNA mutations deeply. In this work, we performed panel sequencing encompassing 1,115 cancer-related genes across 16,659 cancer patients, spanning 27 cancer types. We detected 496 germline variants in leukocytes and 11,232 somatic mutations in the cfDNA of all patients. CPGV (Cancer Peripheral blood Gene Variations), a database constructed from this dataset, is the first pan-cancer cfDNA database that encompasses somatic mutations, germline variants, and further comparative analyses of mutations across different cancer types. It bears great promise to serve as a valuable resource for cancer research., (© 2024. The Author(s).)

Multiple sclerosis (MS) is uncommon in China and the standard of care is underdeveloped, with limited utilization of disease-modifying treatment (DMT). An understanding of real-world disease burden (including direct medical, non-medical, and indirect costs, such as loss of productivity), is currently lacking in this population. To investigate the overall burden of managing patients with MS in China, a cross-sectional survey of physicians and their consulting patients with MS was conducted in 2021. Physicians provided information on healthcare resource utilization (HCRU; consultations, hospitalizations, tests, medication) and associated costs. Patients provided data on changes in their life, productivity, and impairment of daily activities due to MS. Results were stratified by disease severity using generalized linear models, with a p value < 0.05 considered statistically significant. Patients with more severe disease had greater HCRU, including hospitalizations, consultations and tests/scans, and incurred higher direct and indirect costs and productivity loss, compared with those with milder disease. However, the use of DMT was higher in patients with mild disease severity. With the low uptake and limited efficacy of non-DMT drugs, Chinese patients with MS experience a high disease burden and significant unmet needs. Therapeutic interventions could help save downstream costs and lessen societal burden., (© 2024. The Author(s).)

Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan-Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis., (© 2024. The Author(s).)

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers., (© 2024. The Author(s).)

CD8 + T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8 + T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8 + T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8 + T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8 + T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8 + T cells. Intriguingly, inhibition of ADAM17 in CD8 + T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8 + T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity., (© 2024. The Author(s).)

A literature review showed that Atg7 biological role was associated with the development and pathogenesis of nervous system, but very few reports focused on Atg7 role on neurogenesis at the region of spinal cord, so that we are committed to explore the subject. Atg7 expression in neural tube is incrementally increased during neurogenesis. Atg7 neural-specific knockout mice demonstrated the impaired motor function and imbalance of neuronal and glial cell differentiation during neurogenesis, which was similarly confirmed in primary neurosphere culture and reversely verified by Atg7 overexpression in unilateral neural tubes of gastrula chicken embryos. Furthermore, activating autophagy in neural stem cells (NSCs) of neurospheres did not rescue Atg7 deficiency-suppressed neuronal differentiation, but Atg7 overexpression on the basis of autophagy inhibition could reverse Atg7 deficiency-suppressed neuronal differentiation, which provides evidence for the existence of Atg7 role of autophagy-independent function. The underlying mechanism is that Atg7 deficiency directly caused the alteration of cell cycle length of NSCs, which is controlled by Atg7 through specifically binding Mdm2, thereby affecting neuronal differentiation during neurogenesis. Eventually, the effect of overexpressing Atg7-promoting neuronal differentiation was proved in spinal cord injury model as well. Taken together, this study revealed that Atg7 was involved in regulating neurogenesis by a non-autophagic signaling process, and this finding also shed light on the potential application in regenerative medicine., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Cyclic GMP-AMP synthase (cGAS) is a key innate immune sensor that recognizes cytosolic DNA to induce immune responses against invading pathogens. The role of cGAS is conventionally recognized as a nucleotidyltransferase to catalyze the synthesis of cGAMP upon recognition of cytosolic DNA, which leads to the activation of STING and production of type I/III interferon to fight against the pathogen. However, given that hepatocytes are lack of functional STING expression, it is intriguing to define the role of cGAS in hepatocellular carcinoma (HCC), the liver parenchymal cells derived malignancy. In this study, we revealed that cGAS was significantly downregulated in clinical HCC tissues, and its dysregulation contributed to the progression of HCC. We further identified cGAS as an immune tyrosine inhibitory motif (ITIM) containing protein, and demonstrated that cGAS inhibited the progression of HCC and increased the response of HCC to sorafenib treatment by suppressing PI3K/AKT/mTORC1 pathway in cellular and animal models. Mechanistically, cGAS recruits SH2-containing tyrosine phosphatase 1 (SHP1) via ITIM, and dephosphorylates p85 in phosphatidylinositol 3-kinase (PI3K), which leads to the suppression of AKT-mTORC1 pathway. Thus, cGAS is identified as a novel tumor suppressor in HCC via its function independent of its conventional role as cGAMP synthase, which indicates a novel therapeutic strategy for advanced HCC by modulating cGAS signaling., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Enhanced oil recovery (EOR) by in situ formation of oil-in-water emulsion in heavy oil cold production technology has received growing interest from the petroleum industry. We present an experimental study of emulsification of model oils prepared by heavy oil and its functional group compositions dissolved into toluene brought into contact with a surfactant solution. The effects of functional group composition, emulsifier concentration, temperature, pH and stirring speed on the emulsification rate of heavy oil was investigated. A second-order kinetic model characterizing the temporal variation of conductivity during the emulsification has been established. The results show that acidic and amphoteric fractions exhibit higher interfacial activity, larger emulsification rate constant and faster emulsification rate. With the increase of emulsifier concentration, the emulsification rate constant increase to the maximum value at a concentration of 0.05 mol/L before decreasing. Temperature increase benefits the emulsification rate and the activation energy of the emulsification process is 40.28 kJ/mol. Higher pH and stirring speed indicate faster emulsification rate. The heterogeneity of emulsions limits the accuracy of dynamic characterization of the emulsification process and the determination method of emulsification rate has always been controversial. The conductivity method we proposed can effectively evaluates the emulsification kinetics. This paper provides theoretical guidance for an in-depth understanding of the mechanism and application of cold recovery technology for heavy oil., (© 2024. The Author(s).)

Wilson's disease is caused by abnormal copper metabolism resulting in deposition in various organs, including the brain, liver, and cornea, thus disrupting organ function. It is characterized by encephalopathy, extrapyramidal symptoms, progressive liver failure, and copper ring deposition in the cornea. Management of this disease should include quality of life maintenance; however, relevant studies on this topic are lacking. This study aimed to assess the factors affecting the quality of life (QoL) of patients with Wilson's disease. A cross-sectional survey using convenience sampling was conducted between July 2020 and March 2021 at the hospital. Data on patient characteristics, 36-item Short-Form General Health Survey, Uniform Wilson Disease Rating Scale, and Hamilton Depression Rating Scale scores were collected. Associations among quality of life depression, anxiety, and Wilson's disease progression were examined using Pearson correlation analysis. Factors affecting the quality of life of patients, including depression, anxiety, liver function, clinical symptoms, diet, liver function, brain magnetic resonance imaging (MRI) findings, disease duration, Barthel Index, and Morse scores were examined using multivariate linear regression analysis. This study included 134 patients with Wilson's disease whose mean age was 29.12 ± 8.59 years. The mean QoL score in the patient group was 71.38 ± 9.55 points and was negatively correlated with anxiety (r = - 0.883, P = 0.000), depression (r = - 0.852 P = 0.000), and clinical symptoms (r = - 0.542, P = 0.000) scores. Anxiety, depression, and clinical symptoms severity are vital factors for the QoL of patients with Wilson's disease. The study provides foundational evidence to design novel interventions, including symptom management, diet, and self-care ability, which can help in improving the quality of life in patients with Wilson's disease and decreasing the burden associated with this disease., (© 2024. The Author(s).)

The high stretchability of two-dimensional (2D) materials has facilitated the possibility of using external strain to manipulate their properties. Hence, strain engineering has emerged as a promising technique for tailoring the performance of 2D materials by controlling the applied elastic strain field. Although various types of strain engineering methods have been proposed, deterministic and controllable generation of the strain in 2D materials remains a challenging task. Here, we report a nanoimprint-induced strain engineering (NISE) strategy for introducing controllable periodic strain profiles on 2D materials. A three-dimensional (3D) tunable strain is generated in a molybdenum disulfide (MoS 2 ) sheet by pressing and conforming to the topography of an imprint mold. Different strain profiles generated in MoS 2 are demonstrated and verified by Raman and photoluminescence (PL) spectroscopy. The strain modulation capability of NISE is investigated by changing the imprint pressure and the patterns of the imprint molds, which enables precise control of the strain magnitudes and distributions in MoS 2 . Furthermore, a finite element model is developed to simulate the NISE process and reveal the straining behavior of MoS 2 . This deterministic and effective strain engineering technique can be easily extended to other materials and is also compatible with common semiconductor fabrication processes; therefore, it provides prospects for advances in broad nanoelectronic and optoelectronic devices., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2024.)

Trichoptera is one of the most evolutionarily successful aquatic insect lineages and is highly valued value in adaptive evolution research. This study presents the chromosome-level genome assemblies of Himalopsyche anomala and Eubasilissa splendida achieved using PacBio, Illumina, and Hi-C sequencing. For H. anomala and E. splendida, assembly sizes were 663.43 and 859.28 Mb, with scaffold N50 lengths of 28.44 and 31.17 Mb, respectively. In H. anomala and E. splendida, we anchored 24 and 29 pseudochromosomes, and identified 11,469 and 10,554 protein-coding genes, respectively. The high-quality genomes of H. anomala and E. splendida provide critical genomic resources for understanding the evolution and ecology of Trichoptera and performing comparative genomics analyses., (© 2024. The Author(s).)

By collecting a large amount of data from various preloading engineering projects, a settlement prediction database was established including up to 15 feature parameters, such as final measured time, magnitude of surcharge loading, porosity ratio, internal friction angle, and others. Furthermore, a settlement prediction model of soft foundation based on random forest (RF) model was also developed. To enhance the accuracy of settlement prediction, the improved sparrow search algorithm (ISSA), which incorporates several enhancements such as the use of Logistic-tent chaotic mapping, adaptive nonlinear inertia-decreasing weight parameters, and Levy flight strategy, was proposed to optimize the hyperparameters of the RF model. The optimization results of various algorithms on benchmark functions revealed that the ISSA algorithm excelled in terms of accuracy and stability when compared to conventional algorithms such as particle swarm optimization and butterfly optimization. The ISSA-RF settlement prediction model was subsequently constructed and applied to practical projects. The results demonstrated that the ISSA-RF model exhibited superior prediction accuracy and applicability compared to the RF model. It can therefore provide valuable guidance for the planning and implementation of preloading engineering projects., (© 2024. The Author(s).)

Li-ion batteries (LIBs) for electric vehicles and aviation demand high energy density, fast charging and a wide operating temperature range, which are virtually impossible because they require electrolytes to simultaneously have high ionic conductivity, low solvation energy and low melting point and form an anion-derived inorganic interphase 1-5 . Here we report guidelines for designing such electrolytes by using small-sized solvents with low solvation energy. The tiny solvent in the secondary solvation sheath pulls out the Li + in the primary solvation sheath to form a fast ion-conduction ligand channel to enhance Li + transport, while the small-sized solvent with low solvation energy also allows the anion to enter the first Li + solvation shell to form an inorganic-rich interphase. The electrolyte-design concept is demonstrated by using fluoroacetonitrile (FAN) solvent. The electrolyte of 1.3 M lithium bis(fluorosulfonyl)imide (LiFSI) in FAN exhibits ultrahigh ionic conductivity of 40.3 mS cm -1 at 25 °C and 11.9 mS cm -1 even at -70 °C, thus enabling 4.5-V graphite||LiNi 0.8 Mn 0.1 Co 0.1 O 2 pouch cells (1.2 Ah, 2.85 mAh cm -2 ) to achieve high reversibility (0.62 Ah) when the cells are charged and discharged even at -65 °C. The electrolyte with small-sized solvents enables LIBs to simultaneously achieve high energy density, fast charging and a wide operating temperature range, which is unattainable for the current electrolyte design but is highly desired for extreme LIBs. This mechanism is generalizable and can be expanded to other metal-ion battery electrolytes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Eliminating conventional pulsed B 0 -gradient coils for magnetic resonance imaging (MRI) can significantly reduce the cost of and increase access to these devices. Phase shifts induced by the Bloch-Siegert shift effect have been proposed as a means for gradient-free, RF spatial encoding for low-field MR imaging. However, nonlinear phasor patterns like those generated from loop coils have not been systematically studied in the context of 2D spatial encoding. This work presents an optimization algorithm to select an efficient encoding trajectory among the nonlinear patterns achievable with a given hardware setup. Performance of encoding trajectories or projections was evaluated through simulated and experimental image reconstructions. Results show that the encodings schemes designed by this algorithm provide more efficient spatial encoding than comparison encoding sets, and the method produces images with the predicted spatial resolution and minimal artifacts. Overall, the work demonstrates the feasibility of performing 2D gradient-free, low-field imaging using the Bloch-Siegert shift which is an important step towards creating low-cost, point-of-care MR systems., (© 2024. The Author(s).)

Skin diseases pose significant challenges in China. Internet health forums offer a platform for millions of users to discuss skin diseases and share images for early intervention, leaving large amount of valuable dermatology images. However, data quality and annotation challenges limit the potential of these resources for developing diagnostic models. In this study, we proposed a deep-learning model that utilized unannotated dermatology images from diverse online sources. We adopted a contrastive learning approach to learn general representations from unlabeled images and fine-tuned the model on coarsely annotated images from Internet forums. Our model classified 22 common skin diseases. To improve annotation quality, we used a clustering method with a small set of standardized validation images. We tested the model on images collected by 33 experienced dermatologists from 15 tertiary hospitals and achieved a 45.05% top-1 accuracy, outperforming the published baseline model by 3%. Accuracy increased with additional validation images, reaching 49.64% with 50 images per category. Our model also demonstrated transferability to new tasks, such as detecting monkeypox, with a 61.76% top-1 accuracy using only 50 additional images in the training process. We also tested our model on benchmark datasets to show the generalization ability. Our findings highlight the potential of unannotated images from online forums for future dermatology applications and demonstrate the effectiveness of our model for early diagnosis and potential outbreak mitigation., (© 2024. The Author(s).)

Electrode-based electrical stimulation underpins several clinical bioelectronic devices, including deep-brain stimulators 1,2 and cardiac pacemakers 3 . However, leadless multisite stimulation is constrained by the technical difficulties and spatial-access limitations of electrode arrays. Optogenetics offers optically controlled random access with high spatiotemporal capabilities, but clinical translation poses challenges 4-6 . Here we show tunable spatiotemporal photostimulation of cardiac systems using a non-genetic platform based on semiconductor-enabled biomodulation interfaces. Through spatiotemporal profiling of photoelectrochemical currents, we assess the magnitude, precision, accuracy and resolution of photostimulation in four leadless silicon-based monolithic photoelectrochemical devices. We demonstrate the optoelectronic capabilities of the devices through optical overdrive pacing of cultured cardiomyocytes (CMs) targeting several regions and spatial extents, isolated rat hearts in a Langendorff apparatus, in vivo rat hearts in an ischaemia model and an in vivo mouse heart model with transthoracic optical pacing. We also perform the first, to our knowledge, optical override pacing and multisite pacing of a pig heart in vivo. Our systems are readily adaptable for minimally invasive clinical procedures using our custom endoscopic delivery device, with which we demonstrate closed-thoracic operations and endoscopic optical stimulation. Our results indicate the clinical potential of the leadless, lightweight and multisite photostimulation platform as a pacemaker in cardiac resynchronization therapy (CRT), in which lead-placement complications are common., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The intrinsic mechanisms that regulate neurotoxic versus neuroprotective astrocyte phenotypes and their effects on central nervous system degeneration and repair remain poorly understood. Here we show that injured white matter astrocytes differentiate into two distinct C3-positive and C3-negative reactive populations, previously simplified as neurotoxic (A1) and neuroprotective (A2) 1,2 , which can be further subdivided into unique subpopulations defined by proliferation and differential gene expression signatures. We find the balance of neurotoxic versus neuroprotective astrocytes is regulated by discrete pools of compartmented cyclic adenosine monophosphate derived from soluble adenylyl cyclase and show that proliferating neuroprotective astrocytes inhibit microglial activation and downstream neurotoxic astrocyte differentiation to promote retinal ganglion cell survival. Finally, we report a new, therapeutically tractable viral vector to specifically target optic nerve head astrocytes and show that raising nuclear or depleting cytoplasmic cyclic AMP in reactive astrocytes inhibits deleterious microglial or macrophage cell activation and promotes retinal ganglion cell survival after optic nerve injury. Thus, soluble adenylyl cyclase and compartmented, nuclear- and cytoplasmic-localized cyclic adenosine monophosphate in reactive astrocytes act as a molecular switch for neuroprotective astrocyte reactivity that can be targeted to inhibit microglial activation and neurotoxic astrocyte differentiation to therapeutic effect. These data expand on and define new reactive astrocyte subtypes and represent a step towards the development of gliotherapeutics for the treatment of glaucoma and other optic neuropathies., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) is a series of artificial compounds which is associated with human health. However, there are few studies on the relationship between PFASs and hypertension. In this study, we examined the association between different kinds of PFASs and hypertension. Multivariable logistic regression and subgroup analysis were adopted to assess the associations between PFASs and hypertension. Spline smoothing plots and linear regression were used to assess the relationship between PFASs and blood pressure. We found a positive association between serum PFDeA concentrations and the prevalence of hypertension after fully adjusting confounders (OR = 1.2, P = 0.01), but other types of PFASs showed no positive results. Subgroup analysis stratified by ethnicity showed there was a stronger relationship among non-Hispanics than Hispanics. Serum PFDeA concentrations were positively associated with systolic pressure (β = 0.7, P< 0.01) and diastolic blood pressure (β = 0.8, P< 0.01) among non-Hispanics who did not take antihypertensive drugs. This study showed that PFDeA exposure was associated with hypertension in Americans who identify as non-Hispanic. There was a positive association between PFDeA and blood pressure in non-Hispanic Americans who did not take antihypertensive drugs., (© 2024. The Author(s).)

Lewis lung carcinoma (LLC), as a widely used preclinical cancer model, has still not been genetically and genomically characterized. Here, we performed a whole-exome sequencing analysis on the LLC cell line to elucidate its molecular characteristics and etiologies. Our data showed that LLC originated from a male mouse belonging to C57BL/6L (a transitional strain between C57BL/6J and C57BL/6N) and contains substantial somatic SNV and InDel mutations (> 20,000). Extensive regional mutation clusters are present in its genome, which were caused mainly by the mutational processes underlying the SBS1, SBS5, SBS15, SBS17a, and SBS21 signatures during frequent structural rearrangements. Thirty three deleterious mutations are present in 30 cancer genes including Kras, Nras, Trp53, Dcc, and Cacna1d. Cdkn2a and Cdkn2b are biallelically deleted from the genome. Five pathways (RTK/RAS, p53, cell cycle, TGFB, and Hippo) are oncogenically deregulated or affected. The major mutational processes in LLC include chromosomal instability, exposure to metabolic mutagens, spontaneous 5-methylcytosine deamination, defective DNA mismatch repair, and reactive oxygen species. Our data also suggest that LLC is a lung cancer similar to human lung adenocarcinoma. This study lays a molecular basis for the more targeted application of LLC in preclinical research., (© 2024. The Author(s).)

Cotton is a significant cash crop and the primary source of natural fiber globally. Among the numerous diseases encountered in cotton production, Verticillium wilt is one of the most serious, caused by the pathogen Verticillium dahliae (V. dahliae). Unfortunately, there are no effective targeted methods to combat this disease. Genomic resources for Verticillium wilt resistance primarily exist in Gossypium barbadense (G. barbadense). Regrettably, there have been limited transcriptomic comparisons between V. dahliae-resistant and -susceptible varieties of G. barbadense due to the scarcity of susceptible resources. In this study, we conducted a transcriptome analysis on both V. dahliae-resistant and -susceptible varieties of G. barbadense at the 0, 12, 24 and 48 hours after V. dahliae inoculation. This comparative transcriptome analysis yielded high-quality data and offered new insights into the molecular mechanisms underlying cotton's resistance against this destructive pathogen., (© 2024. The Author(s).)

Although an increased risk of myocarditis has been observed after vaccination with mRNA encoding severe acute respiratory syndrome coronavirus 2 spike protein, its underlying mechanism has not been elucidated. This study investigated the direct effects of spike receptor-binding domain (S-RBD) on human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs). Immunostaining experiments using ACE2 wild-type (WT) and knockout (KO) iPSC-CMs treated with purified S-RBD demonstrated that S-RBD was bound to ACE2 and internalized into the subcellular space in the iPSC-CMs, depending on ACE2. Immunostaining combined with live cell imaging using a recombinant S-RBD fused to the superfolder GFP (S-RBD-sfGFP) demonstrated that S-RBD was bound to the cell membrane, co-localized with RAB5A, and then delivered from the endosomes to the lysosomes in iPSC-CMs. Quantitative PCR array analysis followed by single cell RNA sequence analysis clarified that S-RBD-sfGFP treatment significantly upregulated the NF-kβ pathway-related gene (CXCL1) in the differentiated non-cardiomyocytes, while upregulated interferon (IFN)-responsive genes (IFI6, ISG15, and IFITM3) in the matured cardiomyocytes. S-RBD-sfGFP treatment promoted protein ISGylation, an ISG15-mediated post-translational modification in ACE2-WT-iPSC-CMs, which was suppressed in ACE2-KO-iPSC-CMs. Our experimental study demonstrates that S-RBD is internalized through the endolysosomal pathway, which upregulates IFN-responsive genes and promotes ISGylation in the iPSC-CMs., (© 2023. The Author(s).)

3D reconstruction is the process of obtaining the three-dimensional shape or surface structure of an object, which is widely used in advanced manufacturing fields such as automotive, aerospace, industrial inspection, and reverse engineering. However, due to the structural characteristics of the component itself, the reflective properties of the coating material, and other factors, there may be specular reflection during image acquisition, making it difficult to achieve complete 3D reconstruction of the component. This paper proposes a method to address the problem of incomplete 3D reconstruction of strongly reflective objects by recognizing outlier points and filling point cloud holes. The proposed View-Transform-PointNet outlier point recognition network improves the alignment of the initial point cloud plane and implements secondary alignment of the point cloud based on the perpendicularity between the outlier plane in mixed reflection and the point cloud plane. The point cloud hole-filling method is based on the principle of outlier formation and approximates a local Gaussian distribution to linear variation. The distance between the end of each outlier plane and the real surface is calculated to repair the depth information of outlier points. The proposed method achieves a 39.4% increase in the number of point cloud filling, a 45.2% increase in the number of triangular mesh faces, a 46.9% increase in surface area, and a chamfer distance (CD) of 0.4471009, which is better than existing geometric repair methods in terms of standard deviation and smoothness. The method improves the alignment of initial point cloud planes and enhances the accuracy of outlier point recognition, which are the main innovative points of this study. The 3D reconstruction of the repaired point cloud model is achieved through Poisson equation and parameter adjustment. The proposed method reduces the error caused by large curvature in the boundary region and improves the smoothness and accuracy of the reconstructed model., (© 2023. The Author(s).)

The association between sugar-sweetened beverages intake and colorectal cancer (CRC) remains controversial. A metaanalysis was performed to clarify the correlation between sugar-sweetened beverages and CRC risk/mortality. A systematic literature search was conducted in PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Sinomed (CBM), Wanfang Data Knowledge Service Platform, and China Science and Technology Journal VIP database. Articles were restricted to be available in any language until March 31, 2022. The highest exposed categories were used to calculate the pooled relative risks (RR) values. Pooled relative risks (RR) and 95% confidence intervals (CI) were used to estimate the association of sugar-sweetened beverages with CRC risk and mortality. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I2 statistic. A total of 17 studies (6 case-control and 11 cohort) involving 557,391 subjects were included in this meta-analysis. The pooled RRs for CRC incidence and mortality among people taking sugar-sweetened beverages were 1.17 (95% CI: 1.07-1.28) and 1.13 (95% CI: 0.99-1.29), respectively. In subgroup analysis, a correlation was found in the distal colon with a pooled RR of 1.41 (95% CI: 1.10-1.80). There was no correlation in the proximal colon with a pooled RR of 1.58 (95% CI: 0.79-3.17). We found statistically significant associations between CRC incidence and sugar-sweetened beverages intake in North America and Oceania, with pooled RRs of 1.16 (95% CI: 1.00-1.33) and 1.32 (95% CI: 1.13-1.55), respectively. In sensitivity analysis, after excluding each study and calculating heterogeneity and effect sizes, there was still a correlation between sugar-sweetened beverages intake and CRC risk. This meta-analysis suggests that sugar-sweetened beverages intake may increase CRC risk, independent of CRC mortality. Whether CRC risk increases with increased sugar-sweetened beverage intake needs further investigation in the future. This meta-analysis aimed to indicate the relationship between sugar-sweetened beverages intake and the risk and mortality of colorectal cancer. A total of 17 studies involving 557,391 subjects were included. The results showed that sugar-sweetened beverages may increase the risk of colorectal cancer but may not be associated with colorectal cancer mortality., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The past decades have witnessed the evolution of electronic and photonic integrated circuits, from application specific to programmable 1,2 . Although liquid-phase DNA circuitry holds the potential for massive parallelism in the encoding and execution of algorithms 3,4 , the development of general-purpose DNA integrated circuits (DICs) has yet to be explored. Here we demonstrate a DIC system by integration of multilayer DNA-based programmable gate arrays (DPGAs). We find that the use of generic single-stranded oligonucleotides as a uniform transmission signal can reliably integrate large-scale DICs with minimal leakage and high fidelity for general-purpose computing. Reconfiguration of a single DPGA with 24 addressable dual-rail gates can be programmed with wiring instructions to implement over 100 billion distinct circuits. Furthermore, to control the intrinsically random collision of molecules, we designed DNA origami registers to provide the directionality for asynchronous execution of cascaded DPGAs. We exemplify this by a quadratic equation-solving DIC assembled with three layers of cascade DPGAs comprising 30 logic gates with around 500 DNA strands. We further show that integration of a DPGA with an analog-to-digital converter can classify disease-related microRNAs. The ability to integrate large-scale DPGA networks without apparent signal attenuation marks a key step towards general-purpose DNA computing., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)